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Epithelial ion transport in rabbit corneas following myopic keratomileusis.
Swinger, C A; Candia, O A; Marcus, S; Barker, B A; Kornmehl, E W
In isolated rabbit corneas that had undergone lamellar keratectomy or myopic keratomileusis, the stimulation of chloride transport by 10(-5) M epinephrine was completely inhibited at 1 week following surgery. At 28 days following surgery, both groups responded to 10(-7) M epinephrine. The response to 10(-5) M amphotericin B was normal both at 1 week and at 28 days following surgery. We conclude that, although the Na-K pump was not affected by the lamellar keratectomy and cryolathing, that either the epithelial beta receptors and/or the cAMP pathway were temporarily inhibited for at least 1 week following surgery. A lamellar keratectomy, therefore, can have an adverse effect on the epithelial transport system of the corneal epithelium even though the epithelium may appear normal clinically.
Laser in situ keratomileusis flap stability in an aviator following aircraft ejection.
Richmond, Christopher J; Barker, Patrick D; Levine, Edgar M; Hofmeister, Elizabeth M
We present the case of a 28-year-old male F/A-18F Super Hornet naval flight officer who ejected from an aircraft at 13 000 feet at a speed in excess of 350 knots 7 years after uneventful laser in situ keratomileusis (LASIK). The patient was evaluated the day after the ejection. No LASIK flap complications or epithelial defects were found, and the corrected distance visual acuity was 20/15 in both eyes.
Dry eye after laser in-situ keratomileusis.
Raoof, Duna; Pineda, Roberto
Laser-assisted in-situ keratomileusis (LASIK) is one of the most commonly performed refractive procedures with excellent visual outcomes. Dry eye syndrome is one of the most frequently seen complications after LASIK, with most patients developing at least some mild dry eye symptoms postoperatively. To achieve improved visual outcomes and greater patient satisfaction, it is essential to identify patients prone to dry eyes preoperatively, and initiate treatment early in the course. Enhanced understanding of the pathophysiology of post-LASIK dry eye will help advance our approach to its management.
Culture-negative ulcerative keratitis after laser in situ keratomileusis.
Lam, D S; Leung, A T; Wu, J T; Fan, D S; Cheng, A C; Wang, Z
A 40-year old man, highly myopic in both eyes, had laser in situ keratomileusis (LASIK) in the left eye in November 1996. Corneal melting and ulceration and fine striae-like interface infiltrates were noticed 1 day postoperatively. There was no response to intensive topical antibiotics in the form of hourly ofloxacin 3% (Tarivid), and satellite lesions developed on day 4. Corneal scrapings for gram stain and culture were done twice. No bacterial or fungal organisms were identified. Intensive topical fortified vancomycin (50 mg/mL) was added, and the lesions resolved gradually over the ensuing 2 weeks. Eighteen months after LASIK, refraction was -1.50 - 0.75 x 105 in the left eye, and uncorrected visual acuity was 20/70, correctable to 20/25 with spectacles.
Lamellar interface fluid accumulation following traumatic corneal perforation and laser in situ keratomileusis.
Bushley, D Matthew; Holzinger, Karl A; Winkle, R Kevin; Le, Lam H; Olkowski, John D
A 41-year-old man with myopic astigmatism had laser in situ keratomileusis (LASIK) in each eye in April 2002. Ten months later, he sustained a central perforating corneal injury to the right eye. One day following repair of the corneal wound, he presented with diffuse corneal epithelial microcystic edema, lamellar interface fluid accumulation, and 20/400 visual acuity. Additional sutures were placed to close a presumed posterior wound gape with complete resolution of the corneal edema and lamellar interface fluid collection. One year later, his best corrected visual acuity measured 20/20+ in the right eye. This case is the first to document lamellar interface fluid accumulation following LASIK owing to traumatic disruption of the corneal endothelium.
Diplopia after laser in situ keratomileusis (LASIK) in a patient with a history of strabismus.
Heinmiller, Laura J; Wasserman, Barry N
In patients with a history of strabismus, refractive surgery can result in decompensation of ocular alignment, with subsequent diplopia. Refractive surgery in the management of strabismus has been described, although it remains controversial. We present a young adult with past history of strabismus surgery and new-onset diplopia after refractive surgery. Binocular diplopia was treated surgically with laser in situ keratomileusis.
Diffuse lamellar keratitis associated with iritis 10 months after laser in situ keratomileusis.
Keszei, V A
A 35-year-old man developed diffuse lamellar keratitis (DLK) 10 months after laser in situ keratomileusis (LASIK). The DLK was associated with acute iritis, not with manipulation of the LASIK flap or epithelium. This case supports the hypothesis that DLK is a nonspecific inflammatory response of the cornea rather than a specific agent causing the syndrome.
Microcapillary sign of flap alignment in femtosecond laser-assisted in situ keratomileusis
Fawzy, Fathy; Wahba, Sherine S; Fawzy, Nader
We present an observational sign that ensures perfect alignment during femtosecond laser-assisted in situ keratomileusis (FS LASIK). Alignment is assured when a microsponge is used to dry the flap and the area of dryness exceeds the area of direct touch of the microsponge. The area might even reach the whole circumference of the flap at the first touch. This sign of alignment can be explained by microcapillary action. This sign was not elicited in flaps created by a microkeratome. PMID:27799731
Comparison of efficacy, safety, and predictability of laser in situ keratomileusis using two laser suites
Meidani, Alexandra; Tzavara, Chara
Purpose The main aim of this study was to compare the efficacy, safety, and predictability of femtosecond laser-assisted in situ keratomileusis performed by two different laser suites in the treatment of myopia for up to 6 months. Methods In this two-site retrospective nonrandomized study, myopic eyes that underwent laser-assisted in situ keratomileusis using IntraLase FS 60 kHz formed group 1 and those using WaveLight FS200 femtosecond laser system formed group 2. Ablation was performed with Visx Star S4 IR and WaveLight EX500 Excimer lasers, respectively, in groups 1 and 2. Both groups were well matched for age, sex, and mean level of preoperative refractive spherical equivalent (MRSE). Uncorrected distance visual acuity, corrected distance visual acuity, and MRSE were evaluated preoperatively and at 1 week, 1 month, and 6 months after treatment. Results Fifty-six eyes of 28 patients were included in the study. At 6-month follow-up postop, 78.6% of eyes in group 1 and 92.8% of eyes in group 2 achieved an uncorrected distance visual acuity of 20/20 or better (P=0.252). 35.7% and 50% in group 1 and group 2, respectively, gained one line (P=0.179). No eye lost lines of corrected distance visual acuity. Twenty-five eyes in group 1 (92.7%) and 27 eyes in group 2 (96.3%) had MRSE within ±0.5 D in the 6-month follow-up (P>0.999). The mean efficacy index at 6 months was similar in group 1 and group 2 (mean 1.10±0.12 [standard deviation] vs 1.10±0.1) (P=0.799). The mean safety index was similar in group 1 and group 2 (mean 1.10±0.10 [standard deviation] vs 1.10±0.09) (P=0.407). Conclusion: The outcomes were excellent between the two laser suites. There were no significant differences at 6-month follow-up postop between the two laser systems. PMID:27601880
Recent advances in laser in situ keratomileusis-associated dry eye.
Xie, Wenjia
Dry eye is the most common complication after laser in situ keratomileusis (LASIK). The major cause of LASIK-associated dry eye is corneal nerve damage. Early identification and treatment of post-operative dry eye are essential to prevent further ocular surface damage. This article reviews the recent studies of LASIK-associated dry eye, including clinical features, aetiology, risk factors, evaluations and treatment. The applications of novel technologies in LASIK-associated dry eye evaluation like anterior segment spectral-domain optical coherence tomography (SD-OCT) and corneal confocal microscopy are also introduced in this review.
Fourth-generation fluoroquinolone-resistant mycobacterial keratitis after laser in situ keratomileusis.
Moshirfar, Majid; Meyer, Jay J; Espandar, Ladan
We report a case of mycobacterial keratitis resistant to fourth-generation fluoroquinolones after laser in situ keratomileusis (LASIK) with fourth-generation fluoroquinolone prophylaxis. While receiving moxifloxacin post LASIK, the patient was diagnosed with moxifloxacin-resistant Mycobacterium chelonae keratitis. Culture susceptibilities revealed isolates resistant to moxifloxacin and gatifloxacin, and treatment with topical amikacin and clarithromycin with oral doxycycline and clarithromycin along with flap amputation was necessary to control the infection. This case demonstrates the potential limitations in the coverage of these antibiotic agents.
Laser in situ keratomileusis in patients with collagen vascular disease: a review of the literature
Simpson, Rachel G; Moshirfar, Majid; Edmonds, Jason N; Christiansen, Steven M; Behunin, Nicholas
Purpose To evaluate the current United States Food and Drug Administration (FDA) recommendations regarding laser in situ keratomileusis (LASIK) surgery in patients with collagen vascular diseases (CVD) and assess whether these patients make appropriate candidates for laser vision correction, and offer treatment recommendations based on identified clinical data. Methods A literature search was conducted using PubMed, Medline, and Ovid to identify all existing studies of LASIK in patients with collagen vascular diseases. The search was conducted without date limitations. Keywords used for the search included MeSH terms: laser in situ keratomileusis, LASIK, refractive surgery, ocular surgery, and cataract surgery connected by "and" with the following MeSH and natural-language terms: collagen vascular disease, rheumatic disease, systemic disease, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, seronegative spondyloarthropathy, HLA B27, ankylosing spondylitis, reactive arthritis, psoriatic arthritis. The abstracts for all studies meeting initial search criteria were reviewed; relevant studies were included. No prospective studies were found; however, four retrospective case studies were identified that examined LASIK surgery in patients with CVD. Several case reports were also identified in similar fashion. Results The FDA considers CVD a relative contraindication to LASIK surgery, due largely to the ocular complications associated with disease in the CVD spectrum. However, recent studies of LASIK in patients with CVD indicate LASIK may be safe for patients with very well-controlled systemic disease, minimal ocular manifestations, and no clinical signs or history of dry-eye symptoms. Conclusion LASIK surgery may be safe in patients with rheumatoid arthritis or systemic lupus erythematosus and the seronegative spondyloarthropathies if stringent preoperative criteria are met. Evidence suggests patients with Sjögren's syndrome are not
Corneal wound healing following laser in situ keratomileusis (LASIK): a histopathological study in rabbits
Kato, T.; Nakayasu, K.; Hosoda, Y.; Watanabe, Y.; Kanai, A.
AIMS—To investigate the histopathological changes of rabbit corneas after laser in situ keratomileusis (LASIK) and to evaluate the corneal wound healing process. METHODS—A LASIK was performed on white rabbit eyes. Postoperatively, rabbits were killed on days 1 and 7, and at 1, 3, and 9 months. RESULTS—Periodic acid Schiff (PAS) positive material and disorganised collagen fibre were seen along the interface of the corneal flap even 9 months after operation. CONCLUSIONS—The wound healing process still continued at 9 months after LASIK indicating that a much longer time than expected was required for corneal wound healing following LASIK. PMID:10535863
Cyanoacrylate repair of laser in situ keratomileusis corneal flap perforation by a snake bite.
Korn, Bobby S; Korn, Tommy S
A 30-year-old man who had laser in situ keratomileusis (LASIK) for myopia 1 year earlier developed a corneal perforation in the left eye from a boa constrictor. The patient presented to the emergency room, and a small corneal perforation just outside the visual axis was diagnosed within the LASIK flap. Cyanoacrylate adhesive was used to close the corneal perforation. The patient went on to full visual recovery with an uncorrected visual acuity of 20/20. This is the first reported case of a penetrating corneal injury from a serpent in an eye that had LASIK. Cyanoacrylate may be used to repair small traumatic corneal perforations with a favorable visual outcome in eyes that have had LASIK.
Intraoperative and Postoperative Complications of Laser in situ Keratomileusis Flap Creation Using IntraLase Femtosecond Laser and Mechanical Microkeratomes
Espandar, Ladan; Meyer, Jay
An essential step of laser in situ keratomileusis surgery is corneal flap creation, Femtosecond (FS)-assisted or mechanical microkeratome. Each type has rare intraoperative and postoperative complication rates. Several recent studies have identified risk factors and guidelines to help manage these complications. Fortunately, studies have shown no loss of best-corrected visual acuity (BCVA) after the management of intraoperative and postoperative complications in IntraLase FS and mechanical microkeratome. Refractive surgeons need to be aware of the types of complications that can occur, how to avoid them and how to manage them to ensure the best possible outcomes. PMID:20543937
Intraoperative and Postoperative Complications of Laser in situ Keratomileusis Flap Creation Using IntraLase Femtosecond Laser and Mechanical Microkeratomes.
Espandar, Ladan; Meyer, Jay
An essential step of laser in situ keratomileusis surgery is corneal flap creation, Femtosecond (FS)-assisted or mechanical microkeratome. Each type has rare intraoperative and postoperative complication rates. Several recent studies have identified risk factors and guidelines to help manage these complications. Fortunately, studies have shown no loss of best-corrected visual acuity (BCVA) after the management of intraoperative and postoperative complications in IntraLase FS and mechanical microkeratome. Refractive surgeons need to be aware of the types of complications that can occur, how to avoid them and how to manage them to ensure the best possible outcomes.
High-speed Optical Coherence Tomography for Management after Laser in Situ Keratomileusis
Avila, Mariana; Li, Yan; Song, Jonathan C.; Huang, David
PURPOSE: To report applications of optical coherence tomography (OCT) in the management of laser in situ keratomileusis (LASIK) related problems. SETTING: Doheny Eye Institute and Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA. METHODS: Five patients referred for LASIK-related problems were enrolled in a prospective observational study. Clinical examination, ultrasound (US) pachymetry, Placido ring slit-scanning corneal topography (Orbscan II, Bausch & Lomb), and high-speed corneal OCT were performed. RESULTS: In cases of regression and keratectasia, OCT provided thickness measurements of the cornea, flap, and posterior stromal bed. Locations of tissue loss and flap interface planes were identified in a case with a recut enhancement complication. The information was used to determine whether further laser ablation was safe, confirm keratectasia, and manage complications. Optical coherence tomography measurements of central corneal thickness agreed well with US pachymetry measurements (difference 6.4 mm G 11.7 [SD]) (P Z .026), while Orbscan significantly underestimated corneal thickness (-67.5 ± 72.5 μm) (P = .17). CONCLUSIONS: High-speed OCT provided noncontact imaging and measurement of LASIK anatomy. It was useful in monitoring LASIK results and evaluating complications. PMID:17081866
Accuracy of Corneal Power Measurements for Intraocular Lens Power Calculation after Myopic Laser In situ Keratomileusis
Helaly, Hany A.; El-Hifnawy, Mohammad A. M.; Shaheen, Mohamed Shafik; Abou El-Kheir, Amr F.
Purpose: To evaluate the accuracy of corneal power measurements for intraocular lens (IOL) power calculation after myopic laser in situ keratomileusis (LASIK). Methods: The study evaluated 45 eyes with a history of myopic LASIK. Corneal power was measured using manual keratometry, automated keratometry, optical biometry, and Scheimflug tomography. Different hypothetical IOL power calculation formulas were performed for each case. Results: The steepest mean K value was measured with manual keratometry (37.48 ± 2.86 D) followed by automated keratometry (37.31 ± 2.83 D) then optical biometry (37.06 ± 2.98 D) followed by Scheimflug tomography (36.55 ± 3.08). None of the K values generated by Scheimflug tomography were steeper than the measurements from the other 3 instruments. Using equivalent K reading (EKR) 4 mm with the Double-K SRK/T formula, the refractive outcome generated 97.8% of cases within ± 2 D, 80.0% of cases within ± 1 D, and 42.2% of cases within ± 0.5 D. The best combination of formulas was "Shammas-PL + Double-K SRK/T formula using EKR 4 mm." Conclusion: Scheimflug tomography imaging using the Holladay EKR 4 mm improved the accuracy of IOL power calculation in post-LASIK eyes. The best option is a combination of formulas. We recommended the use the combined "Shammas-PL ± Double-K SRK/T formula using EKR 4 mm"h for optical outcomes. PMID:26957851
Photorefractive Keratectomy for Residual Myopia after Myopic Laser In Situ Keratomileusis
Fouda, Sameh M.
Purpose. To evaluate the safety, efficacy, and predictability of photorefractive keratectomy (PRK) on the corneal flap for correction of residual myopia following myopic laser in situ keratomileusis (LASIK). Patients and Methods. A retrospective study on eyes retreated by PRK on the corneal flap for residual myopia after LASIK. All eyes had no enough stroma after LASIK sufficient for LASIK enhancement. Data included spherical equivalent (SE), uncorrected and best corrected visual acuity (UCVA and BCVA), central pachymetry, corneal higher order aberrations (HOAs), corneal hysteresis (CH), corneal resistance factor (CRF), and corneal haze. Results. The study included 64 eyes. Before PRK, the mean central pachymetry was 400.21 ± 7.8 μm, the mean SE was −1.74 ± 0.51 D, and the mean UCVA and BCVA were 0.35 ± 0.18 and 0.91 ± 0.07, respectively. 12 months postoperatively, the mean central corneal thickness was 382.41 ± 2.61 μm, the mean SE was −0.18 ± 0.32 D (P < 0.01), and the mean UCVA and BCVA were 0.78 ± 0.14 (P = 0.01) and 0.92 ± 0.13 (P > 0.5), respectively. The safety index was 1.01 and the efficacy index was 0.86. No significant change was observed in corneal HOAs. Conclusions. Residual myopia less than 3 D after LASIK could be safely and effectively treated by PRK and mitomycin C with a high predictability. This prevents postoperative ectasia and avoids the flap related complications but has no significant effect on HOAs. PMID:28168049
Laser in situ keratomileusis for treated myopic anisometropic amblyopia in children
Ghanem, Assad A.; Moad, Ashraf I.; Nematallah, Ehab H.; El-Adawy, Ibrahim T.; Anwar, Ghada M.
Purpose To evaluate the effects of laser in situ keratomileusis (LASIK) in decreasing myopic anisometropia in children with spectacles or contact lens intolerance and its validity in facilitating treatment of resultant myopic anisometropic amblyopia. Patients and methods LASIK was performed in 18 eyes of 18 children having myopic anisometropic amblyopia not successfully treated with the standard amblyopia treatment for 6 months. Children were followed up at 1 week, 1, 2, 6, 12, 18 and 24 months. Postoperative amblyopia therapy was continued with occlusion of the dominant eye for 6 h daily for the first 3 months and then for 4 h per day as long as possible. Results The mean spherical equivalent refraction in the operated eye had reduced significantly from −9.08 ± 1.86D preoperatively to −0.97 ± 1.16D at 2 years postoperatively. The mean spherical equivalent in the non-operated fellow eye was −1.0 ± 1.15D preoperatively and −2.50 ± 1.15D at 2 years. The mean spherical equivalent myopic anisometropia was −7.75 ± 2.25D preoperatively and −0.50 ± 0.31D at 2 years, representing a 93.5% reduction in myopic anisometropia. The mean regression value was −2.28 ± 1.62D, however, 18 eyes (72%) were within 3.0D of the fellow eye. The mean BCVA was significantly improved from 0.72 ± 0.13 preoperatively to 0.47 ± 0.17 by 2 years after LASIK with amblyopia treatment. Conclusion LASIK is a safe and effective alternative method for correcting myopic anisometropic amblyopia, especially in children with spectacles or contact lens intolerance, with more better visual acuity and binocular vision. PMID:23960866
Incidence and Outcomes of Anterior Chamber Gas Bubble during Femtosecond Flap Creation for Laser-Assisted In Situ Keratomileusis.
Rush, Sloan W; Cofoid, Philip; Rush, Ryan B
Purpose. To report the incidence and outcomes of anterior chamber gas bubble formation during femtosecond laser flap creation for laser-assisted in situ keratomileusis (LASIK). Methods. The charts of 2,886 consecutive eyes that underwent femtosecond LASIK from May 2011 through August 2014 were retrospectively reviewed. The incidence, preoperative characteristics, intraoperative details, and postoperative outcomes were analyzed in subjects developing anterior chamber gas bubble formation during the procedure. Results. A total of 4 cases (0.14%) developed anterior chamber gas bubble formation during femtosecond laser flap creation. In all four cases, the excimer laser was unable to successfully track the pupil immediately following the anterior chamber bubble formation, temporarily postponing the completion of the procedure. There was an ethnicity predilection of anterior chamber gas formation toward Asians (p = 0.0055). An uncorrected visual acuity of 20/20 was ultimately achieved in all four cases without further complications. Conclusions. Anterior chamber gas bubble formation during femtosecond laser flap creation for LASIK is an uncommon event that typically results in a delay in treatment completion; nevertheless, it does influence final positive visual outcome.
Laser-assisted In Situ Keratomileusis for Correction of Astigmatism and Increasing Contact Lens Tolerance after Penetrating Keratoplasty
Park, Chang-Hyun; Kim, Su-Young
Purpose To determine effectiveness of laser-assisted in situ keratomileusis (LASIK) in the treatment of astigmatism following penetrating keratoplasty (PK). Methods We performed a retrospective review of medical records of patients who underwent LASIK following PK and had over 1 year of follow-up data. Results Twenty-six patients (26 pairs of eyes) underwent LASIK following PK. Mean age of the patients at the time of LASIK was 40.7 years (range, 26 to 72 years). Following LASIK, the mean cylinder was reduced by 2.4 diopters and mean reduction of cylinder after LASIK was 65.4% from the preoperative values at the last follow-up visit. Uncorrected visual acuity became 20 / 50 or better in 69.2% of the eyes after LASIK. Best-corrected visual acuity became 20 / 50 or better in 73.1% of the eyes after LASIK. All of them were intolerable to contact lenses before LASIK. After LASIK, 6 pairs (23.1%) did not need to use contact lenses and 18 pairs (69.2%) were tolerable to using contact lenses or spectacles. There were no significant endothelial cell density changes 12 months after LASIK (p = 0.239). Conclusions LASIK is effective in the treatment of astigmatism following PK and increases contact lens and spectacle tolerance. PMID:25276076
A comparison of visual acuity, predictability, and visual function outcomes after intracorneal ring segments and laser in situ keratomileusis.
Suiter, B G; Twa, M D; Ruckhofer, J; Schanzlin, D J
PURPOSE: To compare correction of low myopia by intrastromal corneal ring segments (ICRS) and by laser in situ keratomileusis (LASIK) with respect to early visual recovery and refractive outcomes. METHODS: Eighty-two eyes implanted with ICRS in a phase III study for US Food and Drug Administration review were matched with 133 eyes treated with LASIK by criteria of age (> 18 years, < 65 years), preoperative myopia (-1.00 to -3.50 diopters [D]), astigmatism (< or = 1.00 D), single treatment, and attempted full correction. Examinations were performed preoperatively and postoperatively at days 1 and 7 and months 1 and 3. Visual acuity and manifest refraction data were collected retrospectively. Visual function scores were assigned, and summarized results were compared. RESULTS: Uncorrected visual acuity was 20/20 or better at day 1 in 24% of eyes (20/82) after ICRS and in 55% of eyes (73/133) after LASIK, and at month 3 in 75% of eyes (58/77) after ICRS and in 67% of eyes (84/126) after LASIK. Spherical equivalent refraction at month 3 was within +/- 1.00 D of intended correction in 99% of eyes (76/77) after ICRS and in 96% of eyes (121/126) after LASIK. Excellent visual function scores were noted at month 3 in 90% of eyes (69/77) after ICRS and in 78% of eyes (98/126) after LASIK. CONCLUSION: Patients treated with LASIK showed better uncorrected visual acuity immediately following surgery; however, beyond 1 month, patients treated with ICRS achieved better uncorrected visual acuity that continued to improve with time. Visual function scores indicate that ICRS eyes see at higher levels of uncorrected visual acuity than LASIK eyes do with the same refractive error. The ICRS and LASIK were comparable in the correction of mild myopia. PMID:11190040
Modulation of corneal wound healing after excimer laser keratomileusis using topical mitomycin C and steroids
Talamo, J.H.; Gollamudi, S.; Green, W.R.; De La Cruz, Z.; Filatov, V.; Stark, W.J. )
A 193-nm excimer laser system was used to create deep stromal ablations in seven New Zealand white rabbits and shallow ablations in three. Eyes were randomized for treatment with topical mitomycin C, steroids, and erythromycin; topical steroids and erythromycin; or topical erythromycin only. All treatment regimens were instituted twice daily for 14 days. All eyes reepithelialized normally within 3 to 5 days. During 10 weeks of follow-up, all eyes developed moderate reticular subepithelial haze without significant differences among treatment groups. Results of light, fluorescence, and electron microscopic examination showed anterior stromal scarring and markedly reduced new subepithelial collagen formation in the group treated with mitomycin C, corticosteroids, and erythromycin. Focal abnormalities of Descemet's membrane and endothelial abnormalities were present in all treatment groups. Combination therapy with topical steroids, mitomycin C, and erythromycin to control the corneal wound healing response after refractive laser surgery appears promising and warrants further study.
Comparative evaluation of visual outcomes and corneal asphericity after laser-assisted in situ keratomileusis with the six-dimension Amaris excimer laser system
Piao, JunJie; Li, Ying-Jun; Whang, Woong-Joo; Choi, Mihyun; Kang, Min Ji; Lee, Jee Hye; Yoon, Geunyoung; Joo, Choun-Ki
Purpose To compare the visual and refractive outcomes after laser-assisted in situ keratomileusis (LASIK) surgery for correction of myopia or myopic astigmatism using a six-dimensional Amaris excimer laser. Methods In this retrospective cohort study, we enrolled 47 eyes of 28 patients (age: 19–36 years) with myopia or myopic astigmatism. We used the Custom Ablation Manager protocol and performed ablations with the SCHWIND AMARIS system. LASIK flaps were cut with an iFS Advanced Femtosecond Laser. Mean static (SCC) and dynamic cyclotorsion (DCC) were evaluated. Visual and refractive outcomes were evaluated during 6 months' follow-up. Corneal asphericity (Q-value) was analyzed at 4 months postoperatively. Results The spherical equivalent (SE) reduction was statistically significant reduce 1 day after refractive surgery (P < 0.001), with no additional significant changes during follow-up (P = 0.854). SCC registration rates were 81% in the Aberration-Free mode (AF) and 90% in the Corneal Wavefront mode (CW). SCC measurements were within ± 5 degrees in 57% (AF) and 68% (CW) of eyes. Mean DCC was within ± 1 degree in 96% (AF) or 95% (CW) of cases. At 6 months, the uncorrected distance visual acuity was 20/25 or better in all eyes. At last follow-up, both steep and flat keratometry values had significantly flattened in both groups (P < 0.001). Corneal asphericity also increased significantly during the postoperative period for an 8-mm corneal diameter (P < 0.001). Conclusions LASIK for myopia or myopic compound astigmatism correction using the six-dimensional AMARIS 750S excimer laser is safe, effective, and predictable. Postoperative corneal asphericity can be analyzed by linear regression to predict the changes in postoperative corneal asphericity with this approach. PMID:28187180
Femtosecond laser-assisted in situ keratomileusis for the correction of residual ametropia after deep anterior lamellar keratoplasty: a pilot investigation.
Balestrazzi, A; Balestrazzi, A; Menicacci, F; Cartocci, G; Menicacci, F; Michieletto, P; Balestrazzi, E
PurposeTo evaluate the refractive and visual results of one-stage laser-assisted in situ keratomileusis with femtosecond laser (Femto-LASIK) for the correction of residual ametropia after deep anterior lamellar keratoplasty (DALK).MethodsThis retrospective study included 13 eyes of 12 patients, who underwent corneal Femto-LASIK to correct refractive errors after DALK. IntraLase FS150 was used to create a lamellar flap and excimer laser ablation for refractive correction was performed using the Star S4 IR Excimer Laser in eight cases and the Technolas 217z Excimer Laser in Tissue Saving mode in five cases. Perioperative variables of interest included uncorrected (UDVA) and corrected (CDVA) distance visual acuities, manifest refraction and corneal topography.ResultsThe mean spherical equivalent preoperatively was -4.85±2.82 (range, -9.5 to 0 D). At the last visit the mean postoperative spherical equivalent (SE) was -0.44±0.67 D (P<0.05). The mean postoperative UDVA was 0.12±0.12 logMAR. There was a statistically significant increase in CDVA 6 months after Femto-LASIK (P<0.05). Intraoperative and postoperative complications did not develop in this series of eyes.ConclusionsCorrecting the preoperative manifest refractive error with Femto-LASIK led to a significant improvement in the UDVA and CDVA without surgical complications.Eye advance online publication, 7 April 2017; doi:10.1038/eye.2017.44.
Comparison of Intraocular Pressure before and after Laser In Situ Keratomileusis Refractive Surgery Measured with Perkins Tonometry, Noncontact Tonometry, and Transpalpebral Tonometry
Cacho, Isabel; Sanchez-Naves, Juan; Batres, Laura; Pintor, Jesús; Carracedo, Gonzalo
Purpose. To compare the intraocular pressure (IOP) before and after Laser In Situ Keratomileusis (LASIK), measured by Diaton, Perkins, and noncontact air pulse tonometers. Methods. Fifty-seven patients with a mean age of 34.88 were scheduled for myopia LASIK treatment. Spherical equivalent refraction (SER), corneal curvature (K), and central corneal thickness (CCT) and superior corneal thickness (SCT) were obtained before and after LASIK surgery. IOP values before and after surgery were measured using Diaton, Perkins, and noncontact air pulse tonometers. Results. The IOP values before and after LASIK surgery using Perkins tonometer and air tonometers were statistically significant (p < 0.05). However, no significant differences were found (p > 0.05) for IOP values measured with Diaton tonometer. CCT decreases significantly after surgery (p < 0.05) but no statistical differences were found in SCT (p = 0.08). Correlations between pre- and postsurgery were found for all tonometers used, with p = 0.001 and r = 0.434 for the air pulse tonometer, p = 0.008 and r = 0.355 for Perkins, and p < 0.001 and r = 0.637 for Diaton. Conclusion. Transpalpebral tonometry may be useful for measuring postsurgery IOP after myopic LASIK ablation because this technique is not influenced by the treatment. PMID:26167293
[Comparison of the effects of different side-cut angles on corneal biomechanical properties after femtosecond laser assisted-laser in situ keratomileusis].
Li, H; Wang, Y; Dou, R; Wang, L; Xu, L L; Li, X J; Zhang, J M
Objective: To evaluate the effects of side-cut angles on corneal biomechanical properties after femtosecond laser assisted-laser in situ keratomileusis (FS-LASIK). Methods: In this clinical control study, 97 right eyes of 97 patients with myopia and myopic astigmatism undergoing FS-LASIK surgery were included randomly. Two types of side-cut angles were designed for the flap, 90° in 48 eyes and 130° in 49 eyes. The values of corneal resistance factor (CRF), cornea hysteresis (CH) and 37 biomechanical waveform parameters were measured using the ocular response analyzer preoperatively and at 1 and 3 months postoperatively. The comparison between the two groups at different follow-up time points was made with one-way analysis of variance, and the comparison among different follow-up time points in each group was performed with the repeated measures analysis of variance. Results: The mean CRF, CH, p area, h, dive1, dive2, w11 and w21 in both groups showed significant reduction at 1 month postoperatively (group 90°: CRF 10.49 vs. 6.85, CH 10.02 vs. 7.55, p1 area 3 537.54 vs. 1 918.07, h1 404.74 vs. 283.25, dive1 350.63 vs. 243.33, w11 10.50 vs. 7.58. group 130°: CRF 10.14 vs. 6.38, CH 9.93 vs. 7.13, p1 area 3 498.93 vs. 2 038.74, h1 411.93 vs. 304.49, dive1 352.51 vs. 265.12, w11 10.55 vs. 7.78. P<0.001) . The mean CRF, CH, p area, w, h, dive1 and dive2 in both groups showed significant reduction at 3 months postoperatively (group 90°: CRF 10.49 vs. 6.60, CH 10.02 vs. 7.65, p1 area 3537.54 vs. 2042.91, h1 404.74 vs. 307.77, dive1 350.63 vs. 263.33, w11 10.50 vs. 7.58. group 130°: CRF 10.14 vs. 6.45, CH 9.93 vs. 7.67, p1 area 3 498.93 vs. 2 187.97, h1 411.93 vs. 327.39, dive1 352.51 vs. 284.26, w11 10.55 vs. 7.61. P<0.001). The mean path in both groups showed significant increase at 1 and 3 months postoperatively (group 90°: path1 23.14 vs. 30.50 vs. 30.79. group 130°: path1 24.12 vs. 32.18 vs. 31.49. P<0.001). The mean aplhf, bindex, dive2 and path2 between both
Effect of femtosecond and microkeratome flaps creation on the cornea biomechanics during laser in situ keratomileusis: one year follow-up
Sun, Qian; Deng, Zheng-Zheng; Zhou, Yue-Hua; Zhang, Jing; Peng, Xiao-Yan
AIM To compare the corneal biomechanical outcomes at one year after laser in situ keratomileusis (LASIK) with the flaps created by Ziemer and Moria M2 microkeratome with 110 head and -20 blade. METHODS Totally 100 eyes of 50 consecutive patients were enrolled in this prospective study and divided into two groups for corneal flaps created by ZiemerFemto LDV and Moria M2 microkeratome with 110 head and -20 blade. Corneal biomechanical properties including cornea resistance factor (CRF) and cornea hysteresis (CH) were measured before and 1, 3, 6, 12mo after surgery by ocular response analyzer. Central cornea thickness and corneal flap thickness were measured by optical coherence tomography. RESULTS The ablation depth (P=0.693), residual corneal thickness (P=0.453), and postoperative corneal curvature (P=0.264) were not significant different between Ziemer group and Moria 110-20 group after surgery. The residual stromal bed thickness, corneal flap thickness, CH and CRF at 12mo after surgery were significant different between Ziemer group and Moria 110-20 group (P<0.01);Ziemer group gained better corneal biomechanical results. The CRF and CH increased gradually from 1 to 12mo after surgery in Ziemer group, increased from 1 to 6mo but decreased from 6 to 12mo in Moria 110-20 group. Both CRF and CH at one year after surgery increased with the increasing of residual cornea thickness; pre-LASIK CRF, CRF also increased with residual stromal bed thickness, while CH decreased with the increasing of pre-LASIK intraocular pressure and cornea flap thickness (P<0.01). CONCLUSION In one year follow-up, femtosecond laser can provide better cornea flaps with stable cornea biomechanics than mechanical microkeratome. PMID:27803856
Visual Outcomes, Quality of Vision, and Quality of Life of Diffractive Multifocal Intraocular Lens Implantation after Myopic Laser In Situ Keratomileusis: A Prospective, Observational Case Series
Purpose. To report visual performance and quality of life after implantation of a bifocal diffractive multifocal intraocular lens (MIOL) in postmyopic laser in situ keratomileusis (LASIK) patients. Methods. Prospective, observational case series. Patients with prior myopic LASIK who had implantation of Tecnis ZMA00/ZMB00 MIOL (Abbott Medical Optics) at Hong Kong Sanatorium and Hospital were included. Postoperative examinations included monocular and binocular distance, intermediate and near visual acuity (VA), and contrast sensitivity; visual symptoms (0–5); satisfaction (1–5); spectacle independence rate; and quality of life. Results. Twenty-three patients (27 eyes) were included. No intraoperative complications developed. Mean monocular uncorrected VA at distance, intermediate, and near were 0.13 ± 0.15 (standard deviation), 0.22 ± 0.15, and 0.16 ± 0.15, respectively. Corresponding mean values for binocular uncorrected VA were 0.00 ± 0.10, 0.08 ± 0.13, and 0.13 ± 0.10, respectively. No eyes lost >1 line of corrected distance VA. Contrast sensitivity at different spatial frequencies between operated and unoperated eyes did not differ significantly (all P > 0.05). Mean score for halos, night glare, starbursts, and satisfaction were 1.46 ± 1.62, 1.85 ± 1.69, 0.78 ± 1.31, and 3.50 ± 1.02, respectively. Eighteen patients (78%) reported complete spectacle independence. Mean composite score of the quality-of-life questionnaire was 90.31 ± 8.50 out of 100. Conclusions. Implantation of the MIOL after myopic LASIK was safe and achieved good visual performance. PMID:28133543
Corneal Clarity and Visual Outcomes after Small-Incision Lenticule Extraction and Comparison to Femtosecond Laser-Assisted In Situ Keratomileusis
Droutsas, Konstantinos; Sekundo, Walter; Petrak, Michael; Schulze, Stephan
Purpose. To evaluate corneal clarity and visual outcomes after small-incision lenticule extraction (SMILE) and compare them to femtosecond laser-assisted in situ keratomileusis (FS-LASIK). Materials and Methods. Fifty-eight myopic eyes of 33 patients who underwent SMILE were compared to 58 eyes of 33 patients treated with FS-LASIK. All procedures were performed using VisuMax® femtosecond laser and MEL 80® excimer laser (Carl Zeiss Meditec AG, Germany). Pentacam™ (Oculus, Germany) was used for pre- and 3-month postoperative corneal densitometry (CD) analysis. CD was evaluated at 3 optically relevant, concentric radial zones (0–2 mm, 2–6 mm, and 0–6 mm annulus) around the corneal apex and at 3 different anatomical corneal layers (anterior, central, and posterior). Associations of postoperative CD values with the lenticule thickness and ablation depth were examined. Preoperative and postoperative corrected distance visual acuity (CDVA) values were also compared. Results. After SMILE, the total CD (all corneal layers) at 0–6 mm annulus showed no significant change compared to preoperative values (P = 0.259). After FS-LASIK, the total CD was significantly reduced (P = 0.033). Three-month postoperative CD showed no significant differences between the 2 groups for all examined annuli (0–2 mm: P = 0.569; 2–6 mm: P = 0.055; and 0–6 mm: P = 0.686). Total CD after SMILE at 0–6 mm annulus displayed a weak negative association with the lenticule thickness (P = 0.079, R2 = 0.0532) and after FS-LASIK displayed a weak negative association with the ablation depth (P = 0.731, R2 = 0.0015). Postoperative CDVA was similar for both groups (P = 0.517). Conclusion. Quantification of corneal clarity using the Scheimpflug CD showed similar results before and 3 months after SMILE. Compared to FS-LASIK, no significant differences of corneal clarity and CDVA were found 3 months postoperatively.
Photorefractive Keratectomy with Adjunctive Mitomycin C for Residual Error after Laser-Assisted In Situ Keratomileusis Using the Pulzar 213 nm Solid-State Laser: Early Results.
Ng-Darjuan, Maya Fe; Evangelista, Raymond P; Agahan, Archimedes Lee D
Purpose. To evaluate the accuracy, efficacy, stability, and safety of photorefractive keratectomy (PRK) enhancement using the Pulzar 213 nm solid-state laser (SSL) with adjunctive Mitomycin C in eyes previously treated with laser assisted in situ keratomileusis (LASIK) with residual error of refraction. Methods. This is a prospective noncomparative case series of 16 eyes of 12 patients who underwent PRK for residual refractive error after primary LASIK. Mitomycin C 0.02% was used after the PRK to prevent haze formation. Outcomes measured were pre- and postoperative manifest refraction spherical equivalent (MRSE), uncorrected (UDVA) and best-corrected distance visual acuity (CDVA), and slit lamp evidence of corneal complications. Results. The mean UDVA improved from 20/70 preoperatively to 20/30 postoperatively. The average gain in lines for the UDVA was 2.38. After six months of followup, the postoperative MRSE within 0.50 D in 56% (9) of eyes and 94% (15) eyes were within 1.0 diopters of the intended correction. No eyes developed haze all throughout the study. Conclusion. PRK enhancement with adjunctive use of Mitomycin C for the correction of residual error of refraction after LASIK using the Pulzar 213 nm solid-state laser is an accurate, effective, and safe procedure.
A prospective comparison of phakic collamer lenses and wavefront-optimized laser-assisted in situ keratomileusis for correction of myopia
Parkhurst, Gregory D
Purpose The aim of this study was to evaluate and compare night vision and low-luminance contrast sensitivity (CS) in patients undergoing implantation of phakic collamer lenses or wavefront-optimized laser-assisted in situ keratomileusis (LASIK). Patients and methods This is a nonrandomized, prospective study, in which 48 military personnel were recruited. Rabin Super Vision Test was used to compare the visual acuity and CS of Visian implantable collamer lens (ICL) and LASIK groups under normal and low light conditions, using a filter for simulated vision through night vision goggles. Results Preoperative mean spherical equivalent was −6.10 D in the ICL group and −6.04 D in the LASIK group (P=0.863). Three months postoperatively, super vision acuity (SVa), super vision acuity with (low-luminance) goggles (SVaG), super vision contrast (SVc), and super vision contrast with (low luminance) goggles (SVcG) significantly improved in the ICL and LASIK groups (P<0.001). Mean improvement in SVaG at 3 months postoperatively was statistically significantly greater in the ICL group than in the LASIK group (mean change [logarithm of the minimum angle of resolution, LogMAR]: ICL =−0.134, LASIK =−0.085; P=0.032). Mean improvements in SVc and SVcG were also statistically significantly greater in the ICL group than in the LASIK group (SVc mean change [logarithm of the CS, LogCS]: ICL =0.356, LASIK =0.209; P=0.018 and SVcG mean change [LogCS]: ICL =0.390, LASIK =0.259; P=0.024). Mean improvement in SVa at 3 months was comparable in both groups (P=0.154). Conclusion Simulated night vision improved with both ICL implantation and wavefront-optimized LASIK, but improvements were significantly greater with ICLs. These differences may be important in a military setting and may also affect satisfaction with civilian vision correction. PMID:27418804
Small Incision Lenticule Extraction (SMILE) versus Femtosecond Laser-Assisted In Situ Keratomileusis (FS-LASIK) for Myopia: A Systematic Review and Meta-Analysis
Shen, Zeren; Shi, Keda; Yu, Yinhui; Yu, Xiaoning; Lin, Yuchen; Yao, Ke
Purpose The goal of this study was to compare small incision lenticule extraction (SMILE) with femtosecond laser-assisted in situ keratomileusis (FS-LASIK) for treating myopia. Methods The CENTRAL, EMBASE, PubMed databases and a Chinese database (SinoMed) were searched in May of 2016. Twelve studies with 1,076 eyes, which included three randomized controlled trials (RCTs) and nine cohorts, met our inclusion criteria. The overall quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group framework. Data were extracted and analysed at three to six months postoperatively. Primary outcome measures included a loss of one or more lines of best spectacle corrected visual acuity (BSCVA), uncorrected visual acuity (UCVA) of 20/20 or better, mean logMAR UCVA, postoperative mean spherical equivalent (SE) and postoperative refraction within ±1.0 D of the target refraction. Secondary outcome measures included ocular surface disease index (OSDI), tear breakup time (TBUT) and Schirmer's 1 test (S1T) as dry eye parameters, along with corneal sensitivity. Results The overall quality of evidence was considered to be low to very low. Pooled results revealed no significant differences between the two groups with regard to a loss of one or more lines in the BSCVA (OR 1.71; 95% CI: 0.81, 3.63; P = 0.16), UCVA of 20/20 or better (OR 0.71; 95% CI: 0.44, 1.15; P = 0.16), logMAR UCVA (MD 0.00; 95% CI: -0.03, 0.04; P = 0.87), postoperative refractive SE (MD -0.00; 95% CI: -0.05, 0.05; P = 0.97) or postoperative refraction within ±1.0 D of the target refraction (OR 0.78; 95% CI: 0.22, 2.77; P = 0.70) within six months postoperatively. The pooled analysis also indicated that the FS-LASIK group suffered more severely from dry eye symptoms (OSDI; MD -6.68; 95% CI: -11.76, -2.00; P = 0.006) and lower corneal sensitivity (MD 12.40; 95% CI: 10.23, 14.56; P < 0.00001) at six months postoperatively. Conclusions In conclusion
Keratophakia and keratomileusis--clinical results.
Swinger, C A; Barraquer, J I
A random, retrospective study was performed on 158 patients. who underwent keratophakia and keratomileusis for the correction of refractive errors. The primary indication for surgery was high anisometropia. Data on corneal curvature modification, refraction, accuracy, stability, and complications are reported. Both keratophakia and hypermetropic keratomileusis are capable of fully correcting aphakic hyperopia. Myopic keratomileusis corrected up to 16 diopters of myopia in this series. Lamellar refractive keratoplasty appears to have no significant detrimental effect on visual acuity. The majority of myopic patients had an improved best-corrected visual acuity postoperatively. High or irregular astigmatism was not noted following this surgery. The stability of the postoperative curvature appeared to be good with both keratophakia and myopic keratomileusis. Complications in this series were minimal, and one resulted in decreased vision postoperatively. Inaccuracy in achieving the desired refractive result appeared to be the major disadvantage of these techniques.
Refractive keratoplasty. Keratophakia and keratomileusis.
Troutman, R C; Swinger, C
Early experience with the refractive keratoplasty techniques of José Barraquer--keratophakia and hypermetropic keratomileusis is presented. In contradistinction to the alloplastic lens substitutes currently being employed for the integral correction of aphakia, Barraquer's techniques would seem to offer a more permanent, more physiologic, full-time optical correction of the aphakic state. Their use is limited only by the condition of the patient's cornea and, in fact, may be applied not only in aphakia but also in phakic eyes with higher degrees of hyperopia or myopia. In the opinion of the authors, the refractive keratoplasty techniques of Barraquer can be performed by any well-instructed ophthalmic surgeon. These techniques offer to many patients a satisfactory, and potentially a physiologically superior alternative to alloplastic lens substitute for aphakic correction.
Refractive keratoplasty: keratophakia and keratomileusis.
Troutman, R C; Swinger, C
We have presented our early experience with the refractive keratoplasty techniques of Doctor Jose Barraquer--keratophakia and hypermetropic keratomileusis. In contradistinction to the alloplastic lens substitutes currently being employed for the integral correction of aphakia, his techniques would seem to offer a more permanent, more physiologic, full-time optical correction of the aphakic state. Their use is limited only by the condition of the patient's corneaa and, in fact, may be applied not only in aphakia but also in phakic eyes with higher degrees of hyperopia or myopia. In the opinion of the authors, the refractive keratoplasty techniques of Barraquer can be perfored by any well-instructed ophthalmic surgeon. These techniques offer to many patients a satisfactory and potentially a physiologically superior alternative to alloplastic lens substitute for aphakic correction.
Prospective evaluation of myopic keratomileusis.
Swinger, C A; Barker, B A
The initial results of a prospective evaluation of myopic keratomileusis are reported. The procedure was attempted on 42 eyes, with an average follow-up of 10 months. The average reductions of myopia were 7.05 D and 11.59 D when measured by keratometry and refraction, respectively. Regular astigmatism increased by 0.50 D on keratometry, but there was no change in the refractive cylinder. The majority of patients had some irregular astigmatism on corneoscopy. The average percent correction, based on refraction, was 94.1 +/- 24%, and the correlation coefficient was 0.43. Visual rehabilitation was rapid. No patient followed for 1 year or more had a decrease in the best-corrected acuity, and 63% of this group had an average improvement of 1.5 lines with as much as five lines. The final refraction may take up to 6 months to stabilize. Complications consisted of epithelium and debris in the interface and focal necrosis of Bowman's membrane. The technique is difficult but may have application in the visual rehabilitation of the high myope.
Epiretinal Membrane after Laser In Situ Keratomileusis
Paciuc-Beja, Miguel; Garcia, Gerardo; Dalma, Jose; Quiroz-Mercado, Hugo
Multiple posterior segment complications can occur after LASIK. Posterior vitreous detachment, macular holes, retinal hemorrhages, retinal detachment, and several other complications have been described. A case of posterior vitreous detachment with epiretinal membrane in a young adult after LASIK is reported. LASIK surgeons must be aware of the possibility of posterior segment complications after surgery. PMID:23691389
Low-level laser irradiation promotes the proliferation and maturation of keratinocytes during epithelial wound repair
Sperandio, Felipe F.; Simões, Alyne; Corrêa, Luciana; Aranha, Ana Cecília C.; Giudice, Fernanda S.; Hamblin, Michael R.; Sousa, Suzana C.O.M.
Low-level laser therapy (LLLT) has been extensively employed to improve epithelial wound healing, though the exact response of epithelium maturation and stratification after LLLT is unknown. Thus, this study aimed to assess the in vitro growth and differentiation of keratinocytes (KCs) and in vivo wound healing response when treated with LLLT. Human KCs (HaCaT cells) showed an enhanced proliferation with all the employed laser energy densities (3, 6 and 12 J/cm2, 660nm, 100mW), together with an increased expression of Cyclin D1. Moreover, the immunoexpression of proteins related to epithelial proliferation and maturation (p63, CK10, CK14) all indicated a faster maturation of the migrating KCs in the LLLT-treated wounds. In that way, an improved epithelial healing was promoted by LLLT with the employed parameters; this improvement was confirmed by changes in the expression of several proteins related to epithelial proliferation and maturation. PMID:25411997
In vitro inhibition of lens epithelial cell growth by continuous wave Nd:YAG laser
Miyake, K.; Iwata, S.; Ando, F.; Daikuzono, N.; Federman, J.L.
Bovine lens epithelial cells were suspended in MEM medium and subjected to continuous wave, low power, pulsed neodymium:yttrium-aluminum-garnet (Nd:YAG) laser irradiation. The temperature of each suspension was maintained at 36 degrees C. Laser applications ranged from 1 to 10 watts and from 100 to 2000 seconds, but the total dose to each of the epithelial cell suspension was 2000 J. Six to thirty-nine percent of the cells were dead immediately after irradiation. Surviving cells, cultured for 15 days, showed decreased attachment and failed to grow. These preliminary results suggest that the Nd:YAG laser may be used during cataract surgery to prevent subsequent lens epithelial cell proliferation and the resulting vision reduction and glare.
The effect of carbon dioxide laser on wound contraction and epithelial regeneration in rabbits.
Jarmuske, M B; Stranc, M F; Stranc, L C
This study was undertaken to compare objectively healing rates (in rabbits) of wounds caused by CO2 laser with those caused by scalpel. The rates of contraction and epithelialisation of standard wounds were determined with daily measurement of wound area from the time of wounding until the wound had healed. Our results demonstrate significant delays in both wound contraction (p = 0.0001) and epithelialisation (p = 0.0001) for CO2 laser-created wounds when compared to those seen in scalpel-created wounds. Normal epithelial regenerative capacities were demonstrated in the laser group despite the slow onset of epithelial migration. The appearance of the healed areas appeared comparable for both modalities.
In vitro effect of phototherapy with low-intensity laser on HSV-1 and epithelial cells
NASA Astrophysics Data System (ADS)
Eduardo, Fernanda P.; Mehnert, Dolores U.; Monezi, Telma A.; Zezell, Denise M.; Schubert, Mark M.; Eduardo, Carlos P.; Marques, Márcia M.
The effects of phototherapy on herpes lesions have been clinically demonstrated by either preventing the lesion formation or speeding their repair. The aim of this in vitro study was analyze the effect of phototherapy on epithelial cells and HSV-1 in culture. Cultures of HSV-1 and epithelial cells (Vero cell line) were used. The irradiations were done using a GaAlAs laser (660 e 780 nm, 4.0 mm2). One, two and three irradiations with 6 h-intervals were done. The experimental groups were: Control: non-irradiated; 660 nm and 3 J/cm2 (2.8 sec); 660 nm and 5 J/cm2 (3.8 sec); 780 nm and 3 J/cm2 (1.9 sec), and 780 nm and 5 J/cm2 (2.5 sec). The HSV-1 cytopatic effect and the cell viability of irradiated cultures and controls were analyzed in four different conditions: irradiation of non-infected epithelial cells; epithelial cells irradiated prior infection; virus irradiated prior infection; irradiation of HSV infected cells. The mitochondrial activity and cytopathic effects were assessed. The number of irradiations influenced the cell growth positively and proportionally, except for the 660 nm/ 3 J/cm2 group. Any variation in cytopathic effects was observed amongst the experimental groups. The viability of infected cells prior irradiation was significantly higher than that of non-irradiated cultures when 2 irradiations were done. Under the experimental conditions of this study we concluded that phototherapy is capable of enhancing epithelial cell growth and prolonging cell viability of HSV-1 infected cells. Positive benefits of phototherapy could be resultant from prolongation of infected cells viability, corroborating with host defenses.
Er,CR:YSGG lasers induce fewer dysplastic-like epithelial artefacts than CO2 lasers: an in vivo experimental study on oral mucosa.
González-Mosquera, A; Seoane, J; García-Caballero, L; López-Jornet, P; García-Caballero, T; Varela-Centelles, P
Our aim was to assess wounds made by lasers (CO(2) and Er,Cr:YSGG) for their epithelial architectural changes and width of damage. We allocated 60 Sprague-Dawley(®) rats into groups: glossectomy by CO(2) laser at 3 different wattages (n=10 in each); glossectomy by Er,Cr:YSGG laser at two different emissions (n=10 in each), and a control group (n=10). Histological examination assessed both prevalence and site of thermal artefacts for each group. Both lasers (CO(2) and Er,Cr:YSGG) caused the same type of cytological artefacts. The 3W Er,Cr:YSGG laser produced the fewest cytological artefacts/specimen, and was significantly different from the other experimental groups: 3W CO(2) laser (95% CI=0.8 to 1.0); the 6W CO(2) laser (95% CI=0.1 to 2.0) and the 10W CO(2) laser (95% CI=1.1 to 3.0). CO(2) lasers (3-10W) generate epithelial damage that can simulate dysplastic changes with cytological atypia that affects mainly the basal and suprabasal layers. Irradiation with Er,CR:YSGG laser (2-4W) produces significantly fewer cellular artefacts and less epithelial damage, which may be potentially useful for biopsy of oral mucosa.
Ablation of lens epithelial cells with a laser photolysis system: Histopathology, ultrastructure, and immunochemistry
Mamalis, Nick; Grossniklaus, Hans E.; Waring, George O.; Werner, Liliana; Brubaker, Jacob; Davis, Don; Espandar, Ladan; Walker, Rudolf; Thyzel, Reinhardt
PURPOSE To evaluate efficacy of a neodymium:YAG (Nd:YAG) laser photolysis system in removing lens epithelial cells (LECs) and characterize the effect of the laser on laminin and fibronectin involved in LEC adhesion and migration. METHODS Cadaver eyes were evaluated using the Miyake technique. The lenses were removed with phacoemulsification. The modified Nd:YAG laser was used to clean the LECs from the capsule. Only the fornix was cleaned in some eyes and the anterior subcapsular area in other eyes. Some areas were not treated and acted as controls. Standard irrigation/aspiration (I/A) removal of LECs was performed in additional eyes. The eyes were analyzed using light microscopy and immunohistochemical staining. RESULTS Histopathologic evaluation showed that the laser removed the LECs from the anterior lens capsule and from the fornix. Immunohistochemical staining showed fibronectin and laminin staining in the untreated areas that was absent in the treated areas. Standard I/A removal of the LECs showed absence of cells but persistent laminin and fibronectin. Electron microscopy showed epithelial cells in untreated areas with an absence of the LECs and debris in treated areas. CONCLUSIONS The laser photolysis system removed LECs from the anterior lens capsule and capsule fornix. Along with the cells, laminin, fibronectin, and cell debris remained in the untreated areas but were removed by the treatment. This treatment may be useful in preventing posterior capsule opacification. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned. Additional disclosures are found in the footnotes. PMID:20494774
Focal epithelial hyperplasia in a human immuno-deficiency virus patient treated with laser surgery
Galanakis, Alexandros; Palaia, Gaspare; Tenore, Gianluca; Vecchio, Alessandro Del; Romeo, Umberto
Focal epithelial hyperplasia (FEH), or Heck's disease, is a rare disease of the oral mucosa; it is mostly found in children or young adults who are immunosuppressed and who live in regions with low socioeconomic status. It is characterized by asymptomatic papules on the oral mucosa, gingiva, tongue, and lips. Healing can be spontaneous, and treatment is indicated if there are aesthetic or functional complications. Human papillomavirus, especially genotypes 13 and 32, has been associated with FEH and is detected in the majority of lesions. Histopathologically, FEH is characterized by parakeratosis, epithelial hyperplasia, focal acanthosis, and fusion and horizontal outgrowth of epithelial ridges. A 37-year-old male patient was referred to the Department of Oral and Maxillofacial Sciences at the Sapienza University of Rome, complaining of numerous exophytic lesions in his mouth. He stated that the lesions were not painful but he had experienced occasional bleeding after incidental masticatory trauma. He had received no previous treatment for the oral lesions. His medical history revealed that he was human immuno-deficiency virus positive and was a smoker with numerous, asymptomatic oral papules clinically and histologically corresponding to FEH. The labial and buccal mucosa were especially affected by lesions. Surgical treatment was performed using a 532-nm potassium titanyl phosphate laser (SmartLite, Deka, Florence, Italy) in continuous mode with a 300 μm fiber and power of 1.4 W (power density 1980.22 W/cm2). After anesthesia without vasoconstrictors, the lesions were tractioned with sutures or an Allis clamp and then completely excised. The lesions were preserved in 10% formalin for histological examination, which confirmed the clinical diagnosis of FEH. In this case, the laser allowed excellent control of bleeding, without postoperative sutures, and optimal wound healing. PMID:25032206
Focal epithelial hyperplasia in a human immuno-deficiency virus patient treated with laser surgery.
Galanakis, Alexandros; Palaia, Gaspare; Tenore, Gianluca; Vecchio, Alessandro Del; Romeo, Umberto
Focal epithelial hyperplasia (FEH), or Heck's disease, is a rare disease of the oral mucosa; it is mostly found in children or young adults who are immunosuppressed and who live in regions with low socioeconomic status. It is characterized by asymptomatic papules on the oral mucosa, gingiva, tongue, and lips. Healing can be spontaneous, and treatment is indicated if there are aesthetic or functional complications. Human papillomavirus, especially genotypes 13 and 32, has been associated with FEH and is detected in the majority of lesions. Histopathologically, FEH is characterized by parakeratosis, epithelial hyperplasia, focal acanthosis, and fusion and horizontal outgrowth of epithelial ridges. A 37-year-old male patient was referred to the Department of Oral and Maxillofacial Sciences at the Sapienza University of Rome, complaining of numerous exophytic lesions in his mouth. He stated that the lesions were not painful but he had experienced occasional bleeding after incidental masticatory trauma. He had received no previous treatment for the oral lesions. His medical history revealed that he was human immuno-deficiency virus positive and was a smoker with numerous, asymptomatic oral papules clinically and histologically corresponding to FEH. The labial and buccal mucosa were especially affected by lesions. Surgical treatment was performed using a 532-nm potassium titanyl phosphate laser (SmartLite, Deka, Florence, Italy) in continuous mode with a 300 μm fiber and power of 1.4 W (power density 1980.22 W/cm(2)). After anesthesia without vasoconstrictors, the lesions were tractioned with sutures or an Allis clamp and then completely excised. The lesions were preserved in 10% formalin for histological examination, which confirmed the clinical diagnosis of FEH. In this case, the laser allowed excellent control of bleeding, without postoperative sutures, and optimal wound healing.
Re-epithelialization of the skin following CO2 laser resurfacing.
Collawn, S S
Wound healing following CO(2) laser resurfacing of the face is a complex process which must involve a rapid replacement of the ablated epidermis to protect the underlying structures in the skin from desiccation and deeper injury. The majority of cells that regenerate the epidermis come from the hair follicles, and cell movement out of the follicles is monitored using immunofluorescence with antibodies to keratin 17, an intermediate filament protein expressed in the migrating front of cells. This migration is enhanced with occlusive dressings used immediately after the resurfacing procedure. Skin biopsies have been examined at multiple time points following resurfacing, and re-epithelialization begins by 48 h in skin that has been occluded. Skin that has been left open with no treatment forms an eschar and has no keratinocyte migration at 48 h, thus displaying delayed wound healing.
Differential Gene Expression in Explanted Human Retinal Pigment Epithelial Cells 24-Hours Post-Exposure to 532 nm, 3.0 ns Pulsed Laser Light and 1064 nm, 170 ps Pulsed Laser Light 12-Hours Post-Exposure: Results Compendium
Laser Light and 1064 nm, 170 ps Pulsed Laser Light 12-hours Post-Exposure: Results Compendium John W. Obringer Martin D. Johnson Laser and Optics...Explanted Human Retinal Pigment Epithelial Cells 12-hours Post-Exposure to 532 nm, 3.0 ns Pulsed Laser Light and 1064 nm, 170 ps Pulsed Laser Lightl2-hours...Explanted Human Retinal Pigment Epithelial USAFA F05611-02-P-0471 Cells 24-Hours Post-Exposure to 532 nm, 3.0 ns Pulsed Laser-Light and 1064nm, 170 ps Pulsed
Excimer laser surface ablation: a review of recent literature.
O'Brart, David P S
The aim was to review the recently published literature on excimer laser surface ablation procedures, including photorefractive keratectomy (PRK), laser sub-epithelial keratomileusis (LASEK), microkeratome-assisted PRK (epi-LASIK) and trans-epithelial (laser-assisted) PRK, to help elucidate where and how surface ablation may best fit into current refractive surgical practice. The emphasis was on publications within the last three years and included systemic reviews, meta-analyses and randomised controlled trials. Where such evidence did not exist, selective large series cohort studies, case-controlled studies and case series with follow-up preferably greater than six months were examined and included. Refractive and visual outcomes are excellent and comparable to those after LASIK even in complex cases after previous corneal surgery. Indeed, surface ablation combined with corneal collagen cross-linking may be used in selected eyes with biomechanical instability, where LASIK is contraindicated. In addition, there is evidence to suggest that there may be less induction of higher order aberrations with surface techniques. Long-term stability and safety appear to be extremely satisfactory. The literature supports the use of modern excimer laser surface treatments, with outcomes comparable to those after LASIK and evidence of less induction of higher-order aberrations. Follow-up studies at 10 to 20 years indicate excellent stability and safety.
The Combination of Laser Therapy and Metal Nanoparticles in Cancer Treatment Originated From Epithelial Tissues: A Literature Review
Fekrazad, Reza; Naghdi, Nafiseh; Nokhbatolfoghahaei, Hanieh; Bagheri, Hossein
Several methods have been employed for cancer treatment including surgery, chemotherapy and radiation therapy. Today, recent advances in medical science and development of new technologies, have led to the introduction of new methods such as hormone therapy, Photodynamic therapy (PDT), treatments using nanoparticles and eventually combinations of lasers and nanoparticles. The unique features of LASERs such as photo-thermal properties and the particular characteristics of nanoparticles, given their extremely small size, may provide an interesting combined therapeutic effect. The purpose of this study was to review the simultaneous application of lasers and metal nanoparticles for the treatment of cancers with epithelial origin. A comprehensive search in electronic sources including PubMed, Google Scholar and Science Direct was carried out between 2000 and 2013. Among the initial 400 articles, 250 articles applied nanoparticles and lasers in combination, in which more than 50 articles covered the treatment of cancer with epithelial origin. In the future, the combination of laser and nanoparticles may be used as a new or an alternative method for cancer therapy or diagnosis. Obviously, to exclude the effect of laser's wavelength and nanoparticle's properties more animal studies and clinical trials are required as a lack of perfect studies PMID:27330701
Biostimulatory effects of low-level laser therapy on epithelial cells and gingival fibroblasts treated with zoledronic acid
NASA Astrophysics Data System (ADS)
Basso, F. G.; Pansani, T. N.; Turrioni, A. P. S.; Kurachi, C.; Bagnato, V. S.; Hebling, J.; de Souza Costa, C. A.
Low-level laser therapy (LLLT) has been considered as an adjuvant treatment for bisphosphonate-related osteonecrosis, presenting positive clinical outcomes. However, there are no data regarding the effect of LLLT on oral tissue cells exposed to bisphosphonates. This study aimed to evaluate the effects of LLLT on epithelial cells and gingival fibroblasts exposed to a nitrogen-containing bisphosphonate—zoledronic acid (ZA). Cells were seeded in wells of 24-well plates, incubated for 48 h and then exposed to ZA at 5 μM for an additional 48 h. LLLT was performed with a diode laser prototype—LaserTABLE (InGaAsP—780 nm ± 3 nm, 25 mW), at selected energy doses of 0.5, 1.5, 3, 5, and 7 J cm-2 in three irradiation sessions, every 24 h. Cell metabolism, total protein production, gene expression of vascular endothelial growth factor (VEGF) and collagen type I (Col-I), and cell morphology were evaluated 24 h after the last irradiation. Data were statistically analyzed by Kruskal-Wallis and Mann-Whitney tests at 5% significance. Selected LLLT parameters increased the functions of epithelial cells and gingival fibroblasts treated with ZA. Gene expression of VEGF and Col-I was also increased. Specific parameters of LLLT biostimulated fibroblasts and epithelial cells treated with ZA. Analysis of these in vitro data may explain the positive in vivo effects of LLLT applied to osteonecrosis lesions.
High-frequency low-level diode laser irradiation promotes proliferation and migration of primary cultured human gingival epithelial cells.
Ejiri, Kenichiro; Aoki, Akira; Yamaguchi, Yoko; Ohshima, Mitsuhiro; Izumi, Yuichi
In periodontal therapy, the use of low-level diode lasers has recently been considered to improve wound healing of the gingival tissue. However, its effects on human gingival epithelial cells (HGECs) remain unknown. The aim of the present study was to examine whether high-frequency low-level diode laser irradiation stimulates key cell responses in wound healing, proliferation and migration, in primary cultured HGECs in vitro. HGECs were derived from seven independent gingival tissue specimens. Cultured HGECs were exposed to a single session of high-frequency (30 kHz) low-level diode laser irradiation with various irradiation time periods (fluence 5.7-56.7 J/cm(2)). After 20-24 h, cell proliferation was evaluated by WST-8 assay and [(3)H]thymidine incorporation assay, and cell migration was monitored by in vitro wound healing assay. Further, phosphorylation of the mitogen-activated protein kinase (MAPK) pathways after irradiation was investigated by Western blotting. The high-frequency low-level irradiation significantly increased cell proliferation and [(3)H]thymidine incorporation at various irradiation time periods. Migration of the irradiated cells was significantly accelerated compared with the nonirradiated control. Further, the low-level diode laser irradiation induced phosphorylation of MAPK/extracellular signal-regulated protein kinase (ERK) at 5, 15, 60, and 120 min after irradiation. Stress-activated protein kinases/c-Jun N-terminal kinase and p38 MAPK remained un-phosphorylated. The results show that high-frequency low-level diode laser irradiation promotes HGEC proliferation and migration in association with the activation of MAPK/ERK, suggesting that laser irradiation may accelerate gingival wound healing.
Re-epithelialization resulted from prostate basal cells in canine prostatic urethra may represent the ideal healing method after two-micron laser resection of the prostate.
Cao, Ying; Luo, Guang-Heng; Luo, Lei; Yang, Xiu-Shu; Hu, Jian-Xin; Shi, Hua; Huang, Ping; Sun, Zhao-Lin; Xia, Shu-Jie
The purpose of this study is to characterize the re-epithelialization of wound healing in canine prostatic urethra and to evaluate the effect of this re-epithelialization way after two-micron laser resection of the prostate (TmLRP). TmLRP and partial bladder neck mucosa were performed in 15 healthy adult male crossbred canines. Wound specimens were harvested at 3 days, and 1, 2, 3, and 4 weeks after operation, respectively. The histopathologic characteristics were observed by hematoxylin and eosin staining. The expression of cytokeratin 14 (CK14), CK5, CK18, synaptophysin (Syn), chromogranin A (CgA), uroplakin, transforming growth factor-β1 (TGF-β1 ), and TGF-β type II receptor in prostatic urethra wound were examined by immunohistochemistry and real-time polymerase chain reaction, respectively. Van Gieson staining was performed to determine the expression of collagen fibers in prostatic urethra and bladder neck would. The results showed that the re-epithelialization of the prostatic urethra resulted from the mobilization of proliferating epithelial cells from residual prostate tissue under the wound. The proliferating cells expressed CK14, CK5, but not CK18, Syn, and CgA and re-epithelialize expressed uroplakin since 3 weeks. There were enhanced TGF-β1 and TGF-β type II receptor expression in proliferating cells and regenerated cells, which correlated with specific phases of re-epithelialization. Compared with the re-epithelialization of the bladder neck, re-epithelialization of canine prostatic urethra was faster, and the expression of collagen fibers was relatively low. In conclusion, re-epithelialization in canine prostatic urethra resulted from prostate basal cells after TmLRP and this re-epithelialization way may represent the ideal healing method from anatomic repair to functional recovery after injury.
Irradiation with a low-level diode laser induces the developmental endothelial locus-1 gene and reduces proinflammatory cytokines in epithelial cells.
Fujimura, Takeki; Mitani, Akio; Fukuda, Mitsuo; Mogi, Makio; Osawa, Kazuhiro; Takahashi, Shinko; Aino, Makoto; Iwamura, Yuki; Miyajima, Shinichi; Yamamoto, Hiromitsu; Noguchi, Toshihide
We demonstrated previously that low-level diode laser irradiation with an indocyanine green-loaded nanosphere coated with chitosan (ICG-Nano/c) had an antimicrobial effect, and thus could be used for periodontal antimicrobial photodynamic therapy (aPDT). Since little is known about the effects of aPDT on periodontal tissue, we here investigated the effect of low-level laser irradiation, with and without ICG-Nano/c, on cultured epithelial cells. Human oral epithelial cells were irradiated in a repeated pulse mode (duty cycle, 10 %; pulse width, 100 ms; peak power output, 5 W). The expression of the developmental endothelial locus 1 (Del-1), interleukin-6 (IL-6), IL-8, and the intercellular adhesion molecule-1 (ICAM-1) were evaluated in Ca9-22 cells stimulated by laser irradiation and Escherichia coli-derived lipopolysaccharide (LPS). A wound healing assay was carried out on SCC-25 cells irradiated by diode laser with or without ICG-Nano/c. The mRNA expression of Del-1, which is known to have anti-inflammatory activity, was significantly upregulated by laser irradiation (p < 0.01). Concurrently, LPS-induced IL-6 and IL-8 expression was significantly suppressed in the LPS + laser group (p < 0.01). ICAM-1 expression was significantly higher in the LPS + laser group than in the LPS only or control groups. Finally, compared with the control, the migration of epithelial cells was significantly increased by diode laser irradiation with or without ICG-Nano/c. These results suggest that, in addition to its antimicrobial effect, low-level diode laser irradiation, with or without ICG-Nano/c, can suppress excessive inflammatory responses via a mechanism involving Del-1, and assists in wound healing.
STR profiling of epithelial cells identified by X/Y-FISH labelling and laser microdissection using standard and elevated PCR conditions.
Lynch, Laura; Gamblin, Amelia; Vintiner, Sue; Simons, Joanne L
During the investigation of allegations of sexual assault, samples are frequently encountered that contain DNA from a female and a male donor. These may represent contributions of DNA from the complainant and potentially, the offender. Many semen stained samples successfully undergo DNA analysis and interpretation using a differential extraction method that separates sperm from the epithelial cells present in the stain. However, for those mixed cell samples that contain only epithelial cells, separation of any male cells from female cells is problematic. This paper describes the application of fluorescent in situ hybridisation (FISH) for the gender identification of epithelial cells and subsequent recovery of target cells using laser microdissection (LMD). The profiling results obtained from samples of known cell numbers using the Identifiler™ multiplex at standard 28-cycle PCR conditions and, when cell numbers are low, the SGM Plus™ multiplex at elevated 34-cycle PCR conditions (also known as Low Copy Number DNA analysis (LCN)) are described.
Femtosecond Lasers in Ophthalmology: Surgery and Imaging
NASA Astrophysics Data System (ADS)
Bille, J. F.
Ophthalmology has traditionally been the field with prevalent laser applications in medicine. The human eye is one of the most accessible human organs and its transparency for visible and near-infrared light allows optical techniques for diagnosis and treatment of almost any ocular structure. Laser vision correction (LVC) was introduced in the late 1980s. Today, the procedural ease, success rate, and lack of disturbing side-effects in laser assisted in-situ keratomileusis (LASIK) have made it the most frequently performed refractive surgical procedure (keratomileusis(greek): cornea-flap-cutting). Recently, it has been demonstrated that specific aspects of LVC can take advantage of unique light-matter interaction processes that occur with femtosecond laser pulses.
Combining Laser Microsurgery and Finite Element Modeling to Assess Cell-Level Epithelial Mechanics
Hutson, M. Shane; Veldhuis, J.; Ma, Xiaoyan; Lynch, Holley E.; Cranston, P. Graham; Brodland, G. Wayne
Abstract Laser microsurgery and finite element modeling are used to determine the cell-level mechanics of the amnioserosa—a morphogenetically crucial epithelium on the dorsal surface of fruit fly embryos (Drosophila melanogaster). In the experiments, a tightly focused laser ablates a subcellular hole (1 μm in diameter) that passes clean through the epithelium. The surrounding cells recoil from the wound site with a large range of initial recoil velocities. These depend on the embryo's developmental stage and the subcellular wound site. The initial recoil (up to 0.1 s) is well reproduced by a base finite element model, which assumes a uniform effective viscosity inside the cells, a constant tension along each cell-cell boundary, and a large, potentially anisotropic, far-field stress—one that far exceeds the stress equivalent of the cell-edge tensions. After 0.1 s, the experimental recoils slow dramatically. This observation can be reproduced by adding viscoelastic rods along cell edges or as a fine prestressed mesh parallel to the apical and basal membranes of the cell. The mesh also reproduces a number of double-wounding experiments in which successive holes are drilled in a single cell. PMID:20006944
F 2 excimer laser (157 nm) radiation modification and surface ablation of PHEMA hydrogels and the effects on bioactivity: Surface attachment and proliferation of human corneal epithelial cells
NASA Astrophysics Data System (ADS)
Zainuddin; Chirila, Traian V.; Barnard, Zeke; Watson, Gregory S.; Toh, Chiong; Blakey, Idriss; Whittaker, Andrew K.; Hill, David J. T.
Physical and chemical changes at the surface of poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogels modified by ablation with an F 2 excimer laser were investigated experimentally. An important observation was that only the outer exposed surface layers of the hydrogel were affected by the exposure to 157 nm radiation. The effect of the surface changes on the tendency of cells to adhere to the PHEMA was also investigated. A 0.5 cm 2 area of the hydrogel surfaces was exposed to laser irradiation at 157 nm to fluences of 0.8 and 4 J cm -2. The changes in surface topography were analysed by light microscopy and atomic force microscopy, while the surface chemistry was characterized by attenuated total reflection infrared and X-ray photoelectron spectroscopies. Cell-interfacial interactions were examined based on the proliferation of human corneal limbal epithelial (HLE) cells cultured on the laser-modified hydrogels, and on the unexposed hydrogels and tissue culture plastic for comparison. It was observed that the surface topography of laser-exposed hydrogels showed rippled patterns with a surface roughness increasing at the higher exposure dose. The changes in surface chemistry were affected not only by an indirect effect of hydrogen and hydroxyl radicals, formed by water photolysis, on the PHEMA, but also by the direct action of laser radiation on PHEMA if the surface layers of the gel become depleted of water. The laser treatment led to a change in the surface characteristics, with a lower concentration of ester side-chains and the formation of new oxygenated species at the surface. The surface also became more hydrophobic. Most importantly, the surface chemistry and the newly created surface topographical features were able to improve the attachment, spreading and growth of HLE cells.
Oral focal epithelial hyperplasia.
Bassioukas, K; Danielides, V; Georgiou, I; Photos, E; Zagorianakou, P; Skevas, A
Focal epithelial hyperplasia (FEH) or Heck disease, is a rare viral infection of the oral mucosa caused by HPV 13 or HPV 32. In Caucasians there have been only a few cases reported. We present the first case in Greece in a young Caucasian girl in which HPV 13 was detected with PCR analysis. The patient was successfully treated with CO2 laser.
In vitro perforation of human epithelial carcinoma cell with antibody-conjugated biodegradable microspheres illuminated by a single 80 femtosecond near-infrared laser pulse.
Terakawa, Mitsuhiro; Tsunoi, Yasuyuki; Mitsuhashi, Tatsuki
Pulsed laser interaction with small metallic and dielectric particles has been receiving attention as a method of drug delivery to many cells. However, most of the particles are attended by many risks, which are mainly dependent upon particle size. Unlike other widely used particles, biodegradable particles have advantages of being broken down and eliminated by innate metabolic processes. In this paper, the perforation of cell membrane by a focused spot with transparent biodegradable microspheres excited by a single 800 nm, 80 fs laser pulse is demonstrated. A polylactic acid (PLA) sphere, a biodegradable polymer, was used. Fluorescein isothiocyanate (FITC)-dextran and short interfering RNA were delivered into many human epithelial carcinoma cells (A431 cells) by applying a single 80 fs laser pulse in the presence of antibody-conjugated PLA microspheres. The focused intensity was also simulated by the three-dimensional finite-difference time-domain method. Perforation by biodegradable spheres compared with other particles has the potential to be a much safer phototherapy and drug delivery method for patients. The present method can open a new avenue, which is considered an efficient adherent for the selective perforation of cells which express the specific antigen on the cell membrane.
The use of laser microdissection in the identification of suitable reference genes for normalization of quantitative real-time PCR in human FFPE epithelial ovarian tissue samples.
Cai, Jing; Li, Tao; Huang, Bangxing; Cheng, Henghui; Ding, Hui; Dong, Weihong; Xiao, Man; Liu, Ling; Wang, Zehua
Quantitative real-time PCR (qPCR) is a powerful and reproducible method of gene expression analysis in which expression levels are quantified by normalization against reference genes. Therefore, to investigate the potential biomarkers and therapeutic targets for epithelial ovarian cancer by qPCR, it is critical to identify stable reference genes. In this study, twelve housekeeping genes (ACTB, GAPDH, 18S rRNA, GUSB, PPIA, PBGD, PUM1, TBP, HRPT1, RPLP0, RPL13A, and B2M) were analyzed in 50 ovarian samples from normal, benign, borderline, and malignant tissues. For reliable results, laser microdissection (LMD), an effective technique used to prepare homogeneous starting material, was utilized to precisely excise target tissues or cells. One-way analysis of variance (ANOVA) and nonparametric (Kruskal-Wallis) tests were used to compare the expression differences. NormFinder and geNorm software were employed to further validate the suitability and stability of the candidate genes. Results showed that epithelial cells occupied a small percentage of the normal ovary indeed. The expression of ACTB, PPIA, RPL13A, RPLP0, and TBP were stable independent of the disease progression. In addition, NormFinder and geNorm identified the most stable combination (ACTB, PPIA, RPLP0, and TBP) and the relatively unstable reference gene GAPDH from the twelve commonly used housekeeping genes. Our results highlight the use of homogeneous ovarian tissues and multiple-reference normalization strategy, e.g. the combination of ACTB, PPIA, RPLP0, and TBP, for qPCR in epithelial ovarian tissues, whereas GAPDH, the most commonly used reference gene, is not recommended, especially as a single reference gene.
Multifocal papillomavirus epithelial hyperplasia: successful treatment with CO2 laser therapy combined with interferon alpha-2b.
Akyol, Aynur; Anadolu, Rana; Anadolu, Yücel; Ekmekci, Pelin; Gürgey, Erbak; Akay, Nisa
Human papilloma virus (HPV) infections of the oral mucosa presents with various clinical and histopathologic features in relation with the causative HPV type and chronicity and the extent of the infection.1 The entity is known by several names based on histopathologic variations such as focal epithelial hyperplasia, oral florid papillomatosis, verrucous hyperplasia, oral florid verrucosis, and Ackerman's tumor. In recent years, the term multifocal papillomavirus epithelial hyperplasia (MPVEH) has been proposed to define the variant that usually occurs in childhood and is characterized by diffuse confluent papillomatous lesions in the oral mucosa.1 Despite the lesions' benign appearance, early diagnosis and therapy of MPVEH is essential because of its high capacity for progression and its tendency for malign degeneration.
ERIC Educational Resources Information Center
Schewe, Phillip F.
Examines the nature of laser light. Topics include: (1) production and characteristics of laser light; (2) nine types of lasers; (3) five laser techniques including holography; (4) laser spectroscopy; and (5) laser fusion and other applications. (SK)
Corneal epithelial injury thresholds for multiple-pulse exposures to erbium fiber laser radiation at 1.54 μm
NASA Astrophysics Data System (ADS)
McCally, Russell L.
Corneal epithelial damage thresholds for exposures to sequences of pulses of 1.54 μm infrared radiation produced by an Er fiber laser were investigated. Thresholds were determined for sequences of 8 to 128 pulses at a repetition frequency of 10 Hz and 8 to 256 pulses at 20 Hz. The duration of the individual pulses was 0.025 sec and the 1/e diameter of the laser beam was 0.1 cm. The results show that threshold damage is correlated by an empirical power law of the form Hth = CN-β, where Hth is the threshold radiant exposure per pulse, and N is the number of pulses. The constant C is different for the 10 Hz and 20 Hz exposures and, for both cases, is greater than the estimated threshold for a single 0.025 sec pulse. Thus the empirical power law breaks down for small numbers of pulses (viz., N< 8), where it overestimates the damage thresholds. Temperature calculations for the threshold exposure conditions show that a critical temperature model also correlates the multiple-pulse injury thresholds.
Comparison of c-met Expression in Ovarian Epithelial Tumors and Normal Epithelia of the Female Reproductive Tract by Quantitative Laser Scan Microscopy
Huntsman, David; Resau, James H.; Klineberg, Eric; Auersperg, Nelly
The transmembrane tyrosine kinase receptor c-met with its ligand, hepatocyte growth factor/scatter factor (HGF/SF), acts as a mitogen, motogen, and morphogen in many normal epithelia. HGF/SF-met signaling has also been implicated in neoplastic progression and metastasis. In this study, immunofluorescence staining and quantitative laser scanning confocal microscopy were used to measure c-met expression in ovarian surface epithelial tumors from 17 oophorectomy specimens. These specimens were from patients aged 25 to 81 (mean age, 52) and included 10 malignant tumors, 4 borderline tumors, and five benign tumors including a Brenner tumor. For comparison, c-met expression was measured in normal tissues from the same patients, including 4 ovarian surface epithelia, 4 fallopian tube epithelia, 2 endometria, and 3 endocervical epithelia, as well as 3 cases of endometriosis. Relative pixel intensity values of c-met expression ranged from 0.4 in a normal ovarian surface epithelium to 22.3 in a borderline serous tumor. Malignant tumors (mean, 9.6) and borderline tumors (mean, 12.9) had higher average c-met expression levels than normal tissues (mean, 3.6) and endometriosis (mean, 1.8). The expression levels of benign tumors were intermediate (mean, 7.9). Among the normal tissues, c-met expression in fallopian tubes (mean, 8.2; range, 3.4–12.9) was higher than that of the other normal epithelia (mean, 1.6; range, 0.4–4.3). In eight cases where both normal and malignant tissues were sampled, c-met expression was significantly greater in malignant than in normal epithelia (P = 0.01). These findings indicate that c-met plays a role in the biology of the normal tissues examined. They confirm that its expression increases in the malignant progression of ovarian surface epithelial tumors, and suggest that increases comparable to those in frankly malignant carcinomas have already been reached in borderline lesions, ie, early in the neoplastic process. PMID:10433927
Differential Gene Expression in Explanted Human Retinal Pigment Epithelial Cells 12-Hours Post-Exposure to 532 nm, 120 ps Pulsed Laser Light
years or younger, either sex, with no mitigating ocular or retinal pathology such as glaucoma, diabetic retinopathy, retinitis pigmentosa , etc. Donor: The...USAFA TR 2004-01 Differential Gene Expression in Explanted Human Retinal Pigment Epithelial Cells 12-hours Post-Exposure to 532 nm, 120 ps Pulsed...TR 2004-01 This article, "Differential Gene Expression in Explanted Human Retinal Pigment Epithelial Cells 12-hours Post-Exposure to 532 nm, 120 ps
Identification of differentially expressed proteins of gamma-ray irradiated rat intestinal epithelial IEC-6 cells by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionisation-time of flight mass spectrometry.
Bo, Zhang; Yongping, Su; Fengchao, Wang; Guoping, Ai; Yongjiang, Wei
To identify proteins involved in the processes of cellular and molecular response to radiation damage repair in intestinal epithelial IEC-6 cells, we comparatively analyzed the proteome of irradiated IEC-6 cells with that of normal cells. A series of methods were used, including two-dimensional gel electrophoresis (Z-DE), PDQuest software analysis of 2-DE gels, peptide mass fingerprinting based on matrix-assisted laser desorption/ionisation-time of flight-mass spectrometry (MALDI-TOF-MS), and Swiss-Prot database searching, to separate and identify differentially expressed proteins. Western blotting and reverse transcriptase polymerase chain reaction (RT-PCR) were used to validate the differentially expressed proteins. Image analysis revealed that averages of 608 +/- 39 and 595 +/- 31 protein spots were detected in normal and irradiated IEC-6 cells, respectively. Sixteen differential protein spots were isolated from gels, and measured with MALDI-TOF-MS. A total of 14 spots yielded good spectra, and 11 spots matched with known proteins after database searching. These proteins were mainly involved in anti-oxidation, metabolism, and protein post-translational processes. Western blotting confirmed that stress-70 protein was down-regulated by gamma-irradiation. Up-regulation of ERP29 was confirmed by RT-PCR, indicating that it is involved in ionizing radiation. The clues provided by the comparative proteome strategy utilized here will shed light on molecular mechanisms of radiation damage repair in intestinal epithelial cells.
Effects of Laser Printer–Emitted Engineered Nanoparticles on Cytotoxicity, Chemokine Expression, Reactive Oxygen Species, DNA Methylation, and DNA Damage: A Comprehensive in Vitro Analysis in Human Small Airway Epithelial Cells, Macrophages, and Lymphoblasts
Pirela, Sandra V.; Miousse, Isabelle R.; Lu, Xiaoyan; Castranova, Vincent; Thomas, Treye; Qian, Yong; Bello, Dhimiter; Kobzik, Lester; Koturbash, Igor; Demokritou, Philip
Background Engineered nanomaterials (ENMs) incorporated into toner formulations of printing equipment become airborne during consumer use. Although information on the complex physicochemical and toxicological properties of both toner powders and printer-emitted particles (PEPs) continues to grow, most toxicological studies have not used the actual PEPs but rather have primarily used raw toner powders, which are not representative of current exposures experienced at the consumer level during printing. Objectives We assessed the biological responses of a panel of human cell lines to PEPs. Methods Three physiologically relevant cell lines—small airway epithelial cells (SAECs), macrophages (THP-1 cells), and lymphoblasts (TK6 cells)—were exposed to PEPs at a wide range of doses (0.5–100 μg/mL) corresponding to human inhalation exposure durations at the consumer level of 8 hr or more. Following treatment, toxicological parameters reflecting distinct mechanisms were evaluated. Results PEPs caused significant membrane integrity damage, an increase in reactive oxygen species (ROS) production, and an increase in pro-inflammatory cytokine release in different cell lines at doses equivalent to exposure durations from 7.8 to 1,500 hr. Furthermore, there were differences in methylation patterns that, although not statistically significant, demonstrate the potential effects of PEPs on the overall epigenome following exposure. Conclusions The in vitro findings obtained in this study suggest that laser printer–emitted engineered nanoparticles may be deleterious to lung cells and provide preliminary evidence of epigenetic modifications that might translate to pulmonary disorders. Citation Pirela SV, Miousse IR, Lu X, Castranova V, Thomas T, Qian Y, Bello D, Kobzik L, Koturbash I, Demokritou P. 2016. Effects of laser printer–emitted engineered nanoparticles on cytotoxicity, chemokine expression, reactive oxygen species, DNA methylation, and DNA damage: a comprehensive in
Passeron, T
Lasers are a very effective approach for treating many hyperpigmented lesions. They are the gold standard treatment for actinic lentigos and dermal hypermelanocytosis, such as Ota nevus. Becker nevus, hyperpigmented mosaicisms, and lentigines can also be successfully treated with lasers, but they could be less effective and relapses can be observed. However, lasers cannot be proposed for all types of hyperpigmentation. Thus, freckles and café-au-lait macules should not be treated as the relapses are nearly constant. Due to its complex pathophysiology, melasma has a special place in hyperpigmented dermatoses. Q-switched lasers (using standard parameters or low fluency) should not be used because of consistent relapses and the high risk of post-inflammatory hyperpigmentation. Paradoxically, targeting the vascular component of the melasma lesion with lasers could have a beneficial effect. However, these results have yet to be confirmed. In all cases, a precise diagnosis of the type of hyperpigmentation is mandatory before any laser treatment, and the limits and the potential side effects of the treatment must be clearly explained to patients.
Passeron, T
Lasers are a very effective approach for treating many hyperpigmented lesions. They are the gold standard treatment for actinic lentigos and dermal hypermelanocytosis, such as Ota nevus. Becker nevus, hyperpigmented mosaicisms, and lentigines can also be successfully treated with lasers, but they could be less effective and relapses can be observed. However, lasers cannot be proposed for all types of hyperpigmentation. Thus, freckles and café-au-lait macules should not be treated as the relapses are nearly constant. Due to its complex pathophysiology, melasma has a special place in hyperpigmented dermatoses. Q-switched lasers (using standard parameters or low fluency) should not be used because of consistent relapses and the high risk of post-inflammatory hyperpigmentation. Paradoxically, targeting the vascular component of the melasma lesion with lasers could have a beneficial effect. However, these results have yet to be confirmed. In all cases, a precise diagnosis of the type of hyperpigmentation is mandatory before any laser treatment, and the limits and the potential side effects of the treatment must be clearly explained to patients.
Exposing human retinal pigmented epithelial cells to red light in vitro elicits an adaptive response to a subsequent 2-μm laser challenge
NASA Astrophysics Data System (ADS)
Schuster, K. J.; Estlack, L. E.; Wigle, J. C.
The objective of this study was to elucidate cellular mechanisms of protection against laser-induced thermal killing utilizing an in vitro retina model. When exposed to a 1-sec pulse of 2-μm laser radiation 24 hr after illuminating hTERT-RPE cells with red light (preconditioning), the cells are more resistant to thermal challenge than unilluminated controls (adaptive response). Results of efforts to understand the physiology of this effect led us to two genes: Vascular Endothelial Growth Factor C (VEGF-C) and Micro RNA 146a (miR-146a). Transfecting wild type (WT) cells with siRNA for VEGF-C and miR-146a mRNA resulted in knockdown strains (VEGF-C(KD) and miR- 146a(-)) with 10% and 30% (respectively) of the constitutive levels expressed in the WT cells. To induce gene expression, WT or KD cells were preconditioned with 1.44 to 5.40 J/cm2, using irradiances between 0.40 and 1.60 mW/cm2 of either 671-nm (diode) or 637-nm (laser) radiation. Probit analysis was used to calculate threshold damage irradiance, expressed as ED50, between 10 and 100 W/cm2 for the 2-μm laser pulse. In the WT cells there is a significant increase in ED50 (p 0.05) with the maximum response occurring at 2.88 J/cm2 in the preconditioned cells. Neither KD cell strain showed a significant increase in the ED50, although some data suggest the response may just be decreased in the knockdown cells instead of absent. So far the response does not appear to be dependent upon either wavelength (637 vs. 671 nm) or coherence (laser vs. LED), but there is an irradiance dependence.
Use of laser capture microdissection for the assessment of equine lamellar basal epithelial cell signalling in the early stages of laminitis
Leise, B. S.; Watts, M.; Roy, S.; Yilmaz, S.; Alder, H.; Belknap, J. K.
Summary Reason for performing study Dysadhesion of the laminar basal epithelial cells (LBEC) from the underlying dermis is the central event leading to structural failure in equine laminitis. Although many studies of sepsis-related laminitis have reported multiple events occurring throughout the lamellar tissue, there is minimal information regarding signalling events occurring specifically in the LBEC. Objectives To determine the signalling events in the LBECs during the early stages of carbohydrate induced laminitis. Study Design Experimental study. Methods Eight horses were given an overload of carbohydrate (corn starch mixture, CHO) via nasogastric tube. Prior to administration of CHO, lamellar biopsies were taken from the left fore foot (CON). Biopsies were taken from the left hind foot at the onset of fever (DEV) and from the right fore foot at the onset of lameness (OG1). Laminar basal epithelial cells (LBECs) were isolated from cryosections using a LCM microscope. Next generation sequencing (RNA-Seq) was used to identify transcripts expressed in the LBECs for each time point and bioinformatic analysis was performed with thresholds for between group comparisons set at a greater than 2-fold change and p-value ≤0.05. Results Forty genes (22 increased/18 decreased) were significantly different from DEV time vs. CON and 107 genes (57 increased/50 decreased) were significantly different from OG1 time vs. CON. Significant increases in inflammatory genes were present in addition to significantly altered expression of genes related to extracellular matrix composition, stability and turnover. Conclusions Inflammatory response and extracellular matrix regulation signalling was strongly represented at the DEV and OG1 times. These results indicate that the LBEC is not only a casualty but also an active participant in lamellar events leading to structural failure of the digital lamellae in equine laminitis. PMID:24750316
Finite element model of the temperature increase in excised porcine cadaver iris during direct illumination by femtosecond laser pulses
NASA Astrophysics Data System (ADS)
Sun, Hui; Kurtz, Ronald M.; Juhasz, Tibor
In order to model the thermal effect of laser exposure of the iris during laser corneal surgery, we simulated the temperature increase in porcine cadaver iris. The simulation data for the 60 kHz FS60 Laser showed that the temperature increased up to 1.23°C and 2.45°C (at laser pulse energy 1 and 2 µJ, respectively) by the 24 second procedure time. Calculated temperature profiles show good agreement with data obtained from ex vivo experiments using porcine cadaver iris. Simulation results of different types of femtosecond lasers indicate that the Laser in situ keratomileusis procedure does not present a safety hazard to the iris.
Simulation of the temperature increase in human cadaver retina during direct illumination by 150-kHz femtosecond laser pulses
NASA Astrophysics Data System (ADS)
Sun, Hui; Hosszufalusi, Nora; Mikula, Eric R.; Juhasz, Tibor
We have developed a two-dimensional computer model to predict the temperature increase of the retina during femtosecond corneal laser flap cutting. Simulating a typical clinical setting for 150-kHz iFS advanced femtosecond laser (0.8- to 1-μJ laser pulse energy and 15-s procedure time at a laser wavelength of 1053 nm), the temperature increase is 0.2°C. Calculated temperature profiles show good agreement with data obtained from ex vivo experiments using human cadaver retina. Simulation results obtained for different commercial femtosecond lasers indicate that during the laser in situ keratomileusis procedure the temperature increase of the retina is insufficient to induce damage.
Ophthalmic applications of femtosecond lasers
NASA Astrophysics Data System (ADS)
Kurtz, Ron M.; Spooner, Greg J. R.; Sletten, Karin R.; Yen, Kimberly G.; Sayegh, Samir I.; Loesel, Frieder H.; Horvath, Christopher; Liu, HsiaoHua; Elner, Victor; Cabrera, Delia; Muenier, Marie-Helene; Sacks, Zachary S.; Juhasz, Tibor; Miller, Doug L.; Williams, A. R.
We investigated three potential femtosecond laser ophthalmic procedures: intrastromal refractive surgery, transcleral photodisruptive glaucoma surgery and photodisruptive ultrasonic lens surgery. A highly reliable, all-solid-state system was used to investigate tissue effects and demonstrate clinical practicality. Compared with longer duration pulses, femtosecond laser-tissue interactions are characterized by smaller and more deterministic photodisruptive energy thresholds, smaller shock wave and cavitation bubble sizes. Scanning a 5 (mu) spot below the target tissue surface produced contiguous tissue effects. Various scanning patterns were used to evaluate the efficacy, safety, and stability of three intrastromal refractive procedures in animal eyes: corneal flap cutting, keratomileusis, and intrastromal vision correction (IVC). Superior dissection and surface quality results were obtained for the lamellar procedures. IVC in rabbits revealed consistent, stable pachymetric changes, without significant inflammation or corneal transparency degradation. Transcleral photodisruption was evaluated as a noninvasive method for creating partial thickness scleral channels to reduce elevated intraocular pressure associated with glaucoma. Photodisruption at the internal scleral surface was demonstrated by focusing through tissue in vitro without collateral damage. Femtosecond photodisruptions nucleated ultrasonically driven cavitation to demonstrate non-invasive destruction of in vitro lens tissue. We conclude that femtosecond lasers may enable practical novel ophthalmic procedures, offering advantages over current techniques.
Cell volume kinetics of adherent epithelial cells measured by laser scanning reflection microscopy: determination of water permeability changes of renal principal cells.
Maric, K; Wiesner, B; Lorenz, D; Klussmann, E; Betz, T; Rosenthal, W
The water channel aquaporin-2 (AQP2), a key component of the antidiuretic machinery in the kidney, is rapidly regulated by the antidiuretic hormone vasopressin. The hormone exerts its action by inducing a translocation of AQP2 from intracellular vesicles to the cell membrane. This step requires the elevation of intracellular cyclic AMP. We describe here a new method, laser scanning reflection microscopy (LSRM), suitable for determining cellular osmotic water permeability coefficient changes in primary cultured inner medullary collecting duct (IMCD) cells. The recording of vertical-reflection-mode x-z-scan section areas of unstained, living IMCD cells proved useful and valid for the investigation of osmotic water permeability changes. The time-dependent increases of reflection-mode x-z-scan section areas of swelling cells were fitted to a single-exponential equation. The analysis of the time constants of these processes indicates a twofold increase in osmotic water permeability of IMCD cells after treatment of the cells both with forskolin, a cyclic AMP-elevating agent, and with Clostridium difficile toxin B, an inhibitor of Rho proteins that leads to depolymerization of F-actin-containing stress fibers. This indicates that both agents lead to the functional insertion of AQP2 into the cell membrane. Thus, we have established a new functional assay for the study of the regulation of the water permeability at the cellular level. PMID:11259291
Focal epithelial hyperplasia - an update.
Said, Ahmed K; Leao, Jair C; Fedele, Stefano; Porter, Stephen R
Focal epithelial hyperplasia (FEH) is an asymptomatic benign mucosal disease, which is mostly observed in specific groups in certain geographical regions. FEH is usually a disease of childhood and adolescence and is generally associated with people who live in poverty and of low socioeconomic status. Clinically, FEH is typically characterized by multiple, painless, soft, sessile papules, plaques or nodules, which may coalesce to give rise to larger lesions. Human papillomavirus (HPV), especially genotypes 13 and 32, have been associated and detected in the majority of FEH lesions. The clinical examination and social history often allow diagnosis, but histopathological examination of lesional tissue is usually required to confirm the exact diagnosis. FEH sometimes resolves spontaneously however, treatment is often indicated as a consequence of aesthetic effects or any interference with occlusion. There remains no specific therapy for FEH, although surgical removal, laser excision or possibly topical antiviral agents may be of benefit. There remains no evidence that FEH is potentially malignant.
[Focal epithelial hyperplasia].
Vera-Iglesias, E; García-Arpa, M; Sánchez-Caminero, P; Romero-Aguilera, G; Cortina de la Calle, P
Focal epithelial hyperplasia is a rare disease of the oral mucosa caused by the human papilloma virus (HPV). It appears as a benign epithelial growth, usually in the mucosa of the lower lip. It is mainly associated with HPV serotypes 13 and 32 and there is a clear racial predilection for the disease in Native Americans and Eskimos. We describe the case of a 17-year-old girl from Ecuador with multiple papular lesions in both lips that were clinically and histologically consistent with focal epithelial hyperplasia. Analysis by polymerase chain reaction detected HPV serotype 13.
Necrotizing Keratitis after Laser Refractive Surgery in Patients with Inactive Inflammatory Bowel Disease
Aman-Ullah, Muhammad; Gimbel, Howard V.; Purba, Mona K.; van Westenbrugge, John A.
Two cases of necrotizing keratitis following laser refractive corneal surgery, with stable and controlled Crohn's disease are described. A 40-year-old woman developed bilateral stromal inflammation and inferior thinning in the right eye along the flap edge within 1 day of uneventful bilateral IntraLase laser-assisted in situ keratomileusis. The other case is a 30-year-old man who also developed bilateral inferior stromal infiltrates 2 days following photorefractive keratectomy. Both cases were aggressively treated with systemic and topical corticosteroids. The infiltrates in both patients gradually resolved, with one relapse during the 7 months period of follow-up in the first case. These cases highlight the importance of taking precautions considering this and similar autoimmune conditions as a relative contraindication to refractive surgery. PMID:22611369
Refinement of Intraocular Pressure Measurements made by Ocular Response Analyzer following Laser in Situ Keratomileusis using M2 90 Moria Microkeratome for Egyptian Myopic and Astigmatic Patients
Refai, Tamer Adel; Hassanin, Olfat A.
Introduction The Goldmann applanation tonometer readings were noted to be markedly reduced after Lasik surgery using a thin flap technique which is widely used nowadays, to correct a wide range of myopia and astigmatism. The Ocular Response Analyzer (ORA) is considered one of the important tools for refinement of Intraocular Pressure (IOP) measurements. The aim of this study is to evaluate and refine ORA measurements for IOP changes post- M2 90 Moria microkeratome Lasik procedure for Egyptian myopic and astigmatic patients trying to aid in glaucoma diagnosis and management. Methods Thirty-five eyes of nineteen Egyptian patients with myopia or myopic astigmatism who had undergone Lasik procedure using M2 90 Moria microkeratome were included in this consecutive case series study. All cases were subjected to full ophthalmological examination including uncorrected and best corrected visual acuity, refraction, slit lamp examination, Scheimpflug imaging and ORA (Reichert Ophthalmic Instruments, Inc., Buffalo, NY, USA). The refractive errors were measured using an auto refractometer and were confirmed by trial. For the ocular response analyzer, the Goldmann-correlated IOP measurement (IOPg) which simulates IOP measured by Goldmann tonometer and the Corneal-Compensated Intraocular Pressure (IOPcc) that takes corneal biomechanical properties into consideration were reported as well as the Corneal Hysteresis (CH) and the Corneal Resistance Factor (CRF). Cases were examined preoperatively and again about one month after Lasik, after stabilization of eye condition. The collected data were tabulated and analysed with the suitable statistical methods. The mean values and standard deviation were calculated for quantitative data. Comparison tests (t-test) and correlation tests (Pearson) were also performed. Results In our study, involving M2 90 Moria microkeratome Lasik procedure, a highly significant post-Lasik reduction in IOPg (t-test = 8.62 (p<0.01), and a statistically significant reduction in IOPcc (t-test = 3.37 (p<0.05) by ocular response analyzer. The average post-Lasik reduction in IOP in mmHg was 4.84±2.82 for IOPg and 2.23±3.51for IOPcc. A statistically significant correlation (p<0.05) existed between post-Lasik reduction of IOPg and ablation depth as well as preoperative spherical equivalent. A non-significant correlation existed between post-Lasik reduction of IOPcc and both of ablation depth and preoperative spherical equivalent. Conclusions Following Lasik procedure using M2 90 Moria microkeratome, the IOPcc values by ORA were closer to the preoperative values than the IOPg values and the reduction of IOPcc values was not affected by ablation depth (i.e. preoperative spherical equivalent). Therefore, it is advisable to use the IOPcc values by ORA when evaluating post-Lasik patients for glaucoma diagnosis and management, but with the addition of the average value for post-Lasik reduction which in the study was 2.23±3.51mmHg. PMID:28163860
Wound healing after laser surgery.
Hendrick, D A; Meyers, A
Compared with scalpel wounds, CO2 laser wounds show delays in inflammation, collagen production, reepithelialization, and tensile strength in the early stages of healing. Some of these delays are similar to those seen with electrocautery and burn wounds. Later stages compensate for these early deficiencies, because scalpel and laser wounds become more similar in epithelialization and wound strength over time. Healed CO2 laser wounds tend to have less scar contraction than scalpel wounds. Débridement of initial laser wound char, tissue cooling techniques during lasering, and pulsed modes of laser delivery all seem to result in more rapid, favorable healing. Similar wound healing trends have been seen with the CO2 laser in bone, with other lasers, and with laser vascular and neural anastomosis. Biostimulation with low-level laser energy is a complex subject of ongoing investigations.
Normal morphogenesis of epithelial tissues and progression of epithelial tumors
Wang, Chun-Chao; Jamal, Leen; Janes, Kevin A.
Epithelial cells organize into various tissue architectures that largely maintain their structure throughout the life of an organism. For decades, the morphogenesis of epithelial tissues has fascinated scientists at the interface of cell, developmental, and molecular biology. Systems biology offers ways to combine knowledge from these disciplines by building integrative models that are quantitative and predictive. Can such models be useful for gaining a deeper understanding of epithelial morphogenesis? Here, we take inventory of some recurring themes in epithelial morphogenesis that systems approaches could strive to capture. Predictive understanding of morphogenesis at the systems level would prove especially valuable for diseases such as cancer, where epithelial tissue architecture is profoundly disrupted. PMID:21898857
Normal morphogenesis of epithelial tissues and progression of epithelial tumors.
Wang, Chun-Chao; Jamal, Leen; Janes, Kevin A
Epithelial cells organize into various tissue architectures that largely maintain their structure throughout the life of an organism. For decades, the morphogenesis of epithelial tissues has fascinated scientists at the interface of cell, developmental, and molecular biology. Systems biology offers ways to combine knowledge from these disciplines by building integrative models that are quantitative and predictive. Can such models be useful for gaining a deeper understanding of epithelial morphogenesis? Here, we take inventory of some recurring themes in epithelial morphogenesis that systems approaches could strive to capture. Predictive understanding of morphogenesis at the systems level would prove especially valuable for diseases such as cancer, where epithelial tissue architecture is profoundly disrupted.
Oral focal epithelial hyperplasia.
López-Jornet, Pía; Camacho-Alonso, Fabio; Berdugo, Lucero
Focal epithelial hyperplasia (FEH) is a benign, asymptomatic disease. It appears as papules, principally on the lower lip, although it can also be found on the retro-commissural mucosa and tongue and, less frequently, on the upper lip, gingiva and palate. FEH is caused by human papillomavirus subtype 13 or 32. The condition occurs in many populations and ethnic groups. We present the clinical case of a 31-year-old male with lesions that clinically and histologically corresponded to FEH.
Capaldo, Christopher T.; Farkas, Attila E.
Epithelial adhesive cell-to-cell contacts contain large, plasma membrane-spanning multiprotein aggregates that perform vital structural and signaling functions. Three prominent adhesive contacts are the tight junction, adherens junction, and the desmosome. Each junction type has unique cellular functions and a complex molecular composition. In this review, we comment on recent and exciting advances in our understanding of junction composition and function. PMID:24592313
Investigation of the formation mechanism and morphology of the features created in the interior of cornea by femtosecond laser pulses
NASA Astrophysics Data System (ADS)
Guo, Yizang; Vukelic, Sinisa
Laser assisted corneal surgeries often rely on the nonlinear absorption effect of ultrafast lasers to induce features in the interior of the cornea without affecting the surface. In particular, corneal flap formation in femtosecond assisted Laser- Assisted in situ Keratomileusis (LASIK) is based on the bubble creation. This study focuses on the interaction between the tissue and the femtosecond laser. Interior of cornea is treated with tightly focused femtosecond laser pulses. Due to the nature of the process, heating of the tissue within and around the focal volume is practically instantaneous. The affected region is subject to thermoelastic stress that arises with the steep temperature elevation. To predict the size of the region subject to the morphological changes due to the laser treatment, the temperature field is calculated. Cavitation bubble initiation and expansion process, which acts as precursor to the stress induced tissue trauma, is studied as well. Theoretical findings are compared against experimental results. High-speed camera is utilized to assess the laser treatment process, showing the temporal development of the cavitation bubbles. The results obtained in this study facilitate a better understanding of the effects of femtosecond laser assisted corneal surgeries and help in choosing optimal laser parameters.
[Focal epithelial hyperplasia].
Delgado, Yolanda; Torrelo, Antonio; Colmenero, Isabel; Zambrano, Antonio
Focal epithelial hyperplasia (FEH) is a benign proliferation of the oral mucosa with well defined clinical and histological characteristics. It has been associated with infection of the oral mucosa by types 13 and 32 of the human papillomavirus (HPV), and to a lesser extent, with other types. Its clinical course is variable, although it usually persists for months or years; cases with spontaneous resolution have been described, as have others with prolonged persistence. We present the case of an Ecuadorian boy whose visit was motivated by lesions in the oral mucosa consistent with a diagnosis of FEH, which were confirmed in the histological study, and in which HPV type 13 DNA was identified.
Evaluation of thermal load during laser corneal refractive surgery using infrared thermography
NASA Astrophysics Data System (ADS)
Brunsmann, U.; Sauer, U.; Arba-Mosquera, S.; Magnago, T.; Triefenbach, N.
Infrared thermography is used for evaluation of the mean temperature as a measure of thermal load during corneal refractive surgery. An experimental method to determine emissivity and to calibrate the thermografic system is presented. In a case study on the porcine eye two dimensional temperature distributions with lateral resolution of 170 μm and line scans with temporal resolution of 13 μs are discussed with respect to the meaning of mean temperature. Using the newest generation of surgery equipment it is shown, that the mean temperature rise can be kept below 5 °C during myopic laser in situ keratomileusis (LASIK) treatments corresponding to an aberration-free correction of -2.75 diopter.
Epithelial Conduction in Hydromedusae
Mackie, G. O.; Passano, L. M.
Sarsia, Euphysa, and other hydromedusae have been studied by electrophysiological techniques and are found to have nonnervous conducting epithelia resembling those described earlier for siphonophores. Simple, non-muscular epithelia fire singly or repetitively following brief electrical stimuli. The pulses recorded with suction electrodes are biphasic, initially positive, and show amplitudes of 0.75–2.0 mv, durations of 5–15 msec, and velocities of 15–35 cm/sec with short refractory periods. In the swimming muscle (myoepithelium) 2.0–4.0 mv composite events lasting 150–300 msec are associated with contraction waves. Propagation in nonnervous epithelia is typically all-or-none, nondecremental, and unpolarized. The subumbrellar endoderm lamella conducts independently of the adjacent ectoderm. The lower regions of the tentacles do not show propagated epithelial events. The spread of excitation in conducting epithelia and associated effector responses are described. Examples are given of interaction between events seemingly conducted in the nervous system and those in nonnervous epithelia. Either system may excite the other. Spontaneous activity, however, appears to originate in the nervous system. Conduction in nonnervous tissues is unaffected by excess Mg++ in concentrations suppressing presumed nervous activity, although this may not be a wholly adequate criterion for distinguishing components of the two systems. Evidence from old work by Romanes is considered in the light of these findings and the general significance of epithelial conduction is discussed. PMID:4386662
[Focal epithelial hyperplasia of the oral mucosa. A unique manifestation of human papillomavirus].
van der Voort, E A M; Arani, S Fallah; Hegt, V Noordhoek; van Praag, M C G
A 34-year old Creole woman appeared at the dermatology department with white-pink spots on the oral mucosa, which had been there for some time. Histology showed lesions characteristic of focal epithelial hyperplasia. The patient was treated with a CO2 laser. Focal epithelial hyperplasia is a rare benign lesion and is caused by human papillomavirus subtypes 13 or 32; it only appears on the oral mucosa.
Hydraulic fracture during epithelial stretching
Casares, Laura; Vincent, Romaric; Zalvidea, Dobryna; Campillo, Noelia; Navajas, Daniel; Arroyo, Marino; Trepat, Xavier
The origin of fracture in epithelial cell sheets subject to stretch is commonly attributed to excess tension in the cells' cytoskeleton, in the plasma membrane, or in cell-cell contacts. Here we demonstrate that for a variety of synthetic and physiological hydrogel substrates the formation of epithelial cracks is caused by tissue stretching independently of epithelial tension. We show that the origin of the cracks is hydraulic; they result from a transient pressure build-up in the substrate during stretch and compression maneuvers. After pressure equilibration cracks heal readily through actomyosin-dependent mechanisms. The observed phenomenology is captured by the theory of poroelasticity, which predicts the size and healing dynamics of epithelial cracks as a function of the stiffness, geometry and composition of the hydrogel substrate. Our findings demonstrate that epithelial integrity is determined in a tension-independent manner by the coupling between tissue stretching and matrix hydraulics. PMID:25664452
Hydraulic fracture during epithelial stretching
NASA Astrophysics Data System (ADS)
Casares, Laura; Vincent, Romaric; Zalvidea, Dobryna; Campillo, Noelia; Navajas, Daniel; Arroyo, Marino; Trepat, Xavier
The origin of fracture in epithelial cell sheets subject to stretch is commonly attributed to excess tension in the cells' cytoskeleton, in the plasma membrane, or in cell-cell contacts. Here, we demonstrate that for a variety of synthetic and physiological hydrogel substrates the formation of epithelial cracks is caused by tissue stretching independently of epithelial tension. We show that the origin of the cracks is hydraulic; they result from a transient pressure build-up in the substrate during stretch and compression manoeuvres. After pressure equilibration, cracks heal readily through actomyosin-dependent mechanisms. The observed phenomenology is captured by the theory of poroelasticity, which predicts the size and healing dynamics of epithelial cracks as a function of the stiffness, geometry and composition of the hydrogel substrate. Our findings demonstrate that epithelial integrity is determined in a tension-independent manner by the coupling between tissue stretching and matrix hydraulics.
Extensive focal epithelial hyperplasia.
Hashemipour, Maryam Alsadat; Shoryabi, Ali; Adhami, Shahrzad; Mehrabizadeh Honarmand, Hoda
Heck's disease or focal epithelial hyperplasia is a benign contagious disease caused by human papillomavirus types 13 or 32. It occurs with low frequency in the Iranian population. This condition is characterized by the occurrence of multiple, small papules or nodules in the oral cavity, especially on the labial and buccal mucosa and tongue. In some populations, up to 39% of children are affected. Conservative surgical excision of lesions may be performed for diagnostic or aesthetic purposes. The risk of recurrence after this therapy is minimal, and there seems to be no malignant transformation potential. In the present work, we presented the clinical case of a 12-year-old Iranian girl with oral lesions that clinically and histologically correspond to Heck's disease.
Isolation by Size of Epithelial Tumor Cells
Vona, Giovanna; Sabile, Abdelmajid; Louha, Malek; Sitruk, Veronique; Romana, Serge; Schütze, Karin; Capron, Frédérique; Franco, Dominique; Pazzagli, Mario; Vekemans, Michel; Lacour, Bernard; Bréchot, Christian; Paterlini-Bréchot, Patrizia
We have developed a new assay, ISET (isolation by size of epithelial tumor cells), which allows the counting and the immunomorphological and molecular characterization of circulating tumor cells in patients with carcinoma, using peripheral blood sample volumes as small as 1 ml. Using this assay, epithelial tumor cells can be isolated individually by filtration because of their larger size when compared to peripheral blood leukocytes. ISET parameters were defined using peripheral blood spiked with tumor cell lines (HepG2, Hep3B, MCF-7, HeLa, and LNCaP). ISET can detect a single, micropipetted tumor cell, added to 1 ml of blood. We also demonstrate that fluorescence in situ hybridization can be used to perform chromosomal analyses on tumor cells collected using ISET. Polymerase chain reaction-based genetic analyses can be applied to ISET-isolated cells, and, as an example, we demonstrate homozygous p53 deletion in single Hep3B cells after filtration and laser microdissection. Finally, we provide evidence for the in vivo feasibility of ISET in patients with hepatocellular carcinoma undergoing tumor resection. ISET, but not reverse transcriptase-polymerase chain reaction, allowed analysis of cell morphology, counting of tumor cells, and demonstration of tumor microemboli spread into peripheral blood during surgery. Overall, ISET constitutes a novel approach that should open new perpectives in molecular medicine. PMID:10623654
Eosinophils promote epithelial to mesenchymal transition of bronchial epithelial cells.
Yasukawa, Atsushi; Hosoki, Koa; Toda, Masaaki; Miyake, Yasushi; Matsushima, Yuki; Matsumoto, Takahiro; Boveda-Ruiz, Daniel; Gil-Bernabe, Paloma; Nagao, Mizuho; Sugimoto, Mayumi; Hiraguchi, Yukiko; Tokuda, Reiko; Naito, Masahiro; Takagi, Takehiro; D'Alessandro-Gabazza, Corina N; Suga, Shigeru; Kobayashi, Tetsu; Fujisawa, Takao; Taguchi, Osamu; Gabazza, Esteban C
Eosinophilic inflammation and remodeling of the airways including subepithelial fibrosis and myofibroblast hyperplasia are characteristic pathological findings of bronchial asthma. Epithelial to mesenchymal transition (EMT) plays a critical role in airway remodelling. In this study, we hypothesized that infiltrating eosinophils promote airway remodelling in bronchial asthma. To demonstrate this hypothesis we evaluated the effect of eosinophils on EMT by in vitro and in vivo studies. EMT was assessed in mice that received intra-tracheal instillation of mouse bone marrow derived eosinophils and in human bronchial epithelial cells co-cultured with eosinophils freshly purified from healthy individuals or with eosinophilic leukemia cell lines. Intra-tracheal instillation of eosinophils was associated with enhanced bronchial inflammation and fibrosis and increased lung concentration of growth factors. Mice instilled with eosinophils pre-treated with transforming growth factor(TGF)-β1 siRNA had decreased bronchial wall fibrosis compared to controls. EMT was induced in bronchial epithelial cells co-cultured with human eosinophils and it was associated with increased expression of TGF-β1 and Smad3 phosphorylation in the bronchial epithelial cells. Treatment with anti-TGF-β1 antibody blocked EMT in bronchial epithelial cells. Eosinophils induced EMT in bronchial epithelial cells, suggesting their contribution to the pathogenesis of airway remodelling.
Integrins and epithelial cell polarity.
Lee, Jessica L; Streuli, Charles H
Cell polarity is characterised by differences in structure, composition and function between at least two poles of a cell. In epithelial cells, these spatial differences allow for the formation of defined apical and basal membranes. It has been increasingly recognised that cell-matrix interactions and integrins play an essential role in creating epithelial cell polarity, although key gaps in our knowledge remain. This Commentary will discuss the mounting evidence for the role of integrins in polarising epithelial cells. We build a model in which both inside-out signals to polarise basement membrane assembly at the basal surface, and outside-in signals to control microtubule apical-basal orientation and vesicular trafficking are required for establishing and maintaining the orientation of epithelial cell polarity. Finally, we discuss the relevance of the basal integrin polarity axis to cancer. This article is part of a Minifocus on Establishing polarity.
Focal epithelial hyperplasia (Heck disease) related to highly active antiretroviral therapy in an HIV-seropositive child. A report of a case, and a review of the literature.
Feller, L; Khammissa, R A G; Wood, N H; Malema, V; Meyerov, R; Lemmer, J
Focal epithelial hyperplasia is increasingly frequently observed in rural South African communities. HIV-seropositive subjects have a higher prevalence of oral human papillomavirus (HPV) infections than immunocompetent subjects; and paradoxically, the introduction of highly active antiretroviral therapy for treatment of HIV-seropositive subjects is associated with increased frequency of focal epithelial hyperplasia. We describe a case of focal epithelial hyperplasia in an HIV-seropositive child receiving highly active antiretroviral therapy, who was successfully treated by using diode laser ablation.
Theory of epithelial elasticity
NASA Astrophysics Data System (ADS)
Krajnc, Matej; Ziherl, Primož
We propose an elastic theory of epithelial monolayers based on a two-dimensional discrete model of dropletlike cells characterized by differential surface tensions of their apical, basal, and lateral sides. We show that the effective tissue bending modulus depends on the apicobasal differential tension and changes sign at the transition from the flat to the fold morphology. We discuss three mechanisms that stabilize the finite-wavelength fold structures: Physical constraint on cell geometry, hard-core interaction between non-neighboring cells, and bending elasticity of the basement membrane. We show that the thickness of the monolayer changes along the waveform and thus needs to be considered as a variable rather than a parameter. Next we show that the coupling between the curvature and the thickness is governed by the apicobasal polarity and that the amplitude of thickness modulation along the waveform is proportional to the apicobasal differential tension. This suggests that intracellular stresses can be measured indirectly by observing easily measurable morphometric parameters. We also study the mechanics of three-dimensional structures with cylindrical symmetry.
Clinical Outcomes of an Optimized Prolate Ablation Procedure for Correcting Residual Refractive Errors Following Laser Surgery
Chung, Byunghoon; Lee, Hun; Choi, Bong Joon; Seo, Kyung Ryul; Kim, Eung Kwon; Kim, Dae Yune
Purpose The purpose of this study was to investigate the clinical efficacy of an optimized prolate ablation procedure for correcting residual refractive errors following laser surgery. Methods We analyzed 24 eyes of 15 patients who underwent an optimized prolate ablation procedure for the correction of residual refractive errors following laser in situ keratomileusis, laser-assisted subepithelial keratectomy, or photorefractive keratectomy surgeries. Preoperative ophthalmic examinations were performed, and uncorrected distance visual acuity, corrected distance visual acuity, manifest refraction values (sphere, cylinder, and spherical equivalent), point spread function, modulation transfer function, corneal asphericity (Q value), ocular aberrations, and corneal haze measurements were obtained postoperatively at 1, 3, and 6 months. Results Uncorrected distance visual acuity improved and refractive errors decreased significantly at 1, 3, and 6 months postoperatively. Total coma aberration increased at 3 and 6 months postoperatively, while changes in all other aberrations were not statistically significant. Similarly, no significant changes in point spread function were detected, but modulation transfer function increased significantly at the postoperative time points measured. Conclusions The optimized prolate ablation procedure was effective in terms of improving visual acuity and objective visual performance for the correction of persistent refractive errors following laser surgery. PMID:28243019
Integrins and epithelial cell polarity
Lee, Jessica L.; Streuli, Charles H.
ABSTRACT Cell polarity is characterised by differences in structure, composition and function between at least two poles of a cell. In epithelial cells, these spatial differences allow for the formation of defined apical and basal membranes. It has been increasingly recognised that cell–matrix interactions and integrins play an essential role in creating epithelial cell polarity, although key gaps in our knowledge remain. This Commentary will discuss the mounting evidence for the role of integrins in polarising epithelial cells. We build a model in which both inside-out signals to polarise basement membrane assembly at the basal surface, and outside-in signals to control microtubule apical–basal orientation and vesicular trafficking are required for establishing and maintaining the orientation of epithelial cell polarity. Finally, we discuss the relevance of the basal integrin polarity axis to cancer. This article is part of a Minifocus on Establishing polarity. For further reading, please see related articles: 'ERM proteins at a glance' by Andrea McClatchey (J. Cell Sci. 127, 3199–3204). 'Establishment of epithelial polarity – GEF who's minding the GAP?' by Siu Ngok et al. (J. Cell Sci. 127, 3205–3215). PMID:24994933
Focal epithelial hyperplasia: Case report.
Puriene, Alina; Rimkevicius, Arunas; Gaigalas, Mindaugas
The purpose of the present article is to present a 15 year-old patient with focal epithelial hyperplasia and to review the references on the subject-related etiological, pathological, diagnostic and treatment aspects. Focal epithelial hyperplasia is a rare human papilloma virus (HPV) related to oral lesion with very low frequency within our population. Surgical treatment with a biopsy was performed, acanthosis and parakeratosis are consistent histopathological features, since the patient had no history of sexual contact and HIV infection, the virus was probably acquired from environmental sources.
Ion Channels in Epithelial Cells
NASA Astrophysics Data System (ADS)
Palmer, Lawrence G.
Ion channels in epithelial cells serve to move ions, and in some cases fluid, between compartments of the body. This function of the transfer of material is fundamentally different from that of the transfer of information, which is the main job of most channels in excitable cells. Nevertheless the basic construction of the channels is similar in many respects in the two tissue types. This chapter reviews the nature of channels in epithelia and discusses how their functions have evolved to accomplish the basic tasks for which they are responsible. I will focus on three channel types: epithelial Na+ channels, inward-rectifier K+ channels, and CFTR Cl- channels.
Concept for image-guided vitreo-retinal fs-laser surgery: adaptive optics and optical coherence tomography for laser beam shaping and positioning
NASA Astrophysics Data System (ADS)
Matthias, Ben; Brockmann, Dorothee; Hansen, Anja; Horke, Konstanze; Knoop, Gesche; Gewohn, Timo; Zabic, Miroslav; Krüger, Alexander; Ripken, Tammo
Fs-lasers are well established in ophthalmic surgery as high precision tools for corneal flap cutting during laser in situ keratomileusis (LASIK) and increasingly utilized for cutting the crystalline lens, e.g. in assisting cataract surgery. For addressing eye structures beyond the cornea, an intraoperative depth resolved imaging is crucial to the safety and success of the surgical procedure due to interindividual anatomical disparities. Extending the field of application even deeper to the posterior eye segment, individual eye aberrations cannot be neglected anymore and surgery with fs-laser is impaired by focus degradation. Our demonstrated concept for image-guided vitreo-retinal fs-laser surgery combines adaptive optics (AO) for spatial beam shaping and optical coherence tomography (OCT) for focus positioning guidance. The laboratory setup comprises an adaptive optics assisted 800 nm fs-laser system and is extended by a Fourier domain optical coherence tomography system. Phantom structures are targeted, which mimic tractional epiretinal membranes in front of excised porcine retina within an eye model. AO and OCT are set up to share the same scanning and focusing optics. A Hartmann-Shack sensor is employed for aberration measurement and a deformable mirror for aberration correction. By means of adaptive optics the threshold energy for laser induced optical breakdown is lowered and cutting precision is increased. 3D OCT imaging of typical ocular tissue structures is achieved with sufficient resolution and the images can be used for orientation of the fs-laser beam. We present targeted dissection of the phantom structures and its evaluation regarding retinal damage.
Laser-assisted subepithelial keratectomy (LASEK) versus photorefractive keratectomy (PRK) for correction of myopia
Li, Shi-Ming; Zhan, Siyan; Li, Si-Yuan; Peng, Xiao-Xia; Hu, Jing; Law, Hua Andrew; Wang, Ning-Li
Background Myopia (near-sightedness or short-sightedness) is a condition in which the refractive power of the eye is greater than required. The most frequent complaint of people with myopia is blurred distance vision, which can be eliminated by conventional optical aids such as spectacles or contact lenses, or by refractive surgery procedures such as photorefractive keratectomy (PRK) and laser epithelial keratomileusis (LASEK). PRK uses laser to remove the corneal stroma. Similar to PRK, LASEK first creates an epithelial flap and then replaces it after ablating the corneal stroma. The relative benefits and harms of LASEK and PRK, as shown in different trials, warrant a systematic review. Objectives The objective of this review is to compare LASEK versus PRK for correction of myopia by evaluating their efficacy and safety in terms of postoperative uncorrected visual acuity, residual refractive error, and associated complications. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision group Trials Register) (2015 Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to December 2015), EMBASE (January 1980 to December 2015), Latin American and Caribbean Health Sciences (LILACS) (January 1982 to December 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 15 December 2015. We used the Science Citation Index and searched the reference lists of the included trials to identify relevant trials for this review. Selection criteria We included in this review randomized controlled trials (RCTs) comparing LASEK versus PRK for correction of myopia. Trial participants
Endomicroscopy imaging of epithelial structures using tissue autofluorescence
NASA Astrophysics Data System (ADS)
Lin, Bevin; Urayama, Shiro; Saroufeem, Ramez M. G.; Matthews, Dennis L.; Demos, Stavros G.
We explore autofluorescence endomicroscopy as a potential tool for real-time visualization of epithelial tissue microstructure and organization in a clinical setting. The design parameters are explored using two experimental systems--an Olympus Medical Systems Corp. stand-alone clinical prototype probe, and a custom built bench-top rigid fiber conduit prototype. Both systems entail ultraviolet excitation at 266 nm and/or 325 nm using compact laser sources. Preliminary results using ex vivo animal and human tissue specimens suggest that this technology can be translated toward in vivo application to address the need for real-time histology.
Computational modeling of epithelial tissues.
Smallwood, Rod
There is an extensive literature on the computational modeling of epithelial tissues at all levels from subcellular to whole tissue. This review concentrates on behavior at the individual cell to whole tissue level, and particularly on organizational aspects, and provides an indication of where information from other areas, such as the modeling of angiogenesis, is relevant. The skin, and the lining of all of the body cavities (lung, gut, cervix, bladder etc) are epithelial tissues, which in a topological sense are the boundary between inside and outside the body. They are thin sheets of cells (usually of the order of 0.5 mm thick) without extracellular matrix, have a relatively simple structure, and contain few types of cells. They have important barrier, secretory and transport functions, which are essential for the maintenance of life, so homeostasis and wound healing are important aspects of the behavior of epithelial tissues. Carcinomas originate in epithelial tissues.There are essentially two approaches to modeling tissues--to start at the level of the tissue (i.e., a length scale of the order of 1 mm) and develop generalized equations for behavior (a continuum approach); or to start at the level of the cell (i.e., a length scale of the order of 10 µm) and develop tissue behavior as an emergent property of cellular behavior (an individual-based approach). As will be seen, these are not mutually exclusive approaches, and they come in a variety of flavors.
Femtosecond laser beam propagation through corneal tissue: Evaluation of therapeutic laser-stimulated second and third- harmonic generation
NASA Astrophysics Data System (ADS)
Calhoun, William R., III
One of the most recent advancements in laser technology is the development of ultrashort pulsed femtosecond lasers (FSLs). FSLs are improving many fields due to their unique extreme precision, low energy and ablation characteristics. In the area of laser medicine, ophthalmic surgeries have seen very promising developments. Some of the most commonly performed surgical operations in the world, including laser-assisted in-situ keratomileusis (LASIK), lens replacement (cataract surgery), and keratoplasty (cornea transplant), now employ FSLs for their unique abilities that lead to improved clinical outcome and patient satisfaction. The application of FSLs in medical therapeutics is a recent development, and although they offer many benefits, FSLs also stimulate nonlinear optical effects (NOEs), many of which were insignificant with previously developed lasers. NOEs can change the laser characteristics during propagation through a medium, which can subsequently introduce unique safety concerns for the surrounding tissues. Traditional approaches for characterizing optical effects, laser performance, safety and efficacy do not properly account for NOEs, and there remains a lack of data that describe NOEs in clinically relevant procedures and tissues. As FSL technology continues to expand towards new applications, FSL induced NOEs need to be better understood in order to ensure safety as FSL medical devices and applications continue to evolve at a rapid pace. In order to improve the understanding of FSL-tissue interactions related to NOEs stimulated during laser beam propagation though corneal tissue, research investigations were conducted to evaluate corneal optical properties and determine how corneal tissue properties including corneal layer, collagen orientation and collagen crosslinking, and laser parameters including pulse energy, repetition rate and numerical aperture affect second and third-harmonic generation (HG) intensity, duration and efficiency. The results of
Comparison of self-reported quality of vision outcomes after myopic LASIK with two femtosecond lasers: a prospective, eye-to-eye study
Sáles, Christopher S; Manche, Edward E
Purpose To compare self-reported quality of vision (QoV) outcomes after myopic LASIK (laser-assisted in situ keratomileusis) with two femtosecond lasers. Design Prospective, randomized, eye-to-eye study. Methods Consecutive myopic patients were treated with wavefront-guided LASIK bilaterally. Eyes were randomized according to ocular dominance. The flap of one eye was made with the IntraLase FS 60 kHz femtosecond laser with a conventional 70° side-cut, and the flap of the fellow eye was made with the IntraLase iFS 150 kHz femtosecond laser with an inverted 130° side-cut. Patients completed the validated, Rasch-tested, linear-scaled 30-item QoV questionnaire preoperatively and at Months 1, 3, 6, and 12. Results The study enrolled 120 fellow eyes in 60 patients. None of the measured QoV parameters exhibited statistically significant differences between the groups preoperatively or at any postoperative time point. Conclusion Creating LASIK flaps with an inverted side-cut using a 150 kHz femtosecond laser and with a conventional 70° side-cut using a 60 kHz femtosecond laser resulted in no significant differences in self-reported QoV assessed by the QoV questionnaire. PMID:27621589
Experimental control of excitable embryonic tissues: three stimuli induce rapid epithelial contraction
Joshi, Sagar D.; von Dassow, Michelangelo; Davidson, Lance. A.
Cell generated contractility is a major driver of morphogenesis during processes such as epithelial bending and epithelial-to-mesenchymal transitions. Previous studies of contraction in embryos have relied on developmentally programmed cell shape changes such as those that accompany ventral furrow formation in Drosophila, bottle cell formation in Xenopus, ingression in amniote embryos, and neurulation in vertebrate embryos. We have identified three methods to reproducibly and acutely induce contraction in embryonic epithelial sheets: laser activation, electrical stimulation, and nano-perfusion with chemicals released by wounding. Contractions induced by all three methods occur over a similar time scale (1 to 2 min) and lead to reorganization of the F-actin cytoskeleton. By combining induced contractions with micro-aspiration we can simultaneously measure the stiffness of the tissue and the force and work done by contractions. Laser-activation allows real-time visualization of F-actin remodeling during contraction. Perfusion with cell-lysate suggests these three stimuli activate physiologically relevant pathways that maintain epithelial tension or trigger epithelial morphogenesis. Our methods provide the means to control and study cellular contractility and will allow dissection of molecular mechanisms and biomechanics of cellular contractility. PMID:19686733
NASA Technical Reports Server (NTRS)
Koepf, G. A. (Inventor)
A laser apparatus having a pump laser device for producing pump laser energy upon being excited is disclosed. The pump laser device has a resonating cavity for oscillating and amplifying the pump laser energy. A source laser device is used for producing source laser energy upon being excited by the pump laser energy. The source laser device has a resonating cavity for oscillating and amplifying the source laser energy. The source laser's resonating cavity is coupled within a portion of the pump laser's resonating cavity.
Progress Towards Drosophila Epithelial Cell Culture
Simcox, Amanda
Drosophila epithelial research is at the forefront of the field; however, there are no well-characterized epithelial cell lines that could provide a complementary in vitro model for studies conducted in vivo. Here, a protocol is described that produces epithelial cell lines. The method uses genetic manipulation of oncogenes or tumor suppressors to induce embryonic primary culture cells to rapidly progress to permanent cell lines. It is, however, a general method and the type of cells that comprise a given line is not controlled experimentally. Indeed, only a small fraction of the lines produced are epithelial in character. For this reason, additional work needs to be done to develop a more robust epithelial cell-specific protocol. It is expected that Drosophila epithelial cell lines will have great utility for in vitro analysis of epithelial biology, particularly high-throughput analyses such as RNAi screens. PMID:23097097
Erysipelothrix rhusiopathiae exploits cytokeratin 18-positive epithelial cells of porcine tonsillar crypts as an invasion gateway.
Harada, Tomoyuki; Ogawa, Yohsuke; Eguchi, Masahiro; Shi, Fang; Sato, Masumi; Uchida, Kazuyuki; Nakayama, Hiroyuki; Shimoji, Yoshihiro
Tonsils are important organs for mucosal immunity and are gateways for various pathogens, including bacteria and viruses. The purpose of the present study was to reveal how Erysipelothrix rhusiopathiae, the causative agent of swine erysipelas, invades the mucosal epithelium of the tonsils of pigs. Two germ-free piglets were orally infected with E. rhusiopathiae Koganei 65-0.15, an attenuated vaccine strain in Japan, and their tonsils of the soft palate were histologically examined four weeks after infection. Bacterial organisms were observed in dilated crypt lumens and a few epithelial cells of the crypt. Immunohistochemical examination revealed that some epithelial cells of the crypt were positive for cytokeratin (CK) 18, a specific marker for M cells in the Peyer's patches of pigs. Confocal laser scanning microscopy showed that bacterial antigens were present in the cytoplasm of CK 18-positive epithelial cells. Furthermore, an ultramicroscopic examination revealed that the bacteria-containing epithelial cells did not have microfolds or microvilli, both of which are characteristic of membranous epithelial cells (M cells), and that they were in close contact with intraepithelial phagocytes. Thus, the present observations suggest that the tonsillar crypt epithelium is a site of persistent infection for orally administered E. rhusiopathiae, and the bacteria exploit cytokeratin 18-positive epithelial cells of the crypts as portals of entry into the body.
Treatment of focal epithelial hyperplasia with topical imiquimod: report of three cases.
Yasar, Sirin; Mansur, Ayse Tulin; Serdar, Zehra Asiran; Goktay, Fatih; Aslan, Canan
Focal epithelial hyperplasia (Heck disease) is a rare disorder caused by specific types of HPV. It mainly involves oral mucosa and children are affected more frequently. It may persist for years, producing a significant reduction in quality of life. Several treatment modalities such as surgical excision, laser ablation, cryotherapy, electrocauterization, topical, intralesional, systemic interferon, and systemic retinoic acid have been used with inconsistent results and many side effects. Here we report three children of Turkish origin with focal epithelial hyperplasia successfully treated with imiquimod 5% cream. No serious side effects were observed and recurrence did not occur during the 1-year follow-up period.
Quantitative Morphology of Epithelial Folds
Štorgel, Nick; Krajnc, Matej; Mrak, Polona; Štrus, Jasna; Ziherl, Primož
The shape of spatially modulated epithelial morphologies such as villi and crypts is usually associated with the epithelium-stroma area mismatch leading to buckling. We propose an alternative mechanical model based on intraepithelial stresses generated by differential tensions of apical, lateral, and basal sides of cells as well as on the elasticity of the basement membrane. We use it to theoretically study longitudinal folds in simple epithelia and we identify four types of corrugated morphologies: compact, invaginated, evaginated, and wavy. The obtained tissue contours and thickness profiles are compared to epithelial folds observed in invertebrates and vertebrates, and for most samples, the agreement is within the estimated experimental error. Our model establishes the groove-crest modulation of tissue thickness as a morphometric parameter that can, together with the curvature profile, be used to estimate the relative differential apicobasal tension in the epithelium. PMID:26745429
Cellular systems for epithelial invagination
Epithelial invagination is a fundamental module of morphogenesis that iteratively occurs to generate the architecture of many parts of a developing organism. By changing the physical properties such as the shape and/or position of a population of cells, invagination drives processes ranging from reconfiguring the entire body axis during gastrulation, to forming the primordia of the eyes, ears and multiple ducts and glands, during organogenesis. The epithelial bending required for invagination is achieved through a variety of mechanisms involving systems of cells. Here we provide an overview of the different mechanisms, some of which can work in combination, and outline the circumstances in which they apply. This article is part of the themed issue 'Systems morphodynamics: understanding the development of tissue hardware'. PMID:28348256
Ectopic Epithelial Deaminase in IBD
Inflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative colitis (UC) is a chronic intestinal disorder that is caused by...mice (carrying non-functional AID) before and after induction of colitis by oral administration of dextran sulfate sodium (DSS). 1c will...epithelial cells in colitis (months 1-18) 2a will develop and expand the mouse colony of RAG1-deficient KI/KI mice (months 1-6). In order to test the
Vertex Models of Epithelial Morphogenesis
Fletcher, Alexander G.; Osterfield, Miriam; Baker, Ruth E.; Shvartsman, Stanislav Y.
The dynamic behavior of epithelial cell sheets plays a central role during numerous developmental processes. Genetic and imaging studies of epithelial morphogenesis in a wide range of organisms have led to increasingly detailed mechanisms of cell sheet dynamics. Computational models offer a useful means by which to investigate and test these mechanisms, and have played a key role in the study of cell-cell interactions. A variety of modeling approaches can be used to simulate the balance of forces within an epithelial sheet. Vertex models are a class of such models that consider cells as individual objects, approximated by two-dimensional polygons representing cellular interfaces, in which each vertex moves in response to forces due to growth, interfacial tension, and pressure within each cell. Vertex models are used to study cellular processes within epithelia, including cell motility, adhesion, mitosis, and delamination. This review summarizes how vertex models have been used to provide insight into developmental processes and highlights current challenges in this area, including progressing these models from two to three dimensions and developing new tools for model validation. PMID:24896108
Corneal and skin laser exposures from 1540-nm laser pulses
NASA Astrophysics Data System (ADS)
Johnson, Thomas E.; Mitchell, Michael A.; Rico, Pedro J.; Fletcher, David J.; Eurell, Thomas E.; Roach, William P.
Mechanisms of tissue damage are investigated for skin and cornea exposures from 1540 nm ('eye safe') laser single pulses of 0.8 milli-seconds. New skin model data point out the advantages of using the Yucatan mini-pig versus the Yorkshire pig for in-vivo skin laser exposures. Major advantages found include similarities in thickness and melanin content when compared with human skin. Histology from Yucatan mini-pig skin exposures and the calculation of an initial ED50 threshold indicate that the main photon tissue interaction may not be solely due to water absorption. In-vitro corneal equivalents compared well with in-vivo rabbit cornea exposure under similar laser conditions. In-vivo and in-vitro histology show that initial energy deposition leading to damage occurs intrastromally, while epithelial cells show no direct injury due to laser light absorption.
Healthcare and a holiday: the risks of LASIK tourism.
Lockington, David; Johnson, Richard; Patel, Dipika V; McGhee, Charles N J
Medical tourism is the practice of travelling overseas for surgery. We describe a patient with low myopia who underwent laser in situ keratomileusis (LASIK) while on holiday in India. She presented to local hospital eye services six weeks post-LASIK with discomfort and reduced vision. She reported three previous LASIK flap lifts in the right eye. Clinical assessment, optical coherence tomography and confocal microscopy demonstrated moderate epithelial ingrowth and reduced visual acuity. Epithelial ingrowth after LASIK may be associated with visual impairment and management is determined by location, magnitude and effect on vision. LASIK tourism may mean patients are less well-informed of risks and lose continuity of professional care.
Expression of p75(NGFR), a Proliferative and Basal Cell Marker, in the Buccal Mucosa Epithelium during Re-epithelialization.
Ishii, Akihiro; Muramatsu, Takashi; Lee, Jong-Min; Higa, Kazunari; Shinozaki, Naoshi; Jung, Han-Sung; Shibahara, Takahiko
We investigated the expression of p75(NGFR), a proliferative and basal cell marker, in the mouse buccal mucosa epithelium during wound healing in order to elucidate the role of epithelial stem cells. Epithelial defects were generated in the epithelium of the buccal mucosa of 6-week-old mice using CO2 laser irradiation. BrdU was immediately administered to mice following laser irradiation. They were then sacrificed after 1, 3, 7, and 14 days. Paraffin sections were prepared and the irradiated areas were analyzed using immunohistochemistry with anti-p75(NGFR), BrdU, PCNA, and CK14 antibodies. During re-epithelialization, PCNA (-)/p75(NGFR) (+) cells extended to the wound, which then closed, whereas PCNA (+)/p75(NGFR) (+) cells were not observed at the edge of the wound. In addition, p75(NGFR) (-)/CK14 (+), which reflected the presence of post-mitotic differentiating cells, was observed in the supra-basal layers of the extended epithelium. BrdU (+)/p75(NGFR) (+), which reflected the presence of epithelial stem cells, was detected sparsely in buccal basal epithelial cells after healing, and disappeared after 7 days. These results suggest that p75(NGFR) (+) keratinocytes are localized in the basal layer, which contains oral epithelial stem cells, and retain the ability to proliferate in order to regenerate the buccal mucosal epithelium.
Focal epithelial hyperplasia: Heck disease.
Cohen, P R; Hebert, A A; Adler-Storthz, K
Two sisters of Mexican ancestry had focal epithelial hyperplasia (FEH). The lesions on the oral mucosa of the older child were initially misinterpreted as representing sexual abuse. Microscopic evaluation of a hematoxylin and eosin-stained section from a lower lip papule demonstrated the histologic features of FEH. Although human papillomavirus (HPV) type 13 and HPV32 have been most consistently present in FEH lesions, types 6, 11, 13, and 32 were not detected in the paraffin-embedded tissue specimen of our patient using an in situ hybridization technique. The lesions persisted or recurred during management using destructive modalities; subsequently, they completely resolved spontaneously.
Force transmission in epithelial tissues.
Vasquez, Claudia G; Martin, Adam C
In epithelial tissues, cells constantly generate and transmit forces between each other. Forces generated by the actomyosin cytoskeleton regulate tissue shape and structure and also provide signals that influence cells' decisions to divide, die, or differentiate. Forces are transmitted across epithelia because cells are mechanically linked through junctional complexes, and forces can propagate through the cell cytoplasm. Here, we review some of the molecular mechanisms responsible for force generation, with a specific focus on the actomyosin cortex and adherens junctions. We then discuss evidence for how these mechanisms promote cell shape changes and force transmission in tissues.
Maximum imaging depth of two-photon autofluorescence microscopy in epithelial tissues.
Durr, Nicholas J; Weisspfennig, Christian T; Holfeld, Benjamin A; Ben-Yakar, Adela
Endogenous fluorescence provides morphological, spectral, and lifetime contrast that can indicate disease states in tissues. Previous studies have demonstrated that two-photon autofluorescence microscopy (2PAM) can be used for noninvasive, three-dimensional imaging of epithelial tissues down to approximately 150 μm beneath the skin surface. We report ex-vivo 2PAM images of epithelial tissue from a human tongue biopsy down to 370 μm below the surface. At greater than 320 μm deep, the fluorescence generated outside the focal volume degrades the image contrast to below one. We demonstrate that these imaging depths can be reached with 160 mW of laser power (2-nJ per pulse) from a conventional 80-MHz repetition rate ultrafast laser oscillator. To better understand the maximum imaging depths that we can achieve in epithelial tissues, we studied image contrast as a function of depth in tissue phantoms with a range of relevant optical properties. The phantom data agree well with the estimated contrast decays from time-resolved Monte Carlo simulations and show maximum imaging depths similar to that found in human biopsy results. This work demonstrates that the low staining inhomogeneity (∼ 20) and large scattering coefficient (∼ 10 mm(-1)) associated with conventional 2PAM limit the maximum imaging depth to 3 to 5 mean free scattering lengths deep in epithelial tissue.
Effect of laser polarization and pulse energy on therapeutic, femtosecond laser-induced second harmonic generation in corneal tissue (Conference Presentation)
NASA Astrophysics Data System (ADS)
Calhoun, William R.; Ilev, Ilko K.
Some of the most commonly performed surgical operations in the world, including laser-assisted in-situ keratomileusis (LASIK), lens replacement (e.g. cataract surgery), and keratoplasty (cornea transplant), now employ therapeutic infrared femtosecond lasers (FSLs) for their extreme precision, low energy delivered into tissue and advanced ablation characteristics. Although the widely exploited applications of FSLs in medical therapeutics offer significant benefits, FSLs must generate very high intensities in order to achieve optical breakdown, the predominant tissue ablative mechanism, which can also stimulate nonlinear optical effects such as harmonic generation, an effect that generates coherent visible and UV light in the case of second- (SHG) and third-harmonic generation (THG), respectively. In order to improve the understanding of HG in corneal tissue, the effect of FSL polarization and pulse energy were investigated. FSL stimulated SHG intensity in corneal tissue was measured as the laser polarization was rotated 360 degrees. Further, the pulse energy at the SHG wavelength were measured for single FSL pulses as the pulse energy at the fundamental wavelength was varied through a range of clinically relevant values. The results of this study revealed SHG intensity oscillated with laser polarization, having a variation greater than 20%. This relationship seems to due to the intrinsic anisotropy of collagen fibril hyperpolarizability, not related to tissue birefringence. SHG pulse energy measurements showed an increase in SHG pulse energy with increasing FSL pulse energy, however conversion efficiency decreased. This may be related to the dynamic relationship between optical breakdown leading to tissue destruction and HG evolution.
Epithelialization in Wound Healing: A Comprehensive Review
Pastar, Irena; Stojadinovic, Olivera; Yin, Natalie C.; Ramirez, Horacio; Nusbaum, Aron G.; Sawaya, Andrew; Patel, Shailee B.; Khalid, Laiqua; Isseroff, Rivkah R.; Tomic-Canic, Marjana
Significance: Keratinocytes, a major cellular component of the epidermis, are responsible for restoring the epidermis after injury through a process termed epithelialization. This review will focus on the pivotal role of keratinocytes in epithelialization, including cellular processes and mechanisms of their regulation during re-epithelialization, and their cross talk with other cell types participating in wound healing. Recent Advances: Discoveries in epidermal stem cells, keratinocyte immune function, and the role of the epidermis as an independent neuroendocrine organ will be reviewed. Novel mechanisms of gene expression regulation important for re-epithelialization, including microRNAs and histone modifications, will also be discussed. Critical Issues: Epithelialization is an essential component of wound healing used as a defining parameter of a successful wound closure. A wound cannot be considered healed in the absence of re-epithelialization. The epithelialization process is impaired in all types of chronic wounds. Future Directions: A comprehensive understanding of the epithelialization process will ultimately lead to the development of novel therapeutic approaches to promote wound closure. PMID:25032064
Epithelialization in Wound Healing: A Comprehensive Review.
Pastar, Irena; Stojadinovic, Olivera; Yin, Natalie C; Ramirez, Horacio; Nusbaum, Aron G; Sawaya, Andrew; Patel, Shailee B; Khalid, Laiqua; Isseroff, Rivkah R; Tomic-Canic, Marjana
Significance: Keratinocytes, a major cellular component of the epidermis, are responsible for restoring the epidermis after injury through a process termed epithelialization. This review will focus on the pivotal role of keratinocytes in epithelialization, including cellular processes and mechanisms of their regulation during re-epithelialization, and their cross talk with other cell types participating in wound healing. Recent Advances: Discoveries in epidermal stem cells, keratinocyte immune function, and the role of the epidermis as an independent neuroendocrine organ will be reviewed. Novel mechanisms of gene expression regulation important for re-epithelialization, including microRNAs and histone modifications, will also be discussed. Critical Issues: Epithelialization is an essential component of wound healing used as a defining parameter of a successful wound closure. A wound cannot be considered healed in the absence of re-epithelialization. The epithelialization process is impaired in all types of chronic wounds. Future Directions: A comprehensive understanding of the epithelialization process will ultimately lead to the development of novel therapeutic approaches to promote wound closure.
CCN1 induces a reversible epithelial-mesenchymal transition in gastric epithelial cells.
Chai, Jianyuan; Norng, Manith; Modak, Cristina; Reavis, Kevin M; Mouazzen, Wasim; Pham, Jennifer
CCN1 is a matricellular protein that activates many genes related to wound healing and tissue remodeling in fibroblasts, but its effect on epithelial cells remains unclear. This study examined the role of CCN1 in epithelial wound healing using rat gastric epithelial cells and rat stomach ulcer as in vitro and in vivo models, respectively. We found that CCN1 expression is highly upregulated in the epithelial cells adjacent to a wound and remains high until the wound is healed. Upregulation of CCN1 activates a transient epithelial-mesenchymal transition in the epithelial cells at the migrating front and drives wound closure. Once the wound is healed, these epithelial cells and their progeny can resume their original epithelial phenotype. We also found that CCN1-induced E-cadherin loss is not due to transcriptional regulation but rather protein degradation due to the collapse of adherens junctions, which is contributed by beta-catenin translocation. CCN1-activated integrin-linked kinase mediates this process. Finally, our in vivo study showed that locally neutralizing CCN1 drastically impairs wound closure, whereas local injection of recombinant CCN1 protein induces expression of vimentin and smooth muscle alpha-actin in normal gastric mucosal epithelial cells and accelerates re-epithelialization during ulcer healing. In conclusion, our study indicates that CCN1 can induce reversible epithelial-mesenchymal transition, and this feature may have great value for clinical wound healing.
The comparison of glycosphingolipids isolated from an epithelial ovarian cancer cell line and a nontumorigenic epithelial ovarian cell line using MALDI-MS and MALDI-MS/MS.
Rajanayake, Krishani K; Taylor, William R; Isailovic, Dragan
Glycosphingolipids (GSLs) are important biomolecules, which are linked to many diseases such as GSL storage disorders and cancer. Consequently, the expression of GSLs may be altered in ovarian cancer cell lines in comparison to apparently healthy cell lines. Here, differential expressions of GSLs in an epithelial ovarian cancer cell line SKOV3 and a nontumorigenic epithelial ovarian cell line T29 were studied using matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) and MALDI-MS/MS. The isolation of GSLs from SKOV3 and T29 cell lines was carried out using Folch partition. GSLs were successfully detected by MALDI-MS, and structurally assigned by a comparison of their MALDI-MS/MS fragmentation patterns with MS/MS data found in SimLipid database. Additionally, LIPID MAPS was used to assign GSL ion masses in MALDI-MS spectra. Seventeen neutral GSLs were identified in Folch partition lower (chloroform/methanol) phases originating from both cell lines, while five globo series neutral GSLs were identified only in the Folch partition lower phase of SKOV3 cell line. Several different sialylated GSLs were detected in Folch partition upper (water/methanol) phases of SKOV3 and T29 cell lines. Overall, this study demonstrates the alteration and increased glycosylation of GSLs in an epithelial ovarian cancer cell line in comparison to a nontumorigenic epithelial ovarian cell line.
Temporal Differential Gene Expression in Explanted Human Retinal Pigment Epithelial Cells at 0.5, 1.0, 3.0, 6.0, 12 and 24 Hours Post-Exposure to 1064 nm, 3.6 ns Pulsed Laser Light
USAFA TR 2005-05 Temporal Differential Gene Expression in Explanted Human Retinal Pigment Epithelial Cells at 0.5, 1.0, 3.0, 6.0, 12 and 24 Hours...AIR FORCE ACADEMY COLORADO 80840 20050630 417 USAFA TR 2005-05 This article, "Temporal Differential Gene Expression in Explanted Human Retinal ...Differential Gene Expression in Explanted Human Retinal Pigment USAFA F05611-02-P-0471 Epithelial Cells at 0.5, 1.0, 3.0, 6.0, 12 and 24-Hours Post-Exposure
Patterning Bacterial Communities on Epithelial Cells
Dwidar, Mohammed; Leung, Brendan M.; Yaguchi, Toshiyuki; Takayama, Shuichi; Mitchell, Robert J.
Micropatterning of bacteria using aqueous two phase system (ATPS) enables the localized culture and formation of physically separated bacterial communities on human epithelial cell sheets. This method was used to compare the effects of Escherichia coli strain MG1655 and an isogenic invasive counterpart that expresses the invasin (inv) gene from Yersinia pseudotuberculosis on the underlying epithelial cell layer. Large portions of the cell layer beneath the invasive strain were killed or detached while the non-invasive E. coli had no apparent effect on the epithelial cell layer over a 24 h observation period. In addition, simultaneous testing of the localized effects of three different bacterial species; E. coli MG1655, Shigella boydii KACC 10792 and Pseudomonas sp DSM 50906 on an epithelial cell layer is also demonstrated. The paper further shows the ability to use a bacterial predator, Bdellovibriobacteriovorus HD 100, to selectively remove the E. coli, S. boydii and P. sp communities from this bacteria-patterned epithelial cell layer. Importantly, predation and removal of the P. Sp was critical for maintaining viability of the underlying epithelial cells. Although this paper focuses on a few specific cell types, the technique should be broadly applicable to understand a variety of bacteria-epithelial cell interactions. PMID:23785519
Epithelial self-organization in fruit fly embryogenesis
NASA Astrophysics Data System (ADS)
Hutson, M. Shane
During fruit fly embryogenesis, there are several morphogenetic events in which sheets of epithelial cells expand, contract and bend due to coordinated intra- and intercellular forces. This tissue-level reshaping is accompanied by changes in the shape and arrangement of individual cells -- changes that can be measured quantitatively and dynamically using modern live-cell imaging techniques. Such data sets represent rich targets for computational modeling of self-organization; however, reproducing the observed cell- and tissue-level reshaping is not enough. The inverse problem of using cell shape changes to determine cell-level forces is ill-posed -- yielding non-unique solutions that cannot discriminate between active changes in cell shape and passive deformation. These non-unique solutions can be tested experimentally using in vivo laser-microsurgery -- i.e., cutting a targeted region of an epithelium and carefully tracking the temporal and spatial dependence of the subsequent strain relaxation. This technique uses a variety of incisions (hole, line or closed curve) to probe different aspects of epithelial mechanics: the local mesoscopic strain; the distribution of intracellular forces; changes in the cell-level power-law rheology; and the question of active versus passive deformation. I will discuss my group's work using laser-microsurgery to investigate two morphogenetic events in fruit fly embryogenesis: germband retraction and dorsal closure. In both cases, we find a substantial active mechanical role for the amnioserosa -- an epithelium that undergoes apoptosis near the end of embryogenesis and makes no part of the fly larva -- in reshaping an adjacent epithelium that becomes the larval epidermis. In these examples, self-organization of the fly embryo relies not only on self-organization of individual tissues, but also on the mechanical interactions between tissues.
Facklam, R.L.
A laser clock includes a linear laser in one embodiment of the clock and a ring laser gyro in the other embodiment. The linear laser is frequency stabilized and utilizes a single active medium in the form of a low pressure gas, such as He-Ne, with a Doppler broadened gain curve. The ring laser gyro is a four frequency laser with a Faraday rotor. Detector and electronic circuitry associated with the laser of each embodiment detects a beat frequency and convert it to a clock signal.
HOLLOW CATHODE LASER FABRICATION 13 4. EXPERIENCE WITH THE BLUE LASER 18 4.1 Operational and Processing Experience 18 4.2 Performance Testing 20 5...34 -. - . •. SECTION 3 BLUE HOLLOW CATHODE LASER FABRICATION This section presents an overview of the steps taken in creating a HCL. There is...to the laser assembly. These steps can actually be considered as the final steps in laser fabrication because some of them involve adding various
Bone marrow-derived lung epithelial cells.
Krause, Diane S
Bone marrow-derived cells can take on the phenotype of epithelial cells and express epithelial-specific genes in multiple organs. Here, we focus on recent data on the appearance of marrow-derived epithelial cells in the adult lung. These findings have garnered significant skepticism because in most cases marrow-derived epithelial cells are very rare, the marrow cell of origin is not known, the techniques for detection have needed improvement, and there seem to be multiple mechanisms by which this occurs. Recent studies have focused on these concerns. Once these important concerns are addressed, further studies on the function(s) of these cells will need to be performed to determine whether this engraftment has any clinical significance-either beneficial or detrimental.
Respiratory epithelial cysts of the orbit.
Goh, Rachel L Z; Hardy, Thomas G; Williams, Richard A; McNab, Alan A
To describe post-traumatic and congenital respiratory epithelial cysts in the orbit, which are rare lesions with only 5 and 13 published cases, respectively. We reviewed all cases of respiratory epithelial cysts diagnosed at three institutions (two tertiary referral hospitals, one private clinic) between 1995 and 2015. We describe 10 cases of post-traumatic respiratory epithelial cyst (age range 23 - 82), presenting a mean of 17.4 years after their original trauma; and 3 congenital cases (age range 17-34). All but one case underwent surgical excision of the cyst and its lining, along with any surgical implant within the cyst. Two were recurrent after incomplete excision. Three presented with acute infection within the cyst. Respiratory epithelial orbital cysts are probably commoner than the paucity of published reports would suggest. Post-traumatic cysts often present many years after trauma, and may become secondarily infected. Complete surgical removal is recommended to prevent future recurrence.
Laser-Assisted In Situ Keratomileusis; Laser vision correction; Nearsightedness - Lasik; Myopia - Lasik ... length of the eye. LASIK uses an excimer laser (an ultraviolet laser) to remove a thin layer ...
Evidence for epithelial-mesenchymal transitions in adult liver cells.
Sicklick, Jason K; Choi, Steve S; Bustamante, Marcia; McCall, Shannon J; Pérez, Elizabeth Hernández; Huang, Jiawen; Li, Yin-Xiong; Rojkind, Marcos; Diehl, Anna Mae
Both myofibroblastic hepatic stellate cells (HSC) and hepatic epithelial progenitors accumulate in damaged livers. In some injured organs, the ability to distinguish between fibroblastic and epithelial cells is sometimes difficult because cells undergo epithelial-mesenchymal transitions (EMT). During EMT, cells coexpress epithelial and mesenchymal cell markers. To determine whether EMT occurs in adult liver cells, we analyzed the expression profile of primary HSC, two HSC lines, and hepatic epithelial progenitors. As expected, all HSC expressed HSC markers. Surprisingly, these markers were also expressed by epithelial progenitors. In addition, one HSC line expressed typical epithelial progenitor mRNAs, and these epithelial markers were inducible in the second HSC line. In normal and damaged livers, small ductular-type cells stained positive for an HSC marker. In conclusion, HSC and hepatic epithelial progenitors both coexpress epithelial and mesenchymal markers, providing evidence that EMT occurs in adult liver cells.
Transcriptome analysis of epithelial and stromal contributions to mammogenesis in three week prepartum cows.
Casey, Theresa; Dover, Heather; Liesman, James; DeVries, Lindsey; Kiupel, Matti; Vandehaar, Michael; Plaut, Karen
Transcriptome analysis of bovine mammary development has provided insight into regulation of mammogenesis. However, previous studies primarily examined expression of epithelial and stromal tissues combined, and consequently did not account for tissue specific contribution to mammary development. Our objective was to identify differences in gene expression in epithelial and intralobular stromal compartments. Tissue was biopsied from non-lactating dairy cows 3 weeks prepartum, cut into explants and incubated for 2 hr with insulin and hydrocortisone. Epithelial and intralobular stromal tissues were isolated with laser capture microdissection. Global gene expression was measured with Bovine Affymetrix GeneChips, and data were preprocessed using RMA method. Moderated t-tests from gene-specific linear model analysis with cell type as a fixed effect showed more than 3,000 genes were differentially expressed between tissues (P<0.05; FDR<0.17). Analysis of epithelial and stromal transcriptomes using Database for Annotation, Visualization and Integrated Discovery (DAVID) and Ingenuity Pathways Analysis (IPA) showed that epithelial and stromal cells contributed distinct molecular signatures. Epithelial signatures were enriched with gene sets for protein synthesis, metabolism and secretion. Stromal signatures were enriched with genes that encoded molecules important to signaling, extracellular matrix composition and remodeling. Transcriptome differences also showed evidence for paracrine interactions between tissues in stimulation of IGF1 signaling pathway, stromal reaction, angiogenesis, neurogenesis, and immune response. Molecular signatures point to the dynamic role the stroma plays in prepartum mammogenesis and highlight the importance of examining the roles of cell types within the mammary gland when targeting therapies and studying mechanisms that affect milk production.
Transcriptome Analysis of Epithelial and Stromal Contributions to Mammogenesis in Three Week Prepartum Cows
Casey, Theresa; Dover, Heather; Liesman, James; DeVries, Lindsey; Kiupel, Matti; VandeHaar, Michael; Plaut, Karen
Transcriptome analysis of bovine mammary development has provided insight into regulation of mammogenesis. However, previous studies primarily examined expression of epithelial and stromal tissues combined, and consequently did not account for tissue specific contribution to mammary development. Our objective was to identify differences in gene expression in epithelial and intralobular stromal compartments. Tissue was biopsied from non-lactating dairy cows 3 weeks prepartum, cut into explants and incubated for 2 hr with insulin and hydrocortisone. Epithelial and intralobular stromal tissues were isolated with laser capture microdissection. Global gene expression was measured with Bovine Affymetrix GeneChips, and data were preprocessed using RMA method. Moderated t-tests from gene-specific linear model analysis with cell type as a fixed effect showed more than 3,000 genes were differentially expressed between tissues (P<0.05; FDR<0.17). Analysis of epithelial and stromal transcriptomes using Database for Annotation, Visualization and Integrated Discovery (DAVID) and Ingenuity Pathways Analysis (IPA) showed that epithelial and stromal cells contributed distinct molecular signatures. Epithelial signatures were enriched with gene sets for protein synthesis, metabolism and secretion. Stromal signatures were enriched with genes that encoded molecules important to signaling, extracellular matrix composition and remodeling. Transcriptome differences also showed evidence for paracrine interactions between tissues in stimulation of IGF1 signaling pathway, stromal reaction, angiogenesis, neurogenesis, and immune response. Molecular signatures point to the dynamic role the stroma plays in prepartum mammogenesis and highlight the importance of examining the roles of cell types within the mammary gland when targeting therapies and studying mechanisms that affect milk production. PMID:21829467
An uncommon focal epithelial hyperplasia manifestation.
dos Santos-Pinto, Lourdes; Giro, Elisa Maria Aparecida; Pansani, Cyneu Aguiar; Ferrari, Junia; Massucato, Elaine Maria Sgavioli; Spolidório, Luis Carlos
Focal epithelial hyperplasia is a rare, contagious disease associated with infection of the oral mucosa by human papillomavirus types 13 or 32, characterized by multiple soft papules of the same color as the adjacent normal mucosa. It mainly affects the lower lip, buccal mucosa, and tongue. The purpose of this case report was to describe a rare verrucal lesion located in the upper gingiva that was clinically and histologically consistent with focal epithelial hyperplasia.
Laser-assisted hair transplantation: histologic comparison between holmium:YAG and CO2 lasers
NASA Astrophysics Data System (ADS)
Chu, Eugene A.; Rabinov, C. Rose; Wong, Brian J.; Krugman, Mark E.
The histological effects of flash-scanned CO2 (λ=10.6μm) and pulsed Holmium:YAG (Ho:YAG, λ=2.12μm) lasers were evaluated in human scalp following the creation of hair transplant recipient channels. Ho:YAG laser irradiation created larger zones of thermal injury adjacent to the laser channels than irradiation with the CO2 laser device. When the two lasers created recipient sites of nearly equal depth, the Holmium:YAG laser caused a larger region of lateral thermal damage (589.30μm) than the CO2 laser (118.07μm). In addition, Holmium:YAG irradiated specimens exhibited fractures or discontinuities beyond the region of clear thermal injury. This shearing effect is consistent with the photoacoustic mechanism of ablation associated with pulsed mid-IR laser irradiation. In contrast, channels created with the CO2 exhibited minimal epithelial disruption and significantly less lateral thermal damage. While the Holmium:YAG laser is a useful tool for ablation soft tissue with minimal char in select applications (sinus surgery, arthroscopic surgery), this study suggests that the use of the CO2 laser for the creation of transplantation recipient channels result in significantly less lateral thermal injury for the laser parameters employed.
Forces driving epithelial wound healing
Veldhuis, Jim H.; Gupta, Mukund; Colombelli, Julien; Muñoz, José J.; Brodland, G. Wayne; Ladoux, Benoit; Trepat, Xavier
A fundamental feature of multicellular organisms is their ability to self-repair wounds through the movement of epithelial cells into the damaged area. This collective cellular movement is commonly attributed to a combination of cell crawling and "purse-string" contraction of a supracellular actomyosin ring. Here we show by direct experimental measurement that these two mechanisms are insufficient to explain force patterns observed during wound closure. At early stages of the process, leading actin protrusions generate traction forces that point away from the wound, showing that wound closure is initially driven by cell crawling. At later stages, we observed unanticipated patterns of traction forces pointing towards the wound. Such patterns have strong force components that are both radial and tangential to the wound. We show that these force components arise from tensions transmitted by a heterogeneous actomyosin ring to the underlying substrate through focal adhesions. The structural and mechanical organization reported here provides cells with a mechanism to close the wound by cooperatively compressing the underlying substrate. PMID:27340423
Forces driving epithelial wound healing
NASA Astrophysics Data System (ADS)
Brugués, Agustí; Anon, Ester; Conte, Vito; Veldhuis, Jim H.; Gupta, Mukund; Colombelli, Julien; Muñoz, José J.; Brodland, G. Wayne; Ladoux, Benoit; Trepat, Xavier
A fundamental feature of multicellular organisms is their ability to self-repair wounds through the movement of epithelial cells into the damaged area. This collective cellular movement is commonly attributed to a combination of cell crawling and `purse-string' contraction of a supracellular actomyosin ring. Here we show by direct experimental measurement that these two mechanisms are insufficient to explain force patterns observed during wound closure. At early stages of the process, leading actin protrusions generate traction forces that point away from the wound, showing that wound closure is initially driven by cell crawling. At later stages, we observed unanticipated patterns of traction forces pointing towards the wound. Such patterns have strong force components that are both radial and tangential to the wound. We show that these force components arise from tensions transmitted by a heterogeneous actomyosin ring to the underlying substrate through focal adhesions. The structural and mechanical organization reported here provides cells with a mechanism to close the wound by cooperatively compressing the underlying substrate.
Intestinal trefoil factor/TFF3 promotes re-epithelialization of corneal wounds.
Paulsen, Friedrich P; Woon, Chee-Wai; Varoga, Deike; Jansen, Anne; Garreis, Fabian; Jäger, Kristin; Amm, Marita; Podolsky, Daniel K; Steven, Philipp; Barker, Nicholas P; Sel, Saadettin
Disorders of wound healing characterized by impaired or delayed re-epithelialization are a serious medical problem. These conditions affect many tissues, are painful, and are difficult to treat. In this study using cornea as a model, we demonstrate the importance of trefoil factor 3 (TFF3, also known as intestinal trefoil factor) in re-epithelialization of wounds. In two different models of corneal wound healing, alkali- and laser-induced corneal wounding, we analyzed the wound healing process in in vivo as well as in combined in vivo/in vitro model in wild type (Tff3(+)(/)(+)) and Tff3-deficient (Tff3(-)(/)(-)) mice. Furthermore, we topically applied different concentrations of recombinant human TFF3 (rTFF3) peptide on the wounded cornea to determine the efficacy of rTFF3 on corneal wound healing. We found that Tff3 peptide is not expressed in intact corneal epithelium, but its expression is extensively up-regulated after epithelial injury. Re-epithelialization of corneal wounds in Tff3(-/-) mice is significantly prolonged in comparison to Tff3(+/+) mice. In addition, exogenous application of rTFF3 to the alkali-induced corneal wounds accelerates significantly in in vivo and in combined in vivo/in vitro model wound healing in Tff3(+/+) and Tff3(-/-) mice. These findings reveal a pivotal role for Tff3 in corneal wound healing mechanism and have broad implications for developing novel therapeutic strategies for treating nonhealing wounds.
Assessment of chimerism in epithelial cancers in transplanted patients.
Leboeuf, Christophe; Ratajczak, Philippe; Vérine, Jérôme; Elbouchtaoui, Morad; Plassa, François; Legrès, Luc; Ferreira, Irmine; Sandid, Wissam; Varna, Mariana; Bousquet, Guilhem; Verneuil, Laurence; Janin, Anne
Cancer is now the most severe complication in the long term in transplant recipients. As most solid-organ or hematopoietic stem-cell transplantations are allogeneic, chimerism studies can be performed on cancers occurring in recipients. We summarize here the different methods used to study chimerism in cancers developing in allogeneic-transplant recipients, analyze their respective advantages and report the main results obtained from these studies. Chimerism analyses of cancers in transplant recipients require methods suited to tissue samples. In the case of gender-mismatched transplantation, the XY chromosomes can be explored using fluorescent in situ hybridization on whole-tissue sections or Y-sequence-specific PCR after the laser microdissection of tumor cells. For cancers occurring after gender-matched transplantation, laser microdissection of tumor cells enables studies of microsatellite markers and high-resolution melting analysis of mitochondrial DNA on genes with marked polymorphism, provided these are different in the donor and the recipient. The results of different studies address the cancers that develop in both recipients and in transplants. The presence of chimeric cells in these two types of cancer implies an exchange of progenitor/stem-cells between transplant and recipient, and the plasticity of these progenitor/stem-cells contributes to epithelial cancers. The presence of chimeric cells in concomitant cancers and preneoplastic lesions implies that the oncogenesis of these cancers progresses through a multistep process.
Epithelial phenotype in total sclerocornea
Yeh, Lung-Kun; Chen, Hung-Chi; Chang, Anna Marie; Ho, Yi-Ju; Chang, Shirley H.L.; Yang, Unique
Purpose To understand whether the epithelial phenotype in total sclerocornea is corneal or conjunctival in origin. Methods Four cases of total sclerocornea (male:female = 1:3; mean age = 5.4±4.3; 1–11 years old) who received penetrating keratoplasty (PKP) at our hospital between 2008 and 2011 were included. Corneal buttons obtained during PKP were used for transmission electron microscopy (TEM) as well as immunoconfocal microscopy for cytokeratins 3, 12, and 13, goblet cell mucin MUC5AC, connexin 43, stem cell markers p63 and ABCG2, laminin-5, and fibronectin. Results After a mean follow-up period of 38.8±14.0 (12–54) months, the grafts remained clear in half of the patients. TEM examination revealed a markedly attenuated Bowman's layer in the scleralized corneas, with irregular and variably thinned collagen lamellar layers, and disorganization and random distribution of collagen fibrils, which were much larger in diameter compared with a normal cornea. Immunoconfocal microscopy showed that keratin 3 was expressed in all four patients, while p63, ABCG2, and MUC5AC were all absent. Cornea-specific keratin 12 was universally expressed in Patients 1 to 3, while mucosa (including conjunctiva)-specific keratin 13 was negative in these patients. Interestingly, keratin 12 and 13 were expressed in Patient 4 in a mutually exclusive manner. Linear expression of laminin-5 in the basement membrane zone and similar expression of fibronectin were observed. Conclusions The epithelia in total sclerocornea are essentially corneal in phenotype, but in the event of massive corneal angiogenesis, invasion by the conjunctival epithelium is possible. PMID:24744607
Visual outcomes of topography-guided excimer laser surgery for treatment of patients with irregular astigmatism.
Ghoreishi, Mohammad; Naderi Beni, Afsaneh; Naderi Beni, Zahra
The aim of this study was to evaluate the efficacy, safety, and predictability of topography-guided treatments to enhance refractive status following other corneal surgical procedures. In a prospective case series study, 28 consecutive eyes of 26 patients with irregular astigmatism after radial keratotomy, corneal transplant, small hyperopic and myopic excimer laser optical zones, and corneal scars were operated. Laser-assisted in situ keratomileusis (LASIK) (n = 8) and photorefractive keratectomy (PRK) (n = 20) were performed using the ALLEGRETTO WAVE excimer laser and topography-guided customized ablation treatment software. Preoperative and postoperative uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), manifest and cycloplegic refraction, and corneal topography with asphericity were analyzed in 12 months follow-up. Uncorrected visual acuity (UCVA) changed from 0.2 ± 0.2 or (20/100 ± 20/100) to 0.51 ± 0.31 or (20/40 ± 20/60) in the LASIK group (P = 0.01) and from 0.34 ± 0.16 or (20/60 ± 20/120) to 0.5 ± 0.23 or (20/40 ± 20/80) in the PRK group (P = 0.01). Refractive cylinder decreased from -3.2 ± 0.84 diopters (D) to -2.06 ± 0.42 D in the LASIK group (P = 0.07) and from -2.25 ± 0.39 D to -1.5 ± 0.23 D in the PRK group (P = 0.008). Best corrected visual acuity did not change significantly in either group. Topography-guided treatment is effective in correcting the irregular astigmatism after refractive surgery. Topography-guided PRK can significantly reduce irregular astigmatism and increase the UCVA and BCVA.
Epithelial cell-extracellular matrix interactions and stem cells in airway epithelial regeneration.
Coraux, Christelle; Roux, Jacqueline; Jolly, Thomas; Birembaut, Philippe
In healthy subjects, the respiratory epithelium forms a continuous lining to the airways and to the environment, and plays a unique role as a barrier against external deleterious agents to protect the airways from the insults. In respiratory diseases such as cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), chronic bronchitis, or asthma, the airway epithelium is frequently remodeled and injured, leading to the impairment of its defense functions. The rapid restoration of the epithelial barrier is crucial for these patients. The complete regeneration of the airway epithelium is a complex phenomenon, including not only the epithelial wound repair but also the epithelial differentiation to reconstitute a fully well differentiated and functional epithelium. The regeneration implies two partners: the epithelial stem/progenitor cells and factors able to regulate this process. Among these factors, epithelial cells-extracellular matrix (ECM) interactions play a crucial role. The secretion of a provisional ECM, the cell-ECM relationships through epithelial receptors, and the remodeling of the ECM by proteases (mainly matrix metalloproteinases) contribute not only to airway epithelial repair by modulating epithelial cell migration and proliferation, but also to the differentiation of repairing cells leading to the complete restoration of the wounded epithelium. A better characterization of resident stem cells and of effectors of the regeneration process is an essential prerequisite to propose new regenerative therapeutics to patients suffering from infectious/inflammatory respiratory diseases.
NASA Astrophysics Data System (ADS)
Balcou, Philippe; Forget, Sébastien Robert-Philip, Isabelle
* Introduction * The Laser in All Its Forms * Gas lasers * Dye lasers * Solid-state lasers * Lasers for Every Taste * The rise of lasers * Lasers of all sizes * The colors of the rainbow... and beyond * Shorter and shorter lasers * Increasingly powerful lasers * Lasers: A Universal Tool? * Cutting, welding, and cleaning * Communicating * Treating illnesses * Measuring * Supplying energy? * Entertaining * Understanding * Conclusion
Veligdan, James T.
A microphone for detecting sound pressure waves includes a laser resonator having a laser gain material aligned coaxially between a pair of first and second mirrors for producing a laser beam. A reference cell is disposed between the laser material and one of the mirrors for transmitting a reference portion of the laser beam between the mirrors. A sensing cell is disposed between the laser material and one of the mirrors, and is laterally displaced from the reference cell for transmitting a signal portion of the laser beam, with the sensing cell being open for receiving the sound waves. A photodetector is disposed in optical communication with the first mirror for receiving the laser beam, and produces an acoustic signal therefrom for the sound waves.
Scrib is required for epithelial cell identity and prevents epithelial to mesenchymal transition in the mouse.
Yamben, Idella F; Rachel, Rivka A; Shatadal, Shalini; Copeland, Neal G; Jenkins, Nancy A; Warming, Soren; Griep, Anne E
The integrity and function of epithelial tissues depend on the establishment and maintenance of defining characteristics of epithelial cells, cell-cell adhesion and cell polarity. Disruption of these characteristics can lead to the loss of epithelial identity through a process called epithelial to mesenchymal transition (EMT), which can contribute to pathological conditions such as tissue fibrosis and invasive cancer. In invertebrates, the epithelial polarity gene scrib plays a critical role in establishing and maintaining cell adhesion and polarity. In this study we asked if the mouse homolog, Scrib, is required for establishment and/or maintenance of epithelial identity in vivo. To do so, we conditionally deleted Scrib in the head ectoderm tissue that gives rise to both the ocular lens and the corneal epithelium. Deletion of Scrib in the lens resulted in a change in epithelial cell shape from cuboidal to flattened and elongated. Early in the process, the cell adhesion protein, E-cadherin, and apical polarity protein, ZO-1, were downregulated and the myofibroblast protein, αSMA, was upregulated, suggesting EMT was occurring in the Scrib deficient lenses. Correlating temporally with the upregulation of αSMA, Smad3 and Smad4, TGFβ signaling intermediates, accumulated in the nucleus and Snail, a TGFβ target and transcriptional repressor of the gene encoding E-cadherin, was upregulated. Pax6, a lens epithelial transcription factor required to maintain lens epithelial cell identity also was downregulated. Loss of Scrib in the corneal epithelium also led to molecular changes consistent with EMT, suggesting that the effect of Scrib deficiency was not unique to the lens. Together, these data indicate that mammalian Scrib is required to maintain epithelial identity and that loss of Scrib can culminate in EMT, mediated, at least in part, through TGFβ signaling.
Urokinase plasminogen activator released by alveolar epithelial cells modulates alveolar epithelial repair in vitro.
Van Leer, Coretta; Stutz, Monika; Haeberli, André; Geiser, Thomas
Intra-alveolar fibrin is formed following lung injury and inflammation and may contribute to the development of pulmonary fibrosis. Fibrin turnover is altered in patients with pulmonary fibrosis, resulting in intra-alveolar fibrin accumulation, mainly due to decreased fibrinolysis. Alveolar type II epithelial cells (AEC) repair the injured alveolar epithelium by migrating over the provisional fibrin matrix. We hypothesized that repairing alveolar epithelial cells modulate the underlying fibrin matrix by release of fibrinolytic activity, and that the degree of fibrinolysis modulates alveolar epithelial repair on fibrin. To test this hypothesis we studied alveolar epithelial wound repair in vitro using a modified epithelial wound repair model with human A549 alveolar epithelial cells cultured on a fibrin matrix. In presence of the inflammatory cytokine interleukin-1beta, wounds increase by 800% in 24 hours mainly due to detachment of the cells, whereas in serum-free medium wound areas decreases by 22.4 +/- 5.2% (p < 0.01). Increased levels of D-dimer, FDP and uPA in the cell supernatant of IL-1beta-stimulated A549 epithelial cells indicate activation of fibrinolysis by activation of the plasmin system. In presence of low concentrations of fibrinolysis inhibitors, including specific blocking anti-uPA antibodies, alveolar epithelial repair in vitro was improved, whereas in presence of high concentrations of fibrinolysis inhibitors, a decrease was observed mainly due to decreased spreading and migration of cells. These findings suggest the existence of a fibrinolytic optimum at which alveolar epithelial repair in vitro is most efficient. In conclusion, uPA released by AEC alters alveolar epithelial repair in vitro by modulating the underlying fibrin matrix.
Early, James W.; Lester, Charles S.
Sequenced pulses of light from an excitation laser with at least two resonator cavities with separate output couplers are directed through a light modulator and a first polarzing analyzer. A portion of the light not rejected by the first polarizing analyzer is transported through a first optical fiber into a first ignitor laser rod in an ignitor laser. Another portion of the light is rejected by the first polarizing analyzer and directed through a halfwave plate into a second polarization analyzer. A first portion of the output of the second polarization analyzer passes through the second polarization analyzer to a second, oscillator, laser rod in the ignitor laser. A second portion of the output of the second polarization analyzer is redirected by the second polarization analyzer to a second optical fiber which delays the beam before the beam is combined with output of the first ignitor laser rod. Output of the second laser rod in the ignitor laser is directed into the first ignitor laser rod which was energized by light passing through the first polarizing analyzer. Combined output of the first ignitor laser rod and output of the second optical fiber is focused into a combustible fuel where the first short duration, high peak power pulse from the ignitor laser ignites the fuel and the second long duration, low peak power pulse directly from the excitation laser sustains the combustion.
NASA Astrophysics Data System (ADS)
Gorbatenko, A. A.; Revina, E. I.
The review is devoted to the major advances in laser sampling. The advantages and drawbacks of the technique are considered. Specific features of combinations of laser sampling with various instrumental analytical methods, primarily inductively coupled plasma mass spectrometry, are discussed. Examples of practical implementation of hybrid methods involving laser sampling as well as corresponding analytical characteristics are presented. The bibliography includes 78 references.
Epithelial uptake of flagella initiates proinflammatory signaling.
Parker, Dane; Prince, Alice
The airway epithelium serves multiple roles in the defense of the lung. Not only does it act as a physical barrier, it acts as a distal extension of the innate immune system. We investigated the role of the airway epithelium in the interaction with flagella, an important virulence factor of the pathogen Pseudomonas aeruginosa, a cause of ventilator associated pneumonia and significant morbidity and mortality in patients with cystic fibrosis. Flagella were required for transmigration across polarized airway epithelial cells and this was a direct consequence of motility, and not a signaling effect. Purified flagella did not alter the barrier properties of the epithelium but were observed to be rapidly endocytosed inside epithelial cells. Neither flagella nor intact P. aeruginosa stimulated epithelial inflammasome signaling. Flagella-dependent signaling required dynamin-based uptake as well as TLR5 and primarily led to the induction of proinflammatory (Tnf, Il6) as well as neutrophil (Cxcl1, Cxcl2, Ccl3) and macrophage (Ccl20) chemokines. Although flagella are important in invasion across the epithelial barrier their shedding in the airway lumen results in epithelial uptake and signaling that has a major role in the initial recruitment of immune cells in the lung.
Microtubules regulate disassembly of epithelial apical junctions
Ivanov, Andrei I; McCall, Ingrid C; Babbin, Brian; Samarin, Stanislav N; Nusrat, Asma; Parkos, Charles A
Background Epithelial tight junction (TJ) and adherens junction (AJ) form the apical junctional complex (AJC) which regulates cell-cell adhesion, paracellular permeability and cell polarity. The AJC is anchored on cytoskeletal structures including actin microfilaments and microtubules. Such cytoskeletal interactions are thought to be important for the assembly and remodeling of apical junctions. In the present study, we investigated the role of microtubules in disassembly of the AJC in intestinal epithelial cells using a model of extracellular calcium depletion. Results Calcium depletion resulted in disruption and internalization of epithelial TJs and AJs along with reorganization of perijunctional F-actin into contractile rings. Microtubules reorganized into dense plaques positioned inside such F-actin rings. Depolymerization of microtubules with nocodazole prevented junctional disassembly and F-actin ring formation. Stabilization of microtubules with either docetaxel or pacitaxel blocked contraction of F-actin rings and attenuated internalization of junctional proteins into a subapical cytosolic compartment. Likewise, pharmacological inhibition of microtubule motors, kinesins, prevented contraction of F-actin rings and attenuated disassembly of apical junctions. Kinesin-1 was enriched at the AJC in cultured epithelial cells and it also accumulated at epithelial cell-cell contacts in normal human colonic mucosa. Furthermore, immunoprecipitation experiments demonstrated association of kinesin-1 with the E-cadherin-catenin complex. Conclusion Our data suggest that microtubules play a role in disassembly of the AJC during calcium depletion by regulating formation of contractile F-actin rings and internalization of AJ/TJ proteins. PMID:16509970
Autoimmune epitheliitis: Sjögren's syndrome.
Skopouli, F N; Moutsopoulos, H M
Sjögren's syndrome (SS), an autoimmune exocrinopathy, is a common, chronic disease of females. Clinical studies of kidney involvement in SS patients have shown that the predominant lesion is interstitial nephritis which produces tubular dysfunction. Studies on lung involvement have previously indicated that one fourth of SS patients suffer from subclinical interstitial lung disease. Re-evaluation, however, of the pulmonary disease using functional, radiologic and histopathologic studies showed that the lesion starts peribronchially. Finally, evaluation of liver disease in SS patients revealed that this consists of a pericholangeal round-cell infiltrate resembling the early lesion of primary biliary cirrhosis. These clinical studies suggest that the systemic manifestations of SS are probably due to the attraction of lymphocytes by different epithelial tissues. Studies of the epithelial cells of minor salivary glands from SS patients have shown that these inappropriately and selectively express HLA class II molecules and the proto-oncogene c-myc. Evaluation of cytokines in the minor salivary glands from these patients by in situ hybridization revealed that the proinflammatory cytokines IL-1 and IL-6 are also produced by the epithelial cells. Finally, proviral DNA has been shown to be incorporated in the DNA of epithelial cells. On the basis of these clinical and laboratory observations, we would like to suggest that the target tissue involved in the autoimmune histopathologic lesions of SS is the epithelium, and therefore we propose the term "Autoimmune Epitheliitis" instead of "Sjögren's syndrome" for this disease.
Functional imaging and assessment of the glucose diffusion rate in epithelial tissues in optical coherence tomography
Larin, K V; Tuchin, V V
Functional imaging, monitoring and quantitative description of glucose diffusion in epithelial and underlying stromal tissues in vivo and controlling of the optical properties of tissues are extremely important for many biomedical applications including the development of noninvasive or minimally invasive glucose sensors as well as for therapy and diagnostics of various diseases, such as cancer, diabetic retinopathy, and glaucoma. Recent progress in the development of a noninvasive molecular diffusion biosensor based on optical coherence tomography (OCT) is described. The diffusion of glucose was studied in several epithelial tissues both in vitro and in vivo. Because OCT provides depth-resolved imaging of tissues with high in-depth resolution, the glucose diffusion is described not only as a function of time but also as a function of depth. (special issue devoted to application of laser technologies in biophotonics and biomedical studies)
Growth requirements of human mammary epithelial cells in culture.
Taylor-Papadimitriou, J; Shearer, M; Stoker, M G
Colony-forming epithelial cells can be separated from the non-dividing "foam cells" in human milk by differential adhesion to glass and freezing. The growth of such partially purified mammary epithelial cells is stimulated by co-culture with non-dividing feeder cells. Foam cells, mitomycin-treated mouse fibroblast lines and human mammary fibroblasts and calf lens epithelial cells are all effective in promoting mammary epithelial cell growth. Contact between epithelial cells and feeders is not required for the growth-promoting effect. The mitogenic effect of epidermal growth factor on mammary epithelial cells also requires feeder cell activity.
Shand, M.L.; Lai, S.T.
A CW laser-pumped emerald laser is reported. A 34 percent output power slope efficiency is observed with longitudinal pumping by a krypton laser in a nearly concentric cavity. The laser has been tuned from 728.8 to 809.0 nm. Losses in emerald are larger than those of alexandrite determined in a similar cavity. The present data also indicate that the excited state absorption minimum is shifted from that of alexandrite. 13 references.
Studying cytokinesis in Drosophila epithelial tissues.
Pinheiro, D; Bellaïche, Y
Epithelial tissue cohesiveness is ensured through cell-cell junctions that maintain both adhesion and mechanical coupling between neighboring cells. During development, epithelial tissues undergo intensive cell proliferation. Cell division, and particularly cytokinesis, is coupled to the formation of new adhesive contacts, thereby preserving tissue integrity and propagating cell polarity. Remarkably, the geometry of the new interfaces is determined by the combined action of the dividing cell and its neighbors. To further understand the interplay between the dividing cell and its neighbors, as well as the role of cell division for tissue morphogenesis, it is important to analyze cytokinesis in vivo. Here we present methods to perform live imaging of cell division in Drosophila epithelial tissues and discuss some aspects of image processing and analysis.
Epithelial Intermediate Filaments: Guardians against Microbial Infection?
Geisler, Florian; Leube, Rudolf E.
Intermediate filaments are abundant cytoskeletal components of epithelial tissues. They have been implicated in overall stress protection. A hitherto poorly investigated area of research is the function of intermediate filaments as a barrier to microbial infection. This review summarizes the accumulating knowledge about this interaction. It first emphasizes the unique spatial organization of the keratin intermediate filament cytoskeleton in different epithelial tissues to protect the organism against microbial insults. We then present examples of direct interaction between viral, bacterial, and parasitic proteins and the intermediate filament system and describe how this affects the microbe-host interaction by modulating the epithelial cytoskeleton, the progression of infection, and host response. These observations not only provide novel insights into the dynamics and function of intermediate filaments but also indicate future avenues to combat microbial infection. PMID:27355965
Odontogenic epithelial stem cells: hidden sources.
Padma Priya, Sivan; Higuchi, Akon; Abu Fanas, Salem; Pooi Ling, Mok; Kumari Neela, Vasantha; Sunil, P M; Saraswathi, T R; Murugan, Kadarkarai; Alarfaj, Abdullah A; Munusamy, Murugan A; Kumar, Suresh
The ultimate goal of dental stem cell research is to construct a bioengineered tooth. Tooth formation occurs based on the well-organized reciprocal interaction of epithelial and mesenchymal cells. The dental mesenchymal stem cells are the best explored, but because the human odontogenic epithelium is lost after the completion of enamel formation, studies on these cells are scarce. The successful creation of a bioengineered tooth is achievable only when the odontogenic epithelium is reconstructed to produce a replica of natural enamel. This article discusses the untapped sources of odontogenic epithelial stem cells in humans, such as those present in the active dental lamina in postnatal life, in remnants of dental lamina (the gubernaculum cord), in the epithelial cell rests of Malassez, and in reduced enamel epithelium. The possible uses of these stem cells in regenerative medicine, not just for enamel formation, are discussed.
Biomarkers for epithelial-mesenchymal transitions.
Zeisberg, Michael; Neilson, Eric G
Somatic cells that change from one mature phenotype to another exhibit the property of plasticity. It is increasingly clear that epithelial and endothelial cells enjoy some of this plasticity, which is easily demonstrated by studying the process of epithelial-mesenchymal transition (EMT). Published reports from the literature typically rely on ad hoc criteria for determining EMT events; consequently, there is some uncertainty as to whether the same process occurs under different experimental conditions. As we discuss in this Personal Perspective, we believe that context and various changes in plasticity biomarkers can help identify at least three types of EMT and that using a collection of criteria for EMT increases the likelihood that everyone is studying the same phenomenon - namely, the transition of epithelial and endothelial cells to a motile phenotype.
Epithelial stem cells and intestinal cancer.
Tan, Shawna; Barker, Nick
The mammalian intestine is comprised of an epithelial layer that serves multiple functions in order to maintain digestive activity as well as intestinal homeostasis. This epithelial layer contains highly proliferative stem cells which facilitate its characteristic rapid regeneration. How these stem cells contribute to tissue repair and normal homeostasis are actively studied, and while we have a greater understanding of the molecular mechanisms and cellular locations that underlie stem cell regulation in this tissue, much still remains undiscovered. This review describes epithelial stem cells in both intestinal and non-intestinal tissues, as well as the strategies that have been used to further characterize the cells. Through a discussion of the current understanding of intestinal self-renewal and tissue regeneration in response to injury, we focus on how dysregulation of critical signaling pathways results in potentially oncogenic aberrations, and highlight issues that should be addressed in order for effective intestinal cancer therapies to be devised.
Scott, Jill R.; Tremblay, Paul L.
A laser device includes a target position, an optical component separated a distance J from the target position, and a laser energy source separated a distance H from the optical component, distance H being greater than distance J. A laser source manipulation mechanism exhibits a mechanical resolution of positioning the laser source. The mechanical resolution is less than a spatial resolution of laser energy at the target position as directed through the optical component. A vertical and a lateral index that intersect at an origin can be defined for the optical component. The manipulation mechanism can auto align laser aim through the origin during laser source motion. The laser source manipulation mechanism can include a mechanical index. The mechanical index can include a pivot point for laser source lateral motion and a reference point for laser source vertical motion. The target position can be located within an adverse environment including at least one of a high magnetic field, a vacuum system, a high pressure system, and a hazardous zone. The laser source and an electro-mechanical part of the manipulation mechanism can be located outside the adverse environment. The manipulation mechanism can include a Peaucellier linkage.
Scott, Jill R.; Tremblay, Paul L.
A laser device includes a target position, an optical component separated a distance J from the target position, and a laser energy source separated a distance H from the optical component, distance H being greater than distance J. A laser source manipulation mechanism exhibits a mechanical resolution of positioning the laser source. The mechanical resolution is less than a spatial resolution of laser energy at the target position as directed through the optical component. A vertical and a lateral index that intersect at an origin can be defined for the optical component. The manipulation mechanism can auto align laser aim through the origin during laser source motion. The laser source manipulation mechanism can include a mechanical index. The mechanical index can include a pivot point for laser source lateral motion and a reference point for laser source vertical motion. The target position can be located within an adverse environment including at least one of a high magnetic field, a vacuum system, a high pressure system, and a hazardous zone. The laser source and an electro-mechanical part of the manipulation mechanism can be located outside the adverse environment. The manipulation mechanism can include a Peaucellier linkage.
Nitric Oxide and Airway Epithelial Barrier Function: Regulation of Tight Junction Proteins and Epithelial Permeability
Olson, Nels; Greul, Anne-Katrin; Hristova, Milena; Bove, Peter F.; Kasahara, David I.; van der Vliet, Albert
Acute airway inflammation is associated with enhanced production of nitric oxide (NO•) and altered airway epithelial barrier function, suggesting a role of NO• or its metabolites in epithelial permeability. While high concentrations of S-nitrosothiols disrupted transepithelial resistance (TER) and increased permeability in 16HBE14o- cells, no significant barrier disruption was observed by NONOates, in spite of altered distribution and expression of some TJ proteins. Barrier disruption of mouse tracheal epithelial (MTE) cell monolayers in response to inflammatory cytokines was independent of NOS2, based on similar effects in MTE cells from NOS2-/- mice and a lack of effect of the NOS2-inhibitor 1400W. Cell pre-incubation with LPS protected MTE cells from TER loss and increased permeability by H2O2, which was independent of NOS2. However, NOS2 was found to contribute to epithelial wound repair and TER recovery after mechanical injury. Overall, our results demonstrate that epithelial NOS2 is not responsible for epithelial barrier dysfunction during inflammation, but may contribute to restoration of epithelial integrity. PMID:19100237
Epithelial-mesenchymal transition can suppress major attributes of human epithelial tumor-initiating cells
Celià-Terrassa, Toni; Meca-Cortés, Óscar; Mateo, Francesca; Martínez de Paz, Alexia; Rubio, Nuria; Arnal-Estapé, Anna; Ell, Brian J.; Bermudo, Raquel; Díaz, Alba; Guerra-Rebollo, Marta; Lozano, Juan José; Estarás, Conchi; Ulloa, Catalina; ρlvarez-Simón, Daniel; Milà, Jordi; Vilella, Ramón; Paciucci, Rosanna; Martínez-Balbás, Marian; García de Herreros, Antonio; Gomis, Roger R.; Kang, Yibin; Blanco, Jerónimo; Fernández, Pedro L.; Thomson, Timothy M.
Malignant progression in cancer requires populations of tumor-initiating cells (TICs) endowed with unlimited self renewal, survival under stress, and establishment of distant metastases. Additionally, the acquisition of invasive properties driven by epithelial-mesenchymal transition (EMT) is critical for the evolution of neoplastic cells into fully metastatic populations. Here, we characterize 2 human cellular models derived from prostate and bladder cancer cell lines to better understand the relationship between TIC and EMT programs in local invasiveness and distant metastasis. The model tumor subpopulations that expressed a strong epithelial gene program were enriched in highly metastatic TICs, while a second subpopulation with stable mesenchymal traits was impoverished in TICs. Constitutive overexpression of the transcription factor Snai1 in the epithelial/TIC-enriched populations engaged a mesenchymal gene program and suppressed their self renewal and metastatic phenotypes. Conversely, knockdown of EMT factors in the mesenchymal-like prostate cancer cell subpopulation caused a gain in epithelial features and properties of TICs. Both tumor cell subpopulations cooperated so that the nonmetastatic mesenchymal-like prostate cancer subpopulation enhanced the in vitro invasiveness of the metastatic epithelial subpopulation and, in vivo, promoted the escape of the latter from primary implantation sites and accelerated their metastatic colonization. Our models provide new insights into how dynamic interactions among epithelial, self-renewal, and mesenchymal gene programs determine the plasticity of epithelial TICs. PMID:22505459
Interaction between submicron COD crystals and renal epithelial cells
Peng, Hua; Ouyang, Jian-Ming; Yao, Xiu-Qiong; Yang, Ru-E
Objectives This study aims to investigate the adhesion characteristics between submicron calcium oxalate dihydrate (COD) with a size of 150 ± 50 nm and African green monkey kidney epithelial cells (Vero cells) before and after damage, and to discuss the mechanism of kidney stone formation. Methods Vero cells were oxidatively injured by hydrogen peroxide to establish a model of injured cells. Scanning electron microscopy was used to observe Vero–COD adhesion. Inductively coupled plasma emission spectrometry was used to quantitatively measure the amount of adhered COD microcrystals. Nanoparticle size analyzer and laser scanning confocal microscopy were performed to measure the change in the zeta potential on the Vero cell surface and the change in osteopontin expression during the adhesion process, respectively. The level of cell injury was evaluated by measuring the changes in malonaldehyde content, and cell viability during the adhesion process. Results The adhesion capacity of Vero cells in the injury group to COD microcrystals was obviously stronger than that of Vero cells in the control group. After adhesion to COD, cell viability dropped, both malonaldehyde content and cell surface zeta potential increased, and the fluorescence intensity of osteopontin decreased because the osteopontin molecules were successfully covered by COD. Submicron COD further damaged the cells during the adhesion process, especially for Vero cells in the control group, leading to an elevated amount of attached microcrystals. Conclusion Submicron COD can further damage injured Vero cells during the adhesion process. The amount of attached microcrystals is proportional to the degree of cell damage. The increased amount of microcrystals that adhered to the injured epithelial cells plays an important role in the formation of early-stage kidney stones. PMID:22973095
Early, James W.; Lester, Charles S.
In the apparatus of the invention, a first excitation laser or other excitation light source is used in tandem with an ignitor laser to provide a compact, durable, engine deployable fuel ignition laser system. Reliable fuel ignition is provided over a wide range of fuel conditions by using a single remote excitation light source for one or more small lasers located proximate to one or more fuel combustion zones. In a third embodiment, alternating short and long pulses of light from the excitation light source are directed into the ignitor laser. Each of the embodiments of the invention can be multiplexed so as to provide laser light energy sequentially to more than one ignitor laser.
Physiology of Epithelial Chloride and Fluid Secretion
Frizzell, Raymond A.; Hanrahan, John W.
Epithelial salt and water secretion serves a variety of functions in different organ systems, such as the airways, intestines, pancreas, and salivary glands. In cystic fibrosis (CF), the volume and/or composition of secreted luminal fluids are compromised owing to mutations in the gene encoding CFTR, the apical membrane anion channel that is responsible for salt secretion in response to cAMP/PKA stimulation. This article examines CFTR and related cellular transport processes that underlie epithelial anion and fluid secretion, their regulation, and how these processes are altered in CF disease to account for organ-specific secretory phenotypes. PMID:22675668
Extensive Focal Epithelial Hyperplasia: A Case Report.
Mansouri, Zahra; Bakhtiari, Sedigheh; Noormohamadi, Robab
Focal epithelial hyperplasia (FEH) or Heck's disease is a rare viral infection of the oral mucosa caused by human papilloma virus especially subtypes 13 or 32. The frequency of this disease varies widely from one geographic region and ethnic groups to another. This paper reports an Iranian case of extensive focal epithelial hyperplasia. A 35-year-old man with FEH is described, in whom the lesions had persisted for more than 25 years. The lesion was diagnosed according to both clinical and histopathological features. Dental practitioner should be aware of these types of lesions and histopathological examination together and a careful clinical observation should be carried out for a definitive diagnosis.
Segmentation and Quantitative Analysis of Epithelial Tissues.
Aigouy, Benoit; Umetsu, Daiki; Eaton, Suzanne
Epithelia are tissues that regulate exchanges with the environment. They are very dynamic and can acquire virtually any shape; at the cellular level, they are composed of cells tightly connected by junctions. Most often epithelia are amenable to live imaging; however, the large number of cells composing an epithelium and the absence of informatics tools dedicated to epithelial analysis largely prevented tissue scale studies. Here we present Tissue Analyzer, a free tool that can be used to segment and analyze epithelial cells and monitor tissue dynamics.
Propagating Stress Waves During Epithelial Expansion
NASA Astrophysics Data System (ADS)
Banerjee, Shiladitya; Utuje, Kazage J. C.; Marchetti, M. Cristina
Coordinated motion of cell monolayers during epithelial wound healing and tissue morphogenesis involves mechanical stress generation. Here we propose a model for the dynamics of epithelial expansion that couples mechanical deformations in the tissue to contractile activity and polarization in the cells. A new ingredient of our model is a feedback between local strain, polarization, and contractility that naturally yields a mechanism for viscoelasticity and effective inertia in the cell monolayer. Using a combination of analytical and numerical techniques, we demonstrate that our model quantitatively reproduces many experimental findings [Nat. Phys. 8, 628 (2012)], including the buildup of intercellular stresses, and the existence of traveling mechanical waves guiding the oscillatory monolayer expansion.
[Gastric epithelial polyps (part two)].
Espejo Romero, Luis Hernán; Navarrete Siancas, Jesús
The following is a statistical report regarding gastric polyps: Frequency determined through endoscopic examinations was 3.6%. The terms hyperplastic polyps and adenomas were used for the classification of epithelial polyps, considering the suprafoveal hyperplasias within the hyperplastic polyps, provided they were elevated lesions. Out of 2,283 polyps, 1,959 were hyperplastic (86%) and 324 were adenomas (14%). When analyzing 780 polyps, 86 (11%) were found to have the Nakamura III category. With regard to topography, in an examination of 2253 polyps, hyperplastic polyps were located as follows: 325 (17%) in the antrum, 1402 (73%) in the body and 202 (10%) in the fundus. Adenomas had a different distribution: 212 (65%) in the antrum, 100 (31%) in the body and 12 (4%) in the fundus. Out of 371 hyperplastic polyps examined, 49% were pediculate and 51% were sessile; on the contrary, 86 % of adenomas were sessile. The average age was 66.2 years in adenoma carriers, 58.5 in those having hyperplastic polyps, and 57.4 for suprafoveal hyperplasias. In 287 adenomas, 94.1% of carriers were over 40 years old. Out of 92 adenomas examined, 21.7% evidenced adenoma metaplasia and 72.8% evidenced metaplasia in adjacent areas. Only 5.5% had no metaplasia. In 105 hyperplastic polyps studied, intestinal metaplasia was found: 16.7% in the polyp and 60% in adjacent areas. No metaplasia was found in the remaining 23.3%. Average size of the adenomas was 14 mm and of hyperplastic polyps, 11 mm. A total of 195 adenomas were smaller than 10 mm. The percentage of malignization in 288 adenomas examined was closely related to their size: 214 (66%) smaller than 20 mm, had a malignization percentage of 7%; 74 (34%) larger than 20 mm, had 51% malignization, and 86.2% malignization was found in adenomas of over 40 mm. Global malignization percentage of adenomas was 18%. However, when adenomas with high grade dysplasia in the 4.1 category of the Viena classification (non-invasive high grade
Adherence of skin bacteria to human epithelial cells.
Romero-Steiner, S; Witek, T; Balish, E
Aerobic and anaerobic bacteria isolated from human axillae were tested for their capacity to adhere to buccal epithelial cells, immortalized human epithelial (HEp-2) cells, and undifferentiated and differentiated human epithelial cells. In general, both aerobic and anaerobic diphtheroids adhered better to differentiated human epithelial cells than to HEp-2 and undifferentiated human epithelial cells (P less than 0.05). Mannose, galactose, fucose, N-acetyl-D-glucosamine, and fibronectin were also assayed for their capacity to inhibit the adherence of diphtheroids to human epithelial cells. A great deal of variability was observed in the capacity of the latter compounds to inhibit the attachment of aerobic diphtheroids to undifferentiated and differentiated epithelial cells. Overall, mannose appeared to be best at inhibiting the adherence of the aerobic diphtheroids to undifferentiated human epithelial cells. Galactose, fucose, N-acetyl-D-glucosamine, and fibronectin showed a greater capacity to inhibit attachment of aerobic diphtheroids to differentiated than to undifferentiated human epithelial cells. The inhibition of adherence to differentiated human epithelial cells varied with the microorganism and the compound tested; however, the highest and most consistent inhibition of adherence (76.1 to 88.6%) was observed with a 5% solution of N-acetyl-D-glucosamine. The in vitro adherence and adherence inhibition assays presented here demonstrate that a number of adhesins and receptors are involved in the adherence of skin bacteria to human epithelial cells and receptors on human epithelial cells are apparently altered during differentiation. PMID:2298877
Interaction with Epithelial Cells Modifies Airway Macrophage Response to Ozone
The initial innate immune response to ozone (03) in the lung is orchestrated by structural cells, such as epithelial cells, and resident immune cells, such as airway macrophages (Macs). We developed an epithelial cell-Mac coculture model to investigate how epithelial cell-derived...
Multifocal epithelial hyperplasia. Report of nine cases.
Ledesma-Montes, Constantino; Vega-Memije, Elisa; Garcés-Ortíz, Maricela; Cardiel-Nieves, Maritza; Juárez-Luna, Claudia
Multifocal epithelial hyperplasia (MEH) is also known as focal epithelial hyperplasia, Heck's disease or multifocal papillomavirus-induced epithelial hyperplasia. It is characterised by the presence of multiple lesions in the oral mucosa of children and it has been associated with the presence of the human papillomavirus. The aim of this study was to determine the clinico-pathological features of the cases diagnosed as MEH in the Service of Dermatology of the Hospital Manuel Gea González (SDHMGG). The files of the SDHMGG were reviewed and all cases diagnosed as MEH were retrieved. Nine MEH cases were found. Most of the patients were 20 year-old or younger (67%) and females were more commonly affected (78%). All patients presented multiple lesions and always, close relatives with similar lesions were found. Lesions were located most commonly in the buccal mucosa, lower lip and commissures. MEH is a soft tissue intraoral condition that needs treatment solely of the traumatised lesions or those with cosmetic problems. Remaining lesions will disappear with the age of the patients. It is suggested that this entity should be named multifocal epithelial hyperplasia since this name describes better the clinico-pathological and microscopic features of the disease.
[Focal epithelial hyperplasia. An unusual clinical aspect].
Bodokh, I; Lacour, J P; Rainero, C; Orth, G; Perrin, C; Hoffman, P; Santini, J; Ortonne, J P
We report a case of focal epithelial hyperplasia in a child born in France of Algerian parents. The clinical appearance was unusual in that certain lesions were verrucous and pediculate. A virological study revealed the presence of papillomavirus 32, one of the two types of HPV specifically associated with this entity.
Iris pigment epithelial cysts in a newborn
Zargar, Shabnam; Prendiville, Kevin John; Martinez, Eladio
Purpose: We report a case of iris pigment epithelial cysts in a newborn and discuss the importance of an accurate diagnosis for prevention of amblyopia. Methods: We describe a case of an abnormal red reflex seen on a newborn exam. Results: A full-term female born via normal spontaneous vaginal delivery without any complications was seen in the newborn nursery. She was noted to have an abnormal eye exam. Pupils were large with circular dark excrescences of the iris pigment epithelium. She was referred to a pediatric ophthalmologist where she was noted to fixate and follow faces. No afferent pupillary defect was seen. OD red reflex was normal whereas OS red reflex was blocked mostly by dark excrescences. A 2–3 mm dark brown lesion was seen in the OD iris and a 3–5 mm dark brown lesion was seen in the OS iris, consistent with a pupillary iris pigment epithelial cyst. Central visual axis was clear OU. Glaucoma was not present and patching was not performed. Observations and clinical photographs were recommended with follow-up in three months. Conclusion: Iris pigment epithelial cysts are uncommonly seen in children. The primary care provider first seeing a newborn must be aware of lesions obscuring a red reflex with appropriate follow-up. Follow-up in three months with IOP measurements is recommended. Iris pigment epithelial cysts in children may be a cause of amblyopia, thus prompt evaluation is important for prognostic purposes and the prevention of amblyopia. PMID:27625966
Cells of Origin of Epithelial Ovarian Cancers
lethal malignancy of the female reproductive system, largely due to the fact that most EOCs are diagnosed only after the cancer has metastasized into the...Epithelial ovarian cancer (EOC) is the most lethal malignancy of the female reproductive system, largely due to the fact that most EOCs are diagnosed only
Epithelial-mesenchymal transition in liver fibrosis
Liver fibrosis is the result of a sustained wound healing response to sustained chronic liver injury, which includes viral, alcoholic and autoimmune hepatitis. Hepatic regeneration is the dominant outcome of liver damage. The outcomes of successful repair are the replacement of dead epithelial cells with healthy epithelial cells, and reconstruction of the normal hepatic structure and function. Prevention of the development of epithelial-mesenchymal transition (EMT) may control and even reverse liver fibrosis. EMT is a critical process for an epithelial cell to undergo a conversion to a mesenchymal phenotype, and is believed to be an inflammation-induced response, which may have a central role in liver fibrosis. The origin of fibrogenic cells in liver fibrosis remains controversial. Numerous studies have investigated the origin of all fibrogenic cells within the liver and the mechanism of the signaling pathways that lead to the activation of EMT programs during numerous chronic liver diseases. The present study aimed to summarize the evidence to explain the possible role of EMT in liver fibrosis. PMID:26998262
Control of lens epithelial cell survival
We have studied the survival requirements of developing lens epithelial cells to test the hypothesis that most cells are programmed to kill themselves unless they are continuously signaled by other cells not to do so. The lens cells survived for weeks in both explant cultures and high-density dissociated cell cultures in the absence of other cells or added serum or protein, suggesting that they do not require signals from other cell types to survive. When cultured at low density, however, they died by apoptosis, suggesting that they depend on other lens epithelial cells for their survival. Lens epithelial cells cultured at high density in agarose gels also survived for weeks, even though they were not in direct contact with one another, suggesting that they can promote one another's survival in the absence of cell- cell contact. Conditioned medium from high density cultures promoted the survival of cells cultured at low density, suggesting that lens epithelial cells support one another's survival by secreting survival factors. We show for the first time that normal cell death occurs within the anterior epithelium in the mature lens, but this death is strictly confined to the region of the anterior suture. PMID:8491781
Do topical antibiotics help corneal epithelial trauma?
King, J. W.; Brison, R. J.
Topical antibiotics are routinely used in emergency rooms to treat corneal trauma, although no published evidence supports this treatment. In a noncomparative clinical trial, 351 patients with corneal epithelial injuries were treated without antibiotics. The infection rate was 0.7%, suggesting that such injuries can be safely and effectively managed without antibiotics. A comparative clinical trial is neither warranted nor feasible. PMID:8268742
Stromal-epithelial interactions in aging and cancer: Senescent fibroblasts alter epithelial cell differentiation
Parrinello, Simona; Coppe, Jean-Philippe; Krtolica, Ana; Campisi, Judith
Cellular senescence suppresses cancer by arresting cells at risk for malignant tumorigenesis. However, senescent cells also secrete molecules that can stimulate premalignant cells to proliferate and form tumors, suggesting the senescence response is antagonistically pleiotropic. We show that premalignant mammary epithelial cells exposed to senescent human fibroblasts in mice irreversibly lose differentiated properties, become invasive and undergo full malignant transformation. Moreover, using cultured mouse or human fibroblasts and non-malignant breast epithelial cells, we show that senescent fibroblasts disrupt epithelial alveolar morphogenesis, functional differentiation, and branching morphogenesis. Further, we identify MMP-3 as the major factor responsible for the effects of senescent fibroblasts on branching morphogenesis. Our findings support the idea that senescent cells contribute to age-related pathology, including cancer, and describe a new property of senescent fibroblasts--the ability to alter epithelial differentiation--that might also explain the loss of tissue function and organization that is a hallmark of aging.
Release of HIV-1 sequestered in the vesicles of oral and genital mucosal epithelial cells by epithelial-lymphocyte interaction
Yasen, Aizezi; Herrera, Rossana; Rosbe, Kristina
Oropharyngeal mucosal epithelia of fetuses/neonates/infants and the genital epithelia of adults play a critical role in HIV-1 mother-to-child transmission and sexual transmission of virus, respectively. To study the mechanisms of HIV-1 transmission through mucosal epithelium, we established polarized tonsil, cervical and foreskin epithelial cells. Analysis of HIV-1 transmission through epithelial cells showed that approximately 0.05% of initially inoculated virions transmigrated via epithelium. More than 90% of internalized virions were sequestered in the endosomes of epithelial cells, including multivesicular bodies (MVBs) and vacuoles. Intraepithelial HIV-1 remained infectious for 9 days without viral release. Release of sequestered intraepithelial HIV-1 was induced by the calcium ionophore ionomycin and by cytochalasin D, which increase intracellular calcium and disrupt the cortical actin of epithelial cells, respectively. Cocultivation of epithelial cells containing HIV-1 with activated peripheral blood mononuclear cells and CD4+ T lymphocytes led to the disruption of epithelial cortical actin and spread of virus from epithelial cells to lymphocytes. Treatment of epithelial cells with proinflammatory cytokines tumor necrosis factor-alpha and interferon gamma also induced reorganization of cortical actin and release of virus. Inhibition of MVB formation by small interfering RNA (siRNA)-mediated silencing of its critical protein hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) expression reduced viral sequestration in epithelial cells and its transmission from epithelial cells to lymphocytes by ~60–70%. Furthermore, inhibition of vacuole formation of epithelial cells by siRNA-inactivated rabankyrin-5 expression also significantly reduced HIV-1 sequestration in epithelial cells and spread of virus from epithelial cells to lymphocytes. Interaction of the intercellular adhesion molecule-1 of epithelial cells with the function-associated antigen-1
Epithelial cell extrusion: Pathways and pathologies.
Gudipaty, Swapna Aravind; Rosenblatt, Jody
To remove dying or unwanted cells from an epithelium while preserving the barrier function of the layer, epithelia use a unique process called cell extrusion. To extrude, the cell fated to die emits the lipid Sphingosine 1 Phosphate (S1P), which binds the G-protein-coupled receptor Sphingosine 1 Phosphate receptor 2 (S1P2) in the neighboring cells that activates Rho-mediated contraction of an actomyosin ring circumferentially and basally. This contraction acts to squeeze the cell out apically while drawing together neighboring cells and preventing any gaps to the epithelial barrier. Epithelia can extrude out cells targeted to die by apoptotic stimuli to repair the barrier in the face of death or extrude live cells to promote cell death when epithelial cells become too crowded. Indeed, because epithelial cells naturally turn over by cell death and division at some of the highest rates in the body, epithelia depend on crowding-induced live cell extrusion to preserve constant cell numbers. If extrusion is defective, epithelial cells rapidly lose contact inhibition and form masses. Additionally, because epithelia act as the first line of defense in innate immunity, preservation of this barrier is critical for preventing pathogens from invading the body. Given its role in controlling constant cell numbers and maintaining barrier function, a number of different pathologies can result when extrusion is disrupted. Here, we review mechanisms and signaling pathways that control epithelial extrusion and discuss how defects in these mechanisms can lead to multiple diseases. We also discuss tactics pathogens have devised to hijack the extrusion process to infect and colonize epithelia.
Vitamin D Enhances Corneal Epithelial Barrier Function
Yin, Zhaohong; Pintea, Victorina; Lin, Yanping; Hammock, Bruce D.
Purpose. The purpose of this study was to determine whether 25-hydroxyvitamin D3 (25(OH)D3) and/or its active metabolite, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), can enhance corneal epithelial barrier function. The authors also determined if corneas contain mRNA for the vitamin D receptor (VDR) and 1α-hydroxylase, the enzyme required to convert 25(OH)D3 to 1,25(OH)2D3, and measured vitamin D metabolite concentrations in aqueous and vitreous humor. Methods. RT-PCR was used to examine mouse, rabbit, and human corneal epithelial VDR and 1α-hydroxylase mRNA. Vitamin D metabolites were measured using a selective vitamin D derivatizing agent and mass spectroscopy. Barrier function experiments were performed by measuring inulin permeability (IP) and/or transepithelial resistance (TER) in control, 25(OH)D3-, and 1,25(OH)2D3-treated human and rabbit corneal epithelial monolayers cultured on permeable inserts. Ca2+ was removed, then reintroduced to the culture medium while IP and TER readings were taken. Occludin levels were examined using Western blotting. Results. All corneal samples were positive for both VDR and 1α-hydroxylase mRNA. All vitamin D metabolites except for unhydroxylated vitamin D3 were detected in aqueous and vitreous humor. Epithelial cells showed increased TER, decreased IP, and increased occludin levels when cultured with 25(OH)D3 and 1,25(OH)2D3. Conclusions. We conclude that corneas contain mRNA for VDR and 1α-hydroxylase as well as significant vitamin D concentrations. 25(OH)D3 and its active metabolite 1,25(OH)2D3, both enhance corneal epithelial barrier function. PMID:21715350
Histopathology of laser skin resurfacing
NASA Astrophysics Data System (ADS)
Thomsen, Sharon L.; Baldwin, Bonnie; Chi, Eric; Ellard, Jeff; Schwartz, Jon A.
Pulsed carbon-dioxide laser skin resurfacing is a purportedly 'non-thermal' procedure enjoying wide application as a cosmetic treatment for skin wrinkles. Treatment success has been based on clinical assessments of skin smoothness. Skin lesions (1 cm2) created by one, two or three superimposed carbon-dioxide laser passes were placed on the backs of 28 'fuzzy' Harlan Sprague Dawley rats. The variable laser irradiation parameters included measured energies ranging from 112 to 387/pulse with pulse widths of 65 and 125 microseconds and a repetition rate of 8 Hz. The square, flat laser beam measured 3 mm2 at the focal point. The lesions were collected from 0 to 10 days after treatment for qualitative and quantitative histopathology. Thermal damage and treatment effect tended to increase in severity and, to a lesser extent, depth with increased delivery parameters. In acute lesions, the vacuolated and fragmented, desiccated and thermally coagulated epidermis was partially removed exposing the underlying thermally coagulated dermal collagen and cells. Epidermal and dermal necrosis and slough occurred between 24 to 72 hours after treatment. Epithelial regeneration originated from the adnexa and the lesion edges. Dermal fibrous scar formation began at 5 days below the regenerated epidermis and became more prominent at 7 and 10 days.
Klebsiella pneumoniae Is Able to Trigger Epithelial-Mesenchymal Transition Process in Cultured Airway Epithelial Cells
Leone, Laura; Mazzetta, Francesca; Martinelli, Daniela; Valente, Sabatino; Alimandi, Maurizio; Raffa, Salvatore; Santino, Iolanda
The ability of some bacterial pathogens to activate Epithelial-Mesenchymal Transition normally is a consequence of the persistence of a local chronic inflammatory response or depends on a direct interaction of the pathogens with the host epithelial cells. In this study we monitored the abilities of the K. pneumoniae to activate the expression of genes related to EMT-like processes and the occurrence of phenotypic changes in airway epithelial cells during the early steps of cell infection. We describe changes in the production of intracellular reactive oxygen species and increased HIF-1α mRNA expression in cells exposed to K. pneumoniae infection. We also describe the upregulation of a set of transcription factors implicated in the EMT processes, such as Twist, Snail and ZEB, indicating that the morphological changes of epithelial cells already appreciable after few hours from the K. pneumoniae infection are tightly regulated by the activation of transcriptional pathways, driving epithelial cells to EMT. These effects appear to be effectively counteracted by resveratrol, an antioxidant that is able to exert a sustained scavenging of the intracellular ROS. This is the first report indicating that strains of K. pneumoniae may promote EMT-like programs through direct interaction with epithelial cells without the involvement of inflammatory cells. PMID:26812644
Effects of CO/sub 2/ laser irradiation on gingiva
Rossmann, J.A.; Gottlieb, S.; Koudelka, B.M.; McQuade, M.J.
A CO/sub 2/ laser (Coherent Medical Model 400) was used to irradiate the gingival tissue of a cynomolgous monkey to determine laser effects on the epithelium and underlying connective tissue. A focal length of 400 mm and a 10-watt power setting at 0.2- and 0.5-second exposure was used. Biopsy results indicated that a 0.2-second duration of CO/sub 2/ laser irradiation was inadequate to completely de-epithelialize the gingival tissue. A 0.5-second exposure exhibited complete epithelial destruction with little or no disturbance of the underlying connective tissue layer and viable connective tissue 1.0 mm below the impact site.
Gourley, P.L.; Gourley, M.F.
Laser technology has advanced dramatically and is an integral part of today's healthcare delivery system. Lasers are used in the laboratory analysis of human blood samples and serve as surgical tools that kill, burn or cut tissue. Recent semiconductor microtechnology has reduced the size o f a laser to the size of a biological cell or even a virus particle. By integrating these ultra small lasers with biological systems, it is possible to create micro-electrical mechanical systems that may revolutionize health care delivery.
Lewis, Owen; Stogran, Edmund M.
Laser apparatus is described wherein an active laser element, such as the disc of a face-pumped laser, is mounted in a housing such that the weight of the element is supported by glass spheres which fill a chamber defined in the housing between the walls of the housing and the edges of the laser element. The uniform support provided by the spheres enable the chamber and the pump side of the laser element to be sealed without affecting the alignment or other optical properties of the laser element. Cooling fluid may be circulated through the sealed region by way of the interstices between the spheres. The spheres, and if desired also the cooling fluid may contain material which absorbs radiation at the wavelength of parasitic emissions from the laser element. These parasitic emissions enter the spheres through the interface along the edge surface of the laser element and it is desirable that the index of refraction of the spheres and cooling fluid be near the index of refraction of the laser element. Thus support, cooling, and parasitic suppression functions are all accomplished through the use of the arrangement.
Early, James W.; Lester, Charles S.
In the apparatus of the invention, a first excitation laser or other excitation light source capable of producing alternating beams of light having different wavelengths is used in tandem with one or more ignitor lasers to provide a compact, durable, engine deployable fuel ignition laser system. Reliable fuel ignition is provided over a wide range of fuel conditions by using the single remote excitation light source for pumping one or more small lasers located proximate to one or more fuel combustion zones with alternating wavelengths of light.
Emerging roles for renal primary cilia in epithelial repair.
Deane, James A; Ricardo, Sharon D
Primary cilia are microscopic sensory antennae that cells in many vertebrate tissues use to gather information about their environment. In the kidney, primary cilia sense urine flow and are essential for the maintenance of epithelial architecture. Defects of this organelle cause the cystic kidney disease characterized by epithelial abnormalities. These findings link primary cilia to the regulation of epithelial differentiation and proliferation, processes that must be precisely controlled during epithelial repair in the kidney. Here, we consider likely roles for primary cilium-based signaling during responses to renal injury and ensuing epithelial repair processes.
Multimegajoule laser design. [Glass lasers
Manes, K.R.; Ozarski, R.G.; Hagen, W.F.; Holzrichtr, J.F.
New technologies make multimegajoule glass lasers economically feasible. We have devised new laser architectures using harmonic switchout, target-plane holographic injection, phase conjugation, continuous apodization, and higher amplifier efficiencies. Our plan for building a multimegajoule laser for a recurring cost under $300 million relies on the following manufacturing economies of scale: high-volume glass production, rapid harmonic-crystal growth, capacitor sizing and packing to increase energy capacity, and part standardization.
Heterodyne laser spectroscopy system
Wyeth, Richard W.; Paisner, Jeffrey A.; Story, Thomas
A heterodyne laser spectroscopy system utilizes laser heterodyne techniques for purposes of laser isotope separation spectroscopy, vapor diagnostics, processing of precise laser frequency offsets from a reference frequency and the like, and provides spectral analysis of a laser beam.
Heterodyne laser spectroscopy system
Wyeth, Richard W.; Paisner, Jeffrey A.; Story, Thomas
A heterodyne laser spectroscopy system utilizes laser heterodyne techniques for purposes of laser isotope separation spectroscopy, vapor diagnostics, processing of precise laser frequency offsets from a reference frequency, and provides spectral analysis of a laser beam.
Neutrophil-induced injury of rat pulmonary alveolar epithelial cells.
Simon, R H; DeHart, P D; Todd, R F
The damage to pulmonary alveolar epithelial cells that occurs in many inflammatory conditions is thought to be caused in part by phagocytic neutrophils. To investigate this process, we exposed monolayers of purified rat alveolar epithelial cells to stimulated human neutrophils and measured cytotoxicity using a 51Cr-release assay. We found that stimulated neutrophils killed epithelial cells by a process that did not require neutrophil-generated reactive oxygen metabolites. Pretreatment of neutrophils with an antibody (anti-Mo1) that reduced neutrophil adherence to epithelial cells limited killing. Although a variety of serine protease inhibitors partially inhibited cytotoxicity, we found that neutrophil cytoplasts, neutrophil lysates, neutrophil-conditioned medium, purified azurophilic or specific granule contents, and purified human neutrophil elastase did not duplicate the injury. We conclude that stimulated neutrophils can kill alveolar epithelial cells in an oxygen metabolite-independent manner. Tight adherence of stimulated neutrophils to epithelial cell monolayers appears to promote epithelial cell killing. Images PMID:3771800
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Matrigel-induced tubular morphogenesis of human eccrine sweat gland epithelial cells.
Lei, Xia; Liu, Bo; Wu, Jinjin; Lu, Yuangang; Yang, Yadong
Human eccrine sweat glands are tubule-structured glands of the skin that are vital in thermoregulation, secretion, and excretion of water and electrolytes. A study of tubular morphogenesis in vitro would facilitate the development of a tissue engineering model for eccrine sweat glands and other tubule-structured glands. Matrigel, a basement membrane matrix, has been shown to promote differentiation and morphogenesis of many different cell types, including tubular cells. This study investigated the growth, differentiation, and tubular morphogenesis of human eccrine sweat gland epithelial cells cultured in Matrigel. Human eccrine gland epithelial cells were isolated and cultured in vitro. The cell growth in Matrigel was evidenced by the formation of cell clusters, which were observed under an inverted microscope. The internal structure of the cell clusters was further investigated by hematoxylin-eosin (HE) staining and confocal laser scanning microscopy (CLSM) of propidium iodide-stained nuclei. The results demonstrated that although on a plastic surface or in a collagen gel the cells could not form tubular structures, they formed tubular structures when cultured in Matrigel. Consequently, we conclude that Matrigel can promote tubular morphogenesis of human eccrine sweat gland epithelial cells.
Active Pedicle Epithelial Flap Transposition Combined with Amniotic Membrane Transplantation for Treatment of Nonhealing Corneal Ulcers
Zhang, Ting; Wang, Yuexin; Jia, Yanni; Liu, Dongle; Li, Suxia; Shi, Weiyun
Introduction. The objective was to evaluate the efficacy of active pedicle epithelial flap transposition combined with amniotic membrane transplantation (AMT) in treating nonhealing corneal ulcers. Material and Methods. Eleven patients (11 eyes) with nonhealing corneal ulcer who underwent the combined surgery were included. Postoperatively, ulcer healing time was detected by corneal fluorescein staining. Visual acuity, intraocular pressure, surgical complications, and recurrence were recorded. Corneal status was inspected by the laser scanning confocal microscopy and anterior segment optical coherence tomography (AS-OCT). Results. The primary diseases were herpes simplex keratitis (8 eyes), corneal graft ulcer (2 eyes), and Stevens-Johnson syndrome (1 eye). All epithelial flaps were intact following surgery, without shedding or displacement. Mean ulcer healing time was 10.8 ± 3.1 days, with a healing rate of 91%. Vision significantly improved from 1.70 to 0.82 log MAR (P = 0.001). A significant decrease in inflammatory cell infiltration and corneal stromal edema was revealed 2 months postoperatively by confocal microscopy and AS-OCT. Corneal ulcer recurred in 1 eye. None of the patients developed major complications. Conclusion. Active pedicle epithelial flap transposition combined with AMT is a simple and effective treatment for nonhealing corneal ulcers. PMID:27830086
Collective epithelial migration drives kidney repair after acute injury.
Palmyre, Aurélien; Lee, Jeongeun; Ryklin, Gennadiy; Camarata, Troy; Selig, Martin K; Duchemin, Anne-Laure; Nowak, Paul; Arnaout, M Amin; Drummond, Iain A; Vasilyev, Aleksandr
Acute kidney injury (AKI) is a common and significant medical problem. Despite the kidney's remarkable regenerative capacity, the mortality rate for the AKI patients is high. Thus, there remains a need to better understand the cellular mechanisms of nephron repair in order to develop new strategies that would enhance the intrinsic ability of kidney tissue to regenerate. Here, using a novel, laser ablation-based, zebrafish model of AKI, we show that collective migration of kidney epithelial cells is a primary early response to acute injury. We also show that cell proliferation is a late response of regenerating kidney epithelia that follows cell migration during kidney repair. We propose a computational model that predicts this temporal relationship and suggests that cell stretch is a mechanical link between migration and proliferation, and present experimental evidence in support of this hypothesis. Overall, this study advances our understanding of kidney repair mechanisms by highlighting a primary role for collective cell migration, laying a foundation for new approaches to treatment of AKI.
Scott, Jill R.; Tremblay, Paul L.
A laser device includes a virtual source configured to aim laser energy that originates from a true source. The virtual source has a vertical rotational axis during vertical motion of the virtual source and the vertical axis passes through an exit point from which the laser energy emanates independent of virtual source position. The emanating laser energy is collinear with an orientation line. The laser device includes a virtual source manipulation mechanism that positions the virtual source. The manipulation mechanism has a center of lateral pivot approximately coincident with a lateral index and a center of vertical pivot approximately coincident with a vertical index. The vertical index and lateral index intersect at an index origin. The virtual source and manipulation mechanism auto align the orientation line through the index origin during virtual source motion.
Growth of corneal epithelial cells over in situ therapeutic contact lens after simple limbal epithelial transplantation (SLET).
Bhalekar, Swapnil; Sangwan, Virender S; Basu, Sayan
An 11-year-old boy underwent simple limbal epithelial transplantation (SLET) from the healthy right eye to his left eye for total limbal stem cell deficiency. One month later, corneal surface epithelialised and whitish plaques overlying the transplants were seen inferiorly. Those plaques were adherent to the surface of the contact lens and underlying corneal surface had smooth elevations. Similar findings were noted in a 23-year man following cyanoacrylate glue application for corneal perforation. On histological and immunohistochemical analysis, cells lining the contact lenses were identified as corneal epithelial cells. These cases illustrate epithelial cell growth on the contact lens and epithelial hyperplasia on corresponding surface of the cornea. Exorbitant proliferation of the epithelial cells may be owing to young age; therefore, early contact lens removal after SLET in young age, can possibly avoid epithelial hyperplasia. This also reiterates the possibility of using contact lens as a scaffold to grow epithelial cells.
Transcriptional regulation of epithelial-mesenchymal transition.
Teng, Yingqi; Zeisberg, Michael; Kalluri, Raghu
It has become increasingly obvious that the notion of a terminally differentiated cell is likely a simplified concept. Epithelial-mesenchymal transition (EMT), during which epithelial cells assume a mesenchymal phenotype, is a key event occurring during normal development and pathological processes. Multiple extracellular stimuli and transcriptional regulators can trigger EMT, but how such distinct signaling pathways orchestrate the complex cellular events that facilitate EMT is not well understood. In this issue of the JCI, Venkov et al. report on their examination of fibroblasts resulting from EMT and describe a novel protein-DNA complex that is essential for transcription of fibroblast-specific protein 1 (FSP1) and sufficient to induce early EMT events (see the related article beginning on page 482). Collectively, their results suggest that this complex is an important regulator of the EMT transcriptome.
Transcriptional regulation of epithelial-mesenchymal transition
Teng, Yingqi; Zeisberg, Michael; Kalluri, Raghu
It has become increasingly obvious that the notion of a terminally differentiated cell is likely a simplified concept. Epithelial-mesenchymal transition (EMT), during which epithelial cells assume a mesenchymal phenotype, is a key event occurring during normal development and pathological processes. Multiple extracellular stimuli and transcriptional regulators can trigger EMT, but how such distinct signaling pathways orchestrate the complex cellular events that facilitate EMT is not well understood. In this issue of the JCI, Venkov et al. report on their examination of fibroblasts resulting from EMT and describe a novel protein-DNA complex that is essential for transcription of fibroblast-specific protein 1 (FSP1) and sufficient to induce early EMT events (see the related article beginning on page 482). Collectively, their results suggest that this complex is an important regulator of the EMT transcriptome. PMID:17273552
Extensive Focal Epithelial Hyperplasia: A Case Report
Mansouri, Zahra; Bakhtiari, Sedigheh; Noormohamadi, Robab
Focal epithelial hyperplasia (FEH) or Heck's disease is a rare viral infection of the oral mucosa caused by human papilloma virus especially subtypes 13 or 32. The frequency of this disease varies widely from one geographic region and ethnic groups to another. This paper reports an Iranian case of extensive focal epithelial hyperplasia. A 35-year-old man with FEH is described, in whom the lesions had persisted for more than 25 years. The lesion was diagnosed according to both clinical and histopathological features. Dental practitioner should be aware of these types of lesions and histopathological examination together and a careful clinical observation should be carried out for a definitive diagnosis. PMID:26351501
Mechanics of epithelial tissue homeostasis and morphogenesis.
Guillot, Charlène; Lecuit, Thomas
Epithelia are robust tissues that support the structure of embryos and organs and serve as effective barriers against pathogens. Epithelia also chemically separate different physiological environments. These vital functions require tight association between cells through the assembly of junctions that mechanically stabilize the tissue. Remarkably, epithelia are also dynamic and can display a fluid behavior. Cells continuously die or divide, thereby allowing functional tissue homeostasis. Epithelial cells can change shape or intercalate as tissues deform during morphogenesis. We review the mechanical basis of tissue robustness and fluidity, with an emphasis on the pivotal role of junction dynamics. Tissue fluidity emerges from local active stresses acting at cell interfaces and allows the maintenance of epithelial organization during morphogenesis and tissue renewal.
Epithelial Proliferation on Curved Toroidal Surfaces
NASA Astrophysics Data System (ADS)
Chang, Ya-Wen; Cruz, Ricardo; Fragkopoulos, Alexandros; Marquez, Samantha; Garcia, Andres; Fernandez-Nieves, Alberto
Cellular environment influences a multitude of cellular functions by providing chemical and physical signals that modulate cell behavior, dynamics, development, and eventually survival. In strongly interacting epithelial cells, cells coordinate their behavior to respond to mechanical constraints in 2D. Local differences in tissue tension has also been shown to impact cell reproduction within an epithelial-cell sheet. Much less is known about how cells respond to out-of-plane curvatures. Here, we describe the proliferation of MDCK on toroidal hydrogel substrates, which unlike spheres or planes, have regions of both positive and negative Gaussian curvature. Additionally, the range of curvatures can be controlled by varying the size and aspect ratio of the torus, allowing us to quantify the relation between substrate curvature and cell proliferation.
Effect of suction on macular thickness and retinal nerve fiber layer thickness during LASIK used femtosecond laser and Moria M2 microkeratome
Zhang, Jing; Zhou, Yue-Hua
AIM To compare the effect of suction on the macular thickness and retinal nerve fiber layer (RNFL) thickness during laser in situ keratomileusis (LASIK) used Ziemer FEMTO LDV femtosecond laser (Ziemer group) and Moria M2 automated microkeratome (Moria group) for flap creation. METHODS Fourier-domain optical coherence tomography (FD-OCT) was used to measure macular thickness, ganglion cell complex thickness and (RNFL) thickness of 204 eyes of 102 patients with the Ziemer femtosecond laser (102 eyes) and the Moria M2 microkeratome (102 eyes) before surgery and 30min; 1, 3d; 1wk; 1, 3mo; 1y after surgery. RESULTS The average foveal thickness and parafoveal retinal thickness 30min after the surgery were statistically more than that before surgery (Ziemer P<0.001, P=0.003 and Moria P=0.001, P=0.006) and the effect was less in the Ziemer group than that in the Moria group (P all<0.05). The ganglion cell complex thickness was not significantly changed in both groups (P all>0.05). The RNFL thickness was statistically less 30min after surgery in both groups (P=0.014, P<0.001), but the influence was less in Ziemer group than that in Moria group (P=0.038). However, the RNFL thickness had recovered to the preoperative level only 1d after surgery. CONCLUSION The suction of femtosecond laser and mechanical microkeratome led to the increase in macular central fovea thickness and the decrease in RNFL thickness values at the early stage after LASIK. The effect of suction on macular and the RNFL thicknesses in Ziemer group is smaller than that in Moria group. PMID:26309879
Focal epithelial hyperplasia in a Turkish family.
Gökahmetoğlu, Selma; Ferahbaş, Ayten; Canöz, Özlem
Focal epithelial hyperplasia (FEH) is a benign proliferative condition that is more frequently found in children of certain ethnic groups. Human papillomavirus (HPV) 13 and 32 genotypes has been consistently detected in these lesions. In this study a daughter, mother and father had FEH, and HPV 13 was shown by sequence analysis in the lesions of these patients. Cryotherapy was applied to the lesions and the lesions improved, but did not recover properly. In conclusion, HPV genotyping should be performed in FEH cases.
Extensive focal epithelial hyperplasia: case report.
Durso, Braz Campos; Pinto, José Marcelo Vargas; Jorge, Jacks; de Almeida, Oslei Paes
Focal epithelial hyperplasia (FEH) is a rare benign lesion caused by human papillomavirus subtype 13 or 32. The condition occurs in numerous populations and ethnic groups. A higher incidence in close communities and among family members indicates infectious pathogenesis. A 21-year-old woman with FEH is described, in whom the lesions had persisted for 10 years. A literature review is also presented, with emphasis on manifestations in the oral mucosa and histopathological features.
High throughput laser processing
Harley, Gabriel; Pass, Thomas; Cousins, Peter John; Viatella, John
A solar cell is formed using a solar cell ablation system. The ablation system includes a single laser source and several laser scanners. The laser scanners include a master laser scanner, with the rest of the laser scanners being slaved to the master laser scanner. A laser beam from the laser source is split into several laser beams, with the laser beams being scanned onto corresponding wafers using the laser scanners in accordance with one or more patterns. The laser beams may be scanned on the wafers using the same or different power levels of the laser source.
Fate-mapping of the epithelial seam during palatal fusion rules out epithelial-mesenchymal transformation.
Vaziri Sani, Forugh; Hallberg, Kristina; Harfe, Brian D; McMahon, Andrew P; Linde, Anders; Gritli-Linde, Amel
During palatogenesis, fusion of the palatine shelves is a crucial event, the failure of which results in the birth defect, cleft palate. The fate of the midline epithelial seam (MES), which develops transiently upon contact of the two palatine shelves, is still strongly debated. Three major mechanisms underlying the regression of the MES upon palatal fusion have been proposed: (1) apoptosis has been evidenced by morphological and molecular criteria; (2) epithelial-mesenchymal transformation has been suggested based on ultrastructural and lipophilic dye cell labeling observations; and (3) migration of MES cells toward the oral and nasal areas has been proposed following lipophilic dye cell labeling. To verify whether epithelial-mesenchymal transformation of MES cells takes place during murine palatal fusion, we used the Cre/lox system to genetically mark Sonic hedgehog- and Keratin-14-expressing palatal epithelial cells and to identify their fate in vivo. Our analyses provide conclusive evidence that rules out the occurrence of epithelial-mesenchymal transformation of MES cells.
CUX1/Wnt signaling regulates Epithelial Mesenchymal Transition in EBV infected epithelial cells
Malizia, Andrea P.; Lacey, Noreen; Walls, Dermot; Egan, Jim J.; Doran, Peter P.
Idiopathic pulmonary fibrosis (IPF) is a refractory and lethal interstitial lung disease characterized by alveolar epithelial cells apoptosis, fibroblast proliferation and extra-cellular matrix protein deposition. EBV, localised to alveolar epithelial cells of pulmonary fibrosis patients is associated with a poor prognosis. A strategy based on microarray-differential gene expression analysis to identify molecular drivers of EBV-associated lung fibrosis was utilized. Alveolar epithelial cells were infected with EBV to identify genes whose expression was altered following TGF{beta}1-mediated lytic phase. EBV lytic reactivation by TGF{beta}1 drives a selective alteration in CUX1 variant (a) (NCBI accession number NM{sub 1}81552) expression, inducing activation of non-canonical Wnt pathway mediators, implicating it in Epithelial Mesenchymal Transition (EMT), the molecular event underpinning scar production in tissue fibrosis. The role of EBV in EMT can be attenuated by antiviral strategies and inhibition of Wnt signaling by using All-Trans Retinoic Acids (ATRA). Activation of non-canonical Wnt signaling pathway by EBV in epithelial cells suggests a novel mechanism of EMT via CUX1 signaling. These data present a framework for further description of the link between infectious agents and fibrosis, a significant disease burden.
Characteristics and pharmacological regulation of epithelial Na+ channel (ENaC) and epithelial Na+ transport.
Marunaka, Yoshinori
Epithelial Na(+) transport participates in control of various body functions and conditions: e.g., homeostasis of body fluid content influencing blood pressure, control of amounts of fluids covering the apical surface of alveolar epithelial cells at appropriate levels for normal gas exchange, and prevention of bacterial/viral infection. Epithelial Na(+) transport via the transcellular pathway is mediated by the entry step of Na(+) across the apical membrane via Epithelial Na(+) Channel (ENaC) located at the apical membrane, and the extrusion step of Na(+) across the basolateral membrane via the Na(+),K(+)-ATPase located at the basolateral membrane. The rate-limiting step of the epithelial Na(+) transport via the transcellular pathway is generally recognized to be the entry step of Na(+) across the apical membrane via ENaC. Thus, up-/down-regulation of ENaC essentially participates in regulatory systems of blood pressure and normal gas exchange. Amount of ENaC-mediated Na(+) transport is determined by the number of ENaCs located at the apical membrane, activity (open probability) of individual ENaC located at the apical membrane, single channel conductance of ENaC located at the apical membrane, and driving force for the Na(+) entry via ENaCs across the apical membrane. In the present review article, I discuss the characteristics of ENaC and how these factors are regulated.
Epithelial-mesenchymal transitions of bile duct epithelial cells in primary hepatolithiasis.
Zhao, Lijin; Yang, Rigao; Cheng, Long; Wang, Maijian; Jiang, Yan; Wang, Shuguang
The purpose of this study was to explore the role of epithelial-mesenchymal transition in the pathogenesis of hepatolithiasis. Thirty-one patients with primary hepatolithiasis were enrolled in this study. Expressions of E-cadherin, alpha-catenin, alpha-SMA, vimentin, S100A4, TGF-beta1 and P-smad2/3 in hepatolithiasis bile duct epithelial cells were examined by immunohistochemistry staining. The results showed that the expressions of the epithelial markers E-cadherin and alpha-catenin were frequently lost in hepatolithiasis (32.3% and 25.9% of cases, respectively), while the mesenchymal markers vimentin, alpha-SMA and S100A4 were found to be present in hepatolithiasis (35.5%, 29.0%, and 32.3% of cases, respectively). The increased mesenchymal marker expression was correlated with decreased epithelial marker expression. The expressions of TGF-beta1 and P-smad2/3 in hepatolithiasis were correlated with the expression of S100A4. These data indicate that TGF-beta1-mediated epithelial-mesenchymal transition might be involved in the formation of hepatolithiasis.
Epithelial-mesenchymal, mesenchymal-epithelial, and endothelial-mesenchymal transitions in malignant tumors: An update
Gurzu, Simona; Turdean, Sabin; Kovecsi, Attila; Contac, Anca Otilia; Jung, Ioan
Epithelial-to-mesenchymal transition (EMT) represents conversion of an epithelial cell in an elongated cell with mesenchymal phenotype, which can occur in physiologic and pathologic processes such as embryogenesis (type 1 EMT), wound healing and/or fibrosis (type 2 EMT) and malignant tumors (type 3 EMT). The proliferation rate, metastasizing and recurrence capacity, as also the individualized response at chemotherapics, in both epithelial and mesenchymal malignant tumors is known to be influenced by reversible switch between EMT and mesenchymal-to-epithelial transition (MET). Although much research work has already been done in these fields, the specific molecular pathways of EMT, relating to the tumor type and tumor localization, are yet to be elucidated. In this paper, based on the literature and personal experience of the authors, an update in the field of EMT vs MET in epithelial and mesenchymal tumors is presented. The authors tried to present the latest data about the particularities of these processes, and also of the so-called endothelial-to-mesenchymal transition, based on tumor location. The EMT-angiogenesis link is discussed as a possible valuable parameter for clinical follow-up and targeted therapeutic oncologic management. The paper begins with presentation of the basic aspects of EMT, its classification and assessment possibilities, and concludes with prognostic and therapeutic perspectives. The particularities of EMT and MET in gastric and colorectal carcinomas, pancreatic cancer, hepatocellular and cholangiocarcinomas, and lung, breast and prostate cancers, respectively in sarcomas and gastrointestinal stromal tumors are presented in detail. PMID:25984514
Intermediate filaments: a role in epithelial polarity
Oriolo, Andrea S.; Wald, Flavia A.; Ramsauer, Victoria P.; Salas, Pedro J.I.
Intermediate filaments have long been considered mechanical components of the cell that provide resistance to deformation stress. Practical experimental problems, including insolubility, lack of good pharmacological antagonists, and the paucity of powerful genetic models, have handicapped the research of other functions. In single-layered epithelial cells, keratin intermediate filaments are cortical, either apically polarized or apico-lateral. This review analyzes phenotypes of genetic manipulations of simple epithelial cell keratins in mice and C. elegans that strongly suggest a role of keratins in apico-basal polarization and membrane traffic. Published evidence that intermediate filaments can act as scaffolds for proteins involved in membrane traffic and signaling is also discussed. Such a scaffolding function would generate a highly polarized compartment within the cytoplasm of simple epithelial cells. While in most cases mechanistic explanations for the keratin-null or overexpression phenotypes are still missing, it is hoped investigators will be encouraged to study these as yet poorly understood functions of intermediate filaments. PMID:17425955
Epithelial-mesenchymal transition in gastric cancer
Huang, Lei; Wu, Ruo-Lin; Xu, A-Man
Gastric cancer (GC) is one of the most common malignancies worldwide with poor prognosis for lack of early detection and effective treatment modalities. The significant influence of tumor microenvironment on malignant cells has been extensively investigated in this targeted-therapy era. Epithelial-mesenchymal transition (EMT) is a highly conserved and fundamental process that is critical for embryogenesis and some other pathophysiological processes, especially tumor genesis and progression. Aberrant gastric EMT activation could endow gastric epithelial cells with increased mesenchymal characteristics and less epithelial features, and promote cancer cell stemness, initiation, invasion, metastasis, and chemo-resistance with cellular adhesion molecules especially E-cadherin concomitantly repressed, which allows tumor cells to disseminate and spread throughout the body. Some pathogens, stress, and hypoxia could induce and aggravate GC via EMT, which is significantly correlated with prognosis. GC EMT is modulated by diverse micro-environmental, membrane, and intracellular cues, and could be triggered by various overexpressed transcription factors, which are downstream of several vital cross-talking signaling pathways including TGF-β, Wnt/β-catenin, Notch, etc. microRNAs also contribute significantly to GC EMT modulation. There are currently some agents which could suppress GC EMT, shedding light on novel anti-malignancy strategies. Investigating potential mechanisms modulating GC cell EMT and discovering novel EMT regulators will further elucidate GC biology, and may provide new biomarkers for early GC detection and potentially efficient targets for preventative and curative anti-GC intervention approaches to prevent local and distant invasions. PMID:26807164
Lung epithelial branching program antagonizes alveolar differentiation.
Chang, Daniel R; Martinez Alanis, Denise; Miller, Rachel K; Ji, Hong; Akiyama, Haruhiko; McCrea, Pierre D; Chen, Jichao
Mammalian organs, including the lung and kidney, often adopt a branched structure to achieve high efficiency and capacity of their physiological functions. Formation of a functional lung requires two developmental processes: branching morphogenesis, which builds a tree-like tubular network, and alveolar differentiation, which generates specialized epithelial cells for gas exchange. Much progress has been made to understand each of the two processes individually; however, it is not clear whether the two processes are coordinated and how they are deployed at the correct time and location. Here we show that an epithelial branching morphogenesis program antagonizes alveolar differentiation in the mouse lung. We find a negative correlation between branching morphogenesis and alveolar differentiation temporally, spatially, and evolutionarily. Gain-of-function experiments show that hyperactive small GTPase Kras expands the branching program and also suppresses molecular and cellular differentiation of alveolar cells. Loss-of-function experiments show that SRY-box containing gene 9 (Sox9) functions downstream of Fibroblast growth factor (Fgf)/Kras to promote branching and also suppresses premature initiation of alveolar differentiation. We thus propose that lung epithelial progenitors continuously balance between branching morphogenesis and alveolar differentiation, and such a balance is mediated by dual-function regulators, including Kras and Sox9. The resulting temporal delay of differentiation by the branching program may provide new insights to lung immaturity in preterm neonates and the increase in organ complexity during evolution.
In vitro ultraviolet–induced damage in human corneal, lens, and retinal pigment epithelial cells
Youn, Hyun-Yi; Sivak, Jacob G.; Jones, Lyndon W.
Purpose The purpose was to develop suitable in vitro methods to detect ocular epithelial cell damage when exposed to UV radiation, in an effort to evaluate UV-absorbing ophthalmic biomaterials. Methods Human corneal epithelial cells (HCEC), lens epithelial cells (HLEC), and retinal pigment epithelial cells (ARPE-19) were cultured and Ultraviolet A/Ultraviolet B (UVA/UVB) blocking filters and UVB-only blocking filters were placed between the cells and a UV light source. Cells were irradiated with UV radiations at various energy levels with and without filter protections. Cell viability after exposure was determined using the metabolic dye alamarBlue and by evaluating for changes in the nuclei, mitochondria, membrane permeability, and cell membranes of the cells using the fluorescent dyes Hoechst 33342, rhodamine 123, calcein AM, ethidium homodimer-1, and annexin V. High-resolution images of the cells were taken with a Zeiss 510 confocal laser scanning microscope. Results The alamarBlue assay results of UV-exposed cells without filters showed energy level-dependent decreases in cellular viability. However, UV treated cells with 400 nm LP filter protection showed the equivalent viability to untreated control cells at all energy levels. Also, UV irradiated cells with 320 nm LP filter showed lower cell viability than the unexposed control cells, yet higher viability than UV-exposed cells without filters in an energy level-dependent manner. The confocal microscopy results also showed that UV radiation can cause significant dose-dependent degradations of nuclei and mitochondria in ocular cells. The annexin V staining also showed an increased number of apoptotic cells after UV irradiation. Conclusions The findings suggest that UV-induced HCEC, HLEC, and ARPE-19 cell damage can be evaluated by bioassays that measure changes in the cell nuclei, mitochondria, cell membranes, and cell metabolism, and these assay methods provide a valuable in vitro model for evaluating the
Fairer, George M.; Boernge, James M.; Harris, David W.; Campbell, DeWayne A.; Tuttle, Gene E.; McKeown, Mark H.; Beason, Steven C.
The laser goniometer is an apparatus which permits an operator to sight along a geologic feature and orient a collimated lamer beam to match the attitude of the feature directly. The horizontal orientation (strike) and the angle from horizontal (dip), are detected by rotary incremental encoders attached to the laser goniometer which provide a digital readout of the azimuth and tilt of the collimated laser beam. A microprocessor then translates the square wave signal encoder outputs into an ASCII signal for use by data recording equipment.
NASA Technical Reports Server (NTRS)
Rom, F. E.; Putre, H. A.
The use of an earth-based high-power laser beam to provide energy for earth-launched rocket vehicle is investigated. The laser beam energy is absorbed in an opaque propellant gas and is converted to high-specific-impulse thrust by expanding the heated propellant to space by means of a nozzle. This laser propulsion scheme can produce specific impulses of several thousand seconds. Payload to gross-weight fractions about an order of magnitude higher than those for conventional chemical earth-launched vehicles appear possible. There is a potential for a significant reduction in cost per payload mass in earth orbit.
Robinson, C.P.; Jensen, R.J.; Davis, W.C.; Sullivan, J.A.
This patent relates to a laser system wherein reaction products from the detonation of a condensed explosive expand to form a gaseous medium with low translational temperature but high vibration population. Thermal pumping of the upper laser level and de-excitation of the lower laser level occur during the expansion, resulting in a population inversion. The expansion may be free or through a nozzle as in a gas-dynamic configuration. In one preferred embodiment, the explosive is such that its reaction products are CO$sub 2$ and other species that are beneficial or at least benign to CO$sub 2$ lasing. (auth)
Regulation of Epithelial-Mesenchymal Transition by Transmission of Mechanical Stress through Epithelial Tissues.
Gjorevski, Nikolce; Boghaert, Eline; Nelson, Celeste M
Epithelial-mesenchymal transition (EMT) is a phenotypic shift wherein epithelial cells lose or loosen attachments to their neighbors and assume a mesenchymal-like morphology. EMT drives a variety of developmental processes, but may also be adopted by tumor cells during neoplastic progression. EMT is regulated by both biochemical and physical signals from the microenvironment, including mechanical stress, which is increasingly recognized to play a major role in development and disease progression. Biological systems generate, transmit and concentrate mechanical stress into spatial patterns; these gradients in mechanical stress may serve to spatially pattern developmental and pathologic EMTs. Here we review how epithelial tissues generate and respond to mechanical stress gradients, and highlight the mechanisms by which mechanical stress regulates and patterns EMT.
Polarized fibronectin secretion induced by adenosine regulates bacterial–epithelial interaction in human intestinal epithelial cells
Fibronectin (FN) is a multifunctional protein that plays important roles in many biological processes including cell adhesion and migration, wound healing and inflammation. Cellular FNs are produced by a wide variety of cell types including epithelial cells, which secrete them and often organize them into extensive extracellular matrices at their basal surface. However, regulation of FN synthesis and the polarity of FN secretion by intestinal epithelial cells have not been investigated. In the present study we investigated the role of adenosine, whose levels are up-regulated during inflammation, in modulating FN synthesis, the polarity of FN secretion and the downstream effects of the secreted FN. Polarized monolayers of T84 cells were used as an intestinal epithelial model. Adenosine added to either the apical or basolateral aspect of the cells led to a time- and dose-dependent accumulation of FN in the culture supernatants, polarized to the apical compartment and reached maximal levels 24 h after apical or basolateral addition of adenosine. Confocal microscopy confirmed that FN localized to the apical domain of model intestinal epithelial cells stimulated with apical or basolateral adenosine. The induction of FN was significantly down-regulated in response to the adenosine receptor antagonist alloxazine and was inhibited by cycloheximide. Moreover, adenosine increased FN promoter activity (3.5-fold compared with unstimulated controls) indicating that FN induction is, in part, transcriptionally regulated. Interestingly, we demonstrated that adenosine, as well as apical FN, significantly enhanced the adherence and invasion of Salmonella typhimurium into cultured epithelial cells. In summary, we have shown for the first time that FN, a classic extracellular matrix protein, is secreted into the apical compartment of epithelial cells in response to adenosine. FN may be a critical host factor that modulates adherence and invasion of bacteria, thus playing a key role
Secretion of IL-13 by airway epithelial cells enhances epithelial repair via HB-EGF.
Allahverdian, Sima; Harada, Norihiro; Singhera, Gurpreet K; Knight, Darryl A; Dorscheid, Delbert R
Inappropriate repair after injury to the epithelium generates persistent activation, which may contribute to airway remodeling. In the present study we hypothesized that IL-13 is a normal mediator of airway epithelial repair. Mechanical injury of confluent airway epithelial cell (AEC) monolayers induced expression and release of IL-13 in a time-dependent manner coordinate with repair. Neutralizing of IL-13 secreted from injured epithelial cells by shIL-13Ralpha2.FC significantly reduced epithelial repair. Moreover, exogenous IL-13 enhanced epithelial repair and induced epidermal growth factor receptor (EGFR) phosphorylation. We examined secretion of two EGFR ligands, epidermal growth factor (EGF) and heparin-binding EGF (HB-EGF), after mechanical injury. Our data showed a sequential release of the EGF and HB-EGF by AEC after injury. Interestingly, we found that IL-13 induces HB-EGF, but not EGF, synthesis and release from AEC. IL-13-induced EGFR phosphorylation and the IL-13-reparative effect on AEC are mediated via HB-EGF. Finally, we demonstrated that inhibition of EGFR tyrosine kinase activity by tyrphostin AG1478 increases IL-13 release after injury, suggesting negative feedback between EGFR and IL-13 during repair. Our data, for the first time, showed that IL-13 plays an important role in epithelial repair, and that its effect is mediated through the autocrine release of HB-EGF and activation of EGFR. Dysregulation of EGFR phosphorylation may contribute to a persistent repair phenotype and chronically increased IL-13 release, and in turn result in airway remodeling.
Use of the carbon dioxide laser in guided tissue regeneration wound healing in the beagle dog
NASA Astrophysics Data System (ADS)
Rossmann, Jeffrey A.; Parlar, Ates; Abdel-Ghaffar, Khaled A.; El-Khouli, Amr M.; Israel, Michael
The concept of guided tissue regeneration (GTR) allowing cells from the periodontal ligament and alveolar bone to repopulate the treated root surface has shown the ability to obtain periodontal new attachment. Healing studies have also shown that conventional GTR therapy still does not exclude all the epithelium. This epithelial proliferation apically interferes with the establishment of the new connective tissue attachment to the root surface. The objective of this research study was to examine whether controlled de-epithelialization with the carbon dioxide laser during the healing phase after periodontal surgery, would retard the apical migration of the epithelium and thereby enhance the results obtained through guided tissue regeneration. Eight beagle dogs were used, the experimental side received de-epithelialization with the CO2 laser in conjunction with flap reflection and surgically created buccal osseous defects. Selected defects on each side were treated with ePTFE periodontal membranes. The laser de-epithelialization was repeated every 10 days until removal of the membranes. The control side received the same surgical treatment without laser application. This experimental design allowed histologic study of the new attachment obtained in defects treated with flap debridement with or without laser de-epithelialization and with or without ePTFE membranes. A statistical analysis was performed on the histometric data from 48 teeth in the 8 dogs after 4 months of healing. The results showed significant amounts of new attachment obtained from all four treatment modalities with no statistically significant differences for any one treatment. However, the trend towards enhanced regeneration with the combined treatment of laser and membrane vs. membrane alone or debridement alone was evident. The histologic analysis revealed a significant amount of newly formed `fat cementum' seen only on the laser treated teeth. This feature was the most remarkable finding of the
Anti-Apoptotic Gene Delivery with cyclo-(d-Trp-Tyr) Peptide Nanotube via Eye Drop Following Corneal Epithelial Debridement
Lee, Yu-Hsing; Chang, Shwu-Fen; Liaw, Jiahorng
Corneal keratocyte apoptosis triggered by cornel debridement is one mechanism of corneal disorders. In this study, the feasibility of cyclo-(d-Trp-Tyr) peptide nanotubes (PNTs) as carriers of caspase 3 silence shRNA delivery was assessed. A model of epithelial injury by epithelial debridement was applied to investigate the feasibility of PNTs as gene delivery carriers on corneal injury. First, the PNTs were found within 2 μm in length and 300 nm in width by an atomic force microscope and confocal laser microscope system. Plasmid DNAs were observed to be associated with PNTs by atomic force microscope and confocal laser scanning microscope. The plasmids were associated with tyrosine of PNTs with a binding constant of 2.7 × 108 M−1. The stability of plasmid DNA with PNTs against the DNase was found at 60 min. Using thioflavin T pre-stained PNTs on the corneal eye drop delivery, the distribution of PNTs was in the epithelial and stroma regions. After corneal debridement, the rhodamine-labeled plasmid DNA and thioflavin T pre-stained PNTs were also delivered and could be observed in the stroma of cornea. PNTs complexed with anti-apoptotic plasmid caspase 3 silencing shRNA eye drop delivery decreased 41% of caspase 3 activity after the first dose by caspase 3 activity and Western blot analysis. PMID:26193308
Hassmann-Poznańska, Elzbieta; Skotnicka, Bozena
The aim of the study was assessment of the qualities of laser-assisted myringotomy (LAM) as a treatment for acute and secretory otitis media. Laser-assisted myringotomy was performed on 65 children (113 ears) mean age 6.2 years diagnosed with secretory otitis media (80%), recurrent secretory otitis media (11%) and acute otitis media (9%). Myringotomy was performed under general anesthesia using the OtoLAM device (ESC/Sharplan, Israel). In 64 ears pressure equalisation tubes were inserted after fenestration of the tympanic membrane with laser. Adenoidectomy alone or with tonsillectomy was performed at the same time in 51 cases. Laser tympanostomies remained patent for 7-32 days. All tympanostomies healed with no noticeable scarring. LAM appears to be a safe, and easy to performed, alternative technique in the treatment of otitis media.
Smit, W.A.; Boskma, P.
Unrestricted laser fusion offers nations an opportunity to circumvent arms control agreements and develop thermonuclear weapons. Early laser weapons research sought a clean radiation-free bomb to replace the fission bomb, but this was deceptive because a fission bomb was needed to trigger the fusion reaction and additional radioactivity was induced by generating fast neutrons. As laser-implosion experiments focused on weapons physics, simulating weapons effects, and applications for new weapons, the military interest shifted from developing a laser-ignited hydrogen bomb to more sophisticated weapons and civilian applications for power generation. Civilian and military research now overlap, making it possible for several countries to continue weapons activities and permitting proliferation of nuclear weapons. These countries are reluctant to include inertial confinement fusion research in the Non-Proliferation Treaty. 16 references. (DCK)
Abercrombie, K.R.; Shiels, D.; Rash, T.
This paper describes an invention of a pressure measuring instrument which uses laser radiation to sense the pressure in an enclosed environment by means of measuring the change in refractive index of a gas - which is pressure dependent.
lasers that are optically modified to produce high beam quality at reduced power levels for precision drilling and trepanning. * Nd:YAG lasers with...a smooth, dross-free cut face while the marking consists of a series of precisely placed shallow pits where surface finish and dross are not usually...neodymium:yttrium-aluminum-garnet (Nd:YAG) pulsed cutting data because the technique is considered vital in meeting the detailed precision cutting
NASA Technical Reports Server (NTRS)
Amoco Laser Company, a subsidiary of Amoco Corporation, has developed microlasers for the commercial market based on a JPL concept for optical communications over interplanetary distances. Lasers emit narrow, intense beams of light or other radiation. The beams transmit communication signals, drill, cut or melt materials or remove diseased body tissue. The microlasers cover a broad portion of the spectrum, and performance is improved significantly. Current applications include medical instrumentation, color separation equipment, telecommunications, etc.
Polarized protein transport and lumen formation during epithelial tissue morphogenesis.
Blasky, Alex J; Mangan, Anthony; Prekeris, Rytis
One of the major challenges in biology is to explain how complex tissues and organs arise from the collective action of individual polarized cells. The best-studied model of this process is the cross talk between individual epithelial cells during their polarization to form the multicellular epithelial lumen during tissue morphogenesis. Multiple mechanisms of apical lumen formation have been proposed. Some epithelial lumens form from preexisting polarized epithelial structures. However, de novo lumen formation from nonpolarized cells has recently emerged as an important driver of epithelial tissue morphogenesis, especially during the formation of small epithelial tubule networks. In this review, we discuss the latest findings regarding the mechanisms and regulation of de novo lumen formation in vitro and in vivo.
Polarized Protein Transport and Lumen Formation During Epithelial Tissue Morphogenesis
Blasky, Alex J.; Mangan, Anthony; Prekeris, Rytis
One of the major challenges in biology is to explain how complex tissues and organs arise from the collective action of individual polarized cells. The best-studied model of this process is the cross talk between individual epithelial cells during their polarization to form the multicellular epithelial lumen during tissue morphogenesis. Multiple mechanisms of apical lumen formation have been proposed. Some epithelial lumens form from preexisting polarized epithelial structures. However, de novo lumen formation from nonpolarized cells has recently emerged as an important driver of epithelial tissue morphogenesis, especially during the formation of small epithelial tubule networks. In this review, we discuss the latest findings regarding the mechanisms and regulation of de novo lumen formation in vitro and in vivo. PMID:26359775
Cell Division Drives Epithelial Cell Rearrangements during Gastrulation in Chick.
Firmino, Joao; Rocancourt, Didier; Saadaoui, Mehdi; Moreau, Chloe; Gros, Jerome
During early embryonic development, cells are organized as cohesive epithelial sheets that are continuously growing and remodeled without losing their integrity, giving rise to a wide array of tissue shapes. Here, using live imaging in chick embryo, we investigate how epithelial cells rearrange during gastrulation. We find that cell division is a major rearrangement driver that powers dramatic epithelial cell intercalation events. We show that these cell division-mediated intercalations, which represent the majority of epithelial rearrangements within the early embryo, are absolutely necessary for the spatial patterning of gastrulation movements. Furthermore, we demonstrate that these intercalation events result from overall low cortical actomyosin accumulation within the epithelial cells of the embryo, which enables dividing cells to remodel junctions in their vicinity. These findings uncover a role for cell division as coordinator of epithelial growth and remodeling that might underlie various developmental, homeostatic, or pathological processes in amniotes.
Control of local immunity by airway epithelial cells.
Weitnauer, M; Mijošek, V; Dalpke, A H
The lung is ventilated by thousand liters of air per day. Inevitably, the respiratory system comes into contact with airborne microbial compounds, most of them harmless contaminants. Airway epithelial cells are known to have innate sensor functions, thus being able to detect microbial danger. To avoid chronic inflammation, the pulmonary system has developed specific means to control local immune responses. Even though airway epithelial cells can act as proinflammatory promoters, we propose that under homeostatic conditions airway epithelial cells are important modulators of immune responses in the lung. In this review, we discuss epithelial cell regulatory functions that control reactivity of professional immune cells within the microenvironment of the airways and how these mechanisms are altered in pulmonary diseases. Regulation by epithelial cells can be divided into two mechanisms: (1) mediators regulate epithelial cells' innate sensitivity in cis and (2) factors are produced that limit reactivity of immune cells in trans.
Epithelial Anion Transport as Modulator of Chemokine Signaling
Schnúr, Andrea; Hegyi, Péter; Rousseau, Simon; Lukacs, Gergely L.; Veit, Guido
The pivotal role of epithelial cells is to secrete and absorb ions and water in order to allow the formation of a luminal fluid compartment that is fundamental for the epithelial function as a barrier against environmental factors. Importantly, epithelial cells also take part in the innate immune system. As a first line of defense they detect pathogens and react by secreting and responding to chemokines and cytokines, thus aggravating immune responses or resolving inflammatory states. Loss of epithelial anion transport is well documented in a variety of diseases including cystic fibrosis, chronic obstructive pulmonary disease, asthma, pancreatitis, and cholestatic liver disease. Here we review the effect of aberrant anion secretion with focus on the release of inflammatory mediators by epithelial cells and discuss putative mechanisms linking these transport defects to the augmented epithelial release of chemokines and cytokines. These mechanisms may contribute to the excessive and persistent inflammation in many respiratory and gastrointestinal diseases. PMID:27382190
NASA Technical Reports Server (NTRS)
The principal method of dealing with coronary artery blockage is bypass surgery. A non-surgical alternative available to some patients is balloon angioplasty. For several years, medical researchers have been exploring another alternative that would help a wider circle of patients than the balloon treatment and entail less risk than bypass surgery. A research group is on the verge of an exciting development: laser angioplasty with a 'cool' type of laser, called an excimer laser, that does not damage blood vessel walls and offers non-surgical cleansing of clogged arteries with extraordinary precision. The system is the Dymer 200+ Excimer Laser Angioplasty System, developed by Advanced Intraventional Systems. Used in human clinical tests since 1987, the system is the first fully integrated 'cool' laser capable of generating the requisite laser energy and delivering the energy to target arteries. Thirteen research hospitals in the U.S. have purchased Dymer 200+ systems and used them in clinical trials in 121 peripheral and 555 coronary artery cases. The success rate in opening blocked coronary arteries is 85 percent, with fewer complications than in balloon angioplasty. Food and Drug Administration approval for the system is hoped for in the latter part of 1990. * Advanced Intraventional Systems became Spectranetics in 1994 and discontinued the product.
Yang, Weijian; Adair Gerke, Stephen; Wei Ng, Kar; Rao, Yi; Chase, Christopher; Chang-Hasnain, Connie J.
Cavity optomechanics explores the interaction between optical field and mechanical motion. So far, this interaction has relied on the detuning between a passive optical resonator and an external pump laser. Here, we report a new scheme with mutual coupling between a mechanical oscillator supporting the mirror of a laser and the optical field generated by the laser itself. The optically active cavity greatly enhances the light-matter energy transfer. In this work, we use an electrically-pumped vertical-cavity surface-emitting laser (VCSEL) with an ultra-light-weight (130 pg) high-contrast-grating (HCG) mirror, whose reflectivity spectrum is designed to facilitate strong optomechanical coupling, to demonstrate optomechanically-induced regenerative oscillation of the laser optomechanical cavity. We observe >550 nm self-oscillation amplitude of the micromechanical oscillator, two to three orders of magnitude larger than typical, and correspondingly a 23 nm laser wavelength sweep. In addition to its immediate applications as a high-speed wavelength-swept source, this scheme also offers a new approach for integrated on-chip sensors. PMID:26333804
Chahine algorithm to invert light scattering spectroscopy of epithelial dysplasia
NASA Astrophysics Data System (ADS)
Wang, Qing-Hua; Li, Zhen-Hua; Lai, Jian-Cheng; He, An-Zhi
To perceive the epithelial dysplasia from the light scattering spectroscopy (LSS) is an inverse problem, which can be transformed into the inversion of the size distribution of epithelial-cell nuclei. Based on the simulation of single polarized LSS for epithelial-cell nuclei, Chahine algorithm is adopted to retrieve the size distribution. Numerical results show that Chahine algorithm has high inversion precision for both single-peaked and bimodal models, which implies the potential to increase diagnostic resolution of LSS.
... or contact lenses. Your eye surgeon uses a laser beam to reshape the cornea. This type of ... the 20s. Refractive surgical procedures for nearsightedness include: Laser-assisted in-situ keratomileusis (LASIK). With this procedure, ...
... curvature of your cornea. Refractive surgery methods include: Laser-assisted in-situ keratomileusis ( LASIK). LASIK is a ... cornea. Then your eye surgeon uses an excimer laser to remove layers from the center of your ...
... are variable and may not be long lasting. Laser-assisted in-situ keratomileusis (LASIK). With this procedure, ... your cornea. He or she then uses a laser to remove inner layers of your cornea to ...
Cisplatin and Flavopiridol in Treating Patients With Advanced Ovarian Epithelial Cancer or Primary Peritoneal Cancer
Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Primary Peritoneal Cavity Cancer
Engineering epithelial-stromal interactions in vitro for toxicology assessment.
Belair, David G; Abbott, Barbara D
Crosstalk between epithelial and stromal cells drives the morphogenesis of ectodermal organs during development and promotes normal mature adult epithelial tissue homeostasis. Epithelial-stromal interactions (ESIs) have historically been examined using mammalian models and ex vivo tissue recombination. Although these approaches have elucidated signaling mechanisms underlying embryonic morphogenesis processes and adult mammalian epithelial tissue function, they are limited by the availability of tissue, low throughput, and human developmental or physiological relevance. In this review, we describe how bioengineered ESIs, using either human stem cells or co-cultures of human primary epithelial and stromal cells, have enabled the development of human in vitro epithelial tissue models that recapitulate the architecture, phenotype, and function of adult human epithelial tissues. We discuss how the strategies used to engineer mature epithelial tissue models in vitro could be extrapolated to instruct the design of organotypic culture models that can recapitulate the structure of embryonic ectodermal tissues and enable the in vitro assessment of events critical to organ/tissue morphogenesis. Given the importance of ESIs towards normal epithelial tissue development and function, such models present a unique opportunity for toxicological screening assays to incorporate ESIs to assess the impact of chemicals on mature and developing epidermal tissues.
Malondialdehyde-acetaldehyde adducts decrease bronchial epithelial wound repair.
Wyatt, Todd A; Kharbanda, Kusum K; Tuma, Dean J; Sisson, Joseph H; Spurzem, John R
Most people who abuse alcohol are cigarette smokers. Previously, we have shown that malondialdehyde, an inflammation product of lipid peroxidation, and acetaldehyde, a component of both ethanol metabolism and cigarette smoke, form protein adducts that stimulate protein kinase C (PKC) activation in bronchial epithelial cells. We have also shown that PKC can regulate bronchial epithelial cell wound repair. We hypothesize that bovine serum albumin adducted with malondialdehyde and acetaldehyde (BSA-MAA) decreases bronchial epithelial cell wound repair via binding to scavenger receptors on bronchial epithelial cells. To test this, confluent monolayers of bovine bronchial epithelial cells were grown in serum-free media prior to wounding the cells. Bronchial epithelial cell wound closure was inhibited in a dose-dependent manner (up to 60%) in the presence of BSA-MAA than in media treated cells (Laboratory of Human Carcinogenesis [LHC]-9-Roswell Park Memorial Institute [RPMI]). The specific scavenger receptor ligand, fucoidan, also stimulated PKC activation and decreased wound repair. Pretreatment with fucoidan blocked malondialdehyde-acetaldehyde binding to bronchial epithelial cells. When bronchial epithelial cells were preincubated with a PKC alpha inhibitor, Gö 6976, the inhibition of wound closure by fucoidan and BSA-MAA was blocked. Western blot demonstrated the presence of several scavenger receptors on bronchial epithelial cell membranes, including SRA, SRBI, SRBII, and CD36. Scavenger receptor-mediated activation of PKC alpha may function to reduce wound healing under conditions of alcohol and cigarette smoke exposure where malondialdehyde-acetaldehyde adducts may be present.
Interaction with epithelial cells modifies airway macrophage response to ozone.
Bauer, Rebecca N; Müller, Loretta; Brighton, Luisa E; Duncan, Kelly E; Jaspers, Ilona
The initial innate immune response to ozone (O3) in the lung is orchestrated by structural cells, such as epithelial cells, and resident immune cells, such as airway macrophages (Macs). We developed an epithelial cell-Mac coculture model to investigate how epithelial cell-derived signals affect Mac response to O3. Macs from the bronchoalveolar lavage (BAL) of healthy volunteers were cocultured with the human bronchial epithelial (16HBE) or alveolar (A549) epithelial cell lines. Cocultures, Mac monocultures, and epithelial cell monocultures were exposed to O3 or air, and Mac immunophenotype, phagocytosis, and cytotoxicity were assessed. Quantities of hyaluronic acid (HA) and IL-8 were compared across cultures and in BAL fluid from healthy volunteers exposed to O3 or air for in vivo confirmation. We show that Macs in coculture had increased markers of alternative activation, enhanced cytotoxicity, and reduced phagocytosis compared with Macs in monoculture that differed based on coculture with A549 or 16HBE. Production of HA by epithelial cell monocultures was not affected by O3, but quantities of HA in the in vitro coculture and BAL fluid from volunteers exposed in vivo were increased with O3 exposure, indicating that O3 exposure impairs Mac regulation of HA. Together, we show epithelial cell-Mac coculture models that have many similarities to the in vivo responses to O3, and demonstrate that epithelial cell-derived signals are important determinants of Mac immunophenotype and response to O3.
Ursodeoxycholic acid attenuates colonic epithelial secretory function
Kelly, Orlaith B; Mroz, Magdalena S; Ward, Joseph B J; Colliva, Carolina; Scharl, Michael; Pellicciari, Roberto; Gilmer, John F; Fallon, Padraic G; Hofmann, Alan F; Roda, Aldo; Murray, Frank E; Keely, Stephen J
Dihydroxy bile acids, such as chenodeoxycholic acid (CDCA), are well known to promote colonic fluid and electrolyte secretion, thereby causing diarrhoea associated with bile acid malabsorption. However, CDCA is rapidly metabolised by colonic bacteria to ursodeoxycholic acid (UDCA), the effects of which on epithelial transport are poorly characterised. Here, we investigated the role of UDCA in the regulation of colonic epithelial secretion. Cl− secretion was measured across voltage-clamped monolayers of T84 cells and muscle-stripped sections of mouse or human colon. Cell surface biotinylation was used to assess abundance/surface expression of transport proteins. Acute (15 min) treatment of T84 cells with bilateral UDCA attenuated Cl− secretory responses to the Ca2+ and cAMP-dependent secretagogues carbachol (CCh) and forskolin (FSK) to 14.0 ± 3.8 and 40.2 ± 7.4% of controls, respectively (n= 18, P < 0.001). Investigation of the molecular targets involved revealed that UDCA acts by inhibiting Na+/K+-ATPase activity and basolateral K+ channel currents, without altering their cell surface expression. In contrast, intraperitoneal administration of UDCA (25 mg kg−1) to mice enhanced agonist-induced colonic secretory responses, an effect we hypothesised to be due to bacterial metabolism of UDCA to lithocholic acid (LCA). Accordingly, LCA (50–200 μm) enhanced agonist-induced secretory responses in vitro and a metabolically stable UDCA analogue, 6α-methyl-UDCA, exerted anti-secretory actions in vitro and in vivo. In conclusion, UDCA exerts direct anti-secretory actions on colonic epithelial cells and metabolically stable derivatives of the bile acid may offer a new approach for treating intestinal diseases associated with diarrhoea. PMID:23507881
Laser Physics and Laser Spectroscopy.
effect which limits the power throughout of a device; terbium qallium garnet (TGG), a Faraday isolator material; potassium niobate (KNbO 31 a nonlinear...extending the range of materials grown in fiber form. Two materials to be emphasized are terbium gallium garnet for optical isolators and potassium niobate...for doubling gallium arsenide diode lasers. References 1. R.H. Stolen, "Fiber Raman Lasers", Fiber and Integrated Optics, 3 (1980). 2. E. Ipoen and
[Characteristics of the morphologic changes in an experimental suppurative wound of the perimandibular soft tissues treated by some types of laser radiation].
Poliakova, V V; Shargorodskiĭ, A G; Bazhenov, S M; Naperstnikov, V V
In rabbits isolated CO2 and He-Ne laser irradiation promotes early granulation of wounds and accelerates epithelialization with more complete restitution of the regenerated skin organ specificity. The best effect was achieved when combined laser irradiation was applied. This was further corroborated by the immunohistochemical investigation.
Multifocal epithelial hyperplasia: report of 3 cases.
Tehranchinia, Zohreh; Mozafari, Nikoo; Barikbin, Behrooz; Nadji, Seyed Alireza
Multifocal epithelial hyperplasia (MEH) is a rare disorder characterized by multiple painless discrete and soft flattened papules on the oral mucosa. It is caused by human papilloma virus 13 and 32. The frequency of this disease varies widely from one geographic region to another. Generally it is very rare in Asia. Herein we report 3 Iranian cases with oral lesions, which showed clinical and histopathological characteristics of MEH disease. Two of them were siblings and HPV13 was detected in one of the patients.
Active Tensile Modulus of an Epithelial Monolayer
NASA Astrophysics Data System (ADS)
Vincent, Romaric; Bazellières, Elsa; Pérez-González, Carlos; Uroz, Marina; Serra-Picamal, Xavier; Trepat, Xavier
A general trait of cell monolayers is their ability to exert contractile stresses on their surroundings. The scaling laws that link such contractile stresses with the size and geometry of constituent cells remain largely unknown. In this Letter, we show that the active tension of an epithelial monolayer scales linearly with the size of the constituent cells, a surprisingly simple relationship. The slope of this relationship defines an active tensile modulus, which depends on the concentration of myosin and spans more than 2 orders of magnitude across cell types and molecular perturbations.
Early Cancer Detection at the Epithelial Surface.
Rogalla, Stephan; Contag, Christopher H
Malignant neoplastic lesions derived from epithelial tissue, carcinomas, account for 80% to 100% of all human cancers including some of the most deadly diseases such as cervical and non-small cell lung cancer. Many of these carcinomas present at readily accessible epithelial surfaces offering unique detection opportunities. Effective clinical management of carcinomas is enabled by early detection, at a time when full surgical resection is possible and before invasion of adjacent tissue or significant intravasation into blood vessels leading to metastasis. Good prognosis with long-term disease-free survival is more likely after early detection when progression is limited. At present, detection of carcinomas at epithelial surfaces largely relies on routine inspection with the naked eye (e.g., skin and oropharynx) or simple white light tools (e.g., cervix and colon). Emerging optical tools based on differential refraction, absorption, reflection, scattering, or fluorescence of carcinomas relative to normal tissues enable label-free visualization of neoplasia. However, the differences in intrinsic optical properties of normal and malignant tissues can be subtle, and relying on these may lead to high miss rates. Enhanced optical contrast offered by molecularly targeted agents can be used to improve early detection; and given that optical imaging and sensing tools can be readily combined, integrated systems that image over a range of scales, or detect multiple parameters, can be developed to aid in early detection. Diagnosis is, at present, made by histologic examination of tissue biopsies after identification of suspicious lesions. Miniature and handheld microscopic imaging tools have recently been developed, and integration of these tools with wide-field optical surveillance devices offers both rapid detection and confirmatory histologic examination at the point-of-care, that can provide guidance for biopsy and/or resection. A wide variety of targeted probe strategies
Characterization of Human Mammary Epithelial Stem Cells
Appendix……………………………………………………………………………… 11 Eirew,P., Stingl,J., Raouf,A., Turashvili,G., Aparicio ,S., Emerman,J.T., and Eaves,C.J. A method for... Aparicio , Joanne Emerman and Connie Eaves. A method for quantifying normal human mammary epithelial stem cells with in vivo regenerative ability...Abstracts Peter Eirew, John Stingl, Afshin Raouf, Gulisa Turshvili, Sam Aparicio , Joanne Emerman and Connie Eaves, "Identification of Human Mammary
Characterization of Human Mammary Epithelial Stem Cells
breast is highly expressed by luminal epithelial cells and is less expressed by basal cells19,20. In contrast, CD49f (a6 integrin) has an inverse pattern...mouse stretched on its back. The hose and nose cone from the anesthetic vaporizer are securely attached to one side of the plate, and a heated pad is...the mouse by a nose cone. Check that the mouse has reached surgical anesthesia by loss of pedal withdrawal reflex . ! cautIon Institutional review
Transcriptional Landscape of Glomerular Parietal Epithelial Cells
Gharib, Sina A.; Pippin, Jeffrey W.; Ohse, Takamoto; Pickering, Scott G.; Krofft, Ronald D.; Shankland, Stuart J.
Very little is known about the function of glomerular parietal epithelial cells (PECs). In this study, we performed genome-wide expression analysis on PEC-enriched capsulated vs. PEC-deprived decapsulated rat glomeruli to determine the transcriptional state of PECs under normal conditions. We identified hundreds of differentially expressed genes that mapped to distinct biologic modules including development, tight junction, ion transport, and metabolic processes. Since developmental programs were highly enriched in PECs, we characterized several of their candidate members at the protein level. Collectively, our findings confirm that PECs are multifaceted cells and help define their diverse functional repertoire. PMID:25127402
Topographic confinement of epithelial clusters induces epithelial-to-mesenchymal transition in compliant matrices
Nasrollahi, Samila; Pathak, Amit
Epithelial cells disengage from their clusters and become motile by undergoing epithelial-to-mesenchymal transition (EMT), an essential process for both embryonic development and tumor metastasis. Growing evidence suggests that high extracellular matrix (ECM) stiffness induces EMT. In reality, epithelial clusters reside in a heterogeneous microenvironment whose mechanical properties vary not only in terms of stiffness, but also topography, dimensionality, and confinement. Yet, very little is known about how various geometrical parameters of the ECM might influence EMT. Here, we adapt a hydrogel-microchannels based matrix platform to culture mammary epithelial cell clusters in ECMs of tunable stiffness and confinement. We report a previously unidentified role of ECM confinement in EMT induction. Surprisingly, confinement induces EMT even in the cell clusters surrounded by a soft matrix, which otherwise protects against EMT in unconfined environments. Further, we demonstrate that stiffness-induced and confinement-induced EMT work through cell-matrix adhesions and cytoskeletal polarization, respectively. These findings highlight that both the structure and the stiffness of the ECM can independently regulate EMT, which brings a fresh perspective to the existing paradigm of matrix stiffness-dependent dissemination and invasion of tumor cells. PMID:26728047
Epithelial Notch signaling regulates lung alveolar morphogenesis and airway epithelial integrity
Tsao, Po-Nien; Matsuoka, Chisa; Wei, Shu-Chen; Sato, Atsuyasu; Sato, Susumu; Hasegawa, Koichi; Chen, Hung-kuan; Ling, Thai-Yen; Mori, Munemasa; Cardoso, Wellington V.; Morimoto, Mitsuru
Abnormal enlargement of the alveolar spaces is a hallmark of conditions such as chronic obstructive pulmonary disease and bronchopulmonary dysplasia. Notch signaling is crucial for differentiation and regeneration and repair of the airway epithelium. However, how Notch influences the alveolar compartment and integrates this process with airway development remains little understood. Here we report a prominent role of Notch signaling in the epithelial–mesenchymal interactions that lead to alveolar formation in the developing lung. We found that alveolar type II cells are major sites of Notch2 activation and show by Notch2-specific epithelial deletion (Notch2cNull) a unique contribution of this receptor to alveologenesis. Epithelial Notch2 was required for type II cell induction of the PDGF-A ligand and subsequent paracrine activation of PDGF receptor-α signaling in alveolar myofibroblast progenitors. Moreover, Notch2 was crucial in maintaining the integrity of the epithelial and smooth muscle layers of the distal conducting airways. Our data suggest that epithelial Notch signaling regulates multiple aspects of postnatal development in the distal lung and may represent a potential target for intervention in pulmonary diseases. PMID:27364009
Heterogeneity and stochastic growth regulation of biliary epithelial cells dictate dynamic epithelial tissue remodeling
Kamimoto, Kenji; Kaneko, Kota; Kok, Cindy Yuet-Yin; Okada, Hajime; Miyajima, Atsushi; Itoh, Tohru
Dynamic remodeling of the intrahepatic biliary epithelial tissue plays key roles in liver regeneration, yet the cellular basis for this process remains unclear. We took an unbiased approach based on in vivo clonal labeling and tracking of biliary epithelial cells in the three-dimensional landscape, in combination with mathematical simulation, to understand their mode of proliferation in a mouse liver injury model where the nascent biliary structure formed in a tissue-intrinsic manner. An apparent heterogeneity among biliary epithelial cells was observed: whereas most of the responders that entered the cell cycle upon injury exhibited a limited and tapering growth potential, a select population continued to proliferate, making a major contribution in sustaining the biliary expansion. Our study has highlighted a unique mode of epithelial tissue dynamics, which depends not on a hierarchical system driven by fixated stem cells, but rather, on a stochastically maintained progenitor population with persistent proliferative activity. DOI: http://dx.doi.org/10.7554/eLife.15034.001 PMID:27431614
Topographic confinement of epithelial clusters induces epithelial-to-mesenchymal transition in compliant matrices
NASA Astrophysics Data System (ADS)
Nasrollahi, Samila; Pathak, Amit
Epithelial cells disengage from their clusters and become motile by undergoing epithelial-to-mesenchymal transition (EMT), an essential process for both embryonic development and tumor metastasis. Growing evidence suggests that high extracellular matrix (ECM) stiffness induces EMT. In reality, epithelial clusters reside in a heterogeneous microenvironment whose mechanical properties vary not only in terms of stiffness, but also topography, dimensionality, and confinement. Yet, very little is known about how various geometrical parameters of the ECM might influence EMT. Here, we adapt a hydrogel-microchannels based matrix platform to culture mammary epithelial cell clusters in ECMs of tunable stiffness and confinement. We report a previously unidentified role of ECM confinement in EMT induction. Surprisingly, confinement induces EMT even in the cell clusters surrounded by a soft matrix, which otherwise protects against EMT in unconfined environments. Further, we demonstrate that stiffness-induced and confinement-induced EMT work through cell-matrix adhesions and cytoskeletal polarization, respectively. These findings highlight that both the structure and the stiffness of the ECM can independently regulate EMT, which brings a fresh perspective to the existing paradigm of matrix stiffness-dependent dissemination and invasion of tumor cells.
Epithelial--mesenchymal and mesenchymal--epithelial transitions in carcinoma progression.
Hugo, Honor; Ackland, M Leigh; Blick, Tony; Lawrence, Mitchell G; Clements, Judith A; Williams, Elizabeth D; Thompson, Erik W
Like a set of bookends, cellular, molecular, and genetic changes of the beginnings of life mirror those of one of the most common cause of death--metastatic cancer. Epithelial to mesenchymal transition (EMT) is an important change in cell phenotype which allows the escape of epithelial cells from the structural constraints imposed by tissue architecture, and was first recognized by Elizabeth Hay in the early to mid 1980's to be a central process in early embryonic morphogenesis. Reversals of these changes, termed mesenchymal to epithelial transitions (METs), also occur and are important in tissue construction in normal development. Over the last decade, evidence has mounted for EMT as the means through which solid tissue epithelial cancers invade and metastasize. However, demonstrating this potentially rapid and transient process in vivo has proven difficult and data connecting the relevance of this process to tumor progression is still somewhat limited and controversial. Evidence for an important role of MET in the development of clinically overt metastases is starting to accumulate, and model systems have been developed. This review details recent advances in the knowledge of EMT as it occurs in breast development and carcinoma and prostate cancer progression, and highlights the role that MET plays in cancer metastasis. Finally, perspectives from a clinical and translational viewpoint are discussed.
Use of a microsecond Er:YAG laser in laryngeal surgery reduces collateral thermal injury in comparison to superpulsed CO2 laser.
Böttcher, Arne; Jowett, Nathan; Kucher, Stanislav; Reimer, Rudolph; Schumacher, Udo; Knecht, Rainald; Wöllmer, Wolfgang; Münscher, Adrian; Dalchow, Carsten V
Despite causing significant thermocoagulative insult, use of the carbon dioxide (CO2) laser is considered gold standard in surgery for early stage larynx carcinoma. Limited attention has been paid to the use of the erbium:yttrium-aluminium-garnet (Er:YAG) laser in laryngeal surgery as a means to reduce thermal tissue injury. The objective of this study is to compare the extent of thermal injury and precision of vocal fold incisions made using microsecond Er:YAG and superpulsed CO2 lasers. In the optics laboratory ex vivo porcine vocal folds were incised using Er:YAG and CO2 lasers. Lateral epithelial and subepithelial thermal damage zones and cutting gap widths were histologically determined. Environmental scanning electron microscopy (ESEM) images were examined for signs of carbonization. Temperature rise during Er:YAG laser incisions was determined using infrared thermography (IRT). In comparison to the CO2 laser, Er:YAG laser incisions showed significantly decreased epithelial (236.44 μm) and subepithelial (72.91 μm) damage zones (p < 0.001). Cutting gaps were significantly narrower for CO2 (878.72 μm) compared to Er:YAG (1090.78 μm; p = 0.027) laser. ESEM revealed intact collagen fibres along Er:YAG laser cutting edges without obvious carbonization, in comparison to diffuse carbonization and tissue melting seen for CO2 laser incisions. IRT demonstrated absolute temperature rise below 70 °C for Er:YAG laser incisions. This study has demonstrated significantly reduced lateral thermal damage zones with wider basal cutting gaps for vocal fold incisions made using Er:YAG laser in comparison to those made using CO2 laser.
... this page: //medlineplus.gov/ency/patientinstructions/000905.htm Laser therapy for cancer To use the sharing features ... Lasers are also used on the skin. How Laser Therapy is Used Laser therapy can be used ...
Weil, Bradley S.; Wetherington, Jr., Grady R.
Laser beam monitoring systems include laser-transparent plates set at an angle to the laser beam passing therethrough and light sensor for detecting light reflected from an object on which the laser beam impinges.
Laser Physics and Laser-Tissue Interaction
Welch, A. J.; Torres, Jorge H.; Cheong, Wai-Fung
Within the last few years, lasers have gained increasing use in the management of cardiovascular disease, and laser angioplasty has become a widely performed procedure. For this reason, a basic knowledge of lasers and their applications is essential to vascular surgeons, cardiologists, and interventional radiologists. To elucidate some fundamental concepts regarding laser physics, we describe how laser light is generated and review the properties that make lasers useful in medicine. We also discuss beam profile and spotsize, as well as dosimetric specifications for laser angioplasty. After considering laser-tissue interaction and light propagation in tissue, we explain how the aforementioned concepts apply to direct laser angioplasty and laser-balloon angioplasty. An understanding of these issues should prove useful not only in performing laser angioplasty but in comparing the reported results of various laser applications. (Texas Heart Institute Journal 1989;16:141-9) PMID:15227198
Fabrication of transplantable corneal epithelial and oral mucosal epithelial cell sheets using a novel temperature-responsive closed culture device.
Nakajima, Ryota; Kobayashi, Toyoshige; Kikuchi, Tetsutaro; Kitano, Yuriko; Watanabe, Hiroya; Mizutani, Manabu; Nozaki, Takayuki; Senda, Naoko; Saitoh, Kazuo; Takagi, Ryo; Yamato, Masayuki; Okano, Teruo; Takeda, Shizu
Temperature-responsive culture surfaces make it possible to harvest transplantable carrier-free cell sheets. Here, we applied temperature-responsive polymer for polycarbonate surfaces with previously developed closed culture devices for an automated culture system in order to fabricate transplantable stratified epithelial cell sheets. Histological and immunohistochemical analyses and colony-forming assays revealed that corneal epithelial and oral mucosal epithelial cell sheets could be harvested with the temperature-responsive closed culture devices. The results were similar to those obtained using temperature-responsive culture inserts. These results indicate that the novel temperature-responsive closed culture device is useful for fabricating transplantable stratified epithelial cell sheets.
Volumetric imaging of oral epithelial neoplasia by MPM-SHGM: epithelial connective tissue interface (Conference Presentation)
NASA Astrophysics Data System (ADS)
Pal, Rahul; Yang, Jinping; Qiu, Suimin; Resto, Vicente; McCammon, Susan; Vargas, Gracie
The majority of oral cancers are comprised of oral squamous cell carcinoma in which neoplastic epithelial cells invade across the epithelial connective tissue interface (ECTI). Invasion is preceded by a multi-component process including epithelial hyperproliferation, loss of cell polarity, and remodeling of the extracellular matrix. Multiphoton Autofluorescence Microscopy (MPAM) and Second Harmonic Generation Microscopy (SHGM) show promise for revealing indicators of neoplasia. In particular, volumetric imaging by these methods can reveal aspects of the 3D microstructure that are not possible by other methods and which could both further our understanding of neoplastic transformation and be explored for development of diagnostic approaches in this disease having only 55% 5-year survival rate. MPAM-SHG were applied to reveal the 3D structure of the critical ECTI interface that plays an integral part toward invasion. Epithelial dysplasia was induced in an established hamster model. MPAM-SHGM was applied to lesion sites, using 780 nm excitation (450-600nm emission) for autofluroescence of cellular and extracellular components; 840 nm using 420 nm bandpass filter for SHG. The ECTI surface was identified as the interface at which SHG signal began following the epithelium and was modeled as a 3D surface using Matlab. ECTI surface area and cell features at sites of epithelial expansion where ECTI was altered were measured; Imaged sites were biopsied and processed for histology. ROC analysis using ECTI image metrics indicated the ability to delineate normal from neoplasia with high sensitivity and specificity and it is noteworthy that inflammation did not significantly alter diagnostic potential of MPAM-SHGM .
NASA Astrophysics Data System (ADS)
Tajima, T.; Nakajima, K.; Mourou, G.
The fundamental idea of Laser Wakefield Acceleration (LWFA) is reviewed. An ultrafast intense laser pulse drives coherent wakefield with a relativistic amplitude robustly supported by the plasma. While the large amplitude of wakefields involves collective resonant oscillations of the eigenmode of the entire plasma electrons, the wake phase velocity ˜ c and ultrafastness of the laser pulse introduce the wake stability and rigidity. A large number of worldwide experiments show a rapid progress of this concept realization toward both the high-energy accelerator prospect and broad applications. The strong interest in this has been spurring and stimulating novel laser technologies, including the Chirped Pulse Amplification, the Thin Film Compression, the Coherent Amplification Network, and the Relativistic Mirror Compression. These in turn have created a conglomerate of novel science and technology with LWFA to form a new genre of high field science with many parameters of merit in this field increasing exponentially lately. This science has triggered a number of worldwide research centers and initiatives. Associated physics of ion acceleration, X-ray generation, and astrophysical processes of ultrahigh energy cosmic rays are reviewed. Applications such as X-ray free electron laser, cancer therapy, and radioisotope production etc. are considered. A new avenue of LWFA using nanomaterials is also emerging.
Martin, D.W.; Osterhage, R.J.; Summa, K.M.
A laser device is described comprising an elongated laser medium of crystal material having a cylindrical shape modified to have a flat face formed on one side thereof, a highly heat conducting mounting member having a flat surface on a portion thereof, the medium being mounted on the mounting member with the flat face of the medium in face-to-face relation with the flat surface on the mounting member, a heat sink member having a surface for attaching the mounting member to, a pump source including an array of laser diodes each having opposite ends and positioned in side-by-side single file relation, a second highly heat conducting mounting member having a surface on which the array of laser diodes is positioned, the second mounting member being mounted on the heat sink member wherein the array of laser diodes are in substantial alignment with the axis of the medium along the side thereof opposite from the flat face of the medium.
Hammerling, R.; Budgor, A.B.; Pinto, A.
This book presents the papers given at a conference on solid state lasers. Topics considered at the conference included transition-metal-doped lasers, line-narrowed alexandrite lasers, NASA specification, meteorological lidars, laser materials spectroscopy, laser pumped single pass gain, vibronic laser materials growth, crystal growth methods, vibronic laser theory, cross-fertilization through interdisciplinary fields, and laser action of color centers in diamonds.
Pten Regulates Epithelial Cytodifferentiation during Prostate Development
Lokody, Isabel B.; Francis, Jeffrey C.; Gardiner, Jennifer R.; Erler, Janine T.; Swain, Amanda
Gene expression and functional studies have indicated that the molecular programmes involved in prostate development are also active in prostate cancer. PTEN has been implicated in human prostate cancer and is frequently mutated in this disease. Here, using the Nkx3.1:Cre mouse strain and a genetic deletion approach, we investigate the role of Pten specifically in the developing mouse prostate epithelia. In contrast to its role in other developing organs, this gene is dispensable for the initial developmental processes such as budding and branching. However, as cytodifferentiation progresses, abnormal luminal cells fill the ductal lumens together with augmented epithelial proliferation. This phenotype resembles the hyperplasia seen in postnatal Pten deletion models that develop neoplasia at later stages. Consistent with this, gene expression analysis showed a number of genes affected that are shared with Pten mutant prostate cancer models, including a decrease in androgen receptor regulated genes. In depth analysis of the phenotype of these mice during development revealed that loss of Pten leads to the precocious differentiation of epithelial cells towards a luminal cell fate. This study provides novel insight into the role of Pten in prostate development as part of the process of coordinating the differentiation and proliferation of cell types in time and space to form a functional organ. PMID:26076167
Epithelial Cell Innate Response to Candida albicans
Naglik, J.R.; Moyes, D.
With the advent of treatments and diseases such as AIDS resulting in increasing numbers of patients with suppressed immune systems, fungal diseases are an escalating problem. Candida albicans is the most common of these fungal pathogens, causing infections in many of these patients. It is therefore important to understand how immunity to this fungus is regulated and how it might be manipulated. Although work has been done to identify the receptors, fungal moieties, and responses involved in anti-Candida immunity, most studies have investigated interactions with myeloid or lymphoid cells. Given that the first site of contact of C. albicans with its host is the mucosal epithelial surface, recent studies have begun to focus on interactions of C. albicans with this site. The results are startling yet in retrospect obvious, indicating that epithelial cells play an important role in these interactions, initiating responses and even providing a level of protection. These findings have obvious implications, not just for fungal pathogens, but also for identifying how host organisms can distinguish between commensal and pathogenic microbes. This review highlights some of these recent findings and discusses their importance in the wider context of infection and immunity. PMID:21441481
Quercetin Blocks Airway Epithelial Cell Chemokine Expression
Nanua, Suparna; Zick, Suzanna M.; Andrade, Juan E.; Sajjan, Umadevi S.; Burgess, John R.; Lukacs, Nicholas W.; Hershenson, Marc B.
Quercetin (3,3′,4′,5,7-pentahydroxyflavone), a dietary flavonoid, is an inhibitor of phosphatidylinositol (PI) 3-kinase and potent antioxidant. We hypothesized that quercetin blocks airway epithelial cell chemokine expression via PI 3-kinase–dependent mechanisms. Pretreatment with quercetin and the PI 3–kinase inhibitor LY294002 each reduced TNF-α–induced IL-8 and monocyte chemoattractant protein (MCP)-1 (also called CCL2) expression in cultured human airway epithelial cells. Quercetin also inhibited TNF-α–induced PI 3-kinase activity, Akt phosphorylation, intracellular H2O2 production, NF-κB transactivation, IL-8 promoter activity, and steady-state mRNA levels, consistent with the notion that quercetin inhibits chemokine expression by attenuating NF-κB transactivation via a PI 3-kinase/Akt-dependent pathway. Quercetin also reduced TNF-α–induced chemokine secretion in the presence of the transcriptional inhibitor actinomycin D, while inducing phosphorylation of eukaryotic translation initiation factor (eIF)-2α, suggesting that quercetin attenuates chemokine expression by post-transcriptional as well as transcriptional mechanisms. Finally, we tested the effects of quercetin in cockroach antigen–sensitized and –challenged mice. These mice show MCP-1–dependent airways hyperresponsiveness and inflammation. Quercetin significantly reduced lung MCP-1 and methacholine responsiveness. We conclude that quercetin blocks airway cell chemokine expression via transcriptional and post-transcriptional pathways. PMID:16794257
Epithelial NAIPs protect against colonic tumorigenesis.
Allam, Ramanjaneyulu; Maillard, Michel H; Tardivel, Aubry; Chennupati, Vijaykumar; Bega, Hristina; Yu, Chi Wang; Velin, Dominique; Schneider, Pascal; Maslowski, Kendle M
NLR family apoptosis inhibitory proteins (NAIPs) belong to both the Nod-like receptor (NLR) and the inhibitor of apoptosis (IAP) families. NAIPs are known to form an inflammasome with NLRC4, but other in vivo functions remain unexplored. Using mice deficient for all NAIP paralogs (Naip1-6(Δ/Δ)), we show that NAIPs are key regulators of colorectal tumorigenesis. Naip1-6(Δ/Δ) mice developed increased colorectal tumors, in an epithelial-intrinsic manner, in a model of colitis-associated cancer. Increased tumorigenesis, however, was not driven by an exacerbated inflammatory response. Instead, Naip1-6(Δ/Δ) mice were protected from severe colitis and displayed increased antiapoptotic and proliferation-related gene expression. Naip1-6(Δ/Δ) mice also displayed increased tumorigenesis in an inflammation-independent model of colorectal cancer. Moreover, Naip1-6(Δ/Δ) mice, but not Nlrc4-null mice, displayed hyper-activation of STAT3 and failed to activate p53 18 h after carcinogen exposure. This suggests that NAIPs protect against tumor initiation in the colon by promoting the removal of carcinogen-elicited epithelium, likely in a NLRC4 inflammasome-independent manner. Collectively, we demonstrate a novel epithelial-intrinsic function of NAIPs in protecting the colonic epithelium against tumorigenesis.
Force mapping in epithelial cell migration
du Roure, Olivia; Saez, Alexandre; Buguin, Axel; Austin, Robert H.; Chavrier, Philippe; Siberzan, Pascal; Ladoux, Benoit
We measure dynamic traction forces exerted by epithelial cells on a substrate. The force sensor is a high-density array of elastomeric microfabricated pillars that support the cells. Traction forces induced by cell migration are deduced from the measurement of the bending of these pillars and are correlated with actin localization by fluorescence microscopy. We use a multiple-particle tracking method to estimate the mechanical activity of cells in real time with a high-spatial resolution (down to 2 μm) imposed by the periodicity of the post array. For these experiments, we use differentiated Madin-Darby canine kidney (MDCK) epithelial cells. Our data provide definite information on mechanical forces exerted by a cellular assembly. The maximum intensity of the forces is localized on the edge of the epithelia. Hepatocyte growth factor promotes cell motility and induces strong scattering activity of MDCK cells. Thus, we compare forces generated by MDCK cells in subconfluent epithelia versus isolated cells after hepatocyte growth factor treatment. Maximal-traction stresses at the edge of a monolayer correspond to higher values than those measured for a single cell and may be due to a collective behavior. PMID:15695588
Targeted therapy for epithelial ovarian cancer.
Sharma, Sameer; Odunsi, Kunle
Ovarian cancer is the leading cause of death in women with gynecological malignancies and overall survival for patients with advanced epithelial ovarian cancer (EOC) remains poor. The majority of patients recur after initial treatment. A strategy for improving outcome is to minimise recurrence via targeted therapy in patients after front-line therapy, or more appropriately as consolidation therapy. EOC represents an attractive target because of the biology of the disease and that the bulk of disease occurs in the peritoneal cavity. To initiate targeted therapy, a candidate target must be identified. Innovative approaches via targeted therapy to control metastatic residual EOC are currently under investigation. The targets are molecules and pathways, on which cancer cells depend to proliferate, invade, metastasise and prevent apoptosis. Potential targeted therapies include: proapoptototic therapy, suicide gene therapy, signal transduction, antiangiogenesis, immunotherapy and cytokine therapy. The utilisation of these targets in the clinic demands carefully conducted, well-coordinated but discovery-oriented translational research in the form of clinical trials that can quickly assess alternative strategies or combination of strategies that could result in clinical benefit. Therefore, targeted therapy for epithelial ovarian cancer, especially after complete response to standard regimens, represents a paradigm whose time has come to be nurtured.
Surgery for advanced epithelial ovarian cancer.
Hacker, Neville F; Rao, Archana
Cytoreductive surgery for patients with advanced epithelial ovarian cancer has been practised since the pioneering work of Tom Griffiths in 1975. Further research has demonstrated the prognostic significance of the extent of metastatic disease pre-operatively, and of complete cytoreduction post-operatively. Patients with advanced epithelial ovarian cancer should be referred to high volume cancer units, and managed by multidisciplinary teams. The role of thoracoscopy and resection of intrathoracic disease is presently investigational. In recent years, there has been increasing use of neoadjuvant chemotherapy and interval cytoreductive surgery in patients with poor performance status, which is usually due to large volume ascites and/or large pleural effusions. Neoadjuvant chemotherapy reduces the post-operative morbidity, but if the tumour responds well to the chemotherapy, the inflammatory response makes the surgery more difficult. Post-operative morbidity is generally tolerable, but increases in older patients, and in those having multiple, aggressive surgical procedures, such as bowel resection or diaphragmatic stripping. Primary cytoreductive surgery should be regarded as the gold standard for most patients until a test is developed which would allow the prediction of platinum resistance pre-operatively.
Nuclear microscopy of rat colon epithelial cells
NASA Astrophysics Data System (ADS)
Ren, M.; Rajendran, Reshmi; Ng, Mary; Udalagama, Chammika; Rodrigues, Anna E.; Watt, Frank; Jenner, Andrew Michael
Using Nuclear microscopy, we have investigated iron distributions in the colons of Sprague Dawley rats, in order to elucidate heme uptake. Four groups of five Sprague Dawley rats (mean weight 180 g) were fed different purified diets containing either heme diet (2.5% w/w hemoglobin), high fat diet (HFD) (18% w/w fat, 1% w/w cholesterol), 'western' diet (combination of hemoglobin 2.5% and 18% fat, 1% cholesterol) or control diet (7% w/w fat). After 4 weeks, animals were sacrificed by exsanguination after anaesthesia. Thin sections of frozen colon tissue were taken, freeze dried and scanned using nuclear microscopy utilising the techniques PIXE, RBS and STIM. The new data acquisition system (IonDaq) developed in CIBA was used to obtain high resolution images and line scans were used to map the iron distributions across the colon boundaries. The nuclear microscope results indicate that when HFD is given in addition to heme, the iron content of the epithelial cells that line the colon decreases, and the zinc in the smooth muscle wall increases. This implies that the level of heme and fat in diet has an important role in colon health, possibly by influencing epithelial cells directly or changing luminal composition such as bacterial flora or levels of metabolites and cytotoxins.
Clinical significance of epithelial-mesenchymal transition
The concept of epithelial-mesenchymal transition (EMT), a process where cells change their epithelial towards a mesenchymal phenotype, has gained overwhelming attention especially in the cancer research community. Thousands of scientific reports investigated changes in gene, mRNA and protein expression compatible with EMT and their possible correlation with tumor invasion, metastatic spread or patient prognosis; however, up to now, a proof of clinical significance of the concept is still missing. This review, with a main focus on the role of EMT in tumors, will summarize the basic molecular events underlying EMT including the signaling pathways capable of its induction as well as changes in EMT-associated protein expression and will very briefly touch the role of microRNAs in EMT. We then outline protein markers that are used most frequently for the assessment of EMT in research and diagnostic evaluation of tumor specimens and depict the link between EMT, a cancer stem cell (CSC) phenotype and resistance to conventional antineoplastic therapies. Furthermore, we evaluate a possible correlation between EMT marker expression and patient prognosis as well as current therapeutic concepts targeting the EMT process to slow down or prevent metastatic spread of malignant tumors. PMID:25050175
Epithelial Transport in Inflammatory Bowel Diseases
Ghishan, Fayez K.; Kiela, Pawel R.
The epithelium of the gastrointestinal tract is one of the most versatile tissues in the organism, responsible for providing a tight barrier between dietary and bacterial antigens and the mucosal and systemic immune system, while maintaining efficient digestive and absorptive processes to ensure adequate nutrient and energy supply. Inflammatory Bowel Diseases (IBD; Crohn's disease and ulcerative colitis) are associated with a breakdown of both functions, which in some cases are clearly interrelated. In this updated literature review, we focus on the effects of intestinal inflammation and the associated immune mediators on selected aspects of the transepithelial transport of macro- and micronutrients. The mechanisms responsible for nutritional deficiencies are not always clear and could be related to decreased intake, malabsorption and excess losses. We summarize the known causes of nutrient deficiencies and the mechanism of IBD-associated diarrhea. We also overview the consequences of impaired epithelial transport, which infrequently transcend its primary purpose to affect the gut microbial ecology and epithelial integrity. While some of those regulatory mechanisms are relatively well established, more work needs to be done to determine how inflammatory cytokines can alter the transport process of nutrients across the gastrointestinal and renal epithelia. PMID:24691115
NASA Astrophysics Data System (ADS)
Chen, P.
Recent years have witnessed tremendous progress in our understanding of the cosmos, which in turn points to even deeper questions to be further addressed. Concurrently the laser technology has undergone dramatic revolutions, providing exciting opportunity for science applications. History has shown that the symbiosis between direct observations and laboratory investigation is instrumental in the progress of astrophysics. We believe that this remains true in cosmology. Current frontier phenomena related to particle astrophysics and cosmology typically involve one or more of the following conditions: (1) extremely high energy events;(2) very high density, high temperature processes; (3) super strong field environments. Laboratory experiments using high intensity lasers can calibrate astrophysical observations, investigate underlying dynamics of astrophysical phenomena, and probe fundamental physics in extreme limits. In this article we give an overview of the exciting prospect of laser cosmology. In particular, we showcase its unique capability of investigating frontier cosmology issues such as cosmic accelerator and quantum gravity.
Depth-cumulated epithelial redox ratio and stromal collagen quantity as quantitative intrinsic indicators for differentiating normal, inflammatory, and dysplastic epithelial tissues
NASA Astrophysics Data System (ADS)
Zhuo, Shuangmu; Zheng, Liqin; Chen, Jianxin; Xie, Shusen; Zhu, Xiaoqin; Jiang, Xingshan
Multiphoton microscopy was used to isolate the intrinsic emission contribution of epithelial cellular origins and stromal collagen in normal, inflammatory, and dysplastic epithelial tissues, and quantify the depth-cumulated epithelial redox ratio and stromal collagen quantity. It was found that both inflammatory and dysplastic epithelial tissues display a large decrease in stromal collagen quantity but have very different epithelial redox ratio. These results suggest that probing differences in epithelial redox ratio in addition to stromal collagen quantity can serve as quantitative intrinsic indicators for differentiating normal, inflammatory, and dysplastic epithelial tissues.
Abercrombie, Kevin R.; Shiels, David; Rash, Tim
A pressure measuring instrument that utilizes the change of the refractive index of a gas as a function of pressure and the coherent nature of a laser light to determine the barometric pressure within an environment. As the gas pressure in a closed environment varies, the index of refraction of the gas changes. The amount of change is a function of the gas pressure. By illuminating the gas with a laser light source, causing the wavelength of the light to change, pressure can be quantified by measuring the shift in fringes (alternating light and dark bands produced when coherent light is mixed) in an interferometer.
NASA Technical Reports Server (NTRS)
Palmer, A. J.; Hess, L. D.; Stephens, R. R.
A theoretical and experimental investigation into the possibility of achieving CW discharge pumped excimer laser oscillation is reported. Detailed theoretical modeling of capillary discharge pumping of the XeF and KXe and K2 excimer systems was carried out which predicted the required discharge parameters for reaching laser threshold on these systems. Capillary discharge pumping of the XeF excimer system was investigated experimentally. The experiments revealed a lower excimer level population density than predicted theoretically by about an order of magnitude. The experiments also revealed a fluorine consumption problem in the discharge in agreement with theory.
NASA Astrophysics Data System (ADS)
Landry, A.; Paranjape, M. B.
We consider the possibility of creating a graviton laser. The lasing medium would be a system of contained, ultra cold neutrons. Ultra cold neutrons are a quantum mechanical system that interacts with gravitational fields and with the phonons of the container walls. It is possible to create a population inversion by pumping the system using the phonons. We compute the rate of spontaneous emission of gravitons and the rate of the subsequent stimulated emission of gravitons. The gain obtainable is directly proportional to the density of the lasing medium and the fraction of the population inversion. The applications of a graviton laser would be interesting.
NASA Technical Reports Server (NTRS)
Harper, L. L. (Inventor)
An optical resonator cavity configuration has a unitary mirror with oppositely directed convex and concave reflective surfaces disposed into one fold and concertedly reversing both ends of a beam propagating from a laser rod disposed between two total internal reflection prisms. The optical components are rigidly positioned with perpendicularly crossed virtual rooflines by a compact optical bed. The rooflines of the internal reflection prisms, are arranged perpendicularly to the axis of the laser beam and to the optical axes of the optical resonator components.
Macrophage-derived LIF and IL1B regulate alpha(1,2)fucosyltransferase 2 (Fut2) expression in mouse uterine epithelial cells during early pregnancy.
Jasper, Melinda J; Care, Alison S; Sullivan, Brad; Ingman, Wendy V; Aplin, John D; Robertson, Sarah A
Macrophages accumulate within stromal tissue subjacent to the luminal epithelium in the mouse uterus during early pregnancy after seminal fluid exposure at coitus. To investigate their role in regulating epithelial cell expression of fucosylated structures required for embryo attachment and implantation, fucosyltransferase enzymes Fut1, Fut2 (Enzyme Commission number [EC] 18.104.22.168), and Fut4 (EC 188.8.131.52) and Muc1 and Muc4 mRNAs were quantified by quantitative real-time PCR in uterine epithelial cells after laser capture microdissection in situ or after epithelial cell coculture with macrophages or macrophage-secreted factors. When uterine macrophage recruitment was impaired by mating with seminal plasma-deficient males, epithelial cell Fut2 expression on Day 3.5 postcoitus (pc) was reduced compared to intact-mated controls. Epithelial cell Fut2 was upregulated in vitro by coculture with macrophages or macrophage-conditioned medium (MCM). Macrophage-derived cytokines LIF, IL1B, and IL12 replicated the effect of MCM on Fut2 mRNA expression, and MCM-stimulated expression was inhibited by anti-LIF and anti-IL1B neutralizing antibodies. The effects of acute macrophage depletion on fucosylated structures detected with lectins Ulex europaeus 1 (UEA-1) and Lotus tetragonolobus purpureas (LTP), or LewisX immunoreactivity, were quantified in vivo in Cd11b-dtr transgenic mice. Depletion of macrophages caused a 30% reduction in luminal epithelial UEA-1 staining and a 67% reduction in LewisX staining in uterine tissues of mice hormonally treated to mimic early pregnancy. Together, these data demonstrate that uterine epithelial Fut2 mRNA expression and terminal fucosylation of embryo attachment ligands is regulated in preparation for implantation by factors including LIF and IL1B secreted from macrophages recruited during the inflammatory response to insemination.
Focal epithelial hyperplasia caused by human papillomavirus 13.
Saunders, Natasha R; Scolnik, Dennis; Rebbapragada, Anuradha; Koelink, Eric; Craw, Lindsey; Roth, Sherryn; Aronson, Leya; Perusini, Stephen; Silverman, Michael S
Focal epithelial hyperplasia is a benign, papulo-nodular disease of the oral cavity. It is rare, affecting primarily Native American populations during childhood. It is closely associated with human papillomavirus 13 and 32. This report describes the diagnosis of 2 cases of focal epithelial hyperplasia in children from southern Guyana. The diagnosis was made using clinical criteria, polymerase chain reaction, and DNA sequencing.
Protelytic Regulation of the Intestinal Epithelial Barrier: Mechanisms and Interventions
gene that is required for epithelial barrier homeostasis . The project uses the St14 hypomorphic mouse model of matriptase deficiency to 1) determine...Tumorigenicity-14 (ST14) that is required for epithelial barrier homeostasis . Here, we are investigating matriptase dysregulation and its contribution
ROCK1-directed basement membrane positioning coordinates epithelial tissue polarity.
Daley, William P; Gervais, Elise M; Centanni, Samuel W; Gulfo, Kathryn M; Nelson, Deirdre A; Larsen, Melinda
The basement membrane is crucial for epithelial tissue organization and function. However, the mechanisms by which basement membrane is restricted to the basal periphery of epithelial tissues and the basement membrane-mediated signals that regulate coordinated tissue organization are not well defined. Here, we report that Rho kinase (ROCK) controls coordinated tissue organization by restricting basement membrane to the epithelial basal periphery in developing mouse submandibular salivary glands, and that ROCK inhibition results in accumulation of ectopic basement membrane throughout the epithelial compartment. ROCK-regulated restriction of PAR-1b (MARK2) localization in the outer basal epithelial cell layer is required for basement membrane positioning at the tissue periphery. PAR-1b is specifically required for basement membrane deposition, as inhibition of PAR-1b kinase activity prevents basement membrane deposition and disrupts overall tissue organization, and suppression of PAR-1b together with ROCK inhibition prevents interior accumulations of basement membrane. Conversely, ectopic overexpression of wild-type PAR-1b results in ectopic interior basement membrane deposition. Significantly, culture of salivary epithelial cells on exogenous basement membrane rescues epithelial organization in the presence of ROCK1 or PAR-1b inhibition, and this basement membrane-mediated rescue requires functional integrin β1 to maintain epithelial cell-cell adhesions. Taken together, these studies indicate that ROCK1/PAR-1b-dependent regulation of basement membrane placement is required for the coordination of tissue polarity and the elaboration of tissue structure in the developing submandibular salivary gland.
Airway epithelial IL-15 transforms monocytes into dendritic cells.
Regamey, Nicolas; Obregon, Carolina; Ferrari-Lacraz, Sylvie; van Leer, Coretta; Chanson, Marc; Nicod, Laurent P; Geiser, Thomas
IL-15 has recently been shown to induce the differentiation of functional dendritic cells (DCs) from human peripheral blood monocytes. Since DCs lay in close proximity to epithelial cells in the airway mucosa, we investigated whether airway epithelial cells release IL-15 in response to inflammatory stimuli and thereby induce differentiation and maturation of DCs. Alveolar (A549) and bronchial (BEAS-2B) epithelial cells produced IL-15 spontaneously and in a time- and dose-dependent manner after stimulation with IL-1beta, IFN-gamma, or TNF-alpha. Airway epithelial cell supernatants induced an increase of IL-15Ralpha gene expression in ex vivo monocytes, and stimulated DCs enhanced their IL-15Ralpha gene expression up to 300-fold. Airway epithelial cell-conditioned media induced the differentiation of ex vivo monocytes into partially mature DCs (HLA-DR+, DC-SIGN+, CD14+, CD80-, CD83+, CD86+, CCR3+, CCR6(+), CCR7-). Based on their phenotypic (CD123+, BDCA2+, BDCA4+, BDCA1(-), CD1a-) and functional properties (limited maturation upon stimulation with LPS and limited capacity to induce T cell proliferation), these DCs resembled plasmacytoid DCs. The effects of airway epithelial cell supernatants were largely blocked by a neutralizing monoclonal antibody to IL-15. Thus, our results demonstrate that airway epithelial cell-conditioned media have the capacity to differentiate monocytes into functional DCs, a process substantially mediated by epithelial-derived IL-15.
Phenotypic plasticity in normal breast derived epithelial cells
Background Normal, healthy human breast tissue from a variety of volunteer donors has become available for research thanks to the establishment of the Susan G. Komen for the Cure® Tissue Bank at the IU Simon Cancer Center (KTB). Multiple epithelial (K-HME) and stromal cells (K-HMS) were established from the donated tissue. Explant culture was utilized to isolate the cells from pieces of breast tissue. Selective media and trypsinization were employed to select either epithelial cells or stromal cells. The primary, non-transformed epithelial cells, the focus of this study, were characterized by immunohistochemistry, flow cytometry, and in vitro cell culture. Results All of the primary, non-transformed epithelial cells tested have the ability to differentiate in vitro into a variety of cell types when plated in or on biologic matrices. Cells identified include stratified squamous epithelial, osteoclasts, chondrocytes, adipocytes, neural progenitors/neurons, immature muscle and melanocytes. The cells also express markers of embryonic stem cells. Conclusions The cell culture conditions employed select an epithelial cell that is pluri/multipotent. The plasticity of the epithelial cells developed mimics that seen in metaplastic carcinoma of the breast (MCB), a subtype of triple negative breast cancer; and may provide clues to the origin of this particularly aggressive type of breast cancer. The KTB is a unique biorepository, and the normal breast epithelial cells isolated from donated tissue have significant potential as new research tools. PMID:24915897
Homeostatic Imbalance in Epithelial Ducts and Its Role in Carcinogenesis
Rejniak, Katarzyna A.
An epithelial duct is a well-defined multicellular structure composed of tightly packed cells separating and protecting body compartments that are used for enzyme secretion and its transport across the internal. The structural and functional integrity (homeostasis) of such ducts is vital in carrying many life functions (breathing, lactation, production of hormones). However, the processes involved in maintaining the homeostatic balance are not yet fully understood. On the other hand, the loss of epithelial tissue architecture, such as filled lumens or ductal disorganization, are among the first symptoms of the emerging epithelial tumors (carcinomas). Using the previously developed biomechanical model of epithelial ducts: IBCell, we investigated how different signals and mechanical stimuli imposed on individual epithelial cells can impact the homeostatic (im)balance and integrity of the whole epithelial tissue. We provide a link between erroneous responses of individual epithelial cells to specific signals and the emerging ductal morphologies characteristic for preinvasive cancers observed in pathology specimens, or characteristic for multicellular structures arising from mutated cells cultured in vitro. We summarize our finding in terms of altered properties of epithelial cell polarization, and discuss the relative importance of various polarization signals on the formation of tumor-like multicellular structures. PMID:24278670
Denileukin Diftitox Used in Treating Patients With Advanced Refractory Ovarian Cancer, Primary Peritoneal Carcinoma, or Epithelial Fallopian Tube Cancer
Fallopian Tube Cancer; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Peritoneal Cavity Cancer; Recurrent Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer
Laser pointer induced macular damage: case report and mini review.
Turaka, Kiran; Bryan, J Shepard; Gordon, Alan J; Reddy, Rahul; Kwong, Henry M; Sell, Clive H
To report laser pointer induced damage to retina and choroid and briefly review literature. A case report of a 13-year old Caucasian boy developed blurry central vision and central scotoma in right eye (OD). He was exposed for one minute to class IIIA green laser pointer of 650 nm wavelength and 5 mW power. Clinical examination showed a grayish lesion in foveal region. Ancillary testing revealed disruption of the retinal pigment epithelial (RPE) layer in foveal region and indocyanine green angiography demonstrated evidence of choroidal hypofluorescence suggestive of choroidal infarction in OD. Visual acuity improved from 20/100 to 20/60 in one day and he was treated with tapering doses of oral prednisolone (40 mg) for 3 weeks. Laser pointer with a power of >5 mW caused damage to RPE in the macula. Children should not be given laser pointers as toys especially those with label of danger instructions.
Culture and differentiation of mouse tracheal epithelial cells.
You, Yingjian; Brody, Steven L
Airway epithelial cell biology has been greatly advanced by studies of genetically defined and modified mice; however it is often difficult to isolate, manipulate, and assay epithelial cell-specific responses in vivo. In vitro proliferation and differentiation of mouse airway epithelial cells are made possible by a high-fidelity system for primary culture of mouse tracheal epithelial cells described in this chapter. Using this method, epithelial cells purified from mouse tracheas proliferate in growth factor-enriched medium. Subsequent culture in defined medium and the use of the air-liquid interface condition result in the development of well-differentiated epithelia composed of ciliated and non-ciliated cells with characteristics of native airways. Methods are also provided for manipulation of differentiation and analysis of differentiation and gene expression. These approaches allow the assessment of global responses and those of specific cell subpopulations within the airway epithelium.
Crossroads of Wnt and Hippo in epithelial tissues.
Bernascone, Ilenia; Martin-Belmonte, Fernando
Epithelial tissues undergo constant growth and differentiation during embryonic development and to replace damaged tissue in adult organs. These processes are governed by different signaling pathways that ultimately control the expression of genes associated with cell proliferation, patterning, and death. One essential pathway is Wnt, which controls tubulogenesis in several epithelial organs. Recently, Wnt has been closely linked to other signaling pathways, such as Hippo, that orchestrate proliferation and apoptosis to control organ size. There is evidence that epithelial cell junctions may sequester the transcription factors that act downstream of these signaling pathways, which would represent an important aspect of their functional regulation and their influence on cell behavior. Here, we review the transcriptional control exerted by the Wnt and Hippo signaling pathways during epithelial growth, patterning, and differentiation and recent advances in understanding of the regulation and crosstalk of these pathways in epithelial tissues.
Multi-functionality and plasticity characterize epithelial cells in Hydra
Buzgariu, W; Al Haddad, S; Tomczyk, S; Wenger, Y; Galliot, B
Epithelial sheets, a synapomorphy of all metazoans but porifers, are present as 2 layers in cnidarians, ectoderm and endoderm, joined at their basal side by an extra-cellular matrix named mesoglea. In the Hydra polyp, epithelial cells of the body column are unipotent stem cells that continuously self-renew and concomitantly express their epitheliomuscular features. These multifunctional contractile cells maintain homeostasis by providing a protective physical barrier, by digesting nutrients, by selecting a stable microbiota, and by rapidly closing wounds. In addition, epithelial cells are highly plastic, supporting the adaptation of Hydra to physiological and environmental changes, such as long starvation periods where survival relies on a highly dynamic autophagy flux. Epithelial cells also play key roles in developmental processes as evidenced by the organizer activity they develop to promote budding and regeneration. We propose here an integrative view of the homeostatic and developmental aspects of epithelial plasticity in Hydra. PMID:26716072
Inhibition of corneal epithelial cell migration by cadmium and mercury
Ubels, J.L.; Osgood, T.B. Medical Coll. of Wisconsin, Milwaukee )
In a previous comparative study of corneal healing in fish, the authors observed that corneal epithelial healing occurs very rapidly in vivo in the marine teleost Myoxocephalus octodecimspinosus (longhorn sculpin) with a 6-mm diameter wound on the mammalian cornea. This rapid healing which permits prompt restoration of the epithelial barrier is apparently an adaptation to the large ionic and osmotic gradients between the environment and the intraocular fluids of the fish. These observations suggested that epithelial healing in the sculpin cornea might be useful model in aquatic biomedical toxicology if an in vitro method for measurement of healing rates could be developed. In this report the authors demonstrate that sculpin eyes maintained in short-term organ culture have a rapid corneal epithelial healing response and that this model can be used to demonstrate the toxic effects of heavy metals on epithelial cell migration.
Paradigm Shift in the Management Strategy for Epithelial Ovarian Cancer.
Fujiwara, Keiichi; McAlpine, Jessica N; Lheureux, Stephanie; Matsumura, Noriomi; Oza, Amit M
The hypothesis on the pathogenesis of epithelial ovarian cancer continues to evolve. Although epithelial ovarian cancer had been assumed to arise from the coelomic epithelium of the ovarian surface, it is now becoming clearer that the majority of serous carcinomas arise from epithelium of the distal fallopian tube, whereas clear cell and endometrioid cancers arise from endometriosis. Molecular and genomic characteristics of epithelial ovarian cancer have been extensively investigated. Our understanding of pathogenesis of the various histologic types of ovarian cancer have begun to inform changes to the strategies for management of epithelial ovarian cancer, which represent a paradigm shift not only for treatment but also for prevention, which previously had not been considered achievable. In this article, we will discuss novel attempts at the prevention of high-grade serous ovarian cancer and treatment strategies for two distinct entities in epithelial ovarian cancer: low-grade serous and clear cell ovarian carcinomas, which are relatively rare and resistant to conventional chemotherapy.
The physiological expression of scavenger receptor SR-B1 in canine endometrial and placental epithelial cells and its potential involvement in pathogenesis of pyometra.
Gabriel, C; Becher-Deichsel, A; Hlavaty, J; Mair, G; Walter, I
Pyometra, the purulent inflammation of the uterus, is a common uterine disease of bitches that has potentially life-threatening consequences. The opportunistic bacterial infection of the uterus often progresses into the serious systemic inflammatory response syndrome. In a previous study, we characterized epithelial foam cells in the canine endometrial surface occurring in metestrus, and we regularly observed pronounced epithelial foam-cell formations in pyometra-affected uteri. Therefore, it was assumed that the mechanism behind lipid droplet accumulation in surface epithelial cells might even increase bacterial binding capacity and promote pyometra development. Lipid droplet accumulation in epithelial cells is accomplished via specialized lipid receptors called scavenger receptors (SR). Scavenger receptor class B type 1 (SR-B1) is an important receptor for lipid accumulation in diverse cell types, but it is also a strong binding partner for bacteria, and thereby enhances bacterial adhesion and clinical signs of systemic inflammatory response syndrome. In the present study, after the isolation of metestrous surface epithelial cells from canine uteri by laser capture microdissection, SR-B1 was identified at the messenger RNA (mRNA) level by quantitative real time polymerase chain reaction and also at the protein level by means of immunohistochemistry. In pyometra-affected uteri, SR-B1 mRNA expression was higher than that in the healthy control samples, and SR-B1 protein was expressed in the surface and crypt epithelial cells. Furthermore, to understand the physiological role of SR-B1 expression in the metestrus surface epithelial cells, we investigated its expression in the epithelial cells of the glandular chambers of canine placenta in different stages of gestation because these cells are also characterized by lipid droplet accumulation. SR-B1 was present in the placental epithelial cells of the glandular chambers from 25 to 30 and 45 to 50 days of gestation
Epithelial restitution and wound healing in inflammatory bowel disease
Sturm, Andreas; Dignass, Axel U
Inflammatory bowel disease is characterized by a chronic inflammation of the intestinal mucosa. The mucosal epithelium of the alimentary tract constitutes a key element of the mucosal barrier to a broad spectrum of deleterious substances present within the intestinal lumen including bacterial microorganisms, various dietary factors, gastrointestinal secretory products and drugs. In addition, this mucosal barrier can be disturbed in the course of various intestinal disorders including inflammatory bowel diseases. Fortunately, the integrity of the gastrointestinal surface epithelium is rapidly reestablished even after extensive destruction. Rapid resealing of the epithelial barrier following injuries is accomplished by a process termed epithelial restitution, followed by more delayed mechanisms of epithelial wound healing including increased epithelial cell proliferation and epithelial cell differentiation. Restitution of the intestinal surface epithelium is modulated by a range of highly divergent factors among them a broad spectrum of structurally distinct regulatory peptides, variously described as growth factors or cytokines. Several regulatory peptide factors act from the basolateral site of the epithelial surface and enhance epithelial cell restitution through TGF-β-dependent pathways. In contrast, members of the trefoil factor family (TFF peptides) appear to stimulate epithelial restitution in conjunction with mucin glycoproteins through a TGF-β-independent mechanism from the apical site of the intestinal epithelium. In addition, a number of other peptide molecules like extracellular matrix factors and blood clotting factors and also non-peptide molecules including phospholipids, short-chain fatty acids (SCFA), adenine nucleotides, trace elements and pharmacological agents modulate intestinal epithelial repair mechanisms. Repeated damage and injury of the intestinal surface are key features of various intestinal disorders including inflammatory bowel
Documentation of angiotensin II receptors in glomerular epithelial cells
NASA Technical Reports Server (NTRS)
Sharma, M.; Sharma, R.; Greene, A. S.; McCarthy, E. T.; Savin, V. J.; Cowley, A. W. (Principal Investigator)
Angiotensin II decreases glomerular filtration rate, renal plasma flow, and glomerular capillary hydraulic conductivity. Although angiotensin II receptors have been demonstrated in mesangial cells and proximal tubule cells, the presence of angiotensin II receptors in glomerular epithelial cells has not previously been shown. Previously, we have reported that angiotensin II caused an accumulation of cAMP and a reorganization of the actin cytoskeleton in cultured glomerular epithelial cells. Current studies were conducted to verify the presence of angiotensin II receptors by immunological and non-peptide receptor ligand binding techniques and to ascertain the activation of intracellular signal transduction in glomerular epithelial cells in response to angiotensin II. Confluent monolayer cultures of glomerular epithelial cells were incubated with angiotensin II, with or without losartan and/or PD-123,319 in the medium. Membrane vesicle preparations were obtained by homogenization of washed cells followed by centrifugation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of membrane proteins followed by multiscreen immunoblotting was used to determine the presence of angiotensin II receptor type 1 (AT1) or type 2 (AT2). Angiotensin II-mediated signal transduction in glomerular epithelial cells was studied by measuring the levels of cAMP, using radioimmunoassay. Results obtained in these experiments showed the presence of both AT1 and AT2 receptor types in glomerular epithelial cells. Angiotensin II was found to cause an accumulation of cAMP in glomerular epithelial cells, which could be prevented only by simultaneous use of losartan and PD-123,319, antagonists for AT1 and AT2, respectively. The presence of both AT1 and AT2 receptors and an increase in cAMP indicate that glomerular epithelial cells respond to angiotensin II in a manner distinct from that of mesangial cells or proximal tubular epithelial cells. Our results suggest that glomerular epithelial
NASA Technical Reports Server (NTRS)
Palmer, A. J.; Hess, L. D.; Stephens, R. R.; Pepper, D. M.
The results of a two-year investigation into the possibility of developing continuous wave excimer lasers are reported. The program included the evaluation and selection of candidate molecular systems and discharge pumping techniques. The K Ar/K2 excimer dimer molecules and the xenon fluoride excimer molecule were selected for study; each used a transverse and capillary discharges pumping technique. Experimental and theoretical studies of each of the two discharge techniques applied to each of the two molecular systems are reported. Discharge stability and fluorine consumption were found to be the principle impediments to extending the XeF excimer laser into the continuous wave regime. Potassium vapor handling problems were the principal difficulty in achieving laser action on the K Ar/K2 system. Of the four molecular systems and pumping techniques explored, the capillary discharge pumped K Ar/K2 system appears to be the most likely candidate for demonstrating continuous wave excimer laser action primarily because of its predicted lower pumping threshold and a demonstrated discharge stability advantage.
NASA Astrophysics Data System (ADS)
Mechanical Technology, Incorporated developed a fully automatic laser machining process that allows more precise balancing removes metal faster, eliminates excess metal removal and other operator induced inaccuracies, and provides significant reduction in balancing time. Manufacturing costs are reduced as a result.
Oral epithelial hyperplasia in diabetes mellitus.
Girtan, Mihaela; Zurac, Sabina; Stăniceanu, Florica; Bastian, Alexandra; Popp, Cristiana; Nichita, Luciana; Laba, Elisabeta; Forna, Norina
Diabetes mellitus is one of the chronic systemic disorders with major influences of the oral cavity microenvironment. Oral manifestations of diabetes are diverse; they are represented by candidose, lichen plan, recurrent aphthous stomatitis, gingivitis, salivary disorders, oral mucosa atrophy and rarely hypertrophy; a possible link between oral cancer and diabetes is suspected, both in animal models and humans. We report a case of a young woman with type 1 diabetes with class I Kennedy edentation with mobile denture prosthesis; latter in the clinical follow-up, a hyperplasic lesion of the oral mucosa with p53 expression within the epithelial nuclei was identified, p53 being the more likely pathogenic pathway involved in diabetes-related oral cancer. The approach of this patient required multidisciplinary investigations and careful follow-up.
Dietary factors and epithelial ovarian cancer.
Shu, X. O.; Gao, Y. T.; Yuan, J. M.; Ziegler, R. G.; Brinton, L. A.
Dietary data from a population-based case-control study of 172 epithelial ovarian cancer cases and 172 controls were analysed. A significant (P less than 0.01) dose-response relationship was found between intake of fat from animal sources and risk of ovarian cancer, but plant fat was not associated. Although the effect of animal fat was confounded by education, an adjusted odds ratio of 1.8 persisted for those in the upper quartile compared to the lower quartile of consumption (P for trend = 0.03). After adjustment for animal fat intake, calorific and protein intake had minimal effects on risk. Total vegetables were found to be somewhat protective, but the mechanism of action was unclear. Weight, height and relative weight (weight/height2) were not related to risk of ovarian cancer. PMID:2757927
Cubilin, a multifunctional epithelial receptor: an overview.
Kozyraki, R
Cubilin is a 460-kDa endocytic receptor coexpressed with megalin, a multiligand receptor of the low-density lipoprotein receptor gene family, at the apical pole of epithelial cells in the renal proximal convoluted tubule, visceral yolk sac, ileum, and placenta. The structure of cubilin is unique: it lacks a transmembrane domain and requires megalin for its internalization. The accumulation of 27 interactive CUB domains provides the potential for multiple, possibly independent interactions and functions. Cubilin is involved in the intestinal absorption of vitamin B12, the catabolism of apolipoprotein A-I by the proximal convoluted tubule and more generally in renal protein reabsorption. The role of cubilin on fetomaternal interfaces is not defined but may be related to its ability to bind and internalize high density lipoproteins.
Immunolocalization of epithelial and mesenchymal matrix constituents in association with inner enamel epithelial cells.
Bosshardt, D D; Nanci, A
After crown formation, the enamel organ reorganizes into Hertwig's epithelial root sheath (HERS). Although it is generally accepted that HERS plays an inductive role during root formation, it also has been suggested that it may contribute enamel-related proteins to cementum matrix. By analogy to the enamel-free area (EFA) in rat molars, in which epithelial cells express not only enamel proteins but also "typical" mesenchymal matrix constituents, it has been proposed that HERS cells may also have the potential to produce cementum proteins. To test this hypothesis, we examined the nature of the first matrix layer deposited along the cervical portion of root dentin and the characteristics of the associated cells. Rat molars were processed for postembedding colloidal gold immunolabeling with antibodies to amelogenin (AMEL), ameloblastin (AMBN), bone sialoprotein (BSP), and osteopontin (OPN). To minimize the possibility of false-negative results, several antibodies to AMEL were used. The labelings were compared with those obtained at the EFA. Initial cementum matrix was consistently observed at a time when epithelial cells from HERS covered most of the forming root surface. Cells with mesenchymal characteristics were rarely seen in proximity to the matrix. Both the EFA matrix and initial cementum exhibited collagen fibrils and were intensely immunoreactive for BSP and OPN. AMEL and AMBN were immunodetected at the EFA but not over the initial cementum proper. These two proteins were, however, present at the cervical-most portion of the root where enamel matrix extends for a short distance between dentin and cementum. These data suggest that epithelial cells along the root surface are likely responsible for the deposition of the initial cementum matrix and therefore, like the cells at the EFA, may be capable of producing mesenchymal proteins.
AM251 Suppresses Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells.
Yoshinaga, Tomoyo; Uwabe, Kenichiro; Naito, Shoichi; Higashino, Kenichi; Nakano, Toru; Numata, Yoshito; Kihara, Akio
Epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells is one of the causative mechanisms of kidney fibrosis. In our study, we screened lipophilic compounds using a lipid library including approximately 200 lipids to identify those that suppressed EMT induced by a transforming growth factor (TGF)-β1 stimulus. Initial screening was performed with the immortalized HK-2 renal tubule epithelial cell line. The most promising compounds were further tested in RPTEC primary renal tubule epithelial cells. We found that the synthetic lipid AM251 suppressed two hallmark events associated with EMT, the upregulation of collagen 1A1 (COL1A1) and downregulation of E-cadherin. Though AM251 is known to act as an antagonist for the cannabinoid receptor type 1 (CB1) and an agonist for the G protein-coupled receptor 55 (GRP55), the suppression of EMT by AM251 was not mediated through either receptor. Microarray analyses revealed that AM251 inhibited induction of several EMT transcription factors such as SNAIL1, which is the key inducer of EMT, and the AP-1 transcription factors FOSB and JUNB. Activation of SMAD2/3 and p38 mitogen-activated protein kinase (MAPK) was inhibited by AM251, with greater inhibition of the latter, indicating that AM251 acted upstream of SMAD/p38 MAPK in the TGF-β signaling pathway. Our findings regarding the effects of AM251 on the TGF-β signaling pathway may inform development of a novel therapeutic agent suppressing EMT, thus preventing kidney fibrosis.
AM251 Suppresses Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells
Yoshinaga, Tomoyo; Uwabe, Kenichiro; Naito, Shoichi; Higashino, Kenichi; Nakano, Toru; Numata, Yoshito
Epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells is one of the causative mechanisms of kidney fibrosis. In our study, we screened lipophilic compounds using a lipid library including approximately 200 lipids to identify those that suppressed EMT induced by a transforming growth factor (TGF)-β1 stimulus. Initial screening was performed with the immortalized HK-2 renal tubule epithelial cell line. The most promising compounds were further tested in RPTEC primary renal tubule epithelial cells. We found that the synthetic lipid AM251 suppressed two hallmark events associated with EMT, the upregulation of collagen 1A1 (COL1A1) and downregulation of E-cadherin. Though AM251 is known to act as an antagonist for the cannabinoid receptor type 1 (CB1) and an agonist for the G protein-coupled receptor 55 (GRP55), the suppression of EMT by AM251 was not mediated through either receptor. Microarray analyses revealed that AM251 inhibited induction of several EMT transcription factors such as SNAIL1, which is the key inducer of EMT, and the AP-1 transcription factors FOSB and JUNB. Activation of SMAD2/3 and p38 mitogen-activated protein kinase (MAPK) was inhibited by AM251, with greater inhibition of the latter, indicating that AM251 acted upstream of SMAD/p38 MAPK in the TGF-β signaling pathway. Our findings regarding the effects of AM251 on the TGF-β signaling pathway may inform development of a novel therapeutic agent suppressing EMT, thus preventing kidney fibrosis. PMID:27936102
Cell density determines epithelial migration in culture.
Rosen, P; Misfeldt, D S
The dog kidney epithelial cell line (MDCK) has been shown to exhibit a density-correlated inhibition of growth at approxmately 6.6 X 10(5) cells per cm2. When a confluent monolayer at its maximal density was wounded by removal of a wide swath of cells, migration of the cell sheet into the denuded area occurred. Precise measurements of the rate of migration for 5 day showed that the cells accelerated at a uniform rate of 0.24 micrometer . hr-2 and, by extrapolation, possessed an apparent initial velocity of 2.8 micrometer . hr-1 at the time of wounding. The apparent initial velocity was considered to be the result of a brief (< 10 hr) and rapid acceleration dependent on cell density. To verify this, wounds were made at different densities below the maximum. In these experiments, the cells did not migrate until a "threshold" density of 2.0 X 10(5) cells per cm2 was reached regardless of the density at the time of wounding. At the threshold density, the cell sheet began to accelerate at the previously measured rate (0.24 micrometer . hr-2). Any increase in density by cell division was balanced by cell migration, so that the same threshold density was maintained by the migrating cells. Each migrating cell sustained the movement of the cell sheet at a constant rate of acceleration. It is proposed that an acceleration is, in general, characteristic of the vectorial movement of an epithelial cell sheet. Images PMID:6933523
Glucocorticoid receptor in human respiratory epithelial cells.
Pujolsa, Laura; Mullol, Joaquim; Picado, Cèsar
Inhaled and intranasal glucocorticoids (GCs) are the most common and effective drugs for controlling symptoms and airway inflammation in respiratory diseases such as allergic rhinitis, chronic rhinosinusitis with/without nasal polyps, and asthma, and the respiratory epithelium is a primary target of GC anti-inflammatory actions. GC effects are mediated through the GC receptor (GR). In humans, one single GR gene gives rise to two main GR products, namely GRalpha and GRbeta, which are subject to translational and posttranslational modifications. GRalpha is expressed in virtually all human cells and tissues, including respiratory epithelial cells, and - at least in vitro - is downregulated by GC. GRalpha mediates the anti-inflammatory actions of GC by activating transcription of anti-inflammatory genes through binding of GRalpha to glucocorticoid response elements (GRE) located in the promoter region of target genes, repressing transcription of proinflammatory genes through direct interaction between GRalpha and proinflammatory transcription factors, such as AP-1 and NF-kappaB (transrepression), and also by destabilizing the mRNA of proinflammatory mediators. GRbeta acts as a dominant negative inhibitor of GRalpha-mediated transactivation and transrepression in certain in vitro studies with transfected cells. The GRbeta message is expressed at low levels in numerous tissues and its protein is mainly expressed in inflammatory cells, although it has also been detected in airway epithelial cells. Increased GRbeta expression has been reported in bronchial asthma and nasal polyposis, and after incubation of cells with certain proinflammatory stimuli. However, the role of GRbeta in modulating GC sensitivity in vivo has been highly debated and is as yet unclear.
Epithelial topography for repetitive tooth formation
Gaete, Marcia; Fons, Juan Manuel; Popa, Elena Mădălina; Chatzeli, Lemonia; Tucker, Abigail S.
ABSTRACT During the formation of repetitive ectodermally derived organs such as mammary glands, lateral line and teeth, the tissue primordium iteratively initiates new structures. In the case of successional molar development, new teeth appear sequentially in the posterior region of the jaw from Sox2+ cells in association with the posterior aspect of a pre-existing tooth. The sequence of molar development is well known, however, the epithelial topography involved in the formation of a new tooth is unclear. Here, we have examined the morphology of the molar dental epithelium and its development at different stages in the mouse in vivo and in molar explants. Using regional lineage tracing we show that within the posterior tail of the first molar the primordium for the second and third molar are organized in a row, with the tail remaining in connection with the surface, where a furrow is observed. The morphology and Sox2 expression of the tail retains characteristics reminiscent of the earlier stages of tooth development, such that position along the A-P axes of the tail correlates with different temporal stages. Sox9, a stem/progenitor cell marker in other organs, is expressed mainly in the suprabasal epithelium complementary with Sox2 expression. This Sox2 and Sox9 expressing molar tail contains actively proliferating cells with mitosis following an apico-basal direction. Snail2, a transcription factor implicated in cell migration, is expressed at high levels in the tip of the molar tail while E-cadherin and laminin are decreased. In conclusion, our studies propose a model in which the epithelium of the molar tail can grow by posterior movement of epithelial cells followed by infolding and stratification involving a population of Sox2+/Sox9+ cells. PMID:26538639
Henipavirus pathogenesis in human respiratory epithelial cells.
Escaffre, Olivier; Borisevich, Viktoriya; Carmical, J Russ; Prusak, Deborah; Prescott, Joseph; Feldmann, Heinz; Rockx, Barry
Hendra virus (HeV) and Nipah virus (NiV) are deadly zoonotic viruses for which no vaccines or therapeutics are licensed for human use. Henipavirus infection causes severe respiratory illness and encephalitis. Although the exact route of transmission in human is unknown, epidemiological studies and in vivo studies suggest that the respiratory tract is important for virus replication. However, the target cells in the respiratory tract are unknown, as are the mechanisms by which henipaviruses can cause disease. In this study, we characterized henipavirus pathogenesis using primary cells derived from the human respiratory tract. The growth kinetics of NiV-Malaysia, NiV-Bangladesh, and HeV were determined in bronchial/tracheal epithelial cells (NHBE) and small airway epithelial cells (SAEC). In addition, host responses to infection were assessed by gene expression analysis and immunoassays. Viruses replicated efficiently in both cell types and induced large syncytia. The host response to henipavirus infection in NHBE and SAEC highlighted a difference in the inflammatory response between HeV and NiV strains as well as intrinsic differences in the ability to mount an inflammatory response between NHBE and SAEC. These responses were highest during HeV infection in SAEC, as characterized by the levels of key cytokines (interleukin 6 [IL-6], IL-8, IL-1α, monocyte chemoattractant protein 1 [MCP-1], and colony-stimulating factors) responsible for immune cell recruitment. Finally, we identified virus strain-dependent variability in type I interferon antagonism in NHBE and SAEC: NiV-Malaysia counteracted this pathway more efficiently than NiV-Bangladesh and HeV. These results provide crucial new information in the understanding of henipavirus pathogenesis in the human respiratory tract at an early stage of infection.
Epithelial ovarian cancer: testing the 'androgens hypothesis'.
Olsen, Catherine M; Green, Adèle C; Nagle, Christina M; Jordan, Susan J; Whiteman, David C; Bain, Christopher J; Webb, Penelope M
In 1998, Risch proposed a hypothesis for the pathogenesis of ovarian cancer relating to the role of androgens in stimulating epithelial cell proliferation. Although this hypothesis has been widely discussed, direct evidence to support it is scant. To address this issue, we have conducted a detailed analysis of factors possibly associated with high circulating levels of androgens, including polycystic ovary syndrome (PCOS), hirsutism and acne (all clinically associated with hyperandrogenism) using the data collected in an Australia-wide, population-based case-control study. Cases aged 18-79 years with a new diagnosis of invasive epithelial ovarian cancer (n=1276) or borderline malignant tumour (n=315) were identified through a network of clinics and cancer registries throughout Australia. Controls (n=1508) were selected from the National Electoral Roll. Women self-reported a history of PCOS, acne, hirsutism and also use of testosterone supplements or the androgenic medication Danazol. We found no evidence that a history of PCOS, acne or hirsutism was associated with ovarian cancer overall, or with specific subtypes, with the exception of serous borderline tumours that were positively associated with a history of PCOS (OR 2.6; 95% CI 1.0-6.1). Women who had ever used testosterone supplements had an increased risk of ovarian cancer (OR 3.7; 95% CI 1.1-12.0); however, use of the androgenic medication Danazol did not increase risk (OR 1.0; 95% CI 0.4-2.9). Overall, our results do not support the hypothesis that androgen-related disorders increase the risk of ovarian cancer.
Montelukast suppresses epithelial to mesenchymal transition of bronchial epithelial cells induced by eosinophils.
Hosoki, Koa; Kainuma, Keigo; Toda, Masaaki; Harada, Etsuko; Chelakkot-Govindalayathila, Ayshwarya-Lakshmi; Roeen, Ziaurahman; Nagao, Mizuho; D'Alessandro-Gabazza, Corina N; Fujisawa, Takao; Gabazza, Esteban C
Epithelial to mesenchymal transition (EMT) is a mechanism by which eosinophils can induce airway remodeling. Montelukast, an antagonist of the cysteinyl leukotriene receptor, can suppress airway remodeling in asthma. The purpose of this study was to evaluate whether montelukast can ameliorate airway remodeling by blocking EMT induced by eosinophils. EMT induced was assessed using a co-culture system of human bronchial epithelial cells and human eosinophils or the eosinophilic leukemia cell lines, Eol-1. Montelukast inhibited co-culture associated morphological changes of BEAS-2b cells, decreased the expression of vimentin and collagen I, and increased the expression of E-cadherin. Montelukast mitigated the rise of TGF-β1 production and Smad3 phosphorylation. Co-culture of human eosinophils with BEAS-2B cells significantly enhanced the production of CysLTs compared with BEAS-2B cells or eosinophils alone. The increase of CysLTs was abolished by montelukast pre-treatment. Montelukast had similar effects when co-culture system of Eol-1 and BEAS-2B was used. This study showed that montelukast suppresses eosinophils-induced EMT of airway epithelial cells. This finding may explain the mechanism of montelukast-mediated amelioration of airway remodeling in bronchial asthma.
A comparison of epithelial-to-mesenchymal transition and re-epithelialization.
Leopold, Philip L; Vincent, Jan; Wang, Hongjun
Wound healing and cancer metastasis share a common starting point, namely, a change in the phenotype of some cells from stationary to motile. The term, epithelial-to-mesenchymal transition (EMT) describes the changes in molecular biology and cellular physiology that allow a cell to transition from a sedentary cell to a motile cell, a process that is relevant not only for cancer and regeneration, but also for normal development of multicellular organisms. The present review compares the similarities and differences in cellular response at the molecular level as tumor cells enter EMT or as keratinocytes begin the process of re-epithelialization of a wound. Looking toward clinical interventions that might modulate these processes, the mechanisms and outcomes of current and potential therapies are reviewed for both anti-cancer and pro-wound healing treatments related to the pathways that are central to EMT. Taken together, the comparison of re-epithelialization and tumor EMT serves as a starting point for the development of therapies that can selectively modulate different forms of EMT.
Physical characterization and profiling of airway epithelial derived exosomes using light scattering.
Kesimer, Mehmet; Gupta, Richa
Exosomes and other extracellular vesicles have been gaining interest during the last decade due to their emerging role in biology and, disease pathogenesis and their biomarker potential. Almost all published research related to exosomes and other extracellular vesicles include some form of physical characterization. Therefore, these vesicles should be precisely profiled and characterized physically before studying their biological role as intercellular messengers, biomarkers or therapeutic tools. Using a combination of light scattering techniques, including dynamic light scattering (DLS) and multi-angle laser light scattering combined with size exclusion separation (SEC-MALLS), we physically characterized and compared distinct extracellular vesicles derived from the apical secretions of two different cultured airway epithelial cells. The results indicated that epithelial cells release vesicles with distinct physical properties and sizes. Human primary tracheobronchial cell culture (HTBE) derived vesicles have a hydrodynamic radius (Rh) of approximately 340 nm while their radius of gyration (Rg) is approximately 200 nm. Electron microscopy analysis, however, revealed that their spherical component is 40-100 nm in size, and they carry filamentous, entangled membrane mucins on their surface that increases their overall radius. The mucin decoration on the surface defines their size and charge as measured using light scattering techniques. Their surface properties mirror the properties of the cells from which they are derived. This may provide a unique tool for researchers to elucidate the unanswered questions in normal airway biology and innate and adaptive defense, including the remodeling of airways during inflammation, tumorigenesis and metastasis.
Characteristics of functionalized nano-hydroxyapatite and internalization by human epithelial cell
NASA Astrophysics Data System (ADS)
Yan-Zhong, Zhao; Yan-Yan, Huang; Jun, Zhu; Shai-Hong, Zhu; Zhi-You, Li; Ke-Chao, Zhou
Hydroxyapatite is the main inorganic component of biological bone and tooth enamel, and synthetic hydroxyapatite has been widely used as biomaterials. In this study, a facile method has been developed for the fabrication of arginine-functionalized and europium-doped hydroxyapatite nanoparticles (Arg-Eu-HAP). The synthesized nanoparticles characterized by transmission electron microscopy, X-ray diffractometry, Fourier transform infrared, and Zeta potential analyzer. Its biological properties with DNA binding, cell toxicity, cell binding and intracellular distribution were tested by agarose gel electrophoresis assay, flow cytometry, and fluorescence microscope and laser scanning confocal microscope. The synthesized Arg-Eu-HAP could effectively bind DNA without any cytotoxicity and be internalized into the cytoplasm and perinuclear of human lung epithelial cells.
Occludin S471 Phosphorylation Contributes to Epithelial Monolayer Maturation
Bolinger, Mark T.; Waldschmidt, Helen V.; Larsen, Scott D.; Bewley, Maria C.; Flanagan, John M.
Multiple organ systems require epithelial barriers for normal function, and barrier loss is a hallmark of diseases ranging from inflammation to epithelial cancers. However, the molecular processes regulating epithelial barrier maturation are not fully elucidated. After contact, epithelial cells undergo size-reductive proliferation and differentiate, creating a dense, highly ordered monolayer with high resistance barriers. We provide evidence that the tight junction protein occludin contributes to the regulation of epithelial cell maturation upon phosphorylation of S471 in its coiled-coil domain. Overexpression of a phosphoinhibitory occludin S471A mutant prevents size-reductive proliferation and subsequent tight junction maturation in a dominant manner. Inhibition of cell proliferation in cell-contacted but immature monolayers recapitulated this phenotype. A kinase screen identified G-protein-coupled receptor kinases (GRKs) targeting S471, and GRK inhibitors delayed epithelial packing and junction maturation. We conclude that occludin contributes to the regulation of size-reductive proliferation and epithelial cell maturation in a phosphorylation-dependent manner. PMID:27185880
Correlation between cellular phone use and epithelial parotid gland malignancies.
Duan, Y; Zhang, H Z; Bu, R F
The authors investigated the association between cellular phone use and epithelial parotid gland malignancy. The subjects were 136 cases who were treated for this condition at the authors' hospital from January 1993 to March 2010, and 2051 controls who did not have salivary gland tumours and were admitted to the oral and maxillofacial surgery department during the same period. Logistic analysis was used to examine the relationship between cellular phone use and risk of epithelial parotid gland malignancy and mucoepidermoid carcinoma. Overall, the frequency of cellular phone use was not significantly associated with epithelial parotid gland malignancy. Female gender, advanced age, married status, high income, and smoking were associated with an elevated risk of epithelial parotid gland malignancy, especially mucoepidermoid carcinoma. Residence in a rural area was associated with reduced risk of epithelial parotid gland malignancy. The results suggest a possible dose-response relationship of cellular phone use with epithelial parotid gland malignancy. The authors suggest that the association of cellular phone use and epithelial parotid gland malignancy and mucoepidermoid carcinoma requires further investigation with large prospective studies.
Clinical implications of epithelial cell plasticity in cancer progression.
Aparicio, Luis A; Blanco, Moisés; Castosa, Raquel; Concha, Ángel; Valladares, Manuel; Calvo, Lourdes; Figueroa, Angélica
In the last few years, the role of epithelial cell plasticity in cancer biology research has gained increasing attention. This concept refers to the ability of the epithelial cells to dynamically switch between different phenotypic cellular states. This programme is particularly relevant during the epithelial-to-mesenchymal transition (EMT) in cancer progression. During colonization, epithelial cells first activate the EMT programme to disseminate from a primary tumour to reach a distant tissue site. During this process, cells are transported into the circulation and are able to escape the immune system of the host. Then, a reverse process called mesenchymal-to-epithelial transition (MET) occurs on cells that settle in the distant organs. Although epithelial cell plasticity has an important impact on tumour biology, the clinical relevance of this concept remains to be recapitulated. In this review, we will update the current state of epithelial cell plasticity in cancer progression and its clinical implications for the design of therapeutic strategies, the acquisition of multidrug resistance, and future perspectives for the management of cancer patients.
Technical note: Isolation and characterization of porcine mammary epithelial cells.
Dahanayaka, S; Rezaei, R; Porter, W W; Johnson, G A; Burghardt, R C; Bazer, F W; Hou, Y Q; Wu, Z L; Wu, G
Within the mammary gland, functional synthesis of milk is performed by its epithelial (alveolar) cells. The availability of a stable mammary epithelial cell line is essential for biochemical studies to elucidate cellular and molecular mechanisms responsible for nutritional regulation of lactation. Therefore, porcine mammary epithelial cells (PMEC) were isolated from mammary glands of a 9-mo-old nonpregnant and nonlactating gilt and cultured to establish a nonimmortalized cell line. These cells were characterized by expression of cytokeratin-18 (an intermediate filament specific for epithelial cells), β-casein (a specific marker for mammary epithelial cells), and α-lactalbumin. In culture, the PMEC doubled in number every 24 h and maintained a cobblestone morphology, typical for cultured epithelial cells, for at least 15 passages. Addition of 0.2 to 2 μg/mL prolactin to culture medium for 3 d induced the production of β-casein and α-lactalbumin by PMEC in a dose-dependent manner. Thus, we have successfully developed a useful PMEC line for future studies of cellular and molecular regulation of milk synthesis by mammary epithelial cells of the sow.
Epithelial cells as alternative human biomatrices for comet assay
Rojas, Emilio; Lorenzo, Yolanda; Haug, Kristiane; Nicolaissen, Bjørn; Valverde, Mahara
The comet assay is a valuable experimental tool aimed at mapping DNA damage in human cells in vivo for environmental and occupational monitoring, as well as for therapeutic purposes, such as storage prior to transplant, during tissue engineering, and in experimental ex vivo assays. Furthermore, due to its great versatility, the comet assay allows to explore the use of alternative cell types to assess DNA damage, such as epithelial cells. Epithelial cells, as specialized components of many organs, have the potential to serve as biomatrices that can be used to evaluate genotoxicity and may also serve as early effect biomarkers. Furthermore, 80% of solid cancers are of epithelial origin, which points to the importance of studying DNA damage in these tissues. Indeed, studies including comet assay in epithelial cells have either clear clinical applications (lens and corneal epithelial cells) or examine genotoxicity within human biomonitoring and in vitro studies. We here review improvements in determining DNA damage using the comet assay by employing lens, corneal, tear duct, buccal, and nasal epithelial cells. For some of these tissues invasive sampling procedures are needed. Desquamated epithelial cells must be obtained and dissociated prior to examination using the comet assay, and such procedures may induce varying amounts of DNA damage. Buccal epithelial cells require lysis enriched with proteinase K to obtain free nucleosomes. Over a 30 year period, the comet assay in epithelial cells has been little employed, however its use indicates that it could be an extraordinary tool not only for risk assessment, but also for diagnosis, prognosis of treatments and diseases. PMID:25506353
Epithelial cells as alternative human biomatrices for comet assay.
Rojas, Emilio; Lorenzo, Yolanda; Haug, Kristiane; Nicolaissen, Bjørn; Valverde, Mahara
The comet assay is a valuable experimental tool aimed at mapping DNA damage in human cells in vivo for environmental and occupational monitoring, as well as for therapeutic purposes, such as storage prior to transplant, during tissue engineering, and in experimental ex vivo assays. Furthermore, due to its great versatility, the comet assay allows to explore the use of alternative cell types to assess DNA damage, such as epithelial cells. Epithelial cells, as specialized components of many organs, have the potential to serve as biomatrices that can be used to evaluate genotoxicity and may also serve as early effect biomarkers. Furthermore, 80% of solid cancers are of epithelial origin, which points to the importance of studying DNA damage in these tissues. Indeed, studies including comet assay in epithelial cells have either clear clinical applications (lens and corneal epithelial cells) or examine genotoxicity within human biomonitoring and in vitro studies. We here review improvements in determining DNA damage using the comet assay by employing lens, corneal, tear duct, buccal, and nasal epithelial cells. For some of these tissues invasive sampling procedures are needed. Desquamated epithelial cells must be obtained and dissociated prior to examination using the comet assay, and such procedures may induce varying amounts of DNA damage. Buccal epithelial cells require lysis enriched with proteinase K to obtain free nucleosomes. Over a 30 year period, the comet assay in epithelial cells has been little employed, however its use indicates that it could be an extraordinary tool not only for risk assessment, but also for diagnosis, prognosis of treatments and diseases.
Epithelial cyst of the spleen with foci of ectopic liver.
Del Sordo, Rachele; Bellezza, Guido; Colella, Renato; Mameli, Maria Grazia; Giansanti, Michele; Cavaliere, Antonio
Epithelial cysts account for about 20% of all splenic cysts. Their pathogenesis is unclear, and different authors have proposed many hypotheses. It has been suggested that they are derived from embryonal epithelial inclusions during splenic development, from invagination of capsular surface mesothelium in splenic sulci with subsequent metaplasia, or from trauma. Moreover, a congenital, genetic, or teratomatous origin has also been hypothesized. We describe an unusual case of epithelial splenic cyst with mature liver foci in its wall. This finding supports its possible dysontogenetic origin.
Depth sensitive oblique polarized reflectance spectroscopy of oral epithelial tissue
NASA Astrophysics Data System (ADS)
Jimenez, Maria K.; Lam, Sylvia; Poh, Catherine; Sokolov, Konstantin
Identifying depth-dependent alterations associated with epithelial cancerous lesions can be challenging in the oral cavity where variable epithelial thicknesses and troublesome keratin growths are prominent. Spectroscopic methods with enhanced depth resolution would immensely aid in isolating optical properties associated with malignant transformation. Combining multiple beveled fibers, oblique collection geometry, and polarization gating, oblique polarized reflectance spectroscopy (OPRS) achieves depth sensitive detection. We report promising results from a clinical trial of patients with oral lesions suspected of dysplasia or carcinoma demonstrating the potential of OPRS for the analysis of morphological and architectural changes in the context of multilayer, epithelial oral tissue.
Cholecystokinin octapeptide antagonizes apoptosis in human retinal pigment epithelial cells.
Liu, Yuan; Zhang, Yueling; Gu, Zhaohui; Hao, Lina; Du, Juan; Yang, Qian; Li, Suping; Wang, Liying; Gong, Shilei
Although cholecystokinin octapeptide-8 is important for neurological function, its neuroprotective properties remain unclear. We speculated that cholecystokinin octapeptide-8 can protect human retinal pigment epithelial cells against oxidative injury. In this study, retinal pigment epithelial cells were treated with peroxynitrite to induce oxidative stress. Peroxynitrite triggered apoptosis in these cells, and increased the expression of Fas-associated death domain, Bax, caspa-se-8 and Bcl-2. These changes were suppressed by treatment with cholecystokinin octapeptide-8. These results suggest that cholecystokinin octapeptide-8 can protect human retinal pigment epithelial cells against apoptosis induced by peroxynitrite.
Cholecystokinin octapeptide antagonizes apoptosis in human retinal pigment epithelial cells
Liu, Yuan; Zhang, Yueling; Gu, Zhaohui; Hao, Lina; Du, Juan; Yang, Qian; Li, Suping; Wang, Liying; Gong, Shilei
Although cholecystokinin octapeptide-8 is important for neurological function, its neuroprotective properties remain unclear. We speculated that cholecystokinin octapeptide-8 can protect human retinal pigment epithelial cells against oxidative injury. In this study, retinal pigment epithelial cells were treated with peroxynitrite to induce oxidative stress. Peroxynitrite triggered apoptosis in these cells, and increased the expression of Fas-associated death domain, Bax, caspa-se-8 and Bcl-2. These changes were suppressed by treatment with cholecystokinin octapeptide-8. These results suggest that cholecystokinin octapeptide-8 can protect human retinal pigment epithelial cells against apoptosis induced by peroxynitrite. PMID:25221599
Genetics and epithelial cell dysfunction in cystic fibrosis
Riordan, J.R.; Buchwald, M.
This book examines the advances being made in the study of the physiology, cell biology, and molecular genetics of cystic fibrosis. Emphasis is placed on various areas of research that involve epithelial cells (e.g., the CF-specific phenotypes exhibited by epithelial cells, abnormalities in epithelium ion transport, chloride channel regulation in CF epithelial.) Coverage is presented on the current status of CF, including data on the incidence of the disease, its mode of inheritance, chromosomal localization, genetic heterogeneity, and screening and management.
Probing the luminal microenvironment of reconstituted epithelial microtissues
Cerchiari, Alec E.; Samy, Karen E.; Todhunter, Michael E.; Schlesinger, Erica; Henise, Jeff; Rieken, Christopher; Gartner, Zev J.; Desai, Tejal A.
Polymeric microparticles can serve as carriers or sensors to instruct or characterize tissue biology. However, incorporating microparticles into tissues for in vitro assays remains a challenge. We exploit three-dimensional cell-patterning technologies and directed epithelial self-organization to deliver microparticles to the lumen of reconstituted human intestinal microtissues. We also develop a novel pH-sensitive microsensor that can measure the luminal pH of reconstituted epithelial microtissues. These studies offer a novel approach for investigating luminal microenvironments and drug-delivery across epithelial barriers. PMID:27619235
Commentary: acetaldehyde and epithelial-to-mesenchymal transition in colon.
Rao, Radhakrishna K
Elamin and colleagues in this issue report that acetaldehyde activates Snail, a transcription factor involved in epithelial-to-mesenchymal transition, in an intestinal epithelium. Snail mediates acetaldehyde-induced tight junction disruption and increase in paracellular permeability. Results of this study and other previous studies raise several important questions. This commentary addresses these questions by discussing the acetaldehyde concentration in colon, disruption of epical junctional complexes in the intestinal epithelium by acetaldehyde, and the consequence of long-term exposure to acetaldehyde on colonic epithelial regeneration, carcinogenesis, and metastases. The precise role of acetaldehyde in colonic epithelial modifications and promotion of colorectal cancers still remains to be understood.
The kinetics of epithelial cells in relation to ventilating tubes.
O'Donoghue, G M
Although the precise mechanism of ventilating tube extrusion from the tympanic membrane is undetermined, it has often been attributed to epithelial migration. However, there has been no experimental evidence for such a hypothesis. In this study, epithelial migration was examined on 28 human tympanic membranes in which ventilating tubes had been inserted. It was found that the presence of such tubes did not alter the pattern of migration. It appears unlikely that epithelial migration alone is responsible for the extrusion process. A mechanism for ventilating tube expulsion is proposed which is compatible with clinical and experimental findings.
Keeping abreast of the mammary epithelial hierarchy and breast tumorigenesis.
Visvader, Jane E
The epithelium of the mammary gland exists in a highly dynamic state, undergoing dramatic morphogenetic changes during puberty, pregnancy, lactation, and regression. The recent identification of stem and progenitor populations in mouse and human mammary tissue has provided evidence that the mammary epithelium is organized in a hierarchical manner. Characterization of these normal epithelial subtypes is an important step toward understanding which cells are predisposed to oncogenesis. This review summarizes progress in the field toward defining constituent cells and key molecular regulators of the mammary epithelial hierarchy. Potential relationships between normal epithelial populations and breast tumor subtypes are discussed, with implications for understanding the cellular etiology underpinning breast tumor heterogeneity.
reaction due to decreased adsorption of the species on the catalytic surface. For example, i. . . 41 in the catalytic decomposition of formic acid ...over platinum (Ulmstead and Lin, 1978), the preexcitation of the gaseous formic acid molecules (by a 10 W/cm2 CW CO2 laser) resulted in a 50% increase...attention is given to selective and thermal excitation and the role of multiphonon couplings, heterogeneous catalysis , and chemical vapor deposition and
ERIC Educational Resources Information Center
Hawkins, Harry
This article describes how to construct a laser level. This laser level can be made using a typical 4' (or shorter) bubble level and a small laser point. The laser unit is detachable, so the bubble level can also be used in the conventional way. However, the laser level works better than a simple bubble level. Making this inexpensive device is an…
ERIC Educational Resources Information Center
John, Phillip
Selected infrared laser chemistry topics are discussed including carbon dioxide lasers, infrared quanta and molecules, laser-induced chemistry, structural isomerization (laser purification, sensitized reactions, and dielectric breakdown), and fundamental principles of laser isotope separation, focusing on uranium isotope separation. (JN)
NASA Technical Reports Server (NTRS)
NASA formally launched Project LASER (Learning About Science, Engineering and Research) in March 1990, a program designed to help teachers improve science and mathematics education and to provide 'hands on' experiences. It featured the first LASER Mobile Teacher Resource Center (MTRC), is designed to reach educators all over the nation. NASA hopes to operate several MTRCs with funds provided by private industry. The mobile unit is a 22-ton tractor-trailer stocked with NASA educational publications and outfitted with six work stations. Each work station, which can accommodate two teachers at a time, has a computer providing access to NASA Spacelink. Each also has video recorders and photocopy/photographic equipment for the teacher's use. MTRC is only one of the five major elements within LASER. The others are: a Space Technology Course, to promote integration of space science studies with traditional courses; the Volunteer Databank, in which NASA employees are encouraged to volunteer as tutors, instructors, etc; Mobile Discovery Laboratories that will carry simple laboratory equipment and computers to provide hands-on activities for students and demonstrations of classroom activities for teachers; and the Public Library Science Program which will present library based science and math programs.
Laser nitriding and laser carburizing of surfaces
NASA Astrophysics Data System (ADS)
Schaaf, Peter
Laser irradiation of surfaces with short pulses in reactive atmospheres (nitrogen, methane) can lead to very effective nitrification and carburization via complicated laser-surface-gas-plasma-interactions. This laser nitriding and laser carburizing and their basic underlying phenomena will be presented and partly explained by results of example materials (iron, titanium, aluminum, silicon) where nitride and carbide coatings can be formed by fast and easily by Excimer Laser, Nd:YAG laser, Free Electron Laser and also by femtosecond Ti:sapphire laser. This implies laser pulse durations from the nanosecond to the femtosecond regime and wavelengths from ultra-violet to infrared. The resulting surfaces, thin films, coatings and their properties are investigated by combining Mossbauer Spectroscopy, x-ray diffraction, x-ray absorption spectroscopy, Nanoindentation, Resonant Nuclear Reaction Analysis, and Rutherford Backscattering Spectroscopy.
Cultured human cornea healing process after free-electron-laser ablation
NASA Astrophysics Data System (ADS)
Shen, Jin-Hui; Joos, Karen M.; Shetlar, Debra J.; Robinson, Richard D.; Thind, Gurpreet K.; Edwards, Glenn S.; O'Day, Denis M.
The purpose of this study is to investigate the healing process in cultured human cornea after infrared Free Electron Laser ablation. Fresh human cadaver cornea was ablated using the Free Electron Laser at the amide II band peak (6.45 micrometers ). The cornea was then cultured in an incubator for 18 days. Haze development within the ablated area was monitored during culture. Histologic sections of the cornea showed complete re-epithelialization of the lased area, and ablation of the underlying Bowman's layer and stroma. The endothelium appeared unaffected. Cultured human corneas may provide useful information regarding the healing process following laser ablation.
Photodynamic therapy in the treatment of epithelial potentially malignant disorders of the mouth: advantages and disadvantages
NASA Astrophysics Data System (ADS)
Gaimari, G.; Russo, C.; Palaia, G.; Tenore, G.; Del Vecchio, A.; Romeo, U.
Introduction: Leukoplakia is a potentially malignant epithelial lesion with carcinomatous percentages transformation comprehended between 1% and 7% for the homogeneous forms and from 4% to 15% for the non-homogeneous ones. Their removal can be performed by scalpel or laser surgery (excision or vaporization). Photodynamic therapy (PDT) is a bloodless treatment option, based on the involvement of three elements: light, photosensitizer and oxygen. When the molecules of the photosensitizer are activated by a low power laser, energy is transferred to molecular oxygen creating highly reactive radicals of oxygen, that have a cytotoxic effect on target cells. Aim of the study: According to several studies in Literature, it has been decided to evaluate through an initial clinical trial, the efficacy of PDT using topical aminolevulinic acid (5-ALA) activated by a laser diode (λ = 635 nm) to treat potentially oral malignant lesions and to illustrate the advantages and disadvantages derived from the use of this technique. Materials and Methods: Five patients, affected by oral leukoplakia (OL) and oral verrucous leukoplakia (OVL) on the mucosal cheeks, labial commissure, fornix and retromolar areas, have been treated using the PDT. Irradiation time with Diode laser: 1000s. Irradiation mode: Scanning. 5 cycles of 3 minute + final cycle of 100 seconds. Each cycle has been interrupted by pauses of 3 minutes. Results and conclusion: PDT results to be effective in the treatment of OL, especially on OVL. In fact, OVL, due to its irregularity, has got an area of increased retention for the gel that is more difficult to be removed by salivary flow. This could explain the better results obtained in this case rather than in those ones of OL. Furthermore, the advantages have been represented by: less invasivity, high sensitivity for altered tissues, minimal scar tissue, less side effects and no pain during and after operation. In contrast to this, the disadvantages were: longer treatment
Early wound healing of laser in situ keratomileusis–like flaps after treatment with human corneal stromal stem cells
Morgan, Siân R.; Dooley, Erin P.; Kamma-Lorger, Christina; Funderburgh, James L.; Funderburgh, Martha L.; Meek, Keith M.
Purpose To use a well-established organ culture model to investigate the effects of corneal stromal stem cells on the optical and biomechanical properties of corneal wounds after laser in situ keratomileusis (LASIK)–like flap creation. Setting School of Optometry and Vision Sciences, Cardiff University, Cardiff, Wales, United Kingdom. Design Experimental study. Methods The LASIK-like flaps were produced in sheep corneas. The flap beds were treated with corneal stromal stem cells and were then replaced and allowed to heal for different periods of up to 3 weeks in organ culture. The optical transmission of the cornea, the force required to detach the flap, and the presence of myofibroblasts near the flap bed were measured. Results Corneal stromal stem cell–treated flap beds were statistically significantly more transparent after 3 weeks in culture than the untreated controls. At 3 weeks, the mean force necessary to detach the flap was more than twice the force required for the respective control samples. Concurrently, there were 44% activated cells immediately below the flap margin of the controls compared with 29% in the same region of the corneal stromal stem cell–treated flaps. Conclusions In this system, the presence of corneal stromal stem cells at the wound margin significantly increased the adherence of LASIK-like flaps while maintaining corneal transparency. It is postulated that this is achieved by the deposition of extracellular connective tissue similar to that found in the normal cornea and by the paucity of activated keratocytes (myofibroblasts), which are known to scatter a significant amount of the incident light. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned. PMID:27026456
Comparison of laser in situ ketatomileusis and photorefractive keratectomy for myopia using a mixed-effects model
Mori, Yosai; Miyata, Kazunori; Ono, Takashi; Yagi, Yusuke; Kamiya, Kazutaka; Amano, Shiro
Purpose To compare the results of laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) for myopia using a mixed-effects model. Methods This comparative retrospective study was conducted in 1,127 eyes of 579 patients after LASIK and 270 eyes of 144 patients after PRK who had two or more postoperative follow-ups after 3 months. Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), manifest refractive spherical equivalent (MRSE), percentage of eyes within ± 0.5 diopters (D) and ± 1.0 D of targeted refraction, and central corneal thickness were compared between PRK and LASIK groups using a mixed-effects model. Results Compared with the LASIK group, UCVA in the PRK group was significantly worse in the initial year but was significantly better after 4 years. The average BSCVA was not significantly different between the LASIK and PRK groups after 4 years. The average gain of BSCVA in the PRK group was significantly larger than that of the LASIK group after 2 years. MRSE in the LASIK and PRK groups showed a gradual myopic shift until 6 years after surgery. After 6 years, MRSE in the PRK group remained stable whereas MRSE in the LASIK group continued a myopic shift. The percentages of eyes within ± 0.5 D or ± 1.0 D in the LASIK group were significantly higher than those in the PRK group at 3 months but were significantly lower than those in the PRK group at 10 years. Conclusions PRK for myopia shows better efficacy than LASIK for myopia after 4 years. PMID:28362808
A laser is used for many medical purposes. Because the laser beam is so small and precise, it enables ... without injuring surrounding tissue. Some uses of the laser are retinal surgery, excision of lesions, and cauterization ...
ERIC Educational Resources Information Center
Hill, P. D.
Described are the characteristics of the laser and its effects on the body. Discussed are examples of laser treatments, including angioplasty, ophthalmology, and dermatology. A discussion of lasers of clinical interest and their applications is presented. (YP)
ERIC Educational Resources Information Center
Gibson, A. F.
Discusses the present status and future prospects of laser-driven fusion. Current research (which is classified under three main headings: laser-matter interaction processes, compression, and laser development) is also presented. (HM)
NASA Astrophysics Data System (ADS)
Botez, Dan; Scifres, Don R.
Contributors; 1. Monolithic phase-locked semiconductor laser arrays D. Botez; 2. High power coherent, semiconductor laser master oscillator power amplifiers and amplifier arrays D. F. Welch and D. G. Mehuys; 3. Microoptical components applied to incoherent and coherent laser arrays J. R. Leger; 4. Modeling of diode laser arrays G. R. Hadley; 5. Dynamics of coherent semiconductor laser arrays H. G. Winfuland and R. K. Defreez; 6. High average power semiconductor laser arrays and laser array packaging with an emphasis for pumping solid state lasers R. Solarz; 7. High power diode laser arrays and their reliability D. R. Scifres and H. H. Kung; 8. Strained layer quantum well heterostructure laser arrays J. J. Coleman; 9. Vertical cavity surface emitting laser arrays C. J. Chang-Hasnain; 10. Individually addressed arrays of diode lasers D. Carlin.
... to treat cancer: carbon dioxide (CO 2 ) lasers, argon lasers, and neodymium: yttrium -aluminum-garnet (Nd:YAG) ... can be used with endoscopes. CO 2 and argon lasers can cut the skin's surface without going ...
Galectin-3 Regulates Desmoglein-2 and Intestinal Epithelial Intercellular Adhesion*
Jiang, Kun; Rankin, Carl R.; Nava, Porfirio; Sumagin, Ronen; Kamekura, Ryuta; Stowell, Sean R.; Feng, Mingli; Parkos, Charles A.; Nusrat, Asma
The desmosomal cadherins, desmogleins, and desmocollins mediate strong intercellular adhesion. Human intestinal epithelial cells express the desmoglein-2 isoform. A proteomic screen for Dsg2-associated proteins in intestinal epithelial cells identified a lectin referred to as galectin-3 (Gal3). Gal3 bound to N-linked β-galactosides in Dsg2 extracellular domain and co-sedimented with caveolin-1 in lipid rafts. Down-regulation of Gal3 protein or incubation with lactose, a galactose-containing disaccharide that competitively inhibits galectin binding to Dsg2, decreased intercellular adhesion in intestinal epithelial cells. In the absence of functional Gal3, Dsg2 protein was internalized from the plasma membrane and degraded in the proteasome. These results report a novel role of Gal3 in stabilizing a desmosomal cadherin and intercellular adhesion in intestinal epithelial cells. PMID:24567334
Keratinocyte growth factor induces pancreatic ductal epithelial proliferation.
Yi, E S; Yin, S; Harclerode, D L; Bedoya, A; Bikhazi, N B; Housley, R M; Aukerman, S L; Morris, C F; Pierce, G F; Ulich, T R
Keratinocyte growth factor (KGF) causes a proliferation of pancreatic ductal epithelial cells in adult rats after daily systemic administration for 1 to 2 weeks. Even before the proliferation of intralobular ducts is histologically evident, KGF also induces proliferating cell nuclear antigen expression within the ductal epithelium of intercalated, intralobular, and interlobular ducts. KGF also causes incorporation of 5-bromodeoxyuridine in ductal epithelial cells. Epithelial cell proliferation is histologically most prominent at the level of the intralobular ducts adjacent to and within the islets of Langerhans. Pancreatic ductal proliferation is not histologically apparent in rats sacrificed 7 to 10 days after the cessation of KGF administration. The pancreatic hormones insulin, glucagon, somatostatin, and pancreatic polypeptide are normally distributed within islets that demonstrate intrainsular ductal proliferation. The proliferating ductal epithelium does not show endocrine differentiation as evidenced by the lack of immunoreactivity for pancreatic hormones. KGF is a potent in vivo mitogen for pancreatic ductal epithelial cells.
Probiotics promote gut health through stimulation of epithelial innate immunity.
Pagnini, Cristiano; Saeed, Rubina; Bamias, Giorgos; Arseneau, Kristen O; Pizarro, Theresa T; Cominelli, Fabio
Probiotic formulations are widely available and have a variety of proposed beneficial effects, including promotion of gut health. The mechanisms of action of probiotic bacteria in the intestine are still unclear but are generally attributed to an antiinflammatory effect. Here, we demonstrate that the multiple probiotic formulation VSL#3 prevents the onset of intestinal inflammation by local stimulation of epithelial innate immune responses (i.e., increased production of epithelial-derived TNF-alpha and restoration of epithelial barrier function in vivo). We also demonstrate that probiotic bacteria stimulate epithelial production of TNF-alpha and activate NF-kappaB in vitro. Our results support the hypothesis that probiotics promote gut health through stimulation, rather than suppression, of the innate immune system. Furthermore, our findings provide the perspective that defects in innate immunity may play a critical role in the pathogenesis and progression of intestinal disorders, such as inflammatory bowel disease.
Laser-Induced Photic Injury Phenocopies Macular Dystrophy
Zhang, Lijuan; Zheng, Andrew; Nie, Hongping; Bhavsar, Kavita V.; Xu, Yu; Sliney, David H.; Trokel, Stephen L.; Tsang, Stephen H
Objective To describe the phenotypes associated with laser-induced retinal damage in children. Methods Five patients with maculopathy and reduced visual acuity associated with laser pointer use were evaluated. Best-corrected visual acuity, retinal structure, and function were monitored with color fundus, infrared (IR), and red-free images, fundus autofluorescence (AF), spectral domain-optical coherence tomography (SD-OCT), and full-field electroretinography (ERG). Results All five laser pointer injury patients had retinal lesions resembling a macular dystrophy (1 bilateral and 4 unilateral). These lesions were irregular in shape but all had a characteristic dendritic appearance with linear streaks radiating from the lesion. Photoreceptor damage was present in all patients, but serial OCT monitoring showed that subsequent photoreceptor recovery occurred over time in the eyes of at least 4 patients. 1 patient also had bilateral pigment epithelial detachments (PED). Both hyper- and hypoautofluorecence were observed in the laser damage area. Conclusions In general, OCT and IR images are quite useful to diagnose laser damage, but AF is not as sensitive. Laser pointer damage in children can occasionally be misdiagnosed as a macular dystrophy disease, but the distinctive lesions and OCT features are helpful for differentiating laser damage from other conditions. PMID:26927809
Laser Weapons for Naval Applications
IPG fiber lasers , 10 kW/ fiber 7 • Output wavelength is tunable (can operate in atmospheric window) Free Electron Lasers ...Multiple kilowatts over multiple kilometers • Laser power converters can be highly efficient, > 60 % • Fiber lasers are highly compact and... lasers - Free electron lasers • Background • Laser candidates • Additional capabilities - Power beaming 3 Laser Lethality -
Elevated tropomyosin expression is associated with epithelial-mesenchymal transition of lens epithelial cells.
Kubo, Eri; Hasanova, Nailia; Fatma, Nigar; Sasaki, Hiroshi; Singh, Dhirendra P
Injury to lens epithelial cells (LECs) leads to epithelial-mesenchymal transition (EMT) with resultant fibrosis. The tropomyosin (Tpm) family of cytoskeleton proteins is involved in regulating and stabilizing actin microfilaments. Aberrant expression of Tpms leads to abnormal morphological changes with disintegration of epithelial integrity. The EMT of LECs has been proposed as a major cause of posterior capsule opacification (PCO) after cataract surgery. Using in vivo rodent PCO and human cataractous LECs, we demonstrated that the aberrant expression of rat Tpm and human Tpm1α/2β suggested their association in remodelling of the actin cytoskeleton during EMT of LECs. Expression analysis from abnormally growing LECs after lens extraction revealed elevated expression of α-smooth muscle actin (α-SMA), a marker for EMT. Importantly, these cells displayed increased expression of Tpm1α/2β following EMT/PCO formation. Expression of Tpm1α/2β was up-regulated in LECs isolated from cataractous lenses of Shumiya Cataract Rats (SCRs), compared with non-cataractous lenses. Also, LECs from human patients with nuclear cataract and anterior subcapsular fibrosis (ASF) displayed significantly increased expression of Tpm2β mRNA, suggesting that similar signalling invokes the expression of these molecules in LECs of cataractous SCR and human lenses. EMT was observed in LECs overexpressed with Tpm1α/2β, as evidenced by increased expression of α-SMA. These conditions were correlated with remodelling of actin filaments, possibly leading to EMT/PCO and ASF. The present findings may help clarify the condition of the actin cytoskeleton during morphogenetic EMT, and may contribute to development of Tpm-based inhibitors for postponing PCO and cataractogenesis.
The epithelial barrier is maintained by in vivo tight junction expansion during pathologic intestinal epithelial shedding
Marchiando, Amanda M.; Shen, Le; Graham, W. Vallen; Edelblum, Karen L.; Duckworth, Carrie A.; Guan, Yanfang; Montrose, Marshall H.; Turner, Jerrold R.; Watson, Alastair J.M.
BACKGROUND & AIMS Tumor necrosis factor (TNF) increases intestinal epithelial cell shedding and apoptosis, potentially challenging the barrier between the gastrointestinal lumen and internal tissues. We investigated the mechanism of tight junction remodeling and barrier maintenance, as well as the roles of cytoskeletal regulatory molecules during TNF-induced shedding. METHODS We studied wild-type and transgenic mice that express the fluorescent-tagged proteins enhanced green fluorescent protein–occludin or monomeric red fluorescent protein1–ZO-1. After injection of high doses of TNF (7.5µg, i.p.), laparotomies were performed and segments of small intestine were opened to visualize the mucosa by video confocal microscopy. Pharmacologic inhibitors and knockout mice were used to determine the roles of caspase activation, actomyosin, and microtubule remodeling and membrane trafficking in epithelial shedding. RESULTS Changes detected included redistribution of the tight junction proteins ZO-1 and occluding to lateral membranes of shedding cells. These proteins ultimately formed a funnel around the shedding cell that defined the site of barrier preservation. Claudins, E-cadherin, F-actin, myosin II, Rho-associated kinase (ROCK), and myosin light chain kinase (MLCK) were also recruited to lateral membranes. Caspase activity, myosin motor activity, and microtubules were required to initiate shedding, whereas completion of the process required microfilament remodeling and ROCK, MLCK, and dynamin II activities. CONCLUSIONS Maintenance of the epithelial barrier during TNF-induced cell shedding is a complex process that involves integration of microtubules, microfilaments, and membrane traffic to remove apoptotic cells. This process is accompanied by redistribution of apical junctional complex proteins to form intercellular barriers between lateral membranes and maintain mucosal function. PMID:21237166
Epithelial-Mesenchymal Transition (EMT) Gene Variants and Epithelial Ovarian Cancer (EOC) Risk.
Amankwah, Ernest K; Lin, Hui-Yi; Tyrer, Jonathan P; Lawrenson, Kate; Dennis, Joe; Chornokur, Ganna; Aben, Katja K H; Anton-Culver, Hoda; Antonenkova, Natalia; Bruinsma, Fiona; Bandera, Elisa V; Bean, Yukie T; Beckmann, Matthias W; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A; Brooks-Wilson, Angela; Bunker, Clareann H; Butzow, Ralf; Campbell, Ian G; Carty, Karen; Chen, Zhihua; Chen, Y Ann; Chang-Claude, Jenny; Cook, Linda S; Cramer, Daniel W; Cunningham, Julie M; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; du Bois, Andreas; Despierre, Evelyn; Dicks, Ed; Doherty, Jennifer A; Dörk, Thilo; Dürst, Matthias; Easton, Douglas F; Eccles, Diana M; Edwards, Robert P; Ekici, Arif B; Fasching, Peter A; Fridley, Brooke L; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G; Glasspool, Rosalind; Goodman, Marc T; Gronwald, Jacek; Harrington, Patricia; Harter, Philipp; Hasmad, Hanis N; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A T; Hillemanns, Peter; Hogdall, Claus K; Hogdall, Estrid; Hosono, Satoyo; Iversen, Edwin S; Jakubowska, Anna; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y; Jim, Heather; Kellar, Melissa; Kiemeney, Lambertus A; Krakstad, Camilla; Kjaer, Susanne K; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D; Lee, Alice W; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A; Liang, Dong; Lim, Boon Kiong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F A G; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; McNeish, Ian; Menon, Usha; Milne, Roger L; Modugno, Francesmary; Moysich, Kirsten B; Ness, Roberta B; Nevanlinna, Heli; Eilber, Ursula; Odunsi, Kunle; Olson, Sara H; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Paul, James; Pearce, Celeste L; Pejovic, Tanja; Pelttari, Liisa M; Permuth-Wey, Jennifer; Pike, Malcolm C; Poole, Elizabeth M; Risch, Harvey A; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H; Rudolph, Anja; Runnebaum, Ingo B; Rzepecka, Iwona K; Salvesen, Helga B; Schernhammer, Eva; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C; Spiewankiewicz, Beata; Sucheston-Campbell, Lara; Teo, Soo-Hwang; Terry, Kathryn L; Thompson, Pamela J; Thomsen, Lotte; Tangen, Ingvild L; Tworoger, Shelley S; van Altena, Anne M; Vierkant, Robert A; Vergote, Ignace; Walsh, Christine S; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S; Wicklund, Kristine G; Wilkens, Lynne R; Wu, Anna H; Wu, Xifeng; Woo, Yin-Ling; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Kelemen, Linda E; Berchuck, Andrew; Schildkraut, Joellen M; Ramus, Susan J; Goode, Ellen L; Monteiro, Alvaro N A; Gayther, Simon A; Narod, Steven A; Pharoah, Paul D P; Sellers, Thomas A; Phelan, Catherine M
Epithelial-mesenchymal transition (EMT) is a process whereby epithelial cells assume mesenchymal characteristics to facilitate cancer metastasis. However, EMT also contributes to the initiation and development of primary tumors. Prior studies that explored the hypothesis that EMT gene variants contribute to epithelial ovarian carcinoma (EOC) risk have been based on small sample sizes and none have sought replication in an independent population. We screened 15,816 single-nucleotide polymorphisms (SNPs) in 296 genes in a discovery phase using data from a genome-wide association study of EOC among women of European ancestry (1,947 cases and 2,009 controls) and identified 793 variants in 278 EMT-related genes that were nominally (P < 0.05) associated with invasive EOC. These SNPs were then genotyped in a larger study of 14,525 invasive-cancer patients and 23,447 controls. A P-value <0.05 and a false discovery rate (FDR) <0.2 were considered statistically significant. In the larger dataset, GPC6/GPC5 rs17702471 was associated with the endometrioid subtype among Caucasians (odds ratio (OR) = 1.16, 95% CI = 1.07-1.25, P = 0.0003, FDR = 0.19), whereas F8 rs7053448 (OR = 1.69, 95% CI = 1.27-2.24, P = 0.0003, FDR = 0.12), F8 rs7058826 (OR = 1.69, 95% CI = 1.27-2.24, P = 0.0003, FDR = 0.12), and CAPN13 rs1983383 (OR = 0.79, 95% CI = 0.69-0.90, P = 0.0005, FDR = 0.12) were associated with combined invasive EOC among Asians. In silico functional analyses revealed that GPC6/GPC5 rs17702471 coincided with DNA regulatory elements. These results suggest that EMT gene variants do not appear to play a significant role in the susceptibility to EOC.
Effect of Reproductive History on Mammary Epithelial Biology
Reproductive History on Mammary Epithelial Biology PRINCIPAL INVESTIGATOR: Lewis A. Chodosh, M.D., Ph.D. CONTRACTING ORGANIZATION : University of Pennsylvania...9348 Organization : University of Pennsylvania Those portions of the technical data contained in this report marked as limited rights data shall not...History on Mammary Epithelial DAMD17-99-1-9348 Biology 6. AUTHOR(S) Lewis A. Chodosh, M.D., Ph.D. 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8
Mitochondrial DNA Mutations in Epithelial Ovarian Tumor Progression
histological subtype of ovarian cancer and is the most lethal gynecologic malignancy. The relationship between stage at presentation and survival in serous ...among and within stages of epithelial ovarian cancer , focusing on serous , mucinous and endometrioid subtypes (1-18 Months). a. Collections and...not serous or mucinous epithelial ovarian tumors. Cancer Res 58: 2095-2097, 1998. 7. Aikhionbare FO et al:.: Is cumulative frequency of mitochondrial
Expression and Function of CD44 in Epithelial Ovarian Carcinoma
Sacks, Joelle D.; Barbolina, Maria V.
CD44, a cell surface glycoprotein, has been increasingly implicated in the pathogenesis and progression of epithelial ovarian cancer, the deadliest gynecologic malignancy in women. Here, we review recent reports on the expression and function of CD44 in epithelial ovarian carcinoma. Further functional data for CD44 in peritoneal adhesion and metastatic progression and its association with stem cells is highlighted. Recent studies utilizing CD44 for therapeutic targeting are also discussed. PMID:26569327
Focal epithelial hyperplasia. A rare disease in our area.
Segura-Saint-Gerons, Rafael; Toro-Rojas, Mariano; Ceballos-Salobreña, Alejandro; Aparicio-Soria, Jose Luis; Fuentes-Vaamonde, Helena
Focal epithelial hyperplasia is a benign, asymptomatic disease, occurring with very low frequency within our population. It appears as papules, principally on the lower lip, although it can also be found on the retro-commissural mucosa and tongue, and less frequently on the upper lip, gingiva and palate. We present the clinical case of a 9-year-old Saharan girl with lesions that clinically and histologically corresponded to a focal epithelial hyperplasia.
The Limbal Epithelial Progenitors in the Limbal Niche Environment
Zhang, Yuan; Sun, Hong; Liu, Yongsong; Chen, Shuangling; Cai, Subo; Zhu, Yingting; Guo, Ping
Limbal epithelial progenitors are stem cells located in limbal palisades of vogt. In this review, we present the audience with recent evidence that limbal epithelial progenitors may be a powerful stem cell resource for the cure of human corneal stem cell deficiency. Further understanding of their mechanism may shed lights to the future successful application of stem cell therapy not only to the eye tissue, but also to the other tissues in the human body. PMID:27877075
Stress-Derived Corticotropin Releasing Factor Breaches Epithelial Endotoxin Tolerance
Yu, Yong; Geng, Xiao-Rui; Yang, Gui; Liu, Zhi-Gang; Zheng, Peng-Yuan; Yang, Ping-Chang
Background and aims Loss of the endotoxin tolerance of intestinal epithelium contributes to a number of intestinal diseases. The etiology is not clear. Psychological stress is proposed to compromise the intestinal barrier function. The present study aims to elucidate the role of the stress-derived corticotropin releasing factor (CRF) in breaching the established intestinal epithelial endotoxin tolerance. Methods Epithelial cells of HT-29, T84 and MDCK were exposed to lipopolysaccharide to induce the endotoxin tolerance; the cells were then stimulated with CRF. The epithelial barrier function was determined using as indicators of the endotoxin tolerant status. A water-avoid stress mouse model was employed to test the role of CRF in breaching the established endotoxin tolerance in the intestine. Results The established endotoxin tolerance in the epithelial cell monolayers was broken down by a sequent exposure to CRF and LPS manifesting a marked drop of the transepithelial resistance (TER) and an increase in the permeability to a macromolecular tracer, horseradish peroxidase (HRP). The exposure to CRF also increased the expression of Cldn2 in the epithelial cells, which could be mimicked by over expression of TLR4 in epithelial cells. Over expression of Cldn2 resulted in low TER in epithelial monolayers and high permeability to HRP. After treating mice with the 10-day chronic stress, the intestinal epithelial barrier function was markedly compromised, which could be prevented by blocking either CRF, or TLR4, or Cldn2. Conclusions Psychological stress-derived CRF can breach the established endotoxin tolerance in the intestinal mucosa. PMID:23840363
Mechanical stretch triggers rapid epithelial cell division through Piezo1.
Gudipaty, S A; Lindblom, J; Loftus, P D; Redd, M J; Edes, K; Davey, C F; Krishnegowda, V; Rosenblatt, J
Despite acting as a barrier for the organs they encase, epithelial cells turn over at some of the fastest rates in the body. However, epithelial cell division must be tightly linked to cell death to preserve barrier function and prevent tumour formation. How does the number of dying cells match those dividing to maintain constant numbers? When epithelial cells become too crowded, they activate the stretch-activated channel Piezo1 to trigger extrusion of cells that later die. However, it is unclear how epithelial cell division is controlled to balance cell death at the steady state. Here we show that mammalian epithelial cell division occurs in regions of low cell density where cells are stretched. By experimentally stretching epithelia, we find that mechanical stretch itself rapidly stimulates cell division through activation of the Piezo1 channel. To stimulate cell division, stretch triggers cells that are paused in early G2 phase to activate calcium-dependent phosphorylation of ERK1/2, thereby activating the cyclin B transcription that is necessary to drive cells into mitosis. Although both epithelial cell division and cell extrusion require Piezo1 at the steady state, the type of mechanical force controls the outcome: stretch induces cell division, whereas crowding induces extrusion. How Piezo1-dependent calcium transients activate two opposing processes may depend on where and how Piezo1 is activated, as it accumulates in different subcellular sites with increasing cell density. In sparse epithelial regions in which cells divide, Piezo1 localizes to the plasma membrane and cytoplasm, whereas in dense regions in which cells extrude, it forms large cytoplasmic aggregates. Because Piezo1 senses both mechanical crowding and stretch, it may act as a homeostatic sensor to control epithelial cell numbers, triggering extrusion and apoptosis in crowded regions and cell division in sparse regions.
Ion pump sorting in polarized renal epithelial cells.
Caplan, M J
The plasma membranes of renal epithelial cells are divided into distinct apical and basolateral domains, which contain different inventories of ion transport proteins. Without this polarity vectorial ion and fluid transport would not be possible. Little is known of the signals and mechanisms that renal epithelial cells use to establish and maintain polarized distributions of their ion transport proteins. Analysis of ion pump sorting reveals that multiple complex signals participate in determining and regulating these proteins' subcellular localizations.
[The effect of Actihaemyl on epithelial regeneration (author's transl)].
Holtmann, H W; Gasset, A; Lobo, L; Gravenstein, N
After well-defined chemical and mechanical removal of the corneal epithelium of 40 rabbit eyes 20 eyes were treated with Actihaemyl-Augengel 4 times daily. The epithelial regeneration was compared with the untreated contralateral eye. Under Actihaemyl treatment the healing rate was not accelerated. The well-known healing effect of Actihaemyl on different corneal diseases does not seem to come from improving the epithelial regeneration but is probably the result of a general improvement of corneal metabolism.
Laser accidents: Being Prepared
Barat, K
The goal of the Laser Safety Officer and any laser safety program is to prevent a laser accident from occurring, in particular an injury to a person's eyes. Most laser safety courses talk about laser accidents, causes, and types of injury. The purpose of this presentation is to present a plan for safety offices and users to follow in case of accident or injury from laser radiation.
NASA Astrophysics Data System (ADS)
Cheo, Peter K.
The technology and applications of molecular lasers (MLs) are examined in chapters contributed by leading experts. Topics addressed include ML emission spectra, CO2 TEA lasers, RF-discharge-excited CO2 lasers, high-energy short-pulse CO2 lasers, high-power electron-beam-controlled CO2 lasers, HF/DF chemical lasers, optically pumped FIR MLs, and transients and instabilities in FIR MLs. Extensive diagrams, drawings, graphs, photographs, and tables of numerical data are provided.
Reduced Dynamic Models in Epithelial Transport
Hernández, Julio A.
Most models developed to represent transport across epithelia assume that the cell interior constitutes a homogeneous compartment, characterized by a single concentration value of the transported species. This conception differs significantly from the current view, in which the cellular compartment is regarded as a highly crowded media of marked structural heterogeneity. Can the finding of relatively simple dynamic properties of transport processes in epithelia be compatible with this complex structural conception of the cell interior? The purpose of this work is to contribute with one simple theoretical approach to answer this question. For this, the techniques of model reduction are utilized to obtain a two-state reduced model from more complex linear models of transcellular transport with a larger number of intermediate states. In these complex models, each state corresponds to the solute concentration in an intermediate intracellular compartment. In addition, the numerical studies reveal that it is possible to approximate a general two-state model under conditions where strict reduction of the complex models cannot be performed. These results contribute with arguments to reconcile the current conception of the cell interior as a highly complex medium with the finding of relatively simple dynamic properties of transport across epithelial cells. PMID:23533397
Epithelial Sodium and Chloride Channels and Asthma
Wang, Wen; Ji, Hong-Long
Objective: To focus on the asthmatic pathogenesis and clinical manifestations related to epithelial sodium channel (ENaC)/chlorine ion channel. Data Sources: The data analyzed in this review were the English articles from 1980 to 2015 from journal databases, primarily PubMed and Google Scholar. The terms used in the literature search were: (1) ENaCs; cystic fibrosis (CF) transmembrane conductance regulator (CFTR); asthma/asthmatic, (2) ENaC/sodium salt; CF; asthma/asthmatic, (3) CFTR/chlorine ion channels; asthma/asthmatic, (4) ENaC/sodium channel/scnn1a/scnn1b/scnn1g/scnn1d/amiloride-sensitive/amiloride-inhibtable sodium channels/sodium salt; asthma/asthmatic, lung/pulmonary/respiratory/tracheal/alveolar, and (5) CFTR; CF; asthma/asthmatic (ti). Study Selection: These studies included randomized controlled trials or studies covering asthma pathogenesis and clinical manifestations related to ENaC/chlorine ion channels within the last 25 years (from 1990 to 2015). The data involving chronic obstructive pulmonary disease and CF obtained from individual studies were also reviewed by the authors. Results: Airway surface liquid dehydration can cause airway inflammation and obstruction. ENaC and CFTR are closely related to the airway mucociliary clearance. Ion transporters may play a critical role in pathogenesis of asthmatic exacerbations. Conclusions: Ion channels have been the center of many studies aiming to understand asthmatic pathophysiological mechanisms or to identify therapeutic targets for better control of the disease. PMID:26265620
Stochastic Terminal Dynamics in Epithelial Cell Intercalation
NASA Astrophysics Data System (ADS)
Eule, Stephan; Metzger, Jakob; Reichl, Lars; Kong, Deqing; Zhang, Yujun; Grosshans, Joerg; Wolf, Fred
We found that the constriction of epithelial cell contacts during intercalation in germ band extension in Drosophila embryos follows intriguingly simple quantitative laws. The mean contact length < L > follows < L > (t) ~(T - t) α , where T is the finite collapse time; the time dependent variance of contact length is proportional to the square of the mean; finally the time dependent probability density of the contact lengths remains close to Gaussian during the entire process. These observations suggest that the dynamics of contact collapse can be captured by a stochastic differential equation analytically tractable in small noise approximation. Here, we present such a model, providing an effective description of the non-equilibrium statistical mechanics of contact collapse. All model parameters are fixed by measurements of time dependent mean and variance of contact lengths. The model predicts the contact length covariance function that we obtain in closed form. The contact length covariance function closely matches experimental observations suggesting that the model well captures the dynamics of contact collapse.
Loewenstein, Werner R.; Kanno, Yoshinobu
Membrane permeability of an epithelial cell junction (Drosophila salivary gland) was examined with intracellular microelectrodes and with fluorescent tracers. In contrast to the non-junctional cell membrane surface, which has a low permeability to ions (10-4 mho/cm2), the junctional membrane surface is highly permeable. In fact, it introduces no substantial restriction to ion flow beyond that in the cytoplasm; the resistance through a chain of cells (150 Ω cm) is only slightly greater than in extruded cytoplasm (100 Ω cm). The diffusion resistance along the intercellular space to the exterior, on the other hand, is very high. Here, there exists an ion barrier of, at least, 104Ω cm2. As a result, small ions and fluorescein move rather freely from one cell to the next, but do not leak appreciably through the intercellular space to the exterior. The organ here, rather than the single cell, appears to be the unit of ion environment. The possible underlying structural aspects are discussed. PMID:14206423
Particle uptake and translocation across epithelial membranes.
Thomas, N W; Jenkins, P G; Howard, K A; Smith, M W; Lavelle, E C; Holland, J; Davis, S S
Oral delivery of drugs and vaccines has many advantages over other routes of administration. For example, for vaccination, enteric delivery may result in the induction of a mucosal immune response against pathogens which colonise and invade the mucosa. However, the oral delivery of peptide or protein drugs or antigens is beset with problems, such as gastrointestinal breakdown of labile molecules, low level of macromolecular absorption and, for vaccines, the poor immune response usually elicited by orally administered soluble antigens. Investigations are therefore in progress to develop means of increasing intestinal absorption and decreasing digestion of orally administered molecules. Molecules can be incorporated into biodegradable microparticles to reduce the effect of gut secretions and to enable the absorption of bioactive agents in an unaltered form. The uptake of microparticulates through the gut wall is accepted as a true biological phenomenon but the mechanism and route of uptake have not been established. Furthermore, in general, only small numbers of microparticles are translocated across epithelial membranes, possibly making these systems inappropriate for drug or vaccine delivery. This paper reviews particle uptake across the gastrointestinal tract and describes studies carried out to determine whether a humoral response can be elicited following oral administration of an antigen associated with biodegradable poly(DL lactide-coglycolide) microparticles. The use of lipid delivery vehicles to enhance microparticle uptake and the selective transport of microspheres across M cells is also described. PMID:8982821
Hyaluronan: a critical component of epithelial-mesenchymal and epithelial-carcinoma transitions.
Toole, Bryan P; Zoltan-Jones, Alexandra; Misra, Suniti; Ghatak, Shibnath
Hyaluronan plays a central role in the transition of epithelia to mesenchyme in the embryo and in the acquisition of transformed properties in carcinoma cells. In some cases, hyaluronan is both essential and sufficient for induction of epithelial-mesenchymal transitions (EMTs). Underlying its role are the effects of hyaluronan on receptor kinase activities, cell survival pathways, and multidrug transporters. A more complete understanding of the mechanisms whereby hyaluronan exerts its influences on cell behavior will enhance our understanding of normal and pathological EMTs and may lead to improved therapies for cancer patients.
Sunitinib Malate in Treating Patients With Recurrent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer
Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Primary Peritoneal Cavity Cancer
E1a induces the expression of epithelial characteristics
Cells closely resembling epithelia constitute the first specific cell type in a mammalian embryo. Many other cell types emerge via epithelial- mesenchymal differentiation. The transcription factors and signal transduction pathways involved in this differentiation are being elucidated. I have previously reported (Frisch, 1991) that adenovirus E1a is a tumor suppressor gene in certain human cell lines. In the present report, I demonstrate that E1a expression caused diverse human tumor cells (rhabdomyosarcoma, fibrosarcoma, melanoma, osteosarcoma) and fibroblasts to assume at least two of the following epithelial characteristics: (a) epithelioid morphology; (b) epithelial-type intercellular adhesion proteins localized to newly formed junctional complexes; (c) keratin-containing intermediate filaments; and (d) down- regulation of non-epithelial genes. E1a thus appeared to partially convert diverse human tumor cells into an epithelial phenotype. This provides a new system for molecular analysis of epithelial-mesenchymal interconversions. This effect may also contribute to E1a's tumor suppression activity, possibly through sensitization to anoikis (Frisch, S.M., and H. Francis, 1994. J. Cell Biol. 124:619-626). PMID:7525602
Diversity of Epithelial Stem Cell Types in Adult Lung
Li, Feng; He, Jinxi; Wei, Jun; Cho, William C.; Liu, Xiaoming
Lung is a complex organ lined with epithelial cells. In order to maintain its homeostasis and normal functions following injuries caused by varied extraneous and intraneous insults, such as inhaled environmental pollutants and overwhelming inflammatory responses, the respiratory epithelium normally undergoes regenerations by the proliferation and differentiation of region-specific epithelial stem/progenitor cells that resided in distinct niches along the airway tree. The importance of local epithelial stem cell niches in the specification of lung stem/progenitor cells has been recently identified. Studies using cell differentiating and lineage tracing assays, in vitro and/or ex vivo models, and genetically engineered mice have suggested that these local epithelial stem/progenitor cells within spatially distinct regions along the pulmonary tree contribute to the injury repair of epithelium adjacent to their respective niches. This paper reviews recent findings in the identification and isolation of region-specific epithelial stem/progenitor cells and local niches along the airway tree and the potential link of epithelial stem cells for the development of lung cancer. PMID:25810726
Role of calcium signaling in epithelial bicarbonate secretion.
Jung, Jinsei; Lee, Min Goo
Transepithelial bicarbonate secretion plays a key role in the maintenance of fluid and protein secretion from epithelial cells and the protection of the epithelial cell surface from various pathogens. Epithelial bicarbonate secretion is mainly under the control of cAMP and calcium signaling. While the physiological roles and molecular mechanisms of cAMP-induced bicarbonate secretion are relatively well defined, those induced by calcium signaling remain poorly understood in most epithelia. The present review summarizes the current status of knowledge on the role of calcium signaling in epithelial bicarbonate secretion. Specifically, this review introduces how cytosolic calcium signaling can increase bicarbonate secretion by regulating membrane transport proteins and how it synergizes with cAMP-induced mechanisms in epithelial cells. In addition, tissue-specific variations in the pancreas, salivary glands, intestines, bile ducts, and airways are discussed. We hope that the present report will stimulate further research into this important topic. These studies will provide the basis for future medicines for a wide spectrum of epithelial disorders including cystic fibrosis, Sjögren's syndrome, and chronic pancreatitis.
Analysis of the epithelial damage produced by Entamoeba histolytica infection.
Betanzos, Abigail; Schnoor, Michael; Javier-Reyna, Rosario; García-Rivera, Guillermina; Bañuelos, Cecilia; Pais-Morales, Jonnatan; Orozco, Esther
Entamoeba histolytica is the causative agent of human amoebiasis, a major cause of diarrhea and hepatic abscess in tropical countries. Infection is initiated by interaction of the pathogen with intestinal epithelial cells. This interaction leads to disruption of intercellular structures such as tight junctions (TJ). TJ ensure sealing of the epithelial layer to separate host tissue from gut lumen. Recent studies provide evidence that disruption of TJ by the parasitic protein EhCPADH112 is a prerequisite for E. histolytica invasion that is accompanied by epithelial barrier dysfunction. Thus, the analysis of molecular mechanisms involved in TJ disassembly during E. histolytica invasion is of paramount importance to improve our understanding of amoebiasis pathogenesis. This article presents an easy model that allows the assessment of initial host-pathogen interactions and the parasite invasion potential. Parameters to be analyzed include transepithelial electrical resistance, interaction of EhCPADH112 with epithelial surface receptors, changes in expression and localization of epithelial junctional markers and localization of parasite molecules within epithelial cells.
The role of Epstein-Barr virus in epithelial malignancies.
Tsao, Sai-Wah; Tsang, Chi Man; To, Ka-Fai; Lo, Kwok-Wai
The close association of Epstein-Barr virus (EBV) infection with non-keratinizing nasopharyngeal carcinomas and a subset of gastric carcinomas suggests that EBV infection is a crucial event in these cancers. The difficulties encountered in infecting and transforming primary epithelial cells in experimental systems suggest that the role of EBV in epithelial malignancies is complex and multifactorial in nature. Genetic alterations in the premalignant epithelium may support the establishment of latent EBV infection, which is believed to be an initiation event. Oncogenic properties have been reported in multiple EBV latent genes. The BamH1 A rightwards transcripts (BARTs) and the BART-encoded microRNAs (miR-BARTs) are highly expressed in EBV-associated epithelial malignancies and may induce malignant transformation. However, enhanced proliferation may not be the crucial function of EBV infection in epithelial malignancies, at least in the early stages of cancer development. EBV-encoded gene products may confer anti-apoptotic properties and promote the survival of infected premalignant epithelial cells harbouring genetic alterations. Multiple EBV-encoded microRNAs have been reported to have immune evasion functions. Genetic alterations in host cells, as well as inflammatory stroma, could modulate the expression of EBV genes and alter the growth properties of infected premalignant epithelial cells, encouraging their selection during carcinogenesis.
Role of galectins in re-epithelialization of wounds.
Panjwani, Noorjahan
Re-epithelialization is a critical contributing process in wound healing in the human body. When this process is compromised, impaired or delayed, serious disorders of wound healing may result that are painful, difficult to treat, and affect a variety of human tissues. Recent studies have demonstrated that members of the galectin class of β-galactoside-binding proteins modulate re-epithelialization of wounds by novel carbohydrate-based recognition systems. Galectins constitute a family of widely distributed carbohydrate-binding proteins with the affinity for the β-galactoside-containing glycans found on many cell surface and extracellular matrix (ECM) glycoproteins. There are 15 members of the mammalian galectin family that so far have been identified. Studies of the role of galectins in wound healing have revealed that galectin-3 promotes re-epithelialization of corneal, intestinal and skin wounds; galectin-7 promotes re-epithelialization of corneal, skin, kidney and uterine wounds; and galectins-2 and -4 promote re-epithelialization of intestinal wounds. Promising prospects for developing novel therapeutic strategies for the treatment of problematic, slow- or non-healing wounds are implicit in the findings that galectins stimulate the re-epithelialization of wounds of the cornea, skin, intestinal tract and kidney. Molecular mechanisms by which galectins modulate the process of wound healing are beginning to emerge and are described in this review.
Wound re-epithelialization: modulating keratinocyte migration in wound healing.
Raja; Sivamani, K; Garcia, Miki Shirakawa; Isseroff, R Rivkah
An essential feature of a healed wound is the restoration of an intact epidermal barrier through wound epithelialization, also known as re-epithelialization. The directed migration of keratinocytes is critical to wound epithelialization and defects in this function are associated with the clinical phenotype of chronic non-healing wounds. A complex balance of signaling factors and surface proteins are expressed and regulated in a temporospatial manner that promote keratinocyte motility and survival to activate wound re-epithelialization. The majority of this review focuses on the mechanisms that regulate keratinocyte migration in the re-epithelialization process. This includes a review of cell attachments via desmosomes, hemidesmosomes, and integrins, the expression of keratins, the role of growth factors, cytokines and chemokines, eicosanoids, oxygen tension, antimicrobial peptides, and matrix metalloproteinases. Also reviewed are recently emerging novel mediators of keratinocyte motility including the role of electric fields, and signaling via the acetylcholine and beta-adrenergic receptors. These multiple regulators impact the ability of keratinocytes to migrate from the wound edge or other epidermal reservoirs to efficiently re-epithelialize a breach in the integrity of the epidermis. New discoveries will continue to uncover the elegant network of events that result in restoration of epidermal integrity and complete the wound repair process.
Microfluidic approaches for epithelial cell layer culture and characterisation
Thuenauer, Roland; Rodriguez-Boulan, Enrique; Römer, Winfried
In higher eukaryotes, epithelial cell layers line most body cavities and form selective barriers that regulate the exchange of solutes between compartments. In order to fulfil these functions, the cells assume a polarised architecture and maintain two distinct plasma membrane domains, the apical domain facing the lumen and the basolateral domain facing other cells and the extracellular matrix. Microfluidic biochips offer the unique opportunity to establish novel in vitro models of epithelia in which the in vivo microenvironment of epithelial cells is precisely reconstituted. In addition, analytical tools to monitor biologically relevant parameters can be directly integrated on-chip. In this review we summarise recently developed biochip designs for culturing epithelial cell layers. Since endothelial cell layers, which line blood vessels, have similar barrier functions and polar organisation as epithelial cell layers, we also discuss biochips for culturing endothelial cell layers. Furthermore, we review approaches to integrate tools to analyse and manipulate epithelia and endothelia in microfluidic biochips, including methods to perform electrical impedance spectroscopy, methods to detect substances undergoing trans-epithelial transport via fluorescence, spectrophotometry, and mass spectrometry, techniques to mechanically stimulate cells via stretching and fluid flow-induced shear stress, and methods to carry out high-resolution imaging of vesicular trafficking with light microscopy. Taken together, this versatile microfluidic toolbox enables novel experimental approaches to characterise epithelial monolayers. PMID:24668405
Dynamic epigenetic regulation of the microRNA-200 family mediates epithelial and mesenchymal transitions in human tumorigenesis
Davalos, V; Moutinho, C; Villanueva, A; Boque, R; Silva, P; Carneiro, F; Esteller, M
Epithelial-mesenchymal (EMT) and mesenchymal-epithelial (MET) transitions occur in the development of human tumorigenesis and are part of the natural history of the process to adapt to the changing microenvironment. In this setting, the miR-200 family is recognized as a master regulator of the epithelial phenotype by targeting ZEB1 and ZEB2, two important transcriptional repressors of the cell adherence (E-cadherin) and polarity (CRB3 and LGL2) genes. Recently, the putative DNA methylation associated inactivation of various miR-200 members has been described in cancer. Herein, we show that the miR-200ba429 and miR-200c141 transcripts undergo a dynamic epigenetic regulation linked to EMT or MET phenotypes in tumor progression. The 5′-CpG islands of both miR-200 loci were found unmethylated and coupled to the expression of the corresponding miRNAs in human cancer cell lines with epithelial features, such as low levels of ZEB1/ZEB2 and high expression of E-cadherin, CRB3 and LGL2, while CpG island hypermethylation-associated silencing was observed in transformed cells with mesenchymal characteristics. The recovery of miR-200ba429 and miR-200c141 expression by stable transfection in the hypermethylated cells restored the epithelial markers and inhibited migration in cell culture and tumoral growth and metastasis formation in nude mice. We also discovered, using both cell culture and animal models, that the miR-200 epigenetic silencing is not an static and fixed process but it can be shifted to hypermethylated or unmethylated 5′-CpG island status corresponding to the EMT and MET phenotypes, respectively. In fact, careful laser microdissection in human primary colorectal tumorigenesis unveiled that in normal colon mucosa crypts (epithelia) and stroma (mesenchyma) already are unmethylated and methylated at these loci, respectively; and that the colorectal tumors undergo selective miR-200 hypermethylation of their epithelial component. These findings indicate that the
NASA Astrophysics Data System (ADS)
McLear, Mark
Laser technology has significantly impacted our everyday life. Lasers are now used to correct your vision, clear your arteries, and are used in the manufacturing of such diverse products as automobiles, cigarettes, and computers. Lasers are no longer a research tool looking for an application. They are now an integral part of manufacturing. In the case of Class IV lasers, this explosion in laser applications has exposed thousands of individuals to potential safety hazards including eye damage. Specific protective eyewear designed to attenuate the energy of the laser beam below the maximum permissible exposure is required for Class 3B and Class IV lasers according to laser safety standards.
Walbridge, E.W.
A laser satellite power system (SPS) converts solar power captured by earth-orbiting satellites into electrical power on the earth's surface, the satellite-to-ground transmission of power being effected by laser beam. The laser SPS may be an alternative to the microwave SPS. Microwaves easily penetrate clouds while laser radiation does not. Although there is this major disadvantage to a laser SPS, that system has four important advantages over the microwave alternative: (1) land requirements are much less, (2) radiation levels are low outside the laser ground stations, (3) laser beam sidelobes are not expected to interfere with electromagnetic systems, and (4) the laser system lends itself to small-scale demonstration. After describing lasers and how they work, the report discusses the five lasers that are candidates for application in a laser SPS: electric discharge lasers, direct and indirect solar pumped lasers, free electron lasers, and closed-cycle chemical lasers. The Lockheed laser SPS is examined in some detail. To determine whether a laser SPS will be worthy of future deployment, its capabilities need to be better understood and its attractiveness relative to other electric power options better assessed. First priority should be given to potential program stoppers, e.g., beam attenuation by clouds. If investigation shows these potential program stoppers to be resolvable, further research should investigate lasers that are particularly promising for SPS application.
Banús Gassol, J M
The commission of this article plunged me into doubt. First I should confess that I don't find excuse to escape this part if somebody wants to minimally deepen in the knowledge of the biological effects of this energy source. Secondly, when we talk about results, we use terms made and defined by Physics. Often we have polemics about results, and what really happens is that we don't reach agreements because we refer to different terms to explain the same observation; in conclusion we cannot understand each other because we do not know the adequate terms; for example, hypoxemia as oxygen deficit, which is true in an anemic patient as well as in a low oxygen saturation rate. In consequence, a good review of these concepts seems necessary to me. The third reason is the confusion that exists in our environment, I think sometimes of interest, about properties and effects of different types of laser. Only a minimal knowledge of physics will help us to state the scientific basis for understanding. The problems, nevertheless, accumulate due to the fact that the universe to which this article is directed is formed by urologists. What Physics education should we suppose they have? Superficial? Medium? Is it a collective with a uniform knowledge, being it whatever it is? The implication is clear. The article depth will depend on the answers to these questions. Nevertheless, the aim of the authors is to give a base enough to know what the laser is and how it acts. For that, the answer I gave to my questions is that the reader should understand the article and have enough base for, at least, reading critically the articles about laser published in urological journals.
Valacyclovir for the prevention of recurrent herpes simplex virus eye disease after excimer laser photokeratectomy.
Asbell, P A
PURPOSE: A variety of factors have been reported as inducing the reactivation of latent herpes simplex virus (HSV), among them stress, trauma, and UV radiation. Excimer laser photorefractive keratectomy (PRK) is a surgical procedure utilizing a 193 nm ultraviolet light to alter the curvature of the cornea and hence correct vision. Reactivation of ocular herpes simplex keratitis following such excimer laser PRK has been reported. All published cases of HSV reactivation following excimer laser treatment in humans are reviewed. The present study evaluates whether stress, trauma of the corneal de-epithelialization prior to the laser, or the excimer laser treatment itself to the stromal bed induces this ocular reactivation of the latent HSV, and whether a systemic antiviral agent, valacyclovir, would prevent such laser PRK-induced reactivation of the HSV. METHODS: Forty-three normal 1.5- to 2.5-kg New Zealand white rabbits were infected on the surface of the cornea with HSV-1, strain RE. The animals were monitored until resolution, and then all animals were divided into 5 treatment groups: (1) de-epithelialization only, intraperitoneal (i.p.) saline for 14 days; (2) de-epithelialization plus laser, i.p. saline for 14 days; (3) de-epithelialization plus laser, valacyclovir 50 mg/kg per day i.p. for 14 days; (4) de-epithelialization plus laser, valacyclovir 100 mg/kg per day i.p. for 14 days; (5) de-epithelialization plus laser, valacyclovir 150 mg/kg per day i.p. for 14 days. Animals were evaluated in a masked fashion by clinical examination biweekly and viral cultures biweekly through day 28. RESULTS: The reactivation rates were as follows: group 1, 0%; group 2, 67%; group 3, 50%; group 4, 17%; and group 5, 0%. Viral titers were negative in animals that had no reactivation but persistently positive in those that had reactivation (day 6 through day 28). CONCLUSIONS: Excimer laser (193 nm) treatment can trigger reactivation of ocular herpes disease (67%) and viral
Erythropoietin Induces an Epithelial to Mesenchymal Transition-like Process in Mammary Epithelial Cells MCF10A.
Ordoñez-Moreno, Alejandra; Rodriguez-Monterrosas, Cecilia; Cortes-Reynosa, Pedro; Perez-Carreon, Julio Isael; Perez Salazar, Eduardo
Anemia is associated with chemotherapy treatment in cancer patients. Erythropoietin (EPO) has been used to treat anemia of cancer patients, because it stimulates erythropoiesis. However, treatment of breast cancer patients with EPO has been associated with poor prognosis and decrease of survival. Epithelial to mesenchymal transition (EMT) is a process by which epithelial cells are transdifferentiated to a mesenchymal state. It has been implicated in tumor progression, because epithelial cells acquire the capacity to execute the multiple steps of invasion/metastasis process. However, the role of EPO on EMT process in human mammary epithelial cells has not been studied. In the present study, we demonstrate that EPO promotes a decrease of E-cadherin expression, an increase of N-cadherin, vimentin and Snail2 expression, activation of FAK and Src kinases and an increase of MMP-2 and MMP-9 secretions. Moreover, EPO induces an increase of NFκB DNA binding activity, an increase of binding of p50 and p65 NFκB subunits to Snail1 promoter, migration and invasion in mammary non-tumorigenic epithelial cells MCF10A. In summary, these findings demonstrate, for the first time, that EPO induces an EMT-like process in mammary non-tumorigenic epithelial cells. This article is protected by copyright. All rights reserved.
Gastrin stimulates MMP-1 expression in gastric epithelial cells: putative role in gastric epithelial cell migration.
Kumar, J Dinesh; Steele, Islay; Moore, Andrew R; Murugesan, Senthil V; Rakonczay, Zoltan; Venglovecz, Viktoria; Pritchard, D Mark; Dimaline, Rodney; Tiszlavicz, Laszlo; Varro, Andrea; Dockray, Graham J
The pyloric antral hormone gastrin plays a role in remodeling of the gastric epithelium, but the specific targets of gastrin that mediate these effects are poorly understood. Glandular epithelial cells of the gastric corpus express matrix metalloproteinase (MMP)-1, which is a potential determinant of tissue remodeling; some of these cells express the CCK-2 receptor at which gastrin acts. We have now examined the hypothesis that gastrin stimulates expression of MMP-1 in the stomach. We determined MMP-1 transcript abundance in gastric mucosal biopsies from Helicobacter pylori negative human subjects with normal gastric mucosal histology, who had a range of serum gastrin concentrations due in part to treatment with proton pump inhibitors (PPI). The effects of gastrin were studied on gastric epithelial AGS-GR cells using Western blot and migration assays. In human subjects with increased serum gastrin due to PPI usage, MMP-1 transcript abundance was increased 2-fold; there was also increased MMP-7 transcript abundance but not MMP-3. In Western blots, gastrin increased proMMP-1 abundance, as well that of a minor band corresponding to active MMP-1, in the media of AGS-GR cells, and the response was mediated by protein kinase C and p42/44 MAP kinase. There was also increased MMP-1 enzyme activity. Gastrin-stimulated AGS-GR cell migration in both scratch wound and Boyden chamber assays was inhibited by MMP-1 immunoneutralization. We conclude that MMP-1 expression is a target of gastrin implicated in mucosal remodeling.
Epithelioid peritoneal mesothelioma: a hybrid phenotype within a mesenchymal-epithelial/epithelial-mesenchymal transition framework.
Bozzi, Fabio; Brich, Silvia; Dagrada, Gian Paolo; Negri, Tiziana; Conca, Elena; Cortelazzi, Barbara; Belfiore, Antonino; Perrone, Federica; Gualeni, Ambra Vittoria; Gloghini, Annunziata; Cabras, Antonello; Brenca, Monica; Maestro, Roberta; Zaffaroni, Nadia; Casali, Paolo; Bertulli, Rossella; Deraco, Marcello; Pilotti, Silvana
The aim of this study was to reconsider the biological characteristics of epithelioid malignant peritoneal mesothelioma (E-MpM) in the light of new concepts about epithelial mesenchymal transition and mesenchymal epithelial reverse transition (EMT/MErT) and the role of epigenetic reprogramming in this context. To this end we profiled surgical specimens and derived cells cultures by a number of complementary approaches i.e. immunohistochemistry, immunofluorescence, in situ hybridization, biochemistry, pluripotent stem cell arrays, treatments with cytokines, growth factors and specific inhibitors.The analyses of the surgical specimens showed that i) EZH2 is expressed throughout the spectrum of MpM, ii) that E-MpM (including the high-grade undifferentiated form) are characterised by c-MYC and miRNA 17-5p expression, and iii) that progression to sarcomatoid MpM is dictated by EMT regulators. They also showed that E-MpM expressed c-MET and are enriched in E- and P-cadherins- and VEGFR2-expressing CSCs, thus strongly supporting a role for MErT reprogramming in endowing E-MpM tumour cells with stemness and plasticity, and hence with a drug resistant phenotype. The cell culture-based experiments confirmed the stemness traits and plasticity of E-MpM, and support the view that EZH2 is a druggable target in this tumor.
Epithelial deletion of podoplanin is dispensable for re-epithelialization of skin wounds.
Baars, Sebastian; Bauer, Christine; Szabowski, Sibylle; Hartenstein, Bettina; Angel, Peter
The mucin-like transmembrane protein podoplanin (PDPN) is prominently represented in tumor-associated gene expression signatures of numerous types of cancer including squamous cell carcinoma, and gain-of-function and knockdown approaches in tissue culture strongly suggested an important role of PDPN in cell proliferation, migration and adhesion. PDPN is absent during epidermal homeostasis but is highly expressed in basal keratinocytes during cutaneous wound healing. Enhanced motility of immortalized keratinocytes upon ectopic PDPN overexpression argues for wound healing defects upon podoplanin deficiency in keratinocytes; however, in vivo data that unequivocally define the impact of PDPN by functional studies in a physiologically relevant system are still missing. Here, we have applied an in vivo loss-of-function approach by generating a novel transgenic mouse line with keratinocyte-specific podoplanin deficiency. Performing cutaneous full-thickness excisional wounds to examine re-epithelialization capacity, unexpectedly, no defects were observed in wound healing properties of mutant mice. Similarly, PDPN-deficient primary keratinocytes showed no impairment in migration, adhesion or proliferation. Thus, PDPN function is not rate-limiting for re-epithelialization but may be functionally compensated by an as yet unknown protein. Our data also call for in vivo functional studies on PDPN in settings of skin tumor development and progression to clarify PDPN's role in skin pathology.
Epithelioid peritoneal mesothelioma: a hybrid phenotype within a mesenchymal-epithelial/epithelial-mesenchymal transition framework
Bozzi, Fabio; Brich, Silvia; Dagrada, Gian Paolo; Negri, Tiziana; Conca, Elena; Cortelazzi, Barbara; Belfiore, Antonino; Perrone, Federica; Gualeni, Ambra Vittoria; Gloghini, Annunziata; Cabras, Antonello; Brenca, Monica; Maestro, Roberta; Zaffaroni, Nadia; Casali, Paolo; Bertulli, Rossella; Deraco, Marcello; Pilotti, Silvana
The aim of this study was to reconsider the biological characteristics of epithelioid malignant peritoneal mesothelioma (E-MpM) in the light of new concepts about epithelial mesenchymal transition and mesenchymal epithelial reverse transition (EMT/MErT) and the role of epigenetic reprogramming in this context. To this end we profiled surgical specimens and derived cells cultures by a number of complementary approaches i.e. immunohistochemistry, immunofluorescence, in situ hybridization, biochemistry, pluripotent stem cell arrays, treatments with cytokines, growth factors and specific inhibitors. The analyses of the surgical specimens showed that i) EZH2 is expressed throughout the spectrum of MpM, ii) that E-MpM (including the high-grade undifferentiated form) are characterised by c-MYC and miRNA 17-5p expression, and iii) that progression to sarcomatoid MpM is dictated by EMT regulators. They also showed that E-MpM expressed c-MET and are enriched in E- and P-cadherins- and VEGFR2-expressing CSCs, thus strongly supporting a role for MErT reprogramming in endowing E-MpM tumour cells with stemness and plasticity, and hence with a drug resistant phenotype. The cell culture-based experiments confirmed the stemness traits and plasticity of E-MpM, and support the view that EZH2 is a druggable target in this tumor. PMID:27705913
The Geoscience Laser Altimeter System Laser Transmitter
NASA Technical Reports Server (NTRS)
Afzal, R. S.; Dallas, J. L.; Yu, A. W.; Mamakos, W. A.; Lukemire, A.; Schroeder, B.; Malak, A.
The Geoscience Laser Altimeter System (GLAS), scheduled to launch in 2001, is a laser altimeter and lidar for tile Earth Observing System's (EOS) ICESat mission. The laser transmitter requirements, design and qualification test results for this space- based remote sensing instrument are presented.
Studies on lasers and laser devices
NASA Technical Reports Server (NTRS)
Harris, S. E.; Siegman, A. E.; Young, J. F.
The goal of this grant was to study lasers, laser devices, and uses of lasers for investigating physical phenomena are studied. The active projects included the development of a tunable, narrowband XUV light source and its application to the spectroscopy of core excited atomic states, and the development of a technique for picosecond time resolution spectroscopy of fast photophysical processes.
Ultrastructure observation of middle ear mucosa with laser irradiation
NASA Astrophysics Data System (ADS)
Kang, Mengkui; Yang, Shulan; Fang, Yaoyun; Sun, Jianhe
In order to study the effects of He-Ne laser on the mucosa of middle ear mucosa from 9 patients with chronic otitis media, all of who had slight damp eardrum, were irradiated by low power He-Ne laser ten minutes per day for ten days. Specimen was taken before and after irradiation and observed under scanning electron microscope. It was found that the surface structure of the mucosa was more integral, the arrangement of the epithelial cell was closer together and microvilli arose among the noncilliated cells after irradiation. The inflammatory cell disappeared arid the morphologic structure appeared normal. These data provided the therapeutic evidence for the lower power He-Ne laser irradiation on patients with chronic purulent otitis midia.
Sonic Hedgehog regulates thymic epithelial cell differentiation
Saldaña, José Ignacio; Solanki, Anisha; Lau, Ching-In; Sahni, Hemant; Ross, Susan; Furmanski, Anna L.; Ono, Masahiro; Holländer, Georg; Crompton, Tessa
Sonic Hedgehog (Shh) is expressed in the thymus, where it regulates T cell development. Here we investigated the influence of Shh on thymic epithelial cell (TEC) development. Components of the Hedgehog (Hh) signalling pathway were expressed by TEC, and use of a Gli Binding Site-green fluorescence protein (GFP) transgenic reporter mouse demonstrated active Hh-dependent transcription in TEC in the foetal and adult thymus. Analysis of Shh-deficient foetal thymus organ cultures (FTOC) showed that Shh is required for normal TEC differentiation. Shh-deficient foetal thymus contained fewer TEC than wild type (WT), the proportion of medullary TEC was reduced relative to cortical TEC, and cell surface expression of MHC Class II molecules was increased on both cortical and medullary TEC populations. In contrast, the Gli3-deficient thymus, which shows increased Hh-dependent transcription in thymic stroma, had increased numbers of TEC, but decreased cell surface expression of MHC Class II molecules on both cortical and medullary TEC. Neutralisation of endogenous Hh proteins in WT FTOC led to a reduction in TEC numbers, and in the proportion of mature Aire-expressing medullary TEC, but an increase in cell surface expression of MHC Class II molecules on medullary TEC. Likewise, conditional deletion of Shh from TEC in the adult thymus resulted in alterations in TEC differentiation and consequent changes in T cell development. TEC numbers, and the proportion of mature Aire-expressing medullary TEC were reduced, and cell surface expression of MHC Class II molecules on medullary TEC was increased. Differentiation of mature CD4 and CD8 single positive thymocytes was increased, demonstrating the regulatory role of Shh production by TEC on T cell development. Treatment of human thymus explants with recombinant Shh or neutralising anti-Shh antibody indicated that the Hedgehog pathway is also involved in regulation of differentiation from DP to mature SP T cells in the human thymus. PMID
Pancreatic Mesenchyme Regulates Epithelial Organogenesis throughout Development
Landsman, Limor; Nijagal, Amar; Whitchurch, Theresa J.; VanderLaan, Renee L.; Zimmer, Warren E.; MacKenzie, Tippi C.; Hebrok, Matthias
The developing pancreatic epithelium gives rise to all endocrine and exocrine cells of the mature organ. During organogenesis, the epithelial cells receive essential signals from the overlying mesenchyme. Previous studies, focusing on ex vivo tissue explants or complete knockout mice, have identified an important role for the mesenchyme in regulating the expansion of progenitor cells in the early pancreas epithelium. However, due to the lack of genetic tools directing expression specifically to the mesenchyme, the potential roles of this supporting tissue in vivo, especially in guiding later stages of pancreas organogenesis, have not been elucidated. We employed transgenic tools and fetal surgical techniques to ablate mesenchyme via Cre-mediated mesenchymal expression of Diphtheria Toxin (DT) at the onset of pancreas formation, and at later developmental stages via in utero injection of DT into transgenic mice expressing the Diphtheria Toxin receptor (DTR) in this tissue. Our results demonstrate that mesenchymal cells regulate pancreatic growth and branching at both early and late developmental stages by supporting proliferation of precursors and differentiated cells, respectively. Interestingly, while cell differentiation was not affected, the expansion of both the endocrine and exocrine compartments was equally impaired. To further elucidate signals required for mesenchymal cell function, we eliminated β-catenin signaling and determined that it is a critical pathway in regulating mesenchyme survival and growth. Our study presents the first in vivo evidence that the embryonic mesenchyme provides critical signals to the epithelium throughout pancreas organogenesis. The findings are novel and relevant as they indicate a critical role for the mesenchyme during late expansion of endocrine and exocrine compartments. In addition, our results provide a molecular mechanism for mesenchymal expansion and survival by identifying β-catenin signaling as an essential mediator
Sonic Hedgehog regulates thymic epithelial cell differentiation.
Saldaña, José Ignacio; Solanki, Anisha; Lau, Ching-In; Sahni, Hemant; Ross, Susan; Furmanski, Anna L; Ono, Masahiro; Holländer, Georg; Crompton, Tessa
Sonic Hedgehog (Shh) is expressed in the thymus, where it regulates T cell development. Here we investigated the influence of Shh on thymic epithelial cell (TEC) development. Components of the Hedgehog (Hh) signalling pathway were expressed by TEC, and use of a Gli Binding Site-green fluorescence protein (GFP) transgenic reporter mouse demonstrated active Hh-dependent transcription in TEC in the foetal and adult thymus. Analysis of Shh-deficient foetal thymus organ cultures (FTOC) showed that Shh is required for normal TEC differentiation. Shh-deficient foetal thymus contained fewer TEC than wild type (WT), the proportion of medullary TEC was reduced relative to cortical TEC, and cell surface expression of MHC Class II molecules was increased on both cortical and medullary TEC populations. In contrast, the Gli3-deficient thymus, which shows increased Hh-dependent transcription in thymic stroma, had increased numbers of TEC, but decreased cell surface expression of MHC Class II molecules on both cortical and medullary TEC. Neutralisation of endogenous Hh proteins in WT FTOC led to a reduction in TEC numbers, and in the proportion of mature Aire-expressing medullary TEC, but an increase in cell surface expression of MHC Class II molecules on medullary TEC. Likewise, conditional deletion of Shh from TEC in the adult thymus resulted in alterations in TEC differentiation and consequent changes in T cell development. TEC numbers, and the proportion of mature Aire-expressing medullary TEC were reduced, and cell surface expression of MHC Class II molecules on medullary TEC was increased. Differentiation of mature CD4 and CD8 single positive thymocytes was increased, demonstrating the regulatory role of Shh production by TEC on T cell development. Treatment of human thymus explants with recombinant Shh or neutralising anti-Shh antibody indicated that the Hedgehog pathway is also involved in regulation of differentiation from DP to mature SP T cells in the human thymus.
Phototherapeutic keratectomy for epithelial basement membrane dystrophy
Lee, Wen-Shin; Lam, Carson K; Manche, Edward E
Purpose The purpose of this study was to evaluate the long-term efficacy of phototherapeutic keratectomy (PTK) in treating epithelial basement membrane dystrophy (EBMD). Methods Preoperative and postoperative records were reviewed for 58 eyes of 51 patients with >3 months follow-up (range 3–170 months) treated for EBMD with PTK after failure of conservative medical treatment at Byers Eye Institute of Stanford University. Symptoms, clinical findings, and corrected distance visual acuity (CDVA) were assessed. The primary outcome measure was symptomatic recurrence as measured by erosions or visual complaints >3 months after successful PTK. Results For eyes with visual disturbances (n=30), preoperative CDVA waŝ20/32 (0.24 Log-MAR, SD 0.21) and postoperative CDVA was ~20/25 (0.07 LogMAR, SD 0.12; P<0.0001). Twenty-six eyes (86.7%) responded to treatment, with symptomatic recurrence in 6 eyes (23.1%) at an average of 37.7 months (SD 42.8). For eyes with painful erosions (n=29), preoperative CDVA was ~20/25 (0.12, SD 0.19) and postoperative CDVA was ~20/20 (0.05. SD 0.16; P=0.0785). Twenty-three eyes (79.3%) responded to treatment, with symptomatic recurrence in 3 eyes (13.0%) at an average of 9.7 months (SD 1.5). The probability of being recurrence free after a successful treatment for visual disturbances and erosions at 5 years postoperatively was estimated at 83.0% (95% confidence interval 68.7%–97.0%) and 88.0% (95% confidence interval 65.3%–96.6%), respectively. Conclusion The majority of visual disturbances and painful erosions associated with EBMD respond to PTK. For those with a treatment response, symptomatic relief is maintained over long-term follow-up. PMID:28031698
Human Mammary Luminal Epithelial Cells Contain Progenitors to Myoepithelial Cells
Pechoux, Christine; Gudjonsson, Thorarinn; Ronnov-Jessen, Lone; Bissell, Mina J; Petersen, Ole
The origin of the epithelial and myoepithelial cells in the human breast has not been delineated. In this study we have addressed whether luminal epithelial cells and myoepithelial cells are vertically connected, i.e., whether one is the precursor for the other. We used a primary culture assay allowing preservation of basic phenotypic traits of luminal epithelial and myoepithelial cells in culture. The two cell types were then separated immunomagnetically using antibodies directed against lineage-specific cell surface antigens into at best 100% purity. The cellular identity was ascertained by cytochemistry, immunoblotting, and 2-D gel electrophoresis. Luminal epithelial cells were identified by strong expression of cytokeratins 18 and 19 while myoepithelial cells were recognized by expression of vimentin and {alpha}-smooth muscle actin. We used a previously devised culture medium (CDM4) that allows vigorous expansion of proliferative myoepithelial cells and also devised a medium (CDM6) that allowed sufficient expansion of differentiated luminal epithelial cells based on addition of hepatocyte growth factor/scatter factor. The two different culture media supported each lineage for at least five passages without signs of interconversion. We used parallel cultures where we switched culture media, thus testing the ability of each lineage to convert to the other. Whereas the myoepithelial lineage showed no signs of interconversion, a subset of luminal epithelial cells, gradually, but distinctly, converted to myoepithelial cells. We propose that in the mature human breast, it is the luminal epithelial cell compartment that gives rise to myoepithelial cells rather than the other way around.
Probiotics promote endocytic allergen degradation in gut epithelial cells
Song, Chun-Hua; Liu, Zhi-Qiang; Huang, Shelly; Zheng, Peng-Yuan; Yang, Ping-Chang
Highlights: Black-Right-Pointing-Pointer Knockdown of A20 compromised the epithelial barrier function. Black-Right-Pointing-Pointer The fusion of endosome/lysosome was disturbed in the A20-deficient HT-29 cells. Black-Right-Pointing-Pointer Antigens transported across A20-deficient HT-29 monolayers conserved antigenicity. Black-Right-Pointing-Pointer Probiotic proteins increased the expression of A20 in HT-29 cells. -- Abstract: Background and aims: Epithelial barrier dysfunction plays a critical role in the pathogenesis of allergic diseases; the mechanism is to be further understood. The ubiquitin E3 ligase A20 (A20) plays a role in the endocytic protein degradation in the cells. This study aims to elucidate the role of A20 in the maintenance of gut epithelial barrier function. Methods: Gut epithelial cell line, HT-29 cell, was cultured into monolayers to evaluate the barrier function in transwells. RNA interference was employed to knock down the A20 gene in HT-29 cells to test the role of A20 in the maintenance of epithelial barrier function. Probiotic derived proteins were extracted from the culture supernatants using to enhance the expression of A20 in HT-29 cells. Results: The results showed that the knockdown of A20 compromised the epithelial barrier function in HT-29 monolayers, mainly increased the intracellular permeability. The fusion of endosome/lysosome was disturbed in the A20-deficient HT-29 cells. Allergens collected from the transwell basal chambers of A20-deficient HT-29 monolayers still conserved functional antigenicity. Treating with probiotic derived proteins increased the expression of A20 in HT-29 cells and promote the barrier function. Conclusion: A20 plays an important role in the maintenance of epithelial barrier function as shown by HT-29 monolayer. Probiotic derived protein increases the expression of A20 and promote the HT-29 monolayer barrier function.
Epimorphin Functions as a Key Morphoregulator for Mammary Epithelial Cells
Hirai, H.; Lochter, A.; Galosy, S.; Koshida, S.; Niwa, S.; Bissell, M.J.
Hepatocyte growth factor (HGF) and EGF have been reported to promote branching morphogenesis of mammary epithelial cells. We now show that it is epimorphin that is primarily responsible for this phenomenon. In vivo, epimorphin was detected in the stromal compartment but not in lumenal epithelial cells of the mammary gland; in culture, however, a subpopulation of mammary epithelial cells produced significant amounts of epimorphin. When epimorphin-expressing epithelial cell clones were cultured in collagen gels they displayed branching morphogenesis in the presence of HGF, EGF, keratinocyte growth factor, or fibroblast growth factor, a process that was inhibited by anti-epimorphin but not anti-HGF antibodies. The branch length, however, was roughly proportional to the ability of the factors to induce growth. Accordingly, epimorphin-negative epithelial cells simply grew in a cluster in response to the growth factors and failed to branch. When recombinant epimorphin was added to these collagen gels, epimorphin-negative cells underwent branching morphogenesis. The mode of action of epimorphin on morphogenesis of the gland, however, was dependent on how it was presented to the mammary cells. If epimorphin was overexpressed in epimorphin-negative epithelial cells under regulation of an inducible promoter or was allowed to coat the surface of each epithelial cell in a nonpolar fashion, the cells formed globular, alveoli-like structures with a large central lumen instead of branching ducts. This process was enhanced also by addition of HGF, EGF, or other growth factors and was inhibited by epimorphin antibodies. These results suggest that epimorphin is the primary morphogen in the mammary gland but that growth factors are necessary to achieve the appropriate cell numbers for the resulting morphogenesis to be visualized.
Zinc reduces epithelial barrier compromise induced by human seminal plasma
Mullin, James M.; Diguilio, Katherine M.; Valenzano, Mary C.; Deis, Rachael; Thomas, Sunil; Zurbach, E. Peter; Abdulhaqq, Shaheed; Montaner, Luis J.
Human semen has the potential to modulate the epithelial mucosal tissues it contacts, as seminal plasma (SP) is recognized to contain both pro- and anti-barrier components, yet its effects on epithelial barrier function are largely unknown. We addressed the role of human SP when exposed to the basal-lateral epithelial surface, a situation that would occur clinically with prior mechanical or disease-related injury of the human epithelial mucosal cell layers in contact with semen. The action of SP on claudins-2, -4, -5, and -7 expression, as well as on a target epithelium whose basolateral surface has been made accessible to SP, showed upregulation of claudins-4 and -5 in CACO-2 human epithelial cell layers, despite broad variance in SP-induced modulation of transepithelial electrical resistance and mannitol permeability. Upregulation of claudin-2 by SP also exhibited such variance by SP sample. We characterize individual effects on CACO-2 barrier function of nine factors known to be present abundantly in seminal plasma (zinc, EGF, citrate, spermine, fructose, urea, TGF, histone, inflammatory cytokines) to establish that zinc, spermine and fructose had significant potential to raise CACO-2 transepithelial resistance, whereas inflammatory cytokines and EGF decreased this measure of barrier function. The role of zinc as a dominant factor in determining higher levels of transepithelial resistance and lower levels of paracellular leak were confirmed by zinc chelation and exogenous zinc addition. As expected, SP presentation to the basolateral cell surface also caused a very dramatic yet transient elevation of pErk levels. Results suggest that increased zinc content in SP can compete against the barrier-compromising effect of negative modulators in SP when SP gains access to that epithelium's basolateral surface. Prophylactic elevation of zinc in an epithelial cell layer prior to contact by SP may help to protect an epithelial barrier from invasion by SP-containing STD
Implications of the Hybrid Epithelial/Mesenchymal Phenotype in Metastasis
Jolly, Mohit Kumar; Boareto, Marcelo; Huang, Bin; Jia, Dongya; Lu, Mingyang; Ben-Jacob, Eshel; Onuchic, José N.; Levine, Herbert
Transitions between epithelial and mesenchymal phenotypes – the epithelial to mesenchymal transition (EMT) and its reverse the mesenchymal to epithelial transition (MET) – are hallmarks of cancer metastasis. While transitioning between the epithelial and mesenchymal phenotypes, cells can also attain a hybrid epithelial/mesenchymal (E/M) (i.e., partial or intermediate EMT) phenotype. Cells in this phenotype have mixed epithelial (e.g., adhesion) and mesenchymal (e.g., migration) properties, thereby allowing them to move collectively as clusters. If these clusters reach the bloodstream intact, they can give rise to clusters of circulating tumor cells (CTCs), as have often been seen experimentally. Here, we review the operating principles of the core regulatory network for EMT/MET that acts as a "three-way" switch giving rise to three distinct phenotypes – E, M and hybrid E/M – and present a theoretical framework that can elucidate the role of many other players in regulating epithelial plasticity. Furthermore, we highlight recent studies on partial EMT and its association with drug resistance and tumor-initiating potential; and discuss how cell–cell communication between cells in a partial EMT phenotype can enable the formation of clusters of CTCs. These clusters can be more apoptosis-resistant and have more tumor-initiating potential than singly moving CTCs with a wholly mesenchymal (complete EMT) phenotype. Also, more such clusters can be formed under inflammatory conditions that are often generated by various therapies. Finally, we discuss the multiple advantages that the partial EMT or hybrid E/M phenotype have as compared to a complete EMT phenotype and argue that these collectively migrating cells are the primary "bad actors" of metastasis. PMID:26258068
NASA Astrophysics Data System (ADS)
Katori, H.; Yoneda, H.; Nakagawa, K.; Shimizu, F.
.] -- Ultracold Ytterbium atoms in optical lattices / S. Sugawa ... [et al.] -- Ultracold polar molecules in the rovibrational ground state / J. Deiglmayr ... [et al.] -- Polar molecules near quantum degeneracy / J. Ye and D. S. Jin -- Production of a quantum gas of rovibronic ground-state molecules in an optical lattice / J. G. Danzl ... [et al.] -- Recent progress in x-ray nonlinear optics / K. Tamasaku, K. Sawada, and T. Ishikawa -- Gas in scattering media absorption spectroscopy - laser spectroscopy in unconventional environments / S. Svanberg -- Laser spectroscopy on relativistic ion beams / S. Reinhardt ... [et al.] -- Single frequency microcavity lasers and applications / L. Xu ... [et al.].
NASA Technical Reports Server (NTRS)
Anthony, Thomas R. (Inventor)
This invention provides a method for laser drilling small diameter, closely-spaced, and accurately located holes in a body of material which is transparent or substantially transparent to the laser radiation employed whereby the holes are drilled through the thickness of the body from the surface opposite to that on which the laser beam impinges to the surface of laser beam impingement.
Laser photobiology and photomedicine
Martellucci, S.; Chester, A.N.
This book presents information on the following topics: the physical and biological basis of photobiology and photomedicine; the biological effects and applications of laser technology; photochemotherapy; photobiology and dermatology; surgical and ophthalmological applications of lasers; laser safety; and diagnostics and technological aspects of recent laser developments.
Milewski, J.O.; Sklar, E.
A laser welding process including: (a) using optical ray tracing to make a model of a laser beam and the geometry of a joint to be welded; (b) adjusting variables in the model to choose variables for use in making a laser weld; and (c) laser welding the joint to be welded using the chosen variables. 34 figs.
Milewski, John O.; Sklar, Edward
A laser welding process including: (a) using optical ray tracing to make a model of a laser beam and the geometry of a joint to be welded; (b) adjusting variables in the model to choose variables for use in making a laser weld; and (c) laser welding the joint to be welded using the chosen variables.
Barat, K
The growth of laser development & technology has been remarkable. Unfortunately, a number of traps or obstacles to laser safety have also developed with that growth. The goal of this article is to highlight those traps, in the hope that an aware laser user will avoid them. These traps have been the cause or contributing factor of many a preventable laser accident.
Hagelstein, P.L.
A short wavelength laser is provided that is driven by conventional-laser pulses. A multiplicity of panels, mounted on substrates, are supported in two separated and alternately staggered facing and parallel arrays disposed along an approximately linear path. When the panels are illuminated by the conventional-laser pulses, single pass EUV or soft x-ray laser pulses are produced.
Longitudinal discharge laser baffles
Warner, B.E.; Ault, E.R.
The IR baffles placed between the window and the electrode of a longitudinal discharge laser improve laser performance by intercepting off-axis IR radiation from the laser and in doing so reduce window heating and subsequent optical distortion of the laser beam. 1 fig.
Longitudinal discharge laser baffles
Warner, Bruce E.; Ault, Earl R.
The IR baffles placed between the window and the electrode of a longitudinal discharge laser improve laser performance by intercepting off-axis IR radiation from the laser and in doing so reduce window heating and subsequent optical distortion of the laser beam.
Solar driven lasers for power satellite applications
NASA Technical Reports Server (NTRS)
Taussio, R.; Cassady, P.; Klosterman, E.
The technological feasibility of using multimagawatt lasers for space power transmission is discussed. Candidate lasers include electric discharge lasers, direct optically pumped lasers, and free electron lasers.
NASA Astrophysics Data System (ADS)
Julien, Lucile; Schwob, Catherine
The first laser was built more than 50 years ago, inMay 1960: it was a pulsed ruby laser. It was a simple laboratory curiosity and nobody knew what its usefulness could be. Other devices were rapidly demonstrated, and the variety and number of lasers in the world increased at a huge rate. Currently, the annual laser world market is worth about 6 billion dollars. Thanks to the remarkable properties of laser light, laser applications increase steadily in the domains of industry, building, medicine, telecommunications, etc. One can find many lasers in research laboratories, and they are used more and more in our everyday life and almost everybody has already seen a laser beam. The goal of the first chapter of this book is to explain simply what a laser is, how it is built and how it operates. Firstly, let us point out the outstanding properties of the laser light.
Guenther, B.D.; Buser, R.G.
This overview of tunable lasers describes their applicability to spectroscopy in the ultraviolet and middle infrared ranges; to rapid on-line diagnostics by ultrashort cavity lasers; to exploration, by the free electron laser, for its wide tuning in the far infrared to submillimeter region; to remote detection, in areas such as portable pollution monitors, on-line chemical analyzers, auto exhaust analyzers, and production line controls; to photochemistry; and to other potential areas in diagnostics, communications, and medical and biological sciences. The following lasers are characterized by their tunability: solid state lasers, primarily alexandrite, with a tuning range of ca 1000 Angstroms; color center lasers; semiconductor lasers; dye lasers; gas lasers, where high-pressure CO/sub 2/ discharges are the best known example for a wide tunability range, and research is continuing in systems such as the alkali dimers; and, at wavelengths beyond 10 micrometers, the possibilities beyond Cerenkov and free electron lasers.
Telford, William G
Laser technology has advanced tremendously since the first gas lasers were incorporated into early flow cytometers. Gas lasers have been largely replaced by solid-state laser technology, making virtually any desirable visible light wavelength available for flow cytometry. Multiwavelength, white light, and wavelength tunable lasers are poised to enhance our analytical capabilities even further. In this chapter, I summarize the role that lasers play in cytometry, and the practical characteristics that make a laser appropriate for flow cytometry. I then review the latest single wavelength lasers available for flow cytometry, and how they can be used to excite the ever-expanding array of available fluorochromes. Finally, I review the contribution and potential of the latest tunable laser technology to flow cytometry, and show several examples of these novel sources integrated into production instruments. Technical details and critical parameters for successful application of these lasers for biomedical analysis are covered in depth.
Epithelial NEMO links innate immunity to chronic intestinal inflammation.
Nenci, Arianna; Becker, Christoph; Wullaert, Andy; Gareus, Ralph; van Loo, Geert; Danese, Silvio; Huth, Marion; Nikolaev, Alexei; Neufert, Clemens; Madison, Blair; Gumucio, Deborah; Neurath, Markus F; Pasparakis, Manolis
Deregulation of intestinal immune responses seems to have a principal function in the pathogenesis of inflammatory bowel disease. The gut epithelium is critically involved in the maintenance of intestinal immune homeostasis-acting as a physical barrier separating luminal bacteria and immune cells, and also expressing antimicrobial peptides. However, the molecular mechanisms that control this function of gut epithelial cells are poorly understood. Here we show that the transcription factor NF-kappaB, a master regulator of pro-inflammatory responses, functions in gut epithelial cells to control epithelial integrity and the interaction between the mucosal immune system and gut microflora. Intestinal epithelial-cell-specific inhibition of NF-kappaB through conditional ablation of NEMO (also called IkappaB kinase-gamma (IKKgamma)) or both IKK1 (IKKalpha) and IKK2 (IKKbeta)-IKK subunits essential for NF-kappaB activation-spontaneously caused severe chronic intestinal inflammation in mice. NF-kappaB deficiency led to apoptosis of colonic epithelial cells, impaired expression of antimicrobial peptides and translocation of bacteria into the mucosa. Concurrently, this epithelial defect triggered a chronic inflammatory response in the colon, initially dominated by innate immune cells but later also involving T lymphocytes. Deficiency of the gene encoding the adaptor protein MyD88 prevented the development of intestinal inflammation, demonstrating that Toll-like receptor activation by intestinal bacteria is essential for disease pathogenesis in this mouse model. Furthermore, NEMO deficiency sensitized epithelial cells to tumour-necrosis factor (TNF)-induced apoptosis, whereas TNF receptor-1 inactivation inhibited intestinal inflammation, demonstrating that TNF receptor-1 signalling is crucial for disease induction. These findings demonstrate that a primary NF-kappaB signalling defect in intestinal epithelial cells disrupts immune homeostasis in the gastrointestinal tract
Role of Epithelial-Mesenchyme Transition in Chlamydia Pathogenesis
Igietseme, Joseph U.; Omosun, Yusuf; Stuchlik, Olga; Reed, Matthew S.; Partin, James; He, Qing; Joseph, Kahaliah; Ellerson, Debra; Bollweg, Brigid; George, Zenas; Eko, Francis O.; Bandea, Claudiu; Liu, Hsi; Yang, Genyan; Shieh, Wun-Ju; Pohl, Jan; Karem, Kevin; Black, Carolyn M.
Chlamydia trachomatis genital infection in women causes serious adverse reproductive complications, and is a strong co-factor for human papilloma virus (HPV)-associated cervical epithelial carcinoma. We tested the hypothesis that Chlamydia induces epithelial-mesenchyme transition (EMT) involving T cell-derived TNF-alpha signaling, caspase activation, cleavage inactivation of dicer and dysregulation of micro-RNA (miRNA) in the reproductive epithelium; the pathologic process of EMT causes fibrosis and fertility-related epithelial dysfunction, and also provides the co-factor function for HPV-related cervical epithelial carcinoma. Using a combination of microarrays, immunohistochemistry and proteomics, we showed that chlamydia altered the expression of crucial miRNAs that control EMT, fibrosis and tumorigenesis; specifically, miR-15a, miR-29b, miR-382 and MiR-429 that maintain epithelial integrity were down-regulated, while miR-9, mi-R-19a, miR-22 and miR-205 that promote EMT, fibrosis and tumorigenesis were up-regulated. Chlamydia induced EMT in vitro and in vivo, marked by the suppression of normal epithelial cell markers especially E-cadherin but up-regulation of mesenchymal markers of pathological EMT, including T-cadherin, MMP9, and fibronectin. Also, Chlamydia upregulated pro-EMT regulators, including the zinc finger E-box binding homeobox protein, ZEB1, Snail1/2, and thrombospondin1 (Thbs1), but down-regulated anti-EMT and fertility promoting proteins (i.e., the major gap junction protein connexin 43 (Cx43), Mets1, Add1Scarb1 and MARCKSL1). T cell-derived TNF-alpha signaling was required for chlamydial-induced infertility and caspase inhibitors prevented both infertility and EMT. Thus, chlamydial-induced T cell-derived TNF-alpha activated caspases that inactivated dicer, causing alteration in the expression of reproductive epithelial miRNAs and induction of EMT. EMT causes epithelial malfunction, fibrosis, infertility, and the enhancement of tumorigenesis of HPV
Role of Epithelial-Mesenchyme Transition in Chlamydia Pathogenesis.
Igietseme, Joseph U; Omosun, Yusuf; Stuchlik, Olga; Reed, Matthew S; Partin, James; He, Qing; Joseph, Kahaliah; Ellerson, Debra; Bollweg, Brigid; George, Zenas; Eko, Francis O; Bandea, Claudiu; Liu, Hsi; Yang, Genyan; Shieh, Wun-Ju; Pohl, Jan; Karem, Kevin; Black, Carolyn M
Chlamydia trachomatis genital infection in women causes serious adverse reproductive complications, and is a strong co-factor for human papilloma virus (HPV)-associated cervical epithelial carcinoma. We tested the hypothesis that Chlamydia induces epithelial-mesenchyme transition (EMT) involving T cell-derived TNF-alpha signaling, caspase activation, cleavage inactivation of dicer and dysregulation of micro-RNA (miRNA) in the reproductive epithelium; the pathologic process of EMT causes fibrosis and fertility-related epithelial dysfunction, and also provides the co-factor function for HPV-related cervical epithelial carcinoma. Using a combination of microarrays, immunohistochemistry and proteomics, we showed that chlamydia altered the expression of crucial miRNAs that control EMT, fibrosis and tumorigenesis; specifically, miR-15a, miR-29b, miR-382 and MiR-429 that maintain epithelial integrity were down-regulated, while miR-9, mi-R-19a, miR-22 and miR-205 that promote EMT, fibrosis and tumorigenesis were up-regulated. Chlamydia induced EMT in vitro and in vivo, marked by the suppression of normal epithelial cell markers especially E-cadherin but up-regulation of mesenchymal markers of pathological EMT, including T-cadherin, MMP9, and fibronectin. Also, Chlamydia upregulated pro-EMT regulators, including the zinc finger E-box binding homeobox protein, ZEB1, Snail1/2, and thrombospondin1 (Thbs1), but down-regulated anti-EMT and fertility promoting proteins (i.e., the major gap junction protein connexin 43 (Cx43), Mets1, Add1Scarb1 and MARCKSL1). T cell-derived TNF-alpha signaling was required for chlamydial-induced infertility and caspase inhibitors prevented both infertility and EMT. Thus, chlamydial-induced T cell-derived TNF-alpha activated caspases that inactivated dicer, causing alteration in the expression of reproductive epithelial miRNAs and induction of EMT. EMT causes epithelial malfunction, fibrosis, infertility, and the enhancement of tumorigenesis of HPV
Intracellular mediators of JAM-A-dependent epithelial barrier function.
Monteiro, Ana C; Parkos, Charles A
Junctional adhesion molecule-A (JAM-A) is a critical signaling component of the apical junctional complex, a structure composed of several transmembrane and scaffold molecules that controls the passage of nutrients and solutes across epithelial surfaces. Observations from JAM-A-deficient epithelial cells and JAM-A knockout animals indicate that JAM-A is an important regulator of epithelial paracellular permeability; however, the mechanism(s) linking JAM-A to barrier function are not understood. This review highlights recent findings relevant to JAM-A-mediated regulation of epithelial permeability, focusing on the role of upstream and downstream signaling candidates. We draw on what is known about proteins reported to associate with JAM-A in other pathways and on known modulators of barrier function to propose candidate effectors that may mediate JAM-A regulation of epithelial paracellular permeability. Further investigation of pathways highlighted in this review may provide ideas for novel therapeutics that target debilitating conditions associated with barrier dysfunction, such as inflammatory bowel disease.
[Macroscopic observations on corneal epithelial wound healing in the rabbit].
Hayashi, K
A newly-developed macroscope was applied to observe the healing process of corneal epithelial wound in vivo. After removing epithelium of the central cornea, the changes of the corneal surface were observed with the macroscope and the findings were compared with histological examinations. At 12 hours after abrasion, areas unstained with Richardson's staining (R staining) appeared. In the histological section, a single layer of regenerating epithelial cells covered the same area. At 24 and 36 hours after abrasion, the epithelial defects became smaller but surrounding epithelium was rough and showed dot-like staining with R solution. By 2 days, the epithelial defects disappeared. On macroscopic observation, the central corneal surface showed a pavement-like appearance. Histology revealed that the regenerating epithelium still consisted of one or two layers. At 3 days, dot-like stainings were present only in the center and the corneal surface appeared considerably smooth. Histology also showed that regenerating epithelium became columnar and multilayered, thereby suggesting stratification. By 7 days, the abraded corneal surface had recovered its smooth appearance. Histologic sections also demonstrated that the epithelium had regained its normal structure. Thus, using this macroscope, findings suggesting the process of epithelial migration and proliferation could be observed.
Mechanobiology in Lung Epithelial Cells: Measurements, Perturbations, and Responses
Waters, Christopher M.; Roan, Esra; Navajas, Daniel
Epithelial cells of the lung are located at the interface between the environment and the organism and serve many important functions including barrier protection, fluid balance, clearance of particulate, initiation of immune responses, mucus and surfactant production, and repair following injury. Because of the complex structure of the lung and its cyclic deformation during the respiratory cycle, epithelial cells are exposed to continuously varying levels of mechanical stresses. While normal lung function is maintained under these conditions, changes in mechanical stresses can have profound effects on the function of epithelial cells and therefore the function of the organ. In this review, we will describe the types of stresses and strains in the lungs, how these are transmitted, and how these may vary in human disease or animal models. Many approaches have been developed to better understand how cells sense and respond to mechanical stresses, and we will discuss these approaches and how they have been used to study lung epithelial cells in culture. Understanding how cells sense and respond to changes in mechanical stresses will contribute to our understanding of the role of lung epithelial cells during normal function and development and how their function may change in diseases such as acute lung injury, asthma, emphysema, and fibrosis. PMID:23728969
Identification of Phosphorylation Sites on Extracellular Corneal Epithelial Cell Maspin
Narayan, Malathi; Mirza, Shama P.; Twining, Sally S.
Maspin, a 42-kDa non classical serine protease inhibitor (serpin) is expressed by epithelial cells of various tissues including the cornea. The protein localizes to the nucleus and cytosol, and is present in the extracellular space. While extracellular maspin regulates corneal stromal fibroblast adhesion and inhibits angiogenesis during wound healing in the cornea, the molecular mechanism of its extracellular functions is unclear. We hypothesized that identifying post-translational modifications of maspin, such as phosphorylation, may help decipher its mode of action. The focus of this study was on the identification of phosphorylation sites on extracellular maspin, since the extracellular form of the molecule is implicated in several functions. Multi-stage fragmentation mass spectrometry was used to identify sites of phosphorylation on extracellular corneal epithelial cell maspin. A total of eight serine and threonine phosphorylation sites (Thr50, Ser97, Thr118, Thr157, Ser240, Ser298, Thr310, Ser316) were identified on the extracellular forms of the molecule. Phosphorylation of tyrosine residues on extracellular maspin was not detected on extracellular maspin from corneal epithelial cell, in contrast to breast epithelial cells. This study provides the basis for further investigation into the functional role of phosphorylation of corneal epithelial maspin. PMID:21365746
Epithelial-mesenchymal transition in tissue repair and fibrosis.
Stone, Rivka C; Pastar, Irena; Ojeh, Nkemcho; Chen, Vivien; Liu, Sophia; Garzon, Karen I; Tomic-Canic, Marjana
The epithelial-mesenchymal transition (EMT) describes the global process by which stationary epithelial cells undergo phenotypic changes, including the loss of cell-cell adhesion and apical-basal polarity, and acquire mesenchymal characteristics that confer migratory capacity. EMT and its converse, MET (mesenchymal-epithelial transition), are integral stages of many physiologic processes and, as such, are tightly coordinated by a host of molecular regulators. Converging lines of evidence have identified EMT as a component of cutaneous wound healing, during which otherwise stationary keratinocytes (the resident skin epithelial cells) migrate across the wound bed to restore the epidermal barrier. Moreover, EMT plays a role in the development of scarring and fibrosis, as the matrix-producing myofibroblasts arise from cells of the epithelial lineage in response to injury but are pathologically sustained instead of undergoing MET or apoptosis. In this review, we summarize the role of EMT in physiologic repair and pathologic fibrosis of tissues and organs. We conclude that further investigation into the contribution of EMT to the faulty repair of fibrotic wounds might identify components of EMT signaling as common therapeutic targets for impaired healing in many tissues. Graphical Abstract Model for injury-triggered EMT activation in physiologic wound repair (left) and fibrotic wound healing (right).
DA-6034 Induces [Ca(2+)]i Increase in Epithelial Cells.
Yang, Yu-Mi; Park, Soonhong; Ji, Hyewon; Kim, Tae-Im; Kim, Eung Kweon; Kang, Kyung Koo; Shin, Dong Min
DA-6034, a eupatilin derivative of flavonoid, has shown potent effects on the protection of gastric mucosa and induced the increases in fluid and glycoprotein secretion in human and rat corneal and conjunctival cells, suggesting that it might be considered as a drug for the treatment of dry eye. However, whether DA-6034 induces Ca(2+) signaling and its underlying mechanism in epithelial cells are not known. In the present study, we investigated the mechanism for actions of DA-6034 in Ca(2+) signaling pathways of the epithelial cells (conjunctival and corneal cells) from human donor eyes and mouse salivary gland epithelial cells. DA-6034 activated Ca(2+)-activated Cl(-) channels (CaCCs) and increased intracellular calcium concentrations ([Ca(2+)]i) in primary cultured human conjunctival cells. DA-6034 also increased [Ca(2+)]i in mouse salivary gland cells and human corneal epithelial cells. [Ca(2+)]i increase of DA-6034 was dependent on the Ca(2+) entry from extracellular and Ca(2+) release from internal Ca(2+) stores. Interestingly, these effects of DA-6034 were related to ryanodine receptors (RyRs) but not phospholipase C/inositol 1,4,5-triphosphate (IP3) pathway and lysosomal Ca(2+) stores. These results suggest that DA-6034 induces Ca(2+) signaling via extracellular Ca(2+) entry and RyRs-sensitive Ca(2+) release from internal Ca(2+) stores in epithelial cells.
Plexins function in epithelial repair in both Drosophila and zebrafish
Yoo, Sa Kan; Pascoe, Heath G.; Pereira, Telmo; Kondo, Shu; Jacinto, Antonio; Zhang, Xuewu; Hariharan, Iswar K.
In most multicellular organisms, homeostasis is contingent upon maintaining epithelial integrity. When unanticipated insults breach epithelial barriers, dormant programmes of tissue repair are immediately activated. However, many of the mechanisms that repair damaged epithelia remain poorly characterized. Here we describe a role for Plexin A (PlexA), a protein with particularly well-characterized roles in axonal pathfinding, in the healing of damaged epithelia in Drosophila. Semaphorins, which are PlexA ligands, also regulate tissue repair. We show that Drosophila PlexA has GAP activity for the Rap1 GTPase, which is known to regulate the stability of adherens junctions. Our observations suggest that the inhibition of Rap1 activity by PlexA in damaged Drosophila epithelia allows epithelial remodelling, thus facilitating wound repair. We also demonstrate a role for Plexin A1, a zebrafish orthologue of Drosophila PlexA, in epithelial repair in zebrafish tail fins. Thus, plexins function in epithelial wound healing in diverse taxa. PMID:27452696
Epithelial cell apoptosis facilitates Entamoeba histolytica infection in the gut.
Becker, Stephen M; Cho, Kyou-Nam; Guo, Xiaoti; Fendig, Kirsten; Oosman, Mohammed N; Whitehead, Robert; Cohn, Steven M; Houpt, Eric R
Entamoeba histolytica is the protozoan parasite that causes amebic colitis. The parasite triggers apoptosis on contact with host cells; however, the biological significance of this event during intestinal infection is unclear. We examined the role of apoptosis in a mouse model of intestinal amebiasis. Histopathology revealed that abundant epithelial cell apoptosis occurred in the vicinity of amoeba in histological specimens. Epithelial cell apoptosis occurred rapidly on co-culture with amoeba in vitro as measured by annexin positivity, DNA degradation, and mitochondrial dysfunction. Administration of the pan caspase inhibitor ZVAD decreased the rate and severity of amebic infection in CBA mice by all measures (cecal culture positivity, parasite enzyme-linked immunosorbent assay, and histological scores). Similarly, caspase 3 knockout mice on the resistant C57BL/6 background exhibited even lower cecal parasite antigen burden and culture positive rates than wild type mice. The permissive effect of apoptosis on infection could be tracked to the epithelium, in that transgenic mice that overexpressed Bcl-2 in epithelial cells were more resistant to infection as measured by cecal parasite enzyme-linked immunosorbent assay and histological scores. We concluded that epithelial cell apoptosis in the intestine facilitates amebic infection in this mouse model. The parasite's strategy for inducing apoptosis may point to key virulence factors, and therapeutic maneuvers to diminish epithelial apoptosis may be useful in amebic colitis.
Epithelial cell guidance by self-generated EGF gradients†
Scherber, Cally; Aranyosi, Alexander J.; Kulemann, Birte; Thayer, Sarah P.; Toner, Mehmet; Iliopoulos, Othon
Cancer epithelial cells often migrate away from the primary tumor to invade into the surrounding tissues. Their migration is commonly assumed to be directed by pre-existent spatial gradients of chemokines and growth factors in the target tissues. Unexpectedly however, we found that the guided migration of epithelial cells is possible in vitro in the absence of pre-existent chemical gradients. We observed that both normal and cancer epithelial cells can migrate persistently and reach the exit along the shortest path from microscopic mazes filled with uniform concentrations of media. Using microscale engineering techniques and biophysical models, we uncovered a self-guidance strategy during which epithelial cells generate their own guiding cues under conditions of biochemical confinement. The self-guidance strategy depends on the balance between three interdependent processes: epidermal growth factor (EGF) uptake by the cells (U), the restricted transport of EGF through the structured microenvironment (T), and cell chemotaxis toward the resultant EGF gradients (C). The UTC self-guidance strategy can be perturbed by inhibition of signalling through EGF-receptors and appears to be independent from chemokine signalling. Better understanding of the UTC self-guidance strategy could eventually help devise new ways for modulating epithelial cell migration and delaying cancer cell invasion or accelerating wound healing. PMID:22314635
Biomaterial surface proteomic signature determines interaction with epithelial cells.
Abdallah, Mohamed-Nur; Tran, Simon D; Abughanam, Ghada; Laurenti, Marco; Zuanazzi, David; Mezour, Mohamed A; Xiao, Yizhi; Cerruti, Marta; Siqueira, Walter L; Tamimi, Faleh
Cells interact with biomaterials indirectly through extracellular matrix (ECM) proteins adsorbed onto their surface. Accordingly, it could be hypothesized that the surface proteomic signature of a biomaterial might determine its interaction with cells. Here, we present a surface proteomic approach to test this hypothesis in the specific case of biomaterial-epithelial cell interactions. In particular, we determined the surface proteomic signature of different biomaterials exposed to the ECM of epithelial cells (basal lamina). We revealed that the biomaterial surface chemistry determines the surface proteomic profile, and subsequently the interaction with epithelial cells. In addition, we found that biomaterials with surface chemistries closer to that of percutaneous tissues, such as aminated PMMA and aminated PDLLA, promoted higher selective adsorption of key basal lamina proteins (laminins, nidogen-1) and subsequently improved their interactions with epithelial cells. These findings suggest that mimicking the surface chemistry of natural percutaneous tissues can improve biomaterial-epithelial integration, and thus provide a rationale for the design of improved biomaterial surfaces for skin regeneration and percutaneous medical devices.
Lingual Epithelial Stem Cells and Organoid Culture of Them
Hisha, Hiroko; Tanaka, Toshihiro; Ueno, Hiroo
As tongue cancer is one of the major malignant cancers in the world, understanding the mechanism of maintenance of lingual epithelial tissue, which is known to be the origin of tongue cancer, is unquestionably important. However, the actual stem cells that are responsible for the long-term maintenance of the lingual epithelium have not been identified. Moreover, a simple and convenient culture method for lingual epithelial stem cells has not yet been established. Recently, we have shown that Bmi1-positive cells, residing at the second or third layer of the epithelial cell layer at the base of the interpapillary pit (IPP), were slow-cycling and could supply keratinized epithelial cells for over one year, indicating that Bmi1-positive cells are long-term lingual epithelial stem cells. In addition, we have developed a novel lingual epithelium organoid culture system using a three-dimensional matrix and growth factors. Here, we discuss current progress in the identification of lingual stem cells and future applications of the lingual culture system for studying the regulatory mechanisms of the lingual epithelium and for regenerative medicine. PMID:26828484
Airway epithelial-derived factor relaxes pulmonary vascular smooth muscle.
Farah, Omar R; Li, Dongge; McIntyre, Brendan A S; Pan, Jingyi; Belik, Jaques
The factors controlling the pulmonary vascular resistance under physiological conditions are poorly understood. We have previously reported on an apparent cross talk between the airway and adjacent pulmonary arterial bed where a factor likely derived from the bronchial epithelial cells reduced the magnitude of agonist-stimulated force in the vascular smooth muscle. The main purpose of this investigation was to evaluate whether bronchial epithelial cells release a pulmonary arterial smooth muscle relaxant factor. Conditioned media from SPOC-1 or BEAS-2B, a rat- and a human-derived bronchial epithelial cell line, respectively, were utilized. This media significantly relaxed precontracted adult but not fetal pulmonary arterial muscle in an oxygen tension-dependent manner. This response was mediated via soluble guanylate cyclase, involving AKT/PI3-kinase and neuronal nitric oxide synthase. Airway epithelial cell-conditioned media increased AKT phosphorylation in pulmonary smooth muscle cells (SMC) and reduced intracellular calcium change following ATP stimulation to a significantly greater extent than observed for bronchial SMC. The present data strongly support the evidence for bronchial epithelial cells releasing a stable and soluble factor capable of inducing pulmonary arterial SMC relaxation. We speculate that under physiological conditions, the maintenance of a low pulmonary vascular resistance, postnatally, is in part modulated by the airway epithelium.
Bacillus anthracis lethal toxin reduces human alveolar epithelial barrier function.
Langer, Marybeth; Duggan, Elizabeth Stewart; Booth, John Leland; Patel, Vineet Indrajit; Zander, Ryan A; Silasi-Mansat, Robert; Ramani, Vijay; Veres, Tibor Zoltan; Prenzler, Frauke; Sewald, Katherina; Williams, Daniel M; Coggeshall, Kenneth Mark; Awasthi, Shanjana; Lupu, Florea; Burian, Dennis; Ballard, Jimmy Dale; Braun, Armin; Metcalf, Jordan Patrick
The lung is the site of entry for Bacillus anthracis in inhalation anthrax, the deadliest form of the disease. Bacillus anthracis produces virulence toxins required for disease. Alveolar macrophages were considered the primary target of the Bacillus anthracis virulence factor lethal toxin because lethal toxin inhibits mouse macrophages through cleavage of MEK signaling pathway components, but we have reported that human alveolar macrophages are not a target of lethal toxin. Our current results suggest that, unlike human alveolar macrophages, the cells lining the respiratory units of the lung, alveolar epithelial cells, are a target of lethal toxin in humans. Alveolar epithelial cells expressed lethal toxin receptor protein, bound the protective antigen component of lethal toxin, and were subject to lethal-toxin-induced cleavage of multiple MEKs. These findings suggest that human alveolar epithelial cells are a target of Bacillus anthracis lethal toxin. Further, no reduction in alveolar epithelial cell viability was observed, but lethal toxin caused actin rearrangement and impaired desmosome formation, consistent with impaired barrier function as well as reduced surfactant production. Therefore, by compromising epithelial barrier function, lethal toxin may play a role in the pathogenesis of inhalation anthrax by facilitating the dissemination of Bacillus anthracis from the lung in early disease and promoting edema in late stages of the illness.
Starved epithelial cells uptake extracellular matrix for survival
Muranen, Taru; Iwanicki, Marcin P.; Curry, Natasha L.; Hwang, Julie; DuBois, Cory D.; Coloff, Jonathan L.; Hitchcock, Daniel S.; Clish, Clary B.; Brugge, Joan S.; Kalaany, Nada Y.
Extracellular matrix adhesion is required for normal epithelial cell survival, nutrient uptake and metabolism. This requirement can be overcome by oncogene activation. Interestingly, inhibition of PI3K/mTOR leads to apoptosis of matrix-detached, but not matrix-attached cancer cells, suggesting that matrix-attached cells use alternate mechanisms to maintain nutrient supplies. Here we demonstrate that under conditions of dietary restriction or growth factor starvation, where PI3K/mTOR signalling is decreased, matrix-attached human mammary epithelial cells upregulate and internalize β4-integrin along with its matrix substrate, laminin. Endocytosed laminin localizes to lysosomes, results in increased intracellular levels of essential amino acids and enhanced mTORC1 signalling, preventing cell death. Moreover, we show that starved human fibroblasts secrete matrix proteins that maintain the growth of starved mammary epithelial cells contingent upon epithelial cell β4-integrin expression. Our study identifies a crosstalk between stromal fibroblasts and epithelial cells under starvation that could be exploited therapeutically to target tumours resistant to PI3K/mTOR inhibition. PMID:28071763
Airway epithelial cell wound repair mediated by alpha-dystroglycan.
White, S R; Wojcik, K R; Gruenert, D; Sun, S; Dorscheid, D R
Dystroglycans (DGs) bind laminin matrix proteins in skeletal and cardiac muscle and are expressed in other nonmuscle tissues. However, their expression in airway epithelial cells has not been demonstrated. We examined expression of DGs in the human airway epithelial cell line 1HAEo(-), and in human primary airway epithelial cells. Expression of the common gene for alpha- and beta-DG was demonstrated by reverse transcriptase/ polymerase chain reaction in 1HAEo(-) cells. Protein expression of beta-DG was demonstrated by both Western blot and flow cytometry in cultured cells. Localization of alpha-DG, using both a monoclonal antibody and the alpha-DG binding lectin wheat-germ agglutinin (WGA), was to the cell membrane and nucleus. We then examined the function of DGs in modulating wound repair over laminin matrix. Blocking alpha-DG binding to laminin in 1HAEo(-) monolayers using either glycosyaminoglycans or WGA attenuated cell migration and spreading after mechanical injury. alpha-DG was not expressed in epithelial cells at the wound edge immediately after wound creation, but localized to the cell membrane in these cells within 12 h of injury. These data demonstrate the presence of DGs in airway epithelium. alpha-DG is dynamically expressed and serves as a lectin to bind laminin during airway epithelial cell repair.
Bacillus anthracis Lethal Toxin Reduces Human Alveolar Epithelial Barrier Function
Langer, Marybeth; Duggan, Elizabeth Stewart; Booth, John Leland; Patel, Vineet Indrajit; Zander, Ryan A.; Silasi-Mansat, Robert; Ramani, Vijay; Veres, Tibor Zoltan; Prenzler, Frauke; Sewald, Katherina; Williams, Daniel M.; Coggeshall, Kenneth Mark; Awasthi, Shanjana; Lupu, Florea; Burian, Dennis; Ballard, Jimmy Dale; Braun, Armin
The lung is the site of entry for Bacillus anthracis in inhalation anthrax, the deadliest form of the disease. Bacillus anthracis produces virulence toxins required for disease. Alveolar macrophages were considered the primary target of the Bacillus anthracis virulence factor lethal toxin because lethal toxin inhibits mouse macrophages through cleavage of MEK signaling pathway components, but we have reported that human alveolar macrophages are not a target of lethal toxin. Our current results suggest that, unlike human alveolar macrophages, the cells lining the respiratory units of the lung, alveolar epithelial cells, are a target of lethal toxin in humans. Alveolar epithelial cells expressed lethal toxin receptor protein, bound the protective antigen component of lethal toxin, and were subject to lethal-toxin-induced cleavage of multiple MEKs. These findings suggest that human alveolar epithelial cells are a target of Bacillus anthracis lethal toxin. Further, no reduction in alveolar epithelial cell viability was observed, but lethal toxin caused actin rearrangement and impaired desmosome formation, consistent with impaired barrier function as well as reduced surfactant production. Therefore, by compromising epithelial barrier function, lethal toxin may play a role in the pathogenesis of inhalation anthrax by facilitating the dissemination of Bacillus anthracis from the lung in early disease and promoting edema in late stages of the illness. PMID:23027535
Surgical lasers in dermatology
NASA Astrophysics Data System (ADS)
Szymanczyk, Jacek; Nowakowski, Wlodzimierz; Golebiowska, Aleksandra; Michalska, I.; Mindak, Marek K.
Almost every laser for medical applications was first tried in dermatology. The efficiency of YAG, CO2, and Argon lasers on this area and their potential advantages over conventional methods were mostly evaluated by cosmetic effect of laser therapy. The indications for different laser treatment in such dermatological cases as: angiomas, telangiectasias, pigmented lesions, nevus flammeus congenitus, deep cavernous angiomas, skin neoplasms and condylomata acuminata are discussed in this paper and the results of the laser therapy are also presented.
Lasers, Quality Level 1 - Group 2 32 5.3-3 Kolmogorov-Smirnoff Test - Helium/Neon Lasers, Quality Level 1 33 5.3-4 Welbull Analysis...institutions through- out the United States and Canada. The collected laser data were grouped, analyzed, and statistically tested for homogeneity...sources were Initially contacted by letter questionnaires In which personnel were requested to describe any laser component life test or laser system
Band, Y.B.; Ackerhalt, J.R.; Krasinski, J.S.; Heller, D.F.
Experimental and theoretical studies of intracavity Raman lasers are presented. Advantages of intracavity Raman lasers, particularly for low-emission cross section and broadly tunable vibronic gain media, are described. Experimental studies of a hydrogen gas Raman laser pumped inside the cavity of an alexandrite laser are presented. A theoretical model of the dynamics of a unidirectional intracavity Raman ring laser is developed and solved analytically. This model is adapted to simulate experiments.
Mercury Bromide Laser Research.
Discharge", Optics Lett., 2(3), (March 1978). 7. R. Burnham, "Discharge Pumped Mercuric Halide Dissociation Lasers", Appl. Phys. Lett., 33: 15 (July 1978...laser and fluorescence signals. Neutral density filters served to prevent saturation of the detector during the laser measurements. F. Laser Output as a...REFERENCES . E. J. Schimitschek and J. E. Celto, " Mercuric Bromide Dissociation Laser in an Electric Discharge," Optics Lett. 2(3), March 1978. This
Laser effect in photodynamic therapy of tumors
NASA Astrophysics Data System (ADS)
Ion, Rodica-Mariana; Brezoi, Dragos-Viorel; Neagu, Monica; Manda, Gina; Constantin, Carolina
Photodynamic therapy is a method that provides a reasonable alternative to other treatment modalities for patients with certain cancers, and in some cases may be the preferred treatment. The therapy implies the intravenous administration of a light-sensitive substance, the photosensitizer. The used sensitizer must absorb at long wavelength. For these purposes, the carbon dioxide laser, He-Ne and the argon laser are particularly suitable. In this study we evaluate in vitro the cytotoxic activity of three synthesized metallo-phthalocyanines with absorption bands in the red part of the spectrum: zinc-di-sulphonated phthalocyanine (ZnS IIPc), zinc-tri-sulphonated phthalocyanine (ZnS 3Pc) and zinc-tetrasulphonated phthalocyanine (ZnS 4Pc). Some cellular models have been used in this paper, in order to optimize the conditions of this method, as we are presenting in this paper (LSR-SF(SR) - transplantable sarcoma in rat induced by Rous sarcoma virus strain Schmidt-Ruppin; LSCC-SF(Mc29) - transplantable chicken hepatoma induced by the myelocytomatosis virus Mc29, MCF-7 cell line (human breast adenocarcinoma) derived from a patient with metastatic breast cancer, 8-MG-BA - glioblastoma multiforme 8-MG-BA, K562 - lymphoblastic human cell line, LLC-WRC 256 - Walker epithelial carcinoma. Activation of these photosensitizers retained in the cancerous cells, by red light emitted from a He-Ne laser at λ= 632.8 nm laser system, or by a diode laser emitting at 672 nm, produces a photochemical reaction that results in the selective destruction of tumor cells.
Epithelial-Mesenchymal Transition (EMT) gene variants and Epithelial Ovarian Cancer (EOC) risk
Amankwah, Ernest K.; Lin, Hui-Yi; Tyrer, Jonathan P.; Lawrenson, Kate; Dennis, Joe; Chornokur, Ganna; Aben, Katja KH.; Anton-Culver, Hoda; Antonenkova, Natalia; Bruinsma, Fiona; Bandera, Elisa V.; Bean, Yukie T.; Beckmann, Matthias W.; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A.; Brooks-Wilson, Angela; Bunker, Clareann H.; Butzow, Ralf; Campbell, Ian G.; Carty, Karen; Chen, Zhihua; Chen, Y. Ann; Chang-Claude, Jenny; Cook, Linda S.; Cramer, Daniel W.; Cunningham, Julie M.; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; du Bois, Andreas; Despierre, Evelyn; Dicks, Ed; Doherty, Jennifer A.; Dörk, Thilo; Dürst, Matthias; Easton, Douglas F.; Eccles, Diana M.; Edwards, Robert P.; Ekici, Arif B.; Fasching, Peter A.; Fridley, Brooke L.; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G.; Glasspool, Rosalind; Goodman, Marc T.; Gronwald, Jacek; Harrington, Patricia; Harter, Philipp; Hasmad, Hanis N.; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A.T.; Hillemanns, Peter; Hogdall, Claus K.; Hogdall, Estrid; Hosono, Satoyo; Iversen, Edwin S.; Jakubowska, Anna; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y.; Jim, Heather; Kellar, Melissa; Kiemeney, Lambertus A.; Krakstad, Camilla; Kjaer, Susanne K.; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Alice W.; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A.; Liang, Dong; Lim, Boon Kiong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F.A.G.; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R.; McNeish, Ian; Menon, Usha; Milne, Roger L.; Modugno, Francesmary; Moysich, Kirsten B.; Ness, Roberta B.; Nevanlinna, Heli; Eilber, Ursula; Odunsi, Kunle; Olson, Sara H.; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Paul, James; Pearce, Celeste L.; Pejovic, Tanja; Pelttari, Liisa M.; Permuth-Wey, Jennifer; Pike, Malcolm C.; Poole, Elizabeth M.; Risch, Harvey A.; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H.; Rudolph, Anja; Runnebaum, Ingo B.; Rzepecka, Iwona K.; Salvesen, Helga B.; Schernhammer, Eva; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B.; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C.; Spiewankiewicz, Beata; Sucheston-Campbell, Lara; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J.; Thomsen, Lotte; Tangen, Ingvild L.; Tworoger, Shelley S.; van Altena, Anne M.; Vierkant, Robert A.; Vergote, Ignace; Walsh, Christine S.; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S.; Wicklund, Kristine G.; Wilkens, Lynne R.; Wu, Anna H.; Wu, Xifeng; Woo, Yin-Ling; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Kelemen, Linda E.; Berchuck, Andrew; Schildkraut, Joellen M.; Ramus, Susan J.; Goode, Ellen L.; Monteiro, Alvaro N.A.; Gayther, Simon A.; Narod, Steven A.; Pharoah, Paul D. P.; Sellers, Thomas A.; Phelan, Catherine M.
Introduction Epithelial-mesenchymal transition (EMT) is a process whereby epithelial cells assume mesenchymal characteristics to facilitate cancer metastasis. However, EMT also contributes to the initiation and development of primary tumors. Prior studies that explored the hypothesis that EMT gene variants contribute to EOC risk have been based on small sample sizes and none have sought replication in an independent population. Methods We screened 1254 SNPs in 296 genes in a discovery phase using data from a genome-wide association study of EOC among women of European ancestry (1,947 cases and 2,009 controls) and identified 793 variants in 278 EMT-related genes that were nominally (p<0.05) associated with invasive EOC. These SNPs were then genotyped in a larger study of 14,525 invasive-cancer patients and 23,447 controls. A p-value <0.05 and a false discovery rate (FDR) <0.2 was considered statistically significant. Results In the larger dataset, GPC6/GPC5 rs17702471 was associated with the endometrioid subtype among Caucasians (OR=1.16, 95%CI=1.07–1.25, p=0.0003, FDR=0.19), while F8 rs7053448 (OR=1.69, 95%CI=1.27–2.24, p=0.0003, FDR=0.12), F8 rs7058826 (OR=1.69, 95%CI=1.27–2.24, p=0.0003, FDR=0.12), and CAPN13 rs1983383 (OR=0.79, 95%CI=0.69–0.90, p=0.0005, FDR=0.12) were associated with combined invasive EOC among Asians. In silico functional analyses revealed that GPC6/GPC5 rs17702471 coincided with DNA regulatory elements. Conclusion These results suggest that EMT gene variants do not appear to play a significant role in the susceptibility to EOC. PMID:26399219
Gastrin stimulates MMP-1 expression in gastric epithelial cells: putative role in gastric epithelial cell migration
Kumar, J. Dinesh; Steele, Islay; Moore, Andrew R.; Murugesan, Senthil V.; Rakonczay, Zoltan; Venglovecz, Viktoria; Pritchard, D. Mark; Dimaline, Rodney; Tiszlavicz, Laszlo; Varro, Andrea
The pyloric antral hormone gastrin plays a role in remodeling of the gastric epithelium, but the specific targets of gastrin that mediate these effects are poorly understood. Glandular epithelial cells of the gastric corpus express matrix metalloproteinase (MMP)-1, which is a potential determinant of tissue remodeling; some of these cells express the CCK-2 receptor at which gastrin acts. We have now examined the hypothesis that gastrin stimulates expression of MMP-1 in the stomach. We determined MMP-1 transcript abundance in gastric mucosal biopsies from Helicobacter pylori negative human subjects with normal gastric mucosal histology, who had a range of serum gastrin concentrations due in part to treatment with proton pump inhibitors (PPI). The effects of gastrin were studied on gastric epithelial AGS-GR cells using Western blot and migration assays. In human subjects with increased serum gastrin due to PPI usage, MMP-1 transcript abundance was increased 2-fold; there was also increased MMP-7 transcript abundance but not MMP-3. In Western blots, gastrin increased proMMP-1 abundance, as well that of a minor band corresponding to active MMP-1, in the media of AGS-GR cells, and the response was mediated by protein kinase C and p42/44 MAP kinase. There was also increased MMP-1 enzyme activity. Gastrin-stimulated AGS-GR cell migration in both scratch wound and Boyden chamber assays was inhibited by MMP-1 immunoneutralization. We conclude that MMP-1 expression is a target of gastrin implicated in mucosal remodeling. PMID:25977510
Optical gene transfer by femtosecond laser pulses
NASA Astrophysics Data System (ADS)
Konig, Karsten; Riemann, Iris; Tirlapur, Uday K.
Targeted transfection of cells is an important technique for gene therapy and related biomedical applications. We delineate how high-intensity (1012 W/cm2) near-infrared (NIR) 80 MHz nanojoule femtosecond laser pulses can create highly localised membrane perforations within a minute focal volume, enabling non-invasive direct transfection of mammalian cells with DNA. We suspended Chinese hamster ovarian (CHO), rat kangaroo kidney epithelial (PtK2) and rat fibroblast cells in 0.5 ml culture medium in a sterile miniaturized cell chamber (JenLab GmbH, Jena, Germany) containing 0.2 μg plasmid DNA vector pEGFP-N1 (4.7 kb), which codes for green fluorescent protein (GFP). The NIR laser beam was introduced into a femtosecond laser scanning microscope (JenLab GmbH, Jena, Germany; focussed on the edge of the cell membrane of a target cell for 16 ms. The integration and expression efficiency of EGFP were assessed in situ by two-photon fluorescence-lifetime imaging using time-correlated single photon counting. The unique capability to transfer foreign DNA safely and efficiently into specific cell types (including stem cells), circumventing mechanical, electrical or chemical means, will have many applications, such as targeted gene therapy and DNA vaccination.
Porphyromonas gingivalis genes isolated by screening for epithelial cell attachment.
Duncan, M J; Emory, S A; Almira, E C
Porphyromonas gingivalis is associated with chronic and severe periodontitis in adults. P. gingivalis and the other periodontal pathogens colonize and interact with gingival epithelial cells, but the genes and molecular mechanisms involved are unknown. To dissect the first steps in these interactions, a P. gingivalis expression library was screened for clones which bound human oral epithelial cells. Insert DNA from the recombinant clones did not contain homology to the P. gingivalis fimA gene, encoding fimbrillin, the subunit protein of fimbriae, but showed various degrees of homology to certain cysteine protease-hemagglutinin genes. The DNA sequence of one insert revealed three putative open reading frames which appeared to be in an operon. The relationship between P. gingivalis attachment to epithelial cells and the activities identified by the screen is discussed. PMID:8751909
Hydraulic fracture and resilience of epithelial monolayers under stretch
NASA Astrophysics Data System (ADS)
Arroyo, Marino; Lucantonio, Alessandro; Noselli, Giovanni; Casares, Laura; Desimone, Antonio; Trepat, Xavier
Epithelial monolayers are very simple and prevalent tissues. Their functions include delimiting distinct physicochemical containers and protecting us from pathogens. Epithelial fracture disrupts the mechanical integrity of this barrier, and hence compromises these functions. Here, we show that in addition to the conventional fracture resulting from excessive tissue tension, epithelia can hydraulically fracture under stretch as a result of the poroelastic nature of the matrix. We will provide experimental evidence of this counterintuitive mechanism of fracture, in which cracks appear under compression. Intriguingly, unlike tensional fracture, which is localized and catastrophic, hydraulic epithelial fracture is distributed and reversible. We will also describe the active mechanisms responsible for crack healing, and the physical principles by which the poroelastic matrix contributes to this resilient behavior.
Salivary epithelial cells: an unassuming target site for gene therapeutics
Perez, Paola; Rowzee, Anne M.; Zheng, Changyu; Adriaansen, Janik; Baum, Bruce J.
Salivary glands are classical exocrine glands whose external secretions result in the production of saliva. However, in addition to the secretion of exocrine proteins, salivary epithelial cells are also capable of secreting proteins internally, into the bloodstream. This brief review examines the potential for using salivary epithelial cells as a target site for in situ gene transfer, with an ultimate goal of producing therapeutic proteins for treating both systemic and upper gastrointestinal tract disorders. The review discusses the protein secretory pathways reported to be present in salivary epithelial cells, the viral gene transfer vectors shown useful for transducing these cells, model transgenic secretory proteins examined, and some clinical conditions that might benefit from such salivary gland gene transfer. PMID:20219693
Coronavirus entry and release in polarized epithelial cells: a review.
Cong, Yingying; Ren, Xiaofeng
Most coronaviruses cause respiratory or intestinal infections in their animal or human host. Hence, their interaction with polarized epithelial cells plays a critical role in the onset and outcome of infection. In this paper, we review the knowledge regarding the entry and release of coronaviruses, with particular emphasis on the severe acute respiratory syndrome and Middle East respiratory syndrome coronaviruses. As these viruses approach the epithelial surfaces from the apical side, it is not surprising that coronavirus cell receptors are exposed primarily on the apical domain of polarized epithelial cells. With respect to release, all possibilities appear to occur. Thus, most coronaviruses exit through the apical surface, several through the basolateral one, although the Middle East respiratory syndrome coronavirus appears to use both sides. These observations help us understand the local or systematic spread of the infection within its host as well as the spread of the virus within the host population.
TGF-β induced epithelial-mesenchymal transition modeling
NASA Astrophysics Data System (ADS)
Xenitidis, P.; Seimenis, I.; Kakolyris, S.; Adamopoulos, A.
Epithelial cells may undergo a process called epithelial to mesenchymal transition (EMT). During EMT, cells lose their epithelial characteristics and acquire a migratory ability. Transforming growth factor-beta (TGF-β) signaling is considered to play an important role in EMT by regulating a set of genes through a gene regulatory network (GRN). This work aims at TGF-β induced EMT GRN modeling using publicly available experimental data (gene expression microarray data). The time-series network identification (TSNI) algorithm was used for inferring the EMT GRN. Receiver operating characteristic (ROC) and precision-recall (P-R) curves were constructed and the areas under them were used for evaluating the algorithm performance regarding network inference.
Wound repair: role of immune–epithelial interactions
Leoni, G; Neumann, P-A; Sumagin, R; Denning, TL; Nusrat, A
The epithelium serves as a highly selective barrier at mucosal surfaces. Upon injury, epithelial wound closure is orchestrated by a series of events that emanate from the epithelium itself as well as by the temporal recruitment of immune cells into the wound bed. Epithelial cells adjoining the wound flatten out, migrate, and proliferate to rapidly cover denuded surfaces and re-establish mucosal homeostasis. This process is highly regulated by proteins and lipids, proresolving mediators such as Annexin A1 protein and resolvins released into the epithelial milieu by the epithelium itself and infiltrating innate immune cells including neutrophils and macrophages. Failure to achieve these finely tuned processes is observed in chronic inflammatory diseases that are associated with non-healing wounds. An improved understanding of mechanisms that mediate repair is important in the development of therapeutics aimed to promote mucosal wound repair. PMID:26174765
Development of human epithelial cell systems for radiation risk assessment
NASA Astrophysics Data System (ADS)
Yang, C. H.; Craise, L. M.
The most important health effect of space radiation for astronauts is cancer induction. For radiation risk assessment, an understanding of carcinogenic effect of heavy ions in human cells is most essential. In our laboratory, we have successfully developed a human mammary epithelial cell system for studying the neoplastic transformation in vitro. Growth variants were obtained from heavy ion irradiated immortal mammary cell line. These cloned growth variants can grow in regular tissue culture media and maintain anchorage dependent growth and density inhibition property. Upon further irradiation with high-LET radiation, transformed foci were found. Experimental results from these studies suggest that multiexposure of radiation is required to induce neoplastic transformation of human epithelial cells. This multihits requirement may be due to high genomic stability of human cells. These growth variants can be useful model systems for space flight experiments to determine the carcinogenic effect of space radiation in human epithelial cells.
Development of human epithelial cell systems for radiation risk assessment
NASA Technical Reports Server (NTRS)
Yang, C. H.; Craise, L. M.
The most important health effect of space radiation for astronauts is cancer induction. For radiation risk assessment, an understanding of carcinogenic effect of heavy ions in human cells is most essential. In our laboratory, we have successfully developed a human mammary epithelial cell system for studying the neoplastic transformation in vitro. Growth variants were obtained from heavy ion irradiated immortal mammary cell line. These cloned growth variants can grow in regular tissue culture media and maintain anchorage dependent growth and density inhibition property. Upon further irradiation with high-Linear Energy Transfer (LET) radiation, transformed foci were found. Experimental results from these studies suggest that multiexposure of radiation is required to induce neoplastic tranformation of human epithelial cells. This multihits requirement may be due to high genomic stability of human cells. These growth variants can be useful model systems for space flight experiments to determine the carcinogenic effect of space radiation in human epithelial cells.
Effects of ethanol on an intestinal epithelial cell line
Nano, J.L.; Cefai, D.; Rampal, P. )
The effect of exposure of an intestinal epithelial cell line to various concentrations of ethanol (217 mM (1%) to 652 mM (3%)) during 24, 48, and 72 hr was investigated in vitro using a rat intestinal epithelial cell line (IRD 98). Incubation of these cells in the presence of ethanol significantly decreased cell growth. This inhibition was accompanied by a strong increase in cellular protein. Stimulation of specific disaccharidases, gamma-glutamyl transferase, and aminopeptidase activities by ethanol was dose- and time-dependent. Ethanol induces a change in the relative proportions of the different lipid classes synthesized; triglycerides, fatty acids, and cholesterol esters were preferentially synthethysed. Our findings show that cell lines are good models for investigation of the effects of ethanol, and that alcohol considerably modifies the functions of intestinal epithelial cells.
Autophagy regulates hepatocyte identity and epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions promoting Snail degradation.
Grassi, G; Di Caprio, G; Santangelo, L; Fimia, G M; Cozzolino, A M; Komatsu, M; Ippolito, G; Tripodi, M; Alonzi, T
Epithelial-to-mesenchymal transition (EMT) and the reverse process mesenchymal-to-epithelial transition (MET) are events involved in development, wound healing and stem cell behaviour and contribute pathologically to cancer progression. The identification of the molecular mechanisms underlying these phenotypic conversions in hepatocytes are fundamental to design specific therapeutic strategies aimed at optimising liver repair. The role of autophagy in EMT/MET processes of hepatocytes was investigated in liver-specific autophagy-deficient mice (Alb-Cre;ATG7(fl/fl)) and using the nontumorigenic immortalised hepatocytes cell line MMH. Autophagy deficiency in vivo reduces epithelial markers' expression and increases the levels of mesenchymal markers. These alterations are associated with an increased protein level of the EMT master regulator Snail, without transcriptional induction. Interestingly, we found that autophagy degrades Snail in a p62/SQSTM1 (Sequestosome-1)-dependent manner. Moreover, accordingly to a pro-epithelial function, we observed that autophagy stimulation strongly affects EMT progression, whereas it is necessary for MET. Finally, we found that the EMT induced by TGFβ affects the autophagy flux, indicating that these processes regulate each other. Overall, we found that autophagy regulates the phenotype plasticity of hepatocytes promoting their epithelial identity through the inhibition of the mesenchymal programme.
NANOG regulates epithelial-mesenchymal transition and chemoresistance through activation of the STAT3 pathway in epithelial ovarian cancer.
Liu, Suqing; Sun, Jing; Cai, Bin; Xi, Xiaowei; Yang, Liu; Zhang, Zhenbo; Feng, Youji; Sun, Yunyan
NANOG is a key transcription factor that is overexpressed and plays an important role in various cancers. Its overexpression is associated with highly tumorigenic, drug-resistant, and poor prognosis. However, the underlying mechanism of action of NANOG in ovarian cancer remains unclear. Epithelial-mesenchymal transition (EMT), which is a critical process in cancer invasion and metastasis, is also associated with drug resistance. We determined whether NANOG is associated with EMT and chemoresistance in epithelial ovarian cancer cells. NANOG expression was increased in epithelial ovarian cancer cells (HEY and SKOV3) compared with normal epithelial ovarian cells (Moody). Low expression of NANOG increased the expression of E-cadherin and decreased the expression of vimentin, β-catenin, and Snail. Furthermore, the cell migration and invasion abilities were decreased. The multidrug resistance genes MDR-1 and GST-π were also downregulated when NANOG was lowly expressed. The cells that were transfected with the si-NANOG plasmid were more sensitive to cisplatin compared with the cells that were transfected with empty vector. The data demonstrated that Stat3 was correlated with NANOG-mediated EMT and drug resistance. The silencing of Stat3 expression abrogated NANOG-mediated EMT changes and increased the sensitivity of the cells to chemotherapy. These results suggest that NANOG mediates EMT and drug resistance through activation of the Stat3 pathway in epithelial ovarian cancer.
Downregulation of miR-205 in migrating epithelial tongue facilitates skin wound re-epithelialization by derepressing ITGA5.
Wang, Tao; Zhao, Na; Long, Shuang; Ge, Lan; Wang, Aiping; Sun, Huiqin; Ran, Xinze; Zou, Zhongmin; Wang, Junping; Su, Yongping
Keratinocyte migration is essential for re-epithelialization during skin wound healing, but the molecular mechanisms regulating this cellular response remain to be completely clarified. Here we show that keratinocyte-specific miR-205 is significantly downregulated in the leading edge of the migrating epithelial tongue after skin injury in mice. In HaCaT keratinocytes, miR-205 could be downregulated by TGF-β1 stimulation. And similar to the effect of TGF-β1, miR-205 knockdown could promote keratinocyte migration in wound scratch model in vitro. Furthermore, topical inhibition of miR-205 by administrating Pluronic gel containing antagomir-205 could accelerate re-epithelialization in mouse skin wound model in vivo. Moreover, we identified integrin alpha 5 (ITGA5) as one key functional miR-205 target in the re-epithelialization process and epidermal downregulation of miR-205 may desilence ITGA5 to promote keratinocyte migration. And knockdown of ITGA5 would abolish the pro-migratory effects of miR-205 inhibition in vitro. What's more, we found dysregulation of miR-205 and its target ITGA5 in epidermis of clinical chronic wound samples with persistence of high level miR-205 and absence of ITGA5. Our findings indicate that downregulation of miR-205 in the leading migrating keratinocytes is critical for re-epithelialization and miR-205 may be a potential therapeutic target for chronic wounds.
AMP-18 Targets p21 to Maintain Epithelial Homeostasis
Chen, Peili; Li, Yan Chun; Toback, F. Gary
Dysregulated homeostasis of epithelial cells resulting in disruption of mucosal barrier function is an important pathogenic mechanism in inflammatory bowel diseases (IBD). We have characterized a novel gastric protein, Antrum Mucosal Protein (AMP)-18, that has pleiotropic properties; it is mitogenic, anti-apoptotic and can stimulate formation of tight junctions. A 21-mer synthetic peptide derived from AMP-18 exhibits the same biological functions as the full-length protein and is an effective therapeutic agent in mouse models of IBD. In this study we set out to characterize therapeutic mechanisms and identify molecular targets by which AMP-18 maintains and restores disrupted epithelial homeostasis in cultured intestinal epithelial cells and a mouse model of IBD. Tumor necrosis factor (TNF)-α, a pro-inflammatory cytokine known to mediate gastrointestinal (GI) mucosal injury in IBD, was used to induce intestinal epithelial cell injury, and study the effects of AMP-18 on apoptosis and the cell cycle. An apoptosis array used to search for targets of AMP-18 in cells exposed to TNF-α identified the cyclin-dependent kinase inhibitor p21WAF1/CIP1. Treatment with AMP-18 blunted increases in p21 expression and apoptosis, while reversing disturbed cell cycle kinetics induced by TNF-α. AMP-18 appears to act through PI3K/AKT pathways to increase p21 phosphorylation, thereby reducing its nuclear accumulation to overcome the antiproliferative effects of TNF-α. In vitamin D receptor-deficient mice with TNBS-induced IBD, the observed increase in p21 expression in colonic epithelial cells was suppressed by treatment with AMP peptide. The results indicate that AMP-18 can maintain and/or restore the homeostatic balance between proliferation and apoptosis in intestinal epithelial cells to protect and repair mucosal barrier homeostasis and function, suggesting a therapeutic role in IBD. PMID:25919700
Fibrin glue inhibits migration of ocular surface epithelial cells.
Yeung, A M; Faraj, L A; McIntosh, O D; Dhillon, V K; Dua, H S
PurposeFibrin glue has been used successfully in numerous ophthalmic surgical procedures. Recently, fibrin glue has been used in limbal stem cell transplantation to reduce both operative time and to negate the need for sutures. The aim of this study was to determine the effects of fibrin glue on epithelial cell migration in vitro.MethodsCorneoscleral rims were split to retain the epithelial layer, Bowman's layer, and anterior stroma. Rims were cut into eight equal-sized pieces and were placed directly on culture plates or affixed with fibrin glue. Rims were maintained in culture for 25 days and epithelial cell growth was monitored. Cells were photographed to measure area or growth and immunofluorescence staining of explants for fibrin was performed.ResultsExplants that were glued demonstrated significantly delayed epithelial cell growth and migration as compared with explants without glue. By day 16, all fibrin glue had dissolved and coincided with onset of cell growth from glued explants. Cell growth commenced between days 3 and 4 for control explants without glue and around days 14-16 for explants with fibrin glue.ConclusionsFibrin glue delays epithelial cell migration by acting as a physical barrier and can potentially interfere with explant-derived limbal epithelial cell migration on to the corneal surface. We propose that glue should be used to attach the conjunctival frill of the limbal explant but care should be taken to ensure that the glue does not wrap around the explant if used to secure the explant as well. Strategic use of glue, to attach the recessed conjunctiva, can be advantageous in delaying conjunctival cell migration and reducing the need for sequential sector conjunctival epitheliectomy.
The laryngeal primordium and epithelial lamina. A new interpretation.
Sañudo, J R; Domenech-Mateu, J M
The laryngeal primordium is present in both the laryngotracheal sulcus (LTS) and the primitive pulmonary sac (PPS). Its early period of development may be subdivided into two phases. The first phase (Stage 11) is represented by what is traditionally referred to as the LTS, located directly beneath the PP4 on the ventral wall of the foregut (primary segment), and by the PPS which is situated at its caudal end. The LTS will represent the primordium of the upper or membranous infraglottic cavity region; whereas the PPS, will give rise not only to the bronchial tree, but also to the primordium of the trachea and the lower or cartilaginous region of the infraglottic cavity. The second phase (Stages 13 and 14) is distinguished by the cranial growth of the LTS above the PP4 and therefore by its absorption into the floor of the primitive pharynx in the mesobranchial area (secondary segment), which will develop into the primordium of the vestibule of the larynx. Similarly, we observed that in the development of the laryngeal cavity there are two temporally and spatially separate epithelial structures: the epithelial septum and the epithelial lamina. In this respect we differ from other authors who are of the opinion that there is a single structure (the epithelial lamina). The epithelial septum is a primary structure responsible for the final configuration of the LTS, as it contributes to the development of the lower end of the primary segment of the LTS and also to the creation of the secondary segment. The epithelial lamina is a secondary structure which appears inside the LTS as a result of pressure exerted by the mesenchyme on its lateral walls, without having any effect on the morphogenesis of the LTS. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:2081706
Lipid and protein distribution in epithelial cells assessed with confocal microscopy
NASA Astrophysics Data System (ADS)
Peterson, Kajsa H.; Randen, Michael; Hays, Richard M.; Magnusson, Karl-Eric
Confocal laser scanning microscopy, image processing, and volume visualization were used to characterize the 3-D distribution of lectin receptors, lipid probes, and actin cytoskeleton in epithelial cells. Small intestine-like cells were grown on glass or filter supports and apically labelled with different fluorescent lipid and lectin probes. The restriction of the probes by the tight junctions was studied in living cells. Series of confocal x-y sections were transferred to an image processing system for analysis. The fluorescence intensity within a specified area of all x-y sections was plotted as a function of the vertical position of the sections. The curve inclination was used to describe the degree of restriction to the probes. It was found that lectins were more confined to the apical part than the lipids, which showed varying degree of redistribution to the basolateral membrane. Volume rendering, and specifically animated sequences with varying viewpoint and opacity mapping, were used to visualize the structure of actin cytoskeleton and distribution of lipid and lectin probes. In toad bladder epithelial cells, actin was labelled before and after treatment with the antidiuretic hormone vasopressin. The hormone-induced redistribution of actin in the apical and lateral portion of the cells was measured on x-z scanned images. Ratios of apical-to-lateral intensity were calculated. It was found that the decrease in the ratios after vasopressin treatment was around 30%. The decrease was due to loss of actin apically. This is supposed to facilitate apical fusion of vesicles containing the water-channel forming proteins, being important in water homeostasis.
AMP-18 protects barrier function of colonic epithelial cells: role of tight junction proteins
Walsh-Reitz, Margaret M.; Huang, Erick F.; Musch, Mark W.; Chang, Eugene B.; Martin, Terence E.; Kartha, Sreedharan; Toback, F. Gary
AMP-18, a novel gastric antrum mucosal protein, and a synthetic peptide of amino acids 77-97, have mitogenic and motogenic properties for epithelial cells. The possibility that AMP-18 is also protective was evaluated in the colonic mucosa of mice and monolayer cultures of human colonic epithelial Caco2/bbe (C2) cells. Administration of AMP peptide to mice with dextran sulfate sodium (DSS)-induced colonic injury delayed the onset of bloody diarrhea, and reduced weight loss. Treatment of C2 cells with AMP peptide protected monolayers against decreases in transepithelial electrical resistance (TER) induced by the oxidant monochloramine, indomethacin, or DSS. A molecular mechanism for these barrier-protective effects was sought by asking if AMP peptide acted on specific tight junction (TJ) proteins. Immunoblots of detergent-insoluble fractions of C2 cells treated with AMP peptide exhibited increased accumulation of specific TJ proteins. Occludin immunoreactivity was also increased in detergent-insoluble fractions obtained from colonic mucosal cells of mice injected with AMP peptide. Laser scanning confocal microscopy (CF) supported the capacity of AMP peptide to enhance accumulation of occludin and ZO-1 in TJ domains of C2 cell monolayers, and together with immunoblot analysis showed that the peptide protected against loss of these TJ proteins following oxidant injury. AMP peptide also protected against a fall in TER during disruption of actin filaments by cytochalasin D, and stabilized perijunctional actin during oxidant injury when assessed by CF. These findings suggest that AMP-18 could protect the intestinal mucosal barrier by acting on specific TJ proteins and stabilizing perijunctional actin. PMID:15961882
[Primary thinning and de-epithelialization of microsurgical transplants from the lateral thigh].
Wolff, K D; Plath, T; Frege, J; Hoffmeister, B
To expand the indicational spectrum of the myocutaneous vastus lateralis flap, which is often too voluminous for intraoral application, we performed extreme, primary thinning of the fat and muscle component of this microsurgical transplant in 14 patients. After subfascial localization of the 0.5- to 1.0-mm-thick perforating vessel, it is exposed through the fascia and muscles up to its exit from the descending branch of the lateral circumflex femoral artery. After isolating the perforating vessel, it is no longer necessary to include parts of the vastus lateralis muscle in the flap. The fatty tissue of the remaining epifascial fat component is completely removed except for a ca. 1- to 2-cm-wide cuff of fatty tissue and fascia around the perforating vessel. When performing this primary radical removal of the subcutaneous fatty tissue, care should be taken not to injure the deep subdermal vascular plexus. In addition to the thinning procedure, de-epithelialization of the skin was performed using scalpel blade dissection (five patients) or carbon dioxide laser (6 W, five patients). This thinning technique was used for covering ten intraoral and four extraoral defects and enabled the raising of skin flaps with a thickness of 3-5 mm even in obese patients. The vessel pedicle length of thinned flaps was between 12 and 16 cm; flap size varied between 4 x 5 and 9 x 15 cm, and the donor sites were directly closed. In one case, there was a partial necrosis (20%), but the remaining flaps healed without complications. On the intraoral flaps, a thin, smooth and pliable surface developed after re-epithelialization within 3-6 weeks. The described method expands the application possibilities of the myocutaneous vastus lateralis flap for a large number of intraoral and flat defects with minimal donor-site morbidity.
Nanocrystal waveguide (NOW) laser
Simpson, John T.; Simpson, Marcus L.; Withrow, Stephen P.; White, Clark W.; Jaiswal, Supriya L.
A solid state laser includes an optical waveguide and a laser cavity including at least one subwavelength mirror disposed in or on the optical waveguide. A plurality of photoluminescent nanocrystals are disposed in the laser cavity. The reflective subwavelength mirror can be a pair of subwavelength resonant gratings (SWG), a pair of photonic crystal structures (PC), or a distributed feedback structure. In the case of a pair of mirrors, a PC which is substantially transmissive at an operating wavelength of the laser can be disposed in the laser cavity between the subwavelength mirrors to improve the mode structure, coherence and overall efficiency of the laser. A method for forming a solid state laser includes the steps of providing an optical waveguide, creating a laser cavity in the optical waveguide by disposing at least one subwavelength mirror on or in the waveguide, and positioning a plurality of photoluminescent nanocrystals in the laser cavity.
Cantrell, Cyrus D.; Carbone, Robert J.; Cooper, Ralph
An infrared laser system and method for isotope separation may comprise a molecular gas laser oscillator to produce a laser beam at a first wavelength, Raman spin flip means for shifting the laser to a second wavelength, a molecular gas laser amplifier to amplify said second wavelength laser beam to high power, and optical means for directing the second wavelength, high power laser beam against a desired isotope for selective excitation thereof in a mixture with other isotopes. The optical means may include a medium which shifts the second wavelength high power laser beam to a third wavelength, high power laser beam at a wavelength coincidental with a corresponding vibrational state of said isotope and which is different from vibrational states of other isotopes in the gas mixture.
Cantrell, Cyrus D.; Carbone, Robert J.; Cooper, Ralph S.
An infrared laser system and method for isotope separation may comprise a molecular gas laser oscillator to produce a laser beam at a first wavelength, Raman spin flip means for shifting the laser to a second wavelength, a molecular gas laser amplifier to amplify said second wavelength laser beam to high power, and optical means for directing the second wavelength, high power laser beam against a desired isotope for selective excitation thereof in a mixture with other isotopes. The optical means may include a medium which shifts the second wavelength high power laser beam to a third wavelength, high power laser beam at a wavelength coincidental with a corresponding vibrational state of said isotope and which is different from vibrational states of other isotopes in the gas mixture.
Secretion of alpha 1-antitrypsin by alveolar epithelial cells.
Venembre, P; Boutten, A; Seta, N; Dehoux, M S; Crestani, B; Aubier, M; Durand, G
We have investigated the ability of alveolar epithelial cells (human A549 cell line and rat type-II pneumocytes) to produce alpha 1-antitrypsin (AAT). Northern blot analysis demonstrated the presence of an AAT-specific mRNA transcript in A549 cells. Unstimulated A549 cells secreted immunoreactive AAT at a rate of 0.51 +/- 0.04 ng/10(6) cells/h, with a modified glycosylation compared to serum AAT. AAT formed a complex with neutrophil elastase. Rat type-II pneumocytes secreted immunoreactive AAT. Our results suggest that alveolar epithelial cells could participate in antiprotease defense within the lung through local AAT production.
Metformin inhibits the proliferation of benign prostatic epithelial cells
Ge, Rongbin; Li, Jijun; Johnson, Cameron W.; Rassoulian, Cyrus; Olumi, Aria F.
Objective Benign prostatic hyperplasia (BPH) is the most common proliferative abnormality of the prostate affecting elderly men throughout the world. Epidemiologic studies have shown that diabetes significantly increases the risk of developing BPH, although whether anti-diabetic medications preventing the development of BPH remains to be defined. We have previously found that stromally expressed insulin-like growth factor 1 (IGF-1) promotes benign prostatic epithelial cell proliferation through paracrine mechanisms. Here, we seek to understand if metformin, a first line medication for the treatment of type 2 diabetes, inhibits the proliferation of benign prostatic epithelial cells through reducing the expression of IGF-1 receptor (IGF-1R) and regulating cell cycle. Methods BPE cell lines BPH-1 and P69, murine fibroblasts3T3 and primary human prostatic fibroblasts were cultured and tested in this study. Cell proliferation and the cell cycle were analyzed by MTS assay and flow cytometry, respectively. The expression of IGF-1R was determined by western-blot and immunocytochemistry. The level of IGF-1 secretion in culture medium was measured by ELISA. Results Metformin (0.5-10mM, 6-48h) significantly inhibited the proliferation of BPH-1 and P69 cells in a dose-dependent and time-dependent manner. Treatment with metformin for 24 hours lowered the G2/M cell population by 43.24% in P69 cells and 24.22% in BPH-1 cells. On the other hand, IGF-1 (100ng/mL, 24h) stimulated the cell proliferation (increased by 28.81% in P69 cells and 20.95% in BPH-1 cells) and significantly enhanced the expression of IGF-1R in benign prostatic epithelial cells. Metformin (5mM) abrogated the proliferation of benign prostatic epithelial cells induced by IGF-1. In 3T3 cells, the secretion of IGF-1 was significantly inhibited by metformin from 574.31pg/ml to 197.61pg/ml. The conditioned media of 3T3 cells and human prostatic fibroblasts promoted the proliferation of epithelial cells and the
Oral focal epithelial hyperplasia: report of five cases.
Borborema-Santos, Cristina Maria; Castro, Maria Marta de; Santos, Paulo José Benevides dos; Talhari, Sinésio; Astolfi-Filho, Spartaco
Focal epithelial hyperplasia or Heck's disease is a rare contagious disease caused by human papillomavirus types 13 or 32, initially described among Native American populations. This condition is characterized by the occurrence of multiple small papules or nodules in oral cavity, especially on labial and buccal mucosa and tongue. This report describes the diagnosis of focal epithelial hyperplasia in five Central Amazonian Indians who sought treatment at the Amazonas State Foundation of Tropical Medicine (FMT-AM), using clinical criteria, polymerase chain reaction (PCR) and DNA sequencing.
Cellular contractility changes are sufficient to drive epithelial scattering.
Hoj, Jacob P; Davis, John A; Fullmer, Kendra E; Morrell, David J; Saguibo, Nicholas E; Schuler, Jeffrey T; Tuttle, Kevin J; Hansen, Marc D H
Epithelial scattering occurs when cells disassemble cell-cell junctions, allowing individual epithelial cells to act in a solitary manner. Epithelial scattering occurs frequently in development, where it accompanies epithelial-mesenchymal transitions and is required for individual cells to migrate and invade. While migration and invasion have received extensive research focus, how cell-cell junctions are detached remains poorly understood. An open debate has been whether disruption of cell-cell interactions occurs by remodeling of cell-cell adhesions, increased traction forces through cell substrate adhesions, or some combination of both processes. Here we seek to examine how changes in adhesion and contractility are coupled to drive detachment of individual epithelial cells during hepatocyte growth factor (HGF)/scatter factor-induced EMT. We find that HGF signaling does not alter the strength of cell-cell adhesion between cells in suspension, suggesting that changes in cell-cell adhesion strength might not accompany epithelial scattering. Instead, cell-substrate adhesion seems to play a bigger role, as cell-substrate adhesions are stronger in cells treated with HGF and since rapid scattering in cells treated with HGF and TGFβ is associated with a dramatic increase in focal adhesions. Increases in the pliability of the substratum, reducing cells ability to generate traction on the substrate, alter cells׳ ability to scatter. Further consistent with changes in substrate adhesion being required for cell-cell detachment during EMT, scattering is impaired in cells expressing both active and inactive RhoA mutants, though in different ways. In addition to its roles in driving assembly of both stress fibers and focal adhesions, RhoA also generates myosin-based contractility in cells. We therefore sought to examine how RhoA-dependent contractility contributes to cell-cell detachment. Inhibition of Rho kinase or myosin II induces the same effect on cells, namely an
Solid and papillary epithelial neoplasm of the pancreas
Friedman, A.C.; Lichtenstein, J.E.; Fishman, E.K.; Oertel, J.E.; Dachman, A.H.; Siegelman, S.S.
Solid and papillary epithelial neoplasm of the pancreas is an uncommon low grade malignant tumor histologically distinct from the usual ductal adenocarcinoma and amenable to cure by surgical excision. It tends to occur in black women in their second or third decade of life and has often been misclassified as nonfunctional islet cell tumor or as cystadenoma or cystadenocarcinoma. Twelve cases were reviewed. Sonography and CT of solid and pipillary epithelial neoplasms depict a well-demarcated mass that can be solid, mixed cystic and solid, or largely cystic. The radiologic appearance is dependent on the maintenance of the integrity of the neoplasm versus the extent of retrogressive changes that have occurred.
TRPV channels as thermosensory receptors in epithelial cells.
Lee, Hyosang; Caterina, Michael J
Temperature-sensitive transient receptor potential vanilloid (TRPV) ion channels are critical contributors to normal pain and temperature sensation and therefore represent attractive targets for pain therapy. When these channels were first discovered, most attention was focused on their potential contributions to direct thermal activation of peripheral sensory neurons. However, recent anatomical, physiological, and behavioral studies have provided evidence that TRPV channels expressed in skin epithelial cells may also contribute to thermosensation in vitro and in vivo. Here, we review these studies and speculate on possible communication mechanisms from cutaneous epithelial cells to sensory neurons.
Airway Epithelial miRNA Expression Is Altered in Asthma
Solberg, Owen D.; Ostrin, Edwin J.; Love, Michael I.; Peng, Jeffrey C.; Bhakta, Nirav R.; Nguyen, Christine; Solon, Margaret; Nguyen, Cindy; Barczak, Andrea J.; Zlock, Lorna T.; Blagev, Denitza P.; Finkbeiner, Walter E.; Ansel, K. Mark; Arron, Joseph R.; Erle, David J.
Rationale: Changes in airway epithelial cell differentiation, driven in part by IL-13, are important in asthma. Micro-RNAs (miRNAs) regulate cell differentiation in many systems and could contribute to epithelial abnormalities in asthma. Objectives: To determine whether airway epithelial miRNA expression is altered in asthma and identify IL-13–regulated miRNAs. Methods: We used miRNA microarrays to analyze bronchial epithelial brushings from 16 steroid-naive subjects with asthma before and after inhaled corticosteroids, 19 steroid-using subjects with asthma, and 12 healthy control subjects, and the effects of IL-13 and corticosteroids on cultured bronchial epithelial cells. We used quantitative polymerase chain reaction to confirm selected microarray results. Measurements and Main Results: Most (12 of 16) steroid-naive subjects with asthma had a markedly abnormal pattern of bronchial epithelial miRNA expression by microarray analysis. Compared with control subjects, 217 miRNAs were differentially expressed in steroid-naive subjects with asthma and 200 in steroid-using subjects with asthma (false discovery rate < 0.05). Treatment with inhaled corticosteroids had modest effects on miRNA expression in steroid-naive asthma, inducing a statistically significant (false discovery rate < 0.05) change for only nine miRNAs. qPCR analysis confirmed differential expression of 22 miRNAs that were highly differentially expressed by microarrays. IL-13 stimulation recapitulated changes in many differentially expressed miRNAs, including four members of the miR-34/449 family, and these changes in miR-34/449 family members were resistant to corticosteroids. Conclusions: Dramatic alterations of airway epithelial cell miRNA levels are a common feature of asthma. These alterations are only modestly corrected by inhaled corticosteroids. IL-13 effects may account for some of these alterations, including repression of miR-34/449 family members that have established roles in airway
NASA Technical Reports Server (NTRS)
NASA technology has produced a laser-aided system for surveying land boundaries in difficult terrain. It does the job more accurately than conventional methods, takes only one-third the time normally required, and is considerably less expensive. In surveying to mark property boundaries, the objective is to establish an accurate heading between two "corner" points. This is conventionally accomplished by erecting a "range pole" at one point and sighting it from the other point through an instrument called a theodolite. But how do you take a heading between two points which are not visible to each other, for instance, when tall trees, hills or other obstacles obstruct the line of sight? That was the problem confronting the U.S. Department of Agriculture's Forest Service. The Forest Service manages 187 million acres of land in 44 states and Puerto Rico. Unfortunately, National Forest System lands are not contiguous but intermingled in complex patterns with privately-owned land. In recent years much of the private land has been undergoing development for purposes ranging from timber harvesting to vacation resorts. There is a need for precise boundary definition so that both private owners and the Forest Service can manage their properties with confidence that they are not trespassing on the other's land.
Alexandrite laser pumped by semiconductor lasers
Scheps, R.; Gately, B.M.; Myers, J.F. ); Krasinski, J.S. ); Heller, D.F. )
We report the first operation of a direct diode-pumped tunable chromium-doped solid-state laser. A small alexandrite (Cr:BeAl{sub 2}O{sub 4}) crystal was longitudinally pumped by two visible laser diodes. The threshold pump power was 12 mW using the {ital R}{sub 1} line at 680.4 nm for the pump transition, and the slope efficiency was 25%. The measured laser output bandwidth was 2.1 nm.
Alexandrite laser pumped by semiconductor lasers
NASA Astrophysics Data System (ADS)
Scheps, Richard; Gately, Bernard M.; Myers, Joseph F.; Krasinski, Jerzy S.; Heller, Donald F.
We report the first operation of a direct diode-pumped tunable chromium-doped solid-state laser. A small alexandrite (Cr:BeAl2O4) crystal was longitudinally pumped by two visible laser diodes. The threshold pump power was 12 mW using the R1 line at 680.4 nm for the pump transition, and the slope efficiency was 25%. The measured laser output bandwidth was 2.1 nm.
Alix-mediated assembly of the actomyosin–tight junction polarity complex preserves epithelial polarity and epithelial barrier
Campos, Yvan; Qiu, Xiaohui; Gomero, Elida; Wakefield, Randall; Horner, Linda; Brutkowski, Wojciech; Han, Young-Goo; Solecki, David; Frase, Sharon; Bongiovanni, Antonella; d'Azzo, Alessandra
Maintenance of epithelial cell polarity and epithelial barrier relies on the spatial organization of the actin cytoskeleton and proper positioning/assembly of intercellular junctions. However, how these processes are regulated is poorly understood. Here we reveal a key role for the multifunctional protein Alix in both processes. In a knockout mouse model of Alix, we identified overt structural changes in the epithelium of the choroid plexus and in the ependyma, such as asymmetrical cell shape and size, misplacement and abnormal beating of cilia, blebbing of the microvilli. These defects culminate in excessive cell extrusion, enlargement of the lateral ventricles and hydrocephalus. Mechanistically, we find that by interacting with F-actin, the Par complex and ZO-1, Alix ensures the formation and maintenance of the apically restricted actomyosin–tight junction complex. We propose that in this capacity Alix plays a role in the establishment of apical–basal polarity and in the maintenance of the epithelial barrier. PMID:27336173
NASA Astrophysics Data System (ADS)
Goncharov, I. N.; Dezhin, V. N.; Kutakhov, V. P.; Petukhov, A. V.; Sidorin, V. M.; Sukhar, I. M.
The way in which lasers are being incorporated into the military aircraft of the United States and the countries of Western Europe is discussed. Descriptions are given of laser weapons-guiding systems (including ranger finders and systems for target illumination), laser systems for navigation and flight-safety assurance (gyroscopes, velocity gauges, altimeters, systems providing meteorological data, proximity warning systems), and laser systems for air reconnaissance, communications, and control. Attention is also given to the Glissada laser guide path system, developed in the USSR. The physics of the systems is emphasized in the description and the principles underlying the operation of a laser are discussed in the introduction.
Elavarasu, Sugumari; Naveen, Devisree; Thangavelu, Arthiie
Laser is one of the most captivating technologies in dental practice since Theodore Maiman in 1960 invented the ruby laser. Lasers in dentistry have revolutionized several areas of treatment in the last three and a half decades of the 20(th) century. Introduced as an alternative to mechanical cutting device, laser has now become an instrument of choice in many dental applications. Evidence suggests its use in initial periodontal therapy, surgery, and more recently, its utility in salvaging implant opens up a wide range of applications. More research with better designs are a necessity before lasers can become a part of dental armamentarium. This paper gives an insight to laser in periodontics.
Chase, L.L.; Payne, S.A.
During the decade that has passed since the discovery of the alexandrite laser, many other tunable vibronic sideband lasers based on Cr/sup 3 +/ have been developed. These lasers span the wavelength range from 700 nm to at least 1235 nm. Experimental and theoretical research has provided an understanding of the important factors that influence the performance of these Cr/sup 3 +/ lasers and other solid state vibronic lasers. The intrinsic performance levels of some of the most promising Cr/sup 3 +/ lasers are evaluated from extrapolated slope efficiency measurements. 7 refs., 4 figs., 2 tabs.
Ishii, T.K.
This book is intended to be a textbook for an upper division one-semester electrical engineering course. Students are expected to have had some undegraduate course work in modern physics and in electromagnetic field theory. General aspects regarding devices based on quantum electronics are considered along with gas masers, solid masers, gas lasers, solid lasers, semiconductor lasers, liquid lasers, modulation techniques for lasers, and opto-electrical demodulators and energy convertors. Attention is given to quantum electric harmonic generators, Raman lasers, optical parametric interactions, holograms, optical terms, crystallographic terms, band theory, Schroedinger formulation and Dirac formation, and the quantum number of electrons in a hydrogen atom.
Modulation of Candida albicans attachment to human epithelial cells by bacteria and carbohydrates.
Centeno, A; Davis, C P; Cohen, M S; Warren, M M
The effects of carbohydrates (mannose and dextrose). Escherichia coli 07KL. and Klebsiella pneumoniae on Candida albicans attachment to epithelial cells was studied. Dextrose had no effect on yeast attachment to epithelial cells. Conversely, mannose significantly decreased both yeast and piliated bacterial attachment (E. coli 07KL, heavily piliated K. pneumoniae) whereas having no effect on nonpiliated K. pneumoniae attachment to epithelial cells. The number of yeasts attaching to epithelial cells was enhanced by preincubation of epithelial cells with piliated strains of bacteria, whereas preincubation with nonpiliated strains of bacteria had no effect on yeast attachment. Scanning electron microscopy showed that piliated bacteria and yeasts were juxtaposed on the epithelial cell surface. These data suggest that certain piliated strains of bacteria can enhance C. albicans attachment to epithelial cells and that type 1 pili of bacteria can be a factor in the enhanced attachment of C. albicans to epithelial cells. Images PMID:6132878
Laser peening of metals- enabling laser technology
Dane, C.B.; Hackel, L.A.; Daly, J.; Harrisson, J.
Laser peening, a surface treatment for metals, employs laser induced shocks to create deep and intense residual stresses in critical components. In many applications this technology is proving to be superior to conventional treatments such as shot peening. The laser peening process has generated sufficiently impressive results to move it from a laboratory demonstration phase into a significant industrial process. However until now this evolution has been slowed because a laser system meeting the average power requirements for a high throughput process has been lacking.
Palatal shelves from embryos exposed on gestation day (GD) 12 to either retinoic acid (RA) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) contact but fail to fuse. It is of interest to know if diverse agents that induce clefting via the same etiology also activate the same biochem...
NASA Astrophysics Data System (ADS)
Hollberg, Leo; Bergquist, James Charles; Kasevich, Mark A.
Degenerate gases. Probing vortex pair sizes in the Berezinskii-Kosterlitz-Thouless regime on a two-dimensional lattice of Bose-Einstein condensates / V. Schweikhard ... [et al.]. Interacting Bose-Einstein condensates in random potentials / P. Bouyer ... [et al.]. Towards quantum magnetism with ultracold atoms in optical lattices / I. Bloch -- Precision measurement and fundamental physics. T-violation and the search for a permanent electric dipole moment of the mercury atom / E. N. Fortson -- Quantum information and control I. Quantum information processing and ramsey spectroscopy with trapped ions / C. F. Roos ... [et al.]. Quantum non-demolition counting of photons in a cavity / S. Haroche ... [et al.] -- Ultra-fast control and spectroscopy. Frequency-Comb- assisted mid-infrared spectroscopy / P. de Natale ... [et al.] -- Precision measurement and applications. Precision gravity tests by atom interferometry / G. M. Tino ... [et al.] -- Novel spectroscopic applications. On a variation of the proton-electron mass ratio / W. Ubachs ... [et al.] -- Quantum information and control II. Quantum interface between light and atomic ensembles / H. Krauter ... [et al.] -- Degenerate Fermi gases. An atomic Fermi gas near a P-wave Feshbach resonance / D. S. Jin, J. P. Gaebler and J. T. Stewart. Bragg scattering of correlated atoms from a degenerate Fermi gas / R. J. Ballagh, K. J. Challis and C. W. Gardiner -- Spectroscopy and control of atoms and molecules. Stark and Zeeman deceleration of neutral atoms and molecules / S. D. Hogan ... [et al.]. Generation of coherent, broadband and tunable soft x-ray continuum at the leading edge of the driver laser pulse / A. Jullien ... [et al.]. Controlling neural atoms and photons with optical conveyor belts and ultrathin optical fibers / D. Meschede. W. Alt and A. Rauschenbeutel -- Spectroscopy on the small scale. Wide-field cars-microscopy / C. Heinrich ... [et al.]. Atom nano-optics and nano-lithography / V. I. Balykin ... [et al
Backus, Sterling; Kapteyn, Henry C.; Murnane, Margaret M.
Laser amplifiers and methods for amplifying a laser beam are disclosed. A representative embodiment of the amplifier comprises first and second curved mirrors, a gain medium, a third mirror, and a mask. The gain medium is situated between the first and second curved mirrors at the focal point of each curved mirror. The first curved mirror directs and focuses a laser beam to pass through the gain medium to the second curved mirror which reflects and recollimates the laser beam. The gain medium amplifies and shapes the laser beam as the laser beam passes therethough. The third mirror reflects the laser beam, reflected from the second curved mirror, so that the laser beam bypasses the gain medium and return to the first curved mirror, thereby completing a cycle of a ring traversed by the laser beam. The mask defines at least one beam-clipping aperture through which the laser beam passes during a cycle. The gain medium is pumped, preferably using a suitable pumping laser. The laser amplifier can be used to increase the energy of continuous-wave or, especially, pulsed laser beams including pulses of femtosecond duration and relatively high pulse rate.
Backus, S.; Kapteyn, H.C.; Murnane, M.M.
Laser amplifiers and methods for amplifying a laser beam are disclosed. A representative embodiment of the amplifier comprises first and second curved mirrors, a gain medium, a third mirror, and a mask. The gain medium is situated between the first and second curved mirrors at the focal point of each curved mirror. The first curved mirror directs and focuses a laser beam to pass through the gain medium to the second curved mirror which reflects and recollimates the laser beam. The gain medium amplifies and shapes the laser beam as the laser beam passes therethrough. The third mirror reflects the laser beam, reflected from the second curved mirror, so that the laser beam bypasses the gain medium and return to the first curved mirror, thereby completing a cycle of a ring traversed by the laser beam. The mask defines at least one beam-clipping aperture through which the laser beam passes during a cycle. The gain medium is pumped, preferably using a suitable pumping laser. The laser amplifier can be used to increase the energy of continuous-wave or, especially, pulsed laser beams including pulses of femtosecond duration and relatively high pulse rate. 7 figs.
Phased laser array for generating a powerful laser beam
Holzrichter, John F.; Ruggiero, Anthony J.
A first injection laser signal and a first part of a reference laser beam are injected into a first laser element. At least one additional injection laser signal and at least one additional part of a reference laser beam are injected into at least one additional laser element. The first part of a reference laser beam and the at least one additional part of a reference laser beam are amplified and phase conjugated producing a first amplified output laser beam emanating from the first laser element and an additional amplified output laser beam emanating from the at least one additional laser element. The first amplified output laser beam and the additional amplified output laser beam are combined into a powerful laser beam.
Comparative study of 1,064-nm laser-induced skin burn and thermal skin burn.
Zhang, Yi-Ming; Ruan, Jing; Xiao, Rong; Zhang, Qiong; Huang, Yue-Sheng
Infrared lasers are widely used in medicine, industry, and other fields. While science, medicine, and the society in general have benefited from the many practical uses of lasers, they also have inherent safety issues. Although several procedures have been put forward to protect the skin from non-specific laser-induced damage, individuals receiving laser therapy or researchers who use laser are still at risk for skin damage. This study aims to understand the interaction between laser and the skin, and to investigate the differences between the skin damage caused by 1,064-nm laser and common thermal burns. Skin lesions on Wistar rats were induced by a 1,064-nm CW laser at a maximum output of 40 W and by a copper brass bar attached to an HQ soldering iron. Histological sections of the lesions and the process of wound healing were evaluated. The widths of the epidermal necrosis and dermal denaturalization of each lesion were measured. To observe wound healing, the epithelial gap and wound gap were measured. Masson's trichrome and picrosirius red staining were also used to assess lesions and wound healing. The thermal damage induced by laser intensified significantly in both horizontal dimension and in vertical depth with increased duration of irradiation. Ten days after wounding, the dermal injuries induced by laser were more severe. Compared with the laser-induced skin damage, the skin burn induced by an HQ soldering iron did not show a similar development or increased in severity with the passage of time. The results of this study showed the pattern of skin damage induced by laser irradiation and a heated brass bar. This study also highlighted the difference between laser irradiation and thermal burn in terms of skin damage and wound healing, and offers insight for further treatment.
Scanning laser reflectometry of retinal and subretinal tissues
NASA Astrophysics Data System (ADS)
Elsner, Ann E.; Moraes, L.; Beausencourt, E.; Remky, Andreas; Weiter, J. J.; Walker, J. P.; Wing, G. L.; Burns, Stephen Allan; Raskauskas, P. A.; Kelley, L. M.
Measurements of the human ocular fundus that make use of the light returning through the pupil are called reflectometry. Early reflectometry studies were limited by poor light return from the retina and strong reflections from the anterior surface of the eye. Artifacts produced misleading results in diseases like age-related macular degeneration. Novel laser sources, scanning, confocal optics, and digital imaging provide improved sampling of the signal from the tissues of interest: photoreceptors and retinal pigment epithelial cells. A wider range of wavelengths is now compared, including the near infrared. Reflectometry now provides functional mapping, even in severe pathology.
CCL20, (gamma)(delta) T cells, and IL-22 in corneal epithelial healing
Technology Transfer Automated Retrieval System (TEKTRAN)
After corneal epithelial abrasion, leukocytes and platelets rapidly enter the corneal stroma, and CCR6 (+) IL-17(+) gamma delta T cells migrate into the epithelium. Gamma delta T-cell-deficient (TCRd(-/-)) mice have significantly reduced inflammation and epithelial wound healing. Epithelial CCL20 mR...
Oxidized alginate hydrogels as niche environments for corneal epithelial cells.
Wright, Bernice; De Bank, Paul A; Luetchford, Kim A; Acosta, Fernando R; Connon, Che J
Chemical and biochemical modification of hydrogels is one strategy to create physiological constructs that maintain cell function. The aim of this study was to apply oxidised alginate hydrogels as a basis for development of a biomimetic niche for limbal epithelial stem cells that may be applied to treating corneal dysfunction. The stem phenotype of bovine limbal epithelial cells (LEC) and the viability of corneal epithelial cells (CEC) were examined in oxidised alginate gels containing collagen IV over a 3-day culture period. Oxidation increased cell viability (P ≤ 0.05) and this improved further with addition of collagen IV (P ≤ 0.01). Oxidised gels presented larger internal pores (diameter: 0.2-0.8 µm) than unmodified gels (pore diameter: 0.05-0.1 µm) and were significantly less stiff (P ≤ 0.001), indicating that an increase in pore size and a decrease in stiffness contributed to improved cell viability. The diffusion of collagen IV from oxidised alginate gels was similar to that of unmodified gels suggesting that oxidation may not affect the retention of extracellular matrix proteins in alginate gels. These data demonstrate that oxidised alginate gels containing corneal extracellular matrix proteins can influence corneal epithelial cell function in a manner that may impact beneficially on corneal wound healing therapy.
SIRT1 inhibits the mouse intestinal motility and epithelial proliferation
Technology Transfer Automated Retrieval System (TEKTRAN)
SIRT1 inhibits the mouse intestinal motility and epithelial proliferation. Sirtuin 1 (SIRT1), a NAD+-dependent histone deacetylase, is involved in a wide array of cellular processes, including glucose homeostasis, energy metabolism, proliferation and apoptosis, and immune response. However, it is un...
Mechanisms of Epithelial-Mesenchymal Transition by TGF-β
Wendt, Michael K.; Allington, Tressa M.; Schiemann, William P.
Summary The formation of epithelial cell barriers results from the defined spatiotemporal differentiation of stem cells into a specialized and polarized epithelium, a process termed mesenchymal-epithelial transition. The reverse process, epithelial-mesenchymal transition (EMT), is a metastable process that enables polarized epithelial cells acquire a motile fibroblastoid phenotype. Physiological EMT also plays an essential role in promoting tissue healing, remodeling, or repair in response to a variety of pathological insults. On the other hand, pathophysiological EMT is a critical step in mediating the acquisition of metastatic phenotypes by localized carcinomas. Although metastasis clearly is the most lethal aspect of cancer, our knowledge of the molecular events that govern its development, including those underlying EMT, remain relatively undefined. Transforming growth factor-β (TGF-β) is a multifunctional cytokine that oversees and directs all aspects of cell development, differentiation, and homeostasis, as well as suppresses their uncontrolled proliferation and transformation. Quite dichotomously, tumorigenesis subverts the tumor suppressing function of TGF-β, and in doing so, converts TGF-β to a tumor promoter that stimulates pathophysiological EMT and metastasis. It therefore stands to reason that determining how TGF-β induces EMT in developing neoplasms will enable science and medicine to produce novel pharmacological agents capable of preventing its ability to do so, thereby improving the clinical course of cancer patients. Here we review the cellular, molecular, and microenvironmental mechanisms used by TGF-β to mediate its stimulation of EMT in normal and malignant cells. PMID:19852727