index
stringlengths 10
17
| text
stringlengths 101
18k
| doi
stringlengths 2
72
|
|---|---|---|
pubmed_1022_838 | RATIONALE
Structural characterization and differentiation of three newly synthesized lactose monopalmitate regioisomers at positions O-3, O-3' and O-6' were realized by single-stage matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry (MALDI-TOF/TOF-MS) in the positive ion mode and by high-energy collision-induced dissociation tandem mass spectrometry (CID-MS/MS).
METHODS
A MALDI-TOF/TOF analyzer was utilized for the analysis of these isobaric lactose monopalmitate regioisomers. The CID-MS/MS spectra were acquired using high-energy cid with a 2 kV potential difference between the source acceleration voltage and the collision cell.
RESULTS
High-energy (CID) tandem mass spectrometry (MS/MS) analyses of the sodiated molecules, [M + Na](+), showed distinguishing cross-ring product ions and characteristic fingerprint product ions, which allowed the straight-forward mass spectrometric characterization of these different regiosiomers.
CONCLUSIONS
This investigation allowed us to unravel the novel fragmentation behavior of the sodiated regioisoimer molecules obtained from the mono-substituted D-lactose fatty acid esters using high-energy CID-TOF/TOF-MS/MS analyses. The high-energy CID of the [M + Na](+) ions from the isobaric lactose monopalmitate regioiosmers promoted the formation of characteristic (0,2) A2 cross-ring cleavage product ions. | 10.1002/rcm.6770 |
pubmed_1000_2137 | OBJECTIVE
To review the main cognitive processes regulated by the cerebellum and the anatomical circuits involved in their clinical correlation.
DEVELOPMENT
The cerebellum is generally regarded as a regulator of motor function with a key role in movement coordination. Clinical evidence of the relation of the cerebellum to neural functions typically considered as cortical, is supplied by several neuropsychological alterations detected in both degenerative disorders and acute insult to the region such as vascular event and surgery. More anatomical circuits between the cerebellum and several cortical areas and limbic system, with the ventral pons region as main afference and efference relay of all these pathways. Cerebellar structures that are phylogenetically older such as the floculonodullar lobe, vermix, fastigial nuclei and globus nuclei have a tight relationship to emotional control and autonomic manifestations. More complex circuits are founded in the regulation of learning, motor planning and language. Functional imaging studies have helped to confirm the relationship between the cerebellum and memory processes, finding a selective activation of lateral regions during to cerebellar damage, such a frontal like syndromes, memory deficits and aphasia and even though dysmetria with incoordination between mental process velocity and its motor execution.
CONCLUSIONS
All the data from clinical and functional studies indicate that the cerebellum has a central co-ordinating function not only of movement but also regulating thought. The cerebellum should, therefore, be reconsidered as a complex neurone system at much the same level as the more advanced cortical structures. | pubmed_1000_2137 |
pubmed_793_15311 | The locations of the isolated double bonds and of the pentaene chromophore in lienomycin (I) were established by chemical degradation of I followed by MS and 1H NMR examination of the products. The complete structure of the antibiotic is proposed. | 10.7164/antibiotics.33.998 |
pubmed_859_25179 | Much is known about palliative care needs of persons with dementia and their family. Less is known about how to successfully implement models that address those needs. We present specialist models in the Netherlands (2017-2018) and Northern Ireland (2016-2017) contrasting its evaluations. From implementation failure in the Netherlands compared with successful implementation in Northern Ireland, we learn that recognizing roles and competencies among all involved is essential in developing effective partnership relationships. All of this is facilitated by referral before the end of life and offering various training programs and in-patient and out-patient services and therapies to show benefits early. | 10.3233/JAD-220772 |
pubmed_989_1446 | INTRODUCTION
The clinically licensed drugs used as antibiotics prevent the microbial growth interfering with the biosynthesis of proteins, nucleic acids, microorganism wall biosynthesis or wall permeability, and microbial metabolic pathways. A serious, emerging problem is the arisen of extensive drug resistance afflicting most countries worldwide.
AREAS COVERED
An exciting approach to fight drug resistance is the identification of essential enzymes encoded by pathogen genomes. Inhibition of such enzymes may impair microbial growth or virulence due to interference with crucial metabolic processes. Genome exploration of pathogenic and nonpathogenic microorganisms has revealed carbonic anhydrases (CAs, EC 4.2.1.1) as possible antibacterial targets.
EXPERT OPINION
Balancing the equilibrium between CO2 and HCO3 - is essential for microbial metabolism and is regulated by at least four classes of CAs. Classical CA inhibitors (CAIs) such as ethoxzolamide were shown to kill the gastric pathogen Helicobacter pylori in vitro, whereas acetazolamide and some of its more lipophilic derivatives were shown to be effective against vancomycin-resistant Enterococcus spp., with MICs in the range of 0.007-2 µg/mL, better than linezolid, the only clinically used agent available to date. Such results reinforce the rationale of considering existing and newly designed CAIs as antibacterials with an alternative mechanism of action. | 10.1080/13543776.2020.1811853 |
pubmed_452_19753 | This paper is a review of lidar remote sensing of the aquatic environment. The optical properties of seawater relevant to lidar remote sensing are described. The three main theoretical approaches to understanding the performance of lidar are considered (the time-dependent radiative transfer equation, Monte Carlo simulations, and the quasi-single-scattering assumption). Basic lidar instrument design considerations are presented, and examples of lidar studies from surface vessels, aircraft, and satellites are given. | 10.1364/AO.59.000C92 |
pubmed_635_13257 | AIM
To evaluate the dose-dependent immunogenic properties of poly(lactide-co-glycolide) (PLGA) particles coated with cellobiose as antigen carriers for oral immunization.
METHODS
Two types of PLGA-cellobiose particles (PLGA-cellobiose-1, ~ 0.8 μm and PLGA-cellobiose-2, ~ 1.2 μm) containing non-toxic recombinant subunit B (SbB) of diphtheria toxin fused with enhanced green fluorescent protein were characterized in vitro for their size, shape, antigen loading, and ability to induce phagocytosis. Different doses of antigen, immobilized on the particles (2.5 μg, 25 μg, 250 μg, and 2500 μg per 1 kg of body weight), were administered per os 3 times with intervals of 2 weeks to BALB/c female mice. The antigen-specific IgG and IgA antibodies were estimated in serum by ELISA.
RESULTS
After the first immunization, increase in concentration of blood antitoxic antibodies was detected. Antigen dose 250 μg/kg was the most immunogenic for IgG antibodies induction for both types of PLGA-cellobiose particles. Antigen doses 25 μg/kg and 2.5 μg/kg were the most immunogenic for IgA antibodies induction by PLGA-cellobiose 1 and 2 particles, respectively. The second and the third treatment had no significant effect on the immune response or even reduced it, which could be explained by immune tolerance induction by the antigens delivered per os.
CONCLUSION
Our results suggest that the correct dose of PLGA-cellobiose particles loaded with antigen could significantly increase the humoral immune response against the introduced antigen already after the first immunization. Thus, PLGA particles can be considered as a potent component of oral vaccines. | 10.3325/cmj.2015.56.85 |
pubmed_879_21947 | INTRODUCTION
Asthma morbidity and health-care utilization are known to exhibit a steep socioeconomic gradient. Further investigation into the modulators of this effect is required to identify potentially modifiable factors.
METHODS
We identified a cohort of patients with asthma from the Optimum Patient Care Research Database (OPCRD). We compared demographics, clinical variables, and health-care utilization by quintile of the UK 2011 Indices of Multiple Deprivation based on the location of the patients' general practice. Multivariable analyses were conducted using generalized linear models adjusting for year, age, and sex. We conducted subgroup analyses and interaction tests to investigate the impact of deprivation by age, sex, ethnicity, and treatment step.
RESULTS
Our analysis included 127,040 patients with asthma. Patients from the most deprived socio-economic status (SES) quintile were more likely to report uncontrolled disease (OR: 1.54, 95% CI: 1.16, 2.05) and to have an exacerbation during follow-up (OR: 1.27, 95% CI: 1.13, 1.42) than the least deprived quintile. They had higher blood eosinophils (ratio: 1.03; 95% CI: 1.00, 1.06) and decreased peak flow (ratio: 0.95, 95% CI: 0.94, 0.97) when compared to those in the least deprived quintile. The effect of deprivation on asthma control was greater among those aged over 75 years (OR = 1.81, 95% CI: 1.20, 2.73) compared to those aged less than 35 years (OR: 1.22, 95% CI: 0.85, 1.74; pinteraction=0.019). Similarly, socioeconomic disparities in exacerbations were larger among those from ethnic minority groups (OR: 1.94, 95% CI: 1.40, 2.68) than white patients (OR: 1.24, 95% CI: 1.10, 1.39; pinteraction=0.012).
CONCLUSION
We found worse disease control and increased exacerbation rates among patients with asthma from more deprived areas. There was evidence that the magnitude of socioeconomic disparities was elevated among older patients and those from ethnic minority groups. The drivers of these differences require further exploration. | 10.2147/JAA.S326213 |
pubmed_172_14282 | The efficacy of semisynthetic human insulin (HI) and monocomponent porcine insulin (PI) in treatment of diabetic ketoacidosis (DKA) was compared in 10 (PI) and 11 (HI) patients in a double-blind randomized study. Insulin (8 U/h i.v.), fluid replacement (0.65% NaCl and 5% glucose), and KCl supplements were administered according to a fixed protocol. Glucose, potassium, sodium, creatinine, calcium, phosphate, and free-insulin concentrations were never significantly different during the study. At the start, mean +/- SD of pH was 7.10 +/- 0.14 in the HI group and 7.10 +/- 0.12 in the PI group. The time to reach arbitrary values for pH, bicarbonate, base excess, and beta-hydroxybutyrate was shorter during HI treatment, but the differences were not statistically significant. During HI treatment, the arbitrary value of 1.0 mM of acetoacetate was reached faster than during PI treatment (5.2 +/- 2.6 and 8.4 +/- 0.9 h, respectively; P less than .05). The concentration of acetoacetate was significantly different between the two groups after 6 and 7 h of insulin treatment (6 h: HI 0.82 +/- 0.50 mM and PI 2.19 +/- 1.65 mM, P less than .05; 7 h: HI 0.51 +/- 0.40 mM and PI 1.74 +/- 1.54 mM, P = .05). We conclude that recovery from DKA during treatment with HI might be slightly faster than during treatment with PI. If this difference is real, it does not seem clinically important. | 10.2337/diacare.10.1.49 |
pubmed_345_14761 | OBJECTIVE
To investigate the correlation between serum S100B level and carbon monoxide (CO) poisoning by meta-analysis.
METHODS
By searching both English and Chinese language-based electronic databases (PubMed, EBSCO, Ovid, Springerlink, Wiley, Web of Science, Wanfang databases, China national knowledge infrastructure (CNKI), VIP database, etc.) thoroughly, we tabulated and analyzed the collected data with the use of Comprehensive Meta-analysis 2.0 (CMA 2.0).
RESULTS
Totally 108 studies have been searched initially (92 studies in Chinese, 16 studies in English). Nine case-control studies (4 studies in English, 5 in Chinese) were chosen for an updated meta-analysis including 542 patients with CO poising and 236 healthy controls. Results identified that the serum S100B level were obviously higher than that in healthy controls (SMD=1.600, 95% CI=1.055-2.145, P<0.001). A subgroup based on the ethnicities revealed that the serum S100B level in Caucasian and Asian subgroups was clearly higher than serum S100B level in healthy controls (Asians: SMD=2.0624, 95% CI=1.736-3.511, P<0.001; Caucasians: SMD=0.447, 95% CI=0.197-0.697, P<0.001).
CONCLUSION
Serum S100B level may be correlated with the CO poisoning and could be effective biomarker for early diagnosis and treatment monitoring in CO poisoning. | pubmed_345_14761 |
pubmed_446_13648 | Primary breast cancer often displays only moderately increased glucose metabolism resulting in a low sensitivity of positron emission tomography (PET) using [F-18]fluorodeoxyglucose (FDG) in detecting small breast carcinomas, locoregional micrometastases and non-enlarged tumor infiltrated lymphnodes. In contrast, distant breast cancer metastases are generally characterized by significantly increased metabolic activity compared to normal tissue. Therefore, FDG-PET provides accurate diagnostic information as a whole body imaging modality in staging of breast cancer patients. The metabolic information from FDG-PET/CT is often more sensitive than conventional imaging for the detection of distant metastases, particularly in the recurrent setting. FDG-PET is superior in detecting tumor-involved distant lymphnodes, particularly those which are normal in size, as well as in characterizing enlarged lymphnodes as positive or negative for malignancy. Of note, CT is superior in detecting small lung metastases. Although the overall sensitivity for bone scintigraphy and FDG-PET are comparable, bone scintigraphy seems to be superior in the detection of osteoblastic disease whereas FDG-PET is superior for osteolytic metastases, suggesting a complementary role for both imaging procedures. FDG-PET/MR has an evolving role in breast cancer management, for example in the detection of liver metastases and in the research setting for treatment monitoring. The utilization of PET for prediction of treatment response to primary chemotherapy is an area of active research, using FDG as well as other PET biomarkers including [F-18]Fluoroestradiol, [F-18]Fluorothymidine and integrin targeting tracer for monitoring anti-angiogenic therapy. | pubmed_446_13648 |
pubmed_418_14935 | Neurospora crassa is an established reference organism to investigate carotene biosynthesis and light regulation. However, there is little evidence of its capacity to produce secondary metabolites. Here, we report the role of the fungal-specific regulatory velvet complexes in development and secondary metabolism (SM) in N. crassa Three velvet proteins VE-1, VE-2, VOS-1, and a putative methyltransferase LAE-1 show light-independent nucleocytoplasmic localization. Two distinct velvet complexes, a heterotrimeric VE-1/VE-2/LAE-1 and a heterodimeric VE-2/VOS-1 are found in vivo The heterotrimer-complex, which positively regulates sexual development and represses asexual sporulation, suppresses siderophore coprogen production under iron starvation conditions. The VE-1/VE-2 heterodimer controls carotene production. VE-1 regulates the expression of >15% of the whole genome, comprising mainly regulatory and developmental features. We also studied intergenera functions of the velvet complex through complementation of Aspergillus nidulans veA, velB, laeA, vosA mutants with their N. crassa orthologs ve-1, ve-2, lae-1, and vos-1, respectively. Expression of VE-1 and VE-2 in A. nidulans successfully substitutes the developmental and SM functions of VeA and VelB by forming two functional chimeric velvet complexes in vivo, VelB/VE-1/LaeA and VE-2/VeA/LaeA, respectively. Reciprocally, expression of veA restores the phenotypes of the N. crassa ve-1 mutant. All N. crassa velvet proteins heterologously expressed in A. nidulans are localized to the nuclear fraction independent of light. These data highlight the conservation of the complex formation in N. crassa and A. nidulans However, they also underline the intergenera similarities and differences of velvet roles according to different life styles, niches and ontogenetic processes. | 10.1534/genetics.119.302277 |
pubmed_1100_15410 | The Morris water maze is widely used to evaluate to evaluate the spatial learning ability of rodents under laboratory settings. The present study demonstrates that reproductive male meadow voles, Microtus pennsylvanicus, are able to acquire and retain a spatial water maze task using celestial cues. Voles were able to acquire a modified outdoor Morris water maze task over 4 trials per day, whereby they had to learn and remember the location of a submerged hidden platform, using the position of the sun and associated celestial cues. Their proficiency on this task was related to the availability of the celestial cues, with voles displaying significantly poorer spatial navigation on overcast than clear days and when the testing time (and position of the sun and associated celestial cues) was shifted from morning to afternoon. These findings with meadow voles support the ecological relevance of the water maze task. | 10.1016/0166-4328(94)90013-2 |
pubmed_924_24296 | The two nickel chelates of Schiff bases, 3-hydroxy-N-{2-[(3-hydroxy-N-phenylbutyrimidoyl)-amino]-phenyl}-N'-phenylbutyramidine (M(1)) and bis-4-(ethyliminomethyl)naphthalene-1-ol (M(2)), have been synthesized and explored as ionophores for preparing PVC-based membrane sensors selective to nickel ion. The influences of membrane compositions on the potentiometric response of the electrodes have been found to substantially improve the performance characteristics. The best performance was obtained with the electrode having a membrane composition (w/w; mg) of (M(1)): PVC:NaTPB:CN in the ratio 5:150:5:150. The sensor shows a linear potential response for Ni(2+) over a wide concentration range 1.6x10(-7) to 1.0x10(-2) M with Nernstian compliance (30.0+/-0.2 mV/decade of activity) within pH range 2.5-9.5 and a fast response time of 10 s. The sensor has been found to work satisfactorily in partially non-aqueous media up to 20% (v/v) content of methanol, ethanol, and acetonitrile and could be used for a period of 4 months. The analytical usefulness of the proposed electrode has been evaluated by its application in the determination of nickel in real samples. The practical utility of the membrane electrode has also been observed in the presence of surfactants. | 10.1016/j.aca.2008.06.054 |
pubmed_471_25261 | We successfully performed totally endoscopic single-port robotic surgery. A 50-year-old man with a mediastinal tumor underwent robot-assisted tumor resection. Only one port was placed on the right side of the chest, and a robotic endoscope and two robotic instruments were inserted through the port. The instruments were crossed while avoiding collision. Single-port robotic surgery for a mediastinal tumor using the cross-arm technique was safely achieved with good clinical results and excellent cosmetic results. | 10.1007/s00595-018-1722-z |
pubmed_1041_8197 | We present an experimental and theoretical study of the geometric structure of ultrathin BaTiO(3) films grown on Fe(001). Surface x-ray diffraction reveals that the films are terminated by a BaO layer, while the TiO(2) layer is next to the top Fe layer. Cations in termination layers have incomplete oxygen shells inducing strong vertical relaxations. Onset of polarization is observed at a minimum thickness of two unit cells. Our findings are supported by first-principles calculations providing a quantitative insight into the multiferroic properties on the atomic scale. | 10.1103/PhysRevLett.106.087203 |
pubmed_487_7802 | PURPOSE
We investigated the expression of interleukin-13 receptor alpha2 (IL-13R alpha 2), EphA2, and Fos-related antigen 1 (Fra-1) in astrocytomas and normal brain. We sought to document whether the expression of the three factors changed with progression to higher grade malignancy and whether two or three targets in combination might be sufficient to target all patients with high-grade astrocytomas.
EXPERIMENTAL DESIGN
Immunohistochemistry was done for IL-13R alpha 2, EphA2, and Fra-1 using human brain tumor tissue microarrays containing 30 specimens of WHO grades II and III astrocytomas, 46 glioblastoma multiformes (GBM), and 9 normal brain samples. Sections were scored based on frequency and intensity of expression. Western blotting was done for all three markers using GBM tumor specimens and xenograft cell lines. Two cytotoxins, IL-13.E13K.PE38QQR and ephrinA1-PE38QQR, which target IL-13R alpha 2 or EphA2, respectively, were tested for cytotoxicity against human GBM primary explant cells and established cells.
RESULTS
Expression of all three proteins was significantly higher in GBM compared with normal brain, low-grade, and anaplastic astrocytomas. Greater than 95% of GBM overexpressed at least two of the three markers. Importantly, every GBM overexpressed at least one marker. Human GBM primary explant cells and cell lines were potently killed by IL-13.E13K.PE38QQR and ephrinA1-PE38QQR, in accordance with their level of expression of IL-13R alpha 2 and EphA2, respectively.
CONCLUSIONS
IL-13R alpha 2, EphA2, and Fra-1 are attractive therapeutic targets representing molecular denominators of high-grade astrocytomas. One hundred percent of GBM tumors overexpress at least one of these proteins, providing the basis for rational combinatorial targeted therapies/diagnostics suitable for all patients with this disease. | 10.1158/1078-0432.CCR-07-1990 |
pubmed_0_3541 | The case of a 49-year-old male patient who presented with recurrent pulmonary emboli secondary to a calcified lesion within his inferior vena cava is presented. The diagnosis and relevant literature is reviewed. This is the first time that calcification within the inferior vena cava has presented this way in adults, and it is important to consider this diagnosis in patients presenting with recurrent pulmonary emboli. | 10.1016/j.jvs.2010.07.060 |
pubmed_1119_9026 | Cell volume regulation after swelling has been widely demonstrated and attributed to a loss of KCl in the external medium. But it was also shown in a few cell types that organic cell osmolytes, particularly amino acids, were contributing to volume regulation. These effluxes occurred through a diffusional type of transport. Electrophysiological experiments with patch-clamp electrodes have demonstrated the activation of selective K+ channels in parallel with chloride channels during volume regulation. These chloride channels appear much less selective for a large variety of anions. Many cell osmolytes, not only negatively charged but also neutral ones, are permeable through these channels. When the cells swell in hypotonic media, they loose amino acids and other neutral and negative osmolytes through these channels. It is possible that these channels in astrocytes play an important role in pathological conditions, e.g. brain ischemia, by releasing glutamate in the external medium and contributing to the damaging effect of glutamate in ischemia. | pubmed_1119_9026 |
pubmed_924_3911 | Formalin fixation and paraffin embedding (FFPE) is the most commonly used method worldwide for tissue storage. This method preserves the tissue integrity but causes extensive damage to nucleic acids stored within the tissue. As methods for measuring gene expression such as RT-PCR and microarray are adopted into clinical practice there is an increasing necessity to access the wealth of information locked in the Formalin fixation and paraffin embedding archives. This paper reviews the progress in this field and discusses the unique opportunities that exist for the application of these techniques in the development of personalized medicine. | 10.1007/s00418-008-0479-7 |
pubmed_322_16393 | Gram-negative bacterial infections are a global health problem. The production of beta-lactamase is still the most vital factor leading to beta-lactam resistance. In Trinidad and Tobago, extended spectrum beta-lactamase (ESBL) production has been detected and reported mainly in the isolates of Klebsiella pneumoniae and Escherichia coli and constitutes a public health emergency that causes high morbidity and mortality in some patients. In this literature review, the authors cover vast information on ESBL frequency and laboratory detection using both conventional and molecular methods from clinical data. The aim is to make the reader reflect on how the actual knowledge can be used for rapid detection and understanding of the spread of antimicrobial resistance problems stemming from ESBL production among common Gram-negative organisms in the health care system. | 10.1155/2021/5582755 |
pubmed_588_3128 | We describe a 43-year-old woman with grade 1 chondrosarcoma of the cervical spine who developed neuropathic arthropathy. Plain radiography, computed tomography, and magnetic resonance imaging of the cervical spine revealed a so-called dumbbell tumor. We suggest that this tumor was responsible for the development of neuropathic arthropathy in bilateral hip joints, the left shoulder joint, and the left first metacarpophalangeal joint. This is the first reported case of neuropathic arthropathy secondary to chondrosarcoma of the cervical spine. | 10.1007/s10165-004-0284-7 |
pubmed_940_11616 | A simple and robust method for the separation and quantification of epinephrine in dental anesthetic solutions was developed. The method allows the direct injection of high salt solutions without sample pre-treatment. Large sample plugs (5.7% of the total capillary length) are used for epinephrine determination by selective analyte focusing in capillary electrophoresis. The concentration detection limit for epinephrine is about 5.0 x 10(-7) M (90 ng ml-1) with a commercial UV detector. The separation protocol was validated in terms of its precision, linearity, accuracy and specificity. | 10.1039/a800772a |
pubmed_305_17907 | Hydrogels are under active development for controlled drug delivery, but their clinical translation is limited by low drug loading capacity, deficiencies in mechanical toughness and storage stability, and poor control over the drug release that often results in burst release and short release duration. This work reports a design of composite clay hydrogels, which simultaneously achieve a spectrum of mechanical, storage, and drug loading/releasing properties to address the critical needs from translational perspectives. The clay nanoparticles provide large surface areas to adsorb biological drugs, and assemble into microparticles that are physically trapped within and toughen hydrogel networks. The composite hydrogels demonstrate feasibility of storage, and extended release of large quantities of an insulin-like growth factor-1 mimetic protein (8 mg mL-1 ) over four weeks. The release rate is primarily governed by ionic exchange and can be upregulated by low pH, which is typical for injured tissues. A rodent model of Achilles tendon injury is used to demonstrate that the composite hydrogels allow for highly extended and localized release of biological drugs in vivo, while demonstrating biodegradation and biocompatibility. These attributes make the composite hydrogel a promising system for drug delivery and regenerative medicine. | 10.1002/adhm.201701393 |
pubmed_117_16470 | PURPOSE
Chordomas are rare, slow-growing sarcomas without any accepted prognostic biomarkers. Owing to their proximity to critical neurovascular structures, discovering predictive biomarkers in chordoma has been a significant research effort because it may potentially reduce risky therapies in patients with less aggressive tumors. In response, because cyclin E1 overexpression correlates with patient prognosis in several malignancies, we investigated its expression in chordoma and whether it informs patient prognosis.
METHODS
Seventy-five chordoma patient specimens were enrolled in a tissue microarray (TMA) to evaluate cyclin E1 expression via immunohistochemical staining. Western blot was used to assess cyclin E1 expression in chordoma cell lines and fresh tissues. We then correlated cyclin E1 staining intensity in the TMA to clinicopathological features and chordoma patient outcomes.
RESULTS
Sixty-three percent of the chordoma patient specimens in the TMA, fifty-six percent of the fresh chordoma tissues, and all chordoma cell lines showed high cyclin E1 expression. In TMA analysis, cyclin E1 expression positively correlated to chordoma patient disease status. By survival analysis, high cyclin E1 expression was an independent prognostic risk factor for chordoma patients along with advanced disease status and positive surgical margin.
CONCLUSION
Cyclin E1 is a promising biomarker predicting chordoma patient prognosis. | 10.3389/fonc.2020.596330 |
pubmed_436_20363 | Aquaporins (AQPs) are water channels that regulate water flow in many tissues. As AQP1 is a candidate to regulate placental fluid exchange, we sought to investigate the effect of arginine vasopressin (AVP) and cAMP agonists on AQP1 gene expression in first trimester-derived extravillous cytotrophoblasts (HTR-8/Svneo) and two highly proliferative carcinoma trophoblast-like cell lines but with a number of functional features of the syncytiotrophoblast namely; JAR and JEG-3 cells. Our data demonstrated that AVP (0.1 nM) significantly increased the expression of AQP1 mRNA at 10 h in HTR-8/SVneo and JEG-3 cells (P<0.05). Both SP-cAMP, a membrane-permeable and phosphodiesterase resistant cAMP, and forskolin, an adenylate cyclase stimulator significantly increased AQP1 mRNA expression in all cell lines after 2 h in a dose-dependent manner (P<0.05) with a parallel increase in protein expression. In the time course study, 5 microM of either SP-cAMP or forskolin significantly stimulated AQP1 mRNA expression after 2 h in HTR-8/SVneo cells and after 10 h in JAR and JEG-3 cells. AQP1 protein expression was highest after 20 h in both HTR-8/SVneo and JEG-3 cells (P<0.05). AVP-stimulated cAMP elevation was blocked in the presence of 9-(tetrahydro-2'-furyl) adenine (SQ22536) (100 microM), a cell-permeable adenylate cyclase inhibitor (P<0.05). These results indicate that in trophoblasts-like cells AQP1 gene expression is upregulated by both AVP and cAMP agonists. Furthermore, our data demonstrate that a cAMP-dependent pathway is responsible for the AVP effect on AQP1. Thus, modulation of AQP1 expression by maternal hormones may regulate invasion and fetal-placental-amnion water homeostasis during gestation. | 10.1016/j.lfs.2008.04.014 |
pubmed_393_5372 | The haematological status of 105 healthy fullterm neonates was studied daily during the first week of life. Hb, MCV, RBC, PCV and WBC were determined with a Coulter 5 Counter, white cell differential reticulocyte and platelet counts manually, and ESR by a micromethod on free flowing capillary blood from heel stabs. A decline in Hb, PCV, MCV, RBC values and reticulocyte count was observed over the 7 days. The platelet count however rose slightly. The white cell count initially declined. The polymorphs initially predominant declined as the lymphocytes increased; by 7 days, both were about equal in proportions and together accounted for about 85% of the white cell population. The micro-ESR was very low, rising only slightly over the week. | pubmed_393_5372 |
pubmed_753_3826 | Using findings from a random, computer assisted telephone survey of households, this paper examines influenza and pneumococcal immunisation coverage and predictors of immunisation in 2203 adults with asthma, diabetes or a cardiovascular condition living in Queensland, Australia. 47% and 31% of high-risk persons were immunised against influenza and pneumococcus respectively. Immunisation coverage varied across chronic conditions and increased with age, being significantly higher for those aged 65 years and older and consequently eligible for free vaccination. Poor self reported health status was an independent predictor of pneumococcal vaccination status for people with asthma, diabetes or a cardiovascular condition; however it was only an independent predictor of influenza immunisation status for people with diabetes. Extending free vaccination to all people at risk may increase immunisation rates for younger people with a chronic condition. | 10.1016/j.vaccine.2011.01.116 |
pubmed_386_19943 | The objective of this study is to valuate two biomarkers that may guide nutritional assessment during follow up after intestinal transplantation. We performed a retrospective study on prospectively collected data of insulin-like growth factor-1 (IGF-1) and effluent calprotectin in patients undergoing intestinal transplantation. Optimal nutritional status (ONS) was defined by using the Malnutrition Universal Screening Tool (MUST). IGF-1 and calprotectin were correlated with ONS by Pearson correlation. Eighteen cadaveric intestinal transplants were performed over 1,650 days (median follow up 425 days, range 29-1,650 days). Mean IGF-1 and calprotectin were significantly associated with independent nutrition. Seven patients became malnourished on one or more occasions. During malnutrition the mean IGF-1 was 22 ± 14 ng/ml and calprotectin 1,597 ± 1,055 mcg/g. Mean weight during episodes of malnutrition changed from 64.77 ± 8.76 kg to 59.05 ± 8.5 kg (-8.9 ± 1.25%). Both IGF-1 and calprotectin negatively correlated with ONS (Pearson's r, -0.612, p = 0.014). Patients broadly aligned with three groups: nutritionally replete (normal IGF-1 and normal calprotectin), nutritionally equivocal (normal or low normal IGF-1 and high calprotectin), and malnourished (low IGF-1 and high calprotectin). Patients with low IGF-1 and high calprotectin may have a benign clinical presentation. However it is in their interests to have parenteral nutrition restarted pending further investigation. | 10.3164/jcbn.14-14 |
pubmed_405_25099 | In this work, we evaluate by means of computer simulations the rate for ice homogeneous nucleation for several water models such as TIP4P, TIP4P/2005,TIP4P/ICE, and mW (following the same procedure as in Sanz et al. [J. Am. Chem. Soc. 135, 15008 (2013)]) in a broad temperature range. We estimate the ice-liquid interfacial free-energy, and conclude that for all water models γ decreases as the temperature decreases. Extrapolating our results to the melting temperature, we obtain a value of the interfacial free-energy between 25 and 32 mN/m in reasonable agreement with the reported experimental values. Moreover, we observe that the values of γ depend on the chosen water model and this is a key factor when numerically evaluating nucleation rates, given that the kinetic prefactor is quite similar for all water models with the exception of the mW (due to the absence of hydrogens). Somewhat surprisingly the estimates of the nucleation rates found in this work for TIP4P/2005 are slightly higher than those of the mW model, even though the former has explicit hydrogens. Our results suggest that it may be possible to observe in computer simulations spontaneous crystallization of TIP4P/2005 at about 60 K below the melting point. | 10.1063/1.4897524 |
pubmed_1036_3425 | BACKGROUND
Different smoking cessation programmes have been developed in the last decade but utilization by the elderly is low. We evaluated a pilot mobile smoking cessation service for the Chinese elderly in Hong Kong and identified predictors of quitting.
METHODS
The Mobile Smoking Cessation Programme (MSCP) targeted elderly smokers (aged 60 or above) and provided service in a place that was convenient to the elderly. Trained counsellors provided individual counselling and 4 week's free supply of nicotine replacement therapy (NRT). Follow up was arranged at 1 month by face-to-face and at 3 and 6 months by telephone plus urinary cotinine validation. A structured record sheet was used for data collection. The service was evaluated in terms of process, outcome and cost.
RESULTS
102 governmental and non-governmental social service units and private residential homes for the elderly participated in the MSCP. We held 90 health talks with 3266 elderly (1140 smokers and 2126 non-smokers) attended. Of the 1140 smokers, 365 (32%) received intensive smoking cessation service. By intention-to-treat, the validated 7 day point prevalence quit rate was 20.3% (95% confidence interval: 16.2%-24.8%). Smoking less than 11 cigarettes per day and being adherent to NRT for 4 weeks or more were significant predictors of quitting. The average cost per contact was US$54 (smokers only); per smoker with counselling: US$168; per self-reported quitter: US$594; and per cotinine validated quitter: US$827.
CONCLUSION
This mobile smoking cessation programme was acceptable to elderly Chinese smokers, with quit rate comparable to other comprehensive programmes in the West. A mobile clinic is a promising model to reach the elderly and probably other hard to reach smokers. | 10.1186/1471-2318-8-25 |
pubmed_888_13647 | There is a growing experience with positron emission tomography (PET) in patients with pulmonary nodules or masses. As PET imaging becomes more widely available, it is important to thoughtfully define when application of this technology is warranted. Review of the literature to date suggests that PET imaging for diagnosis of pulmonary lesions is most useful in patients who have a low or intermediate risk of lung cancer as determined by an evaluation of symptoms, risk factors, and radiographic appearance. There is little role for PET in diagnosis in patients with a very low or a high risk of lung cancer, and there is little role in patients with lesions < 1 cm in diameter, or lesions suspected to be an infection, a bronchioloalveolar carcinoma, or a typical carcinoid tumor. | 10.1378/chest.125.6.2294 |
pubmed_638_15252 | PURPOSE
To investigate in vitro, the cellular network activity of the hippocampus in Q54 mice that display spontaneous seizures because of a gain-of-function mutation of the Scn2a sodium channel gene.
METHODS
Extacellular recordings were obtained from CA1 and CA3 pyramidal neurons in hippocampal slices prepared from Q54 transgenic and nontransgenic littermates (WT) under physiologic conditions as well as during periods of orthodromic stimulation of the Schaffer collaterals. Cerebral spinal fluid samples were analyzed and cresyl violet histology of the hippocampus was conducted.
RESULTS
Increased spontaneous extracellular activity was found in both CA1 and CA3 regions of Q54 hippocampal slices. Q54 slices also demonstrated significantly greater spontaneous and afterdischarge activity as well as population spike amplitude and duration following tetanic stimulus in comparison to WT slices. Frequency analysis of tetanically stimulated recordings indicated high-frequency components (100 and 200 Hz) unique to Q45 slices. Analysis of cresyl violet histology supports healthy Q54 slices up to 10 weeks, while Q54 cerebral spinal fluid shows elevated osmolarity.
CONCLUSION
Evidence for hyperexcitability and increased synaptic efficacy in Q54 mice was found by observing spontaneous activity as well as evoked activity. Response to tetanic stimulation included unique high-frequency oscillations, and resulted in an increased population spike amplitude and duration. Histological assessment shows equivalent neuronal development in both experimental groups. The data support the hypothesis that modified Scn2a channels in Q54 mice result in network hyperexcitability of the hippocampus necessary for the development and maintenance of temporal lobe seizures. | 10.1111/j.1528-1167.2007.01413.x |
pubmed_769_4143 | Objetivo. Analizar la asociación entre seropositividad a SARS-CoV-2 y enfermedades crónicas en adultos y adultos mayores mexicanos. Material y métodos. Se utilizó la Encuesta Nacional de Salud y Nutrición 2020 sobre Covid-19 (Ensanut 2020 Covid-19) para evaluar la asociación de seropositividad a SARS-CoV-2 con hipertensión arterial sistémica, diabetes tipo 2, índice de masa corporal, LDL-c elevado, HDL-c bajo, colesterol total elevado e hipertrigliceridemia. Resultados. Se observó una mayor seropositividad en personas con mayor índice de masa corporal. La seroprevalencia fue 25% mayor entre los adultos que presentaban obesidad en comparación con aquellos de peso normal en modelos ajustados (RP: 1.25 IC95%: 1.08,1.46). No se observó asociación entre seropositividad y otras enfermedades crónicas en adultos o adultos mayores. Conclusiones. Las personas con obesidad podrían tener una mayor susceptibilidad a la infección por SARS-CoV-2. Este hallazgo debe ser confirmado con estudios longitudinales. No se encontró evidencia de asociación para otras enfermedades. | 10.21149/13163 |
pubmed_491_9788 | OBJECTIVES
This study sought to assess the diagnostic impact of stress echocardiography (SE) in patients with suspected low-flow, low-gradient aortic stenosis but normal resting transvalvular flow rate.
BACKGROUND
SE may help to distinguish between true severe aortic stenosis and pseudosevere aortic stenosis in patients with low aortic valve area (AVA) and mean gradient. However, if rest flow rate is normal, then SE may not confer any additional diagnostic value, irrespective of resting left ventricular ejection fraction (LVEF) and indexed stroke volume (SVi).
METHODS
Sixty-seven patients with suspected low-flow, low-gradient aortic stenosis who underwent SE were retrospectively studied. Following stratification by rest LVEF, SVi, and flow rate-using cutoffs of 50%, 35 ml/m(2), and 200 ml/s, respectively-we tested for significant changes in AVA during SE.
RESULTS
Mean age was 77 ± 9 years and 60% of patients were male. Mean values for rest variables were as follows: AVA: 0.77 ± 0.12 cm(2); mean gradient: 27 ± 7 mm Hg; flow rate: 182 ± 37 ml/s; SVi: 32 ± 8 ml/m(2); and LVEF: 45 ± 15%. During SE, significant increases in AVA were observed regardless of resting LVEF and SVi state. In patients with rest flow rate ≥200 ml/s, AVA did not increase significantly during stress (rest AVA: 0.90 cm(2) vs. stress AVA: 0.97 cm(2); p = 0.11), and positive predictive value for confirming underlying true severe aortic stenosis was 84%. In adjusted analyses, rest flow rate was the only parameter associated with severe AS (odds ratio: 1.05, 95% confidence interval: 1.0 to 1.1; p = 0.002).
CONCLUSIONS
Rest AVA measured under normal flow rate conditions is likely to reflect the true severity of AS and unlikely to change significantly with SE. Flow normalization may only be required in patients with AVA <1 cm(2) and mean gradient <40 mm Hg when the rest flow rate is <200 ml/s. | 10.1016/j.jcmg.2015.04.021 |
pubmed_107_12370 | Application of the tools of molecular biology to clinical medicine is most apparent than in the development of DNA-based diagnostic and predictive tests. Such tests allow direct examination of the DNA of individuals for the presence or absence of the causative or predisposing molecular defect for a disease or condition. In this and the next two papers, in our series, we will discuss various aspects of genetic testing. We will consider the different types of testing, their current and potential clinical applications and discuss some of the major ethical and legal issues that genetic testing poses. | pubmed_107_12370 |
pubmed_328_17910 | BACKGROUND
Support after bariatric surgery is critical. Access to bariatric support groups is sometimes challenging, leading people to seek support on social media platforms like Facebook. Given the ubiquity of recommendations solicited and provided on Facebook regarding nutrition and bariatric surgery, understanding the content and accuracy of these posts is important.
OBJECTIVES
The primary aim of the present study was to describe the content of nutrition-related information sought on bariatric Facebook support groups/pages. A secondary aim was to evaluate the accuracy of this content.
SETTING
Integrated multispecialty health system.
METHODS
An iterative content analysis process was conducted and resulted in identification of 8 primary coding themes. Additionally, 3 registered dieticians with extensive experience in bariatric surgery and obesity treatment examined posts that provided nutritional recommendations to determine accuracy.
RESULTS
Members most commonly sought advice regarding products and practices to assist in achieving nutritional guidelines (35%). Over half of the posts contained inaccurate content or information that was too ambiguous to determine accuracy; 7% of posts were found to be inaccurate or inconsistent with American Society for Metabolic and Bariatric Surgery nutrition guidelines and expert registered dietician opinions, 22% of posts were found to contain both accurate and inaccurate information, and 24% of posts were considered too ambiguous and required more context to determine the accuracy.
CONCLUSIONS
Results highlight the need for bariatric programs to provide greater nutrition education support to patients postoperatively and to provide caution about the inconsistent nature of some nutrition-related content found on Facebook bariatric support groups. | 10.1016/j.soard.2018.08.017 |
pubmed_314_25021 | BACKGROUND
Chronic hypertension and anticoagulation are important risk factors for the development of intracerebral hemorrhage (ICH). Spontaneous ICH occurring in the Emergency Department (ED) following a normal unenhanced computed tomography (CT) scan of the brain and an acute blood pressure (BP) surge is exceedingly rare and has, to our knowledge, never been reported in the literature.
METHODS
Single case observation in a suburban tertiary care medical center.
RESULTS
A neurologically intact 72-year-old man whose BP and neurologic status were monitored during an ED evaluation suddenly became unresponsive following an acute BP surge. A CT of the brain shortly before the episode was normal; following the episode, a repeat CT demonstrated a large right ganglionic ICH.
CONCLUSIONS
We present a rare case of an elderly man on warfarin who developed a spontaneous ICH during an ED evaluation following an acute BP surge. We propose that the ICH occurred as a result of the BP surge and was contributed to by warfarin anticoagulation. | 10.1007/s12028-010-9352-3 |
pubmed_1111_21667 | In animals, Tandem CCCH Zinc Finger (TZF) proteins can affect gene expression at both transcriptional and post-transcriptional levels. In Arabidopsis thaliana, AtTZF1 is a member of the TZF family characterized by a plant-unique tandem zinc finger motif. AtTZF1 can bind both DNA and RNA in vitro, and it can traffic between the nucleus and cytoplasmic foci. However, no in vivo DNA/RNA targets have been identified so far, and little is known about the molecular mechanisms underlying AtTZF1's profound effects on plant growth, development, and stress responses. In order to determine whether AtTZF1 can function as a transcription factor, transactivation assays were conducted. Results indicated that AtTZF1 fusion proteins could not exert obvious transcriptional activity in a maize protoplast transient expression system. However, this conclusion might be biased due to poor nuclear localization of AtTZF1 fusion proteins in the assay system. | 10.4161/psb.6.5.15104 |
pubmed_689_22038 | Several genetic variants of the cd1- and ef-helices of the Qo site of mitochondrial cytochrome b have been associated with bifenazate resistance in the spider mite Tetranychus urticae, an important crop pest around the world. Maternal inheritance of bifenazate resistance has provided strong evidence for the involvement of many of these mutations alone or in combination. A number of populations highly resistant to bifenazate were uncovered that carried the G126S substitution in combination with other target-site mutations. This G126S mutation has therefore been investigated in several studies in the context of resistance evolution and the development of diagnostic markers. However, experimental data that link bifenazate resistance with the presence of the G126S mutation without additional cd1- and ef-helices mutations, remain very limited. Here, we genotyped 38 T. urticae field populations for cytochrome b and uncovered nine field populations with a fixed or segregating G126S substitution without other target-site mutations in the conserved cd1- and ef-helices of the cytochrome b Qo pocket. Toxicity bioassays showed that all nine field populations were very susceptible to bifenazate, providing strong evidence that G126S alone does not confer bifenazate resistance. These findings also implicate that previous T. urticae populations with G126S found to be low to moderately resistant to bifenazate, evolved alternative mechanisms of resistance, and more importantly, that this mutation cannot be used as a molecular diagnostic for bifenazate resistance. | 10.1007/s10493-021-00668-6 |
pubmed_100_19385 | Consumers often perceive that the modern beef production system has an environmental impact far greater than that of historical systems, with improved efficiency being achieved at the expense of greenhouse gas emissions. The objective of this study was to compare the environmental impact of modern (2007) US beef production with production practices characteristic of the US beef system in 1977. A deterministic model based on the metabolism and nutrient requirements of the beef population was used to quantify resource inputs and waste outputs per billion kilograms of beef. Both the modern and historical production systems were modeled using characteristic management practices, population dynamics, and production data from US beef systems. Modern beef production requires considerably fewer resources than the equivalent system in 1977, with 69.9% of animals, 81.4% of feedstuffs, 87.9% of the water, and only 67.0% of the land required to produce 1 billion kg of beef. Waste outputs were similarly reduced, with modern beef systems producing 81.9% of the manure, 82.3% CH(4), and 88.0% N(2)O per billion kilograms of beef compared with production systems in 1977. The C footprint per billion kilograms of beef produced in 2007 was reduced by 16.3% compared with equivalent beef production in 1977. As the US population increases, it is crucial to continue the improvements in efficiency demonstrated over the past 30 yr to supply the market demand for safe, affordable beef while reducing resource use and mitigating environmental impact. | 10.2527/jas.2010-3784 |
pubmed_421_2112 | We describe the plasma chemistry in a helium flowing atmospheric pressure afterglow (FAPA) used for analytical spectrometry, by means of a quasi-one-dimensional (1D) plasma chemical kinetics model. We study the effect of typical impurities present in the feed gas, as well as the afterglow in ambient humid air. The model provides the species density profiles in the discharge and afterglow regions and the chemical pathways. We demonstrate that H, N, and O atoms are formed in the discharge region, while the dominant reactive neutral species in the afterglow are O3 and NO. He* and He2* are responsible for Penning ionization of O2, N2, H2O, H2, and N, and especially O and H atoms. Besides, He2+ also contributes to ionization of N2, O2, H2O, and O through charge transfer reactions. From the pool of ions created in the discharge, NO+ and (H2O)3H+ are the dominant ions in the afterglow. Moreover, negatively charged clusters, such as NO3H2O- and NO2H2O-, are formed and their pathway is discussed as well. Our model predictions are in line with earlier observations in the literature about the important reagent ions and provide a comprehensive overview of the underlying pathways. The model explains in detail why helium provides a high analytical sensitivity because of high reagent ion formation by both Penning ionization and charge transfer. Such insights are very valuable for improving the analytical performance of this (and other) ambient desorption/ionization source(s). | 10.1021/acs.analchem.0c04076 |
pubmed_623_17939 | OBJECTIVE
Reports of increased level of Myeloperoxidase (MPO) in plasma and placental extracts of Systematic Lupus Erythematosus (SLE) has been proposed that MPO may have an important role in this pregnancy complication. In present study immunohistochemical MPO expression was investigated in placental samples of SLE women compared with normal controls.
MATERIALS AND METHODS
Ten patients with SLE were recruited as case group. Control group was selected from mothers with normal uncomplicated pregnancies. A monoclonal antibody specific for MPO was used for immunohistochemical staining and then the staining was quantified and differences between groups were compared using Mann-Whitney U test.
RESULTS
There were significant differences in the expression levels of MPO in the syncytiotrophoblast cells and the extravillous trophoblast cells between the control and SLE groups (p < 0.05). There were no significant differences in the expression level of MPO in the vascular endothelium and the relative number of the MPO-positive leukocytes in placental tissue between SLE and control groups (p > 0.05).
CONCLUSION
The present study showed that MPO expression is increased in syncytiotrophoblast cells and the extravillous trophoblast cells of SLE placentas compared to healthy subjects. It seems that these changes are able to impress structure and function of placenta and survival of the fetus. | pubmed_623_17939 |
pubmed_391_6 | 1. In two experiments laying hens were treated with an agonist of gonadotrophin releasing hormone (GnRH) to induce a reduction in the secretion of luteinising hormone (LH) and a pause in egg production. 2. In experiment 1, 70-week-old laying hens were either given daily subcutaneous injections of saline for 7 d, offered whole oats for 7 d (nutrient restriction), given daily injections of the GnRH agonist [D-Trp6-Pro9 N-ethyl amide]GnRH for 7 d at 50 micrograms/kg or 100 micrograms/kg or administered 4 biocompatible implants each containing 120 micrograms of the GnRH agonist. 3. Weekly egg production was monitored for 7 weeks and blood samples were taken at weekly intervals and assayed for plasma LH and oestradiol. Egg production was reduced in the birds treated with the agonist (28 to 46% reduction) but not to the same extent as in the birds offered whole oats (92.3% reduction). 4. The treatments also reduced plasma LH and oestradiol in treated hens but again to a greater extent in the birds offered whole oats than the birds treated with the agonist. Egg production and plasma LH and oestradiol increased following the termination of the treatments. 5. The birds fed whole oats suffered a reduction in weight of 16.7% over the treatment period whereas there were increases in the weights of the birds treated with saline, 50 micrograms of GnRH agonist and the implants of GnRH agonist, but no change in birds treated with 100 micrograms of GnRH agonist. 6. The birds fed oats lost feathers over the treatment period but the birds in the other treatment groups suffered no loss. 7. In experiment 2 laying hens were either injected daily with saline or 200 micrograms GnRH agonist and weekly egg production and plasma LH and oestradiol were measured. As egg production was reduced by almost 60% in the birds treated with the agonist but did not completely cease. Reductions in plasma LH and oestradiol were also observed. All variables increased to pretreatment levels once treatment ceased. 8. These data confirm the effects of severely depriving hens of nutrients on egg production and the secretion of LH and oestradiol.(ABSTRACT TRUNCATED AT 400 WORDS) | 10.1080/00071669208417501 |
pubmed_326_2895 | It has been known that neutrophils contain various antimicrobial components in the granules, which contribute to the oxygen-independent host defense mechanism. In this study, we have isolated the two antimicrobial polypeptides from guinea pig neutrophil granules. Urea-SDS-PAGE analysis revealed that the molecular masses of the polypeptides were 11 and 5 kDa under nonreducing conditions. Under reducing conditions, the molecular mass of the 5-kDa polypeptide did not change, whereas the molecular mass of the 11-kDa polypeptide changed to about 5 kDa, suggesting that the 11-kDa polypeptide is a dimer composed of 5-kDa subunits joined with a disulfide bond. The amino acid composition and sequence data indicated that the 5-kDa subunit of the 11-kDa polypeptide contained 9 lysine, 8 arginine, and 1 cysteine residues and that the 11-kDa polypeptide was a homodimer of G1LRKKFRKTRKRIQKLGRKIGKTGRKVWKAWREYGQIPYPCRI43 (4599 Da) joined with one disulfide bond. Amino acid sequence of the 11-kDa polypeptide showed partial homology (19-30%) to the active peptides of rabbit and human cationic antimicrobial proteins of 18 kDa (CAP18), suggesting the 11-kDa polypeptide might be a homologue of CAP18. In contrast, the amino acid analysis of the 5-kDa antibacterial polypeptide revealed that the polypeptide was composed of 41 amino acids (5007 Da) containing 7 lysine, 10 arginine, and 2 cystine residues. However, sequence analysis indicated that the N-terminus of the 5-kDa polypeptide was likely blocked. The 11- and 5-kDa polypeptides showed almost the same antibacterial activities; ED50 values were 30-35 nM against Escherichia coli and 90-120 nM against Staphylococcus aureus, which were 4- to 20-fold lower than those of defensins. Furthermore, the 11- and 5-kDa polypeptide retained the antibacterial activities even at the physiological concentration of NaCl (0.15 M), although the antibacterial activity of defensin was completely lost in the presence of NaCl. | 10.1006/abbi.1996.0166 |
pubmed_600_7398 | Staphylococcus aureus is a Gram-positive bacterium that causes inflammation at infection sites by inducing various inflammatory mediators such as nitric oxide (NO). To identify the staphylococcal virulence factors contributing to NO production, we compared the ability of ethanol-killed wild-type S. aureus and mutant strains lacking lipoteichoic acid (ΔltaS), lipoproteins (Δlgt), or d-alanine (ΔdltA) to stimulate NO production in a murine macrophage cell line, RAW 264.7, and the primary macrophages derived from C57BL/6 mice. Wild-type, ΔltaS, and ΔdltA strains induced NO production in a dose-dependent manner but this response was not observed when the cells were stimulated with the Δlgt strain. Moreover, purified lipoproteins triggered NO production in macrophages. Coincident with NO induction, the wild-type, ΔltaS, and ΔdltA strains induced expression of inducible NO synthase (iNOS) at both mRNA and protein levels whereas Δlgt failed to induce iNOS protein or mRNA. Transient transfection followed by a reporter gene assay and Western blotting experiments demonstrated that wild-type, ΔltaS, and ΔdltA strains, but not the Δlgt strain, induced substantial activation of NF-κB and STAT1 phosphorylation, both of which are known to be crucial for iNOS expression. Moreover, wild-type, ΔltaS, and ΔdltA strains increased Toll-like receptor 2 (TLR2) activation, which is known to mediate S. aureus-induced innate immunity, whereas the Δlgt strain did not. Collectively, these results suggest that lipoproteins in the cell wall of S. aureus play a major role in the induction of NO production in murine macrophages through activation of the TLR2 receptor. | pubmed_600_7398 |
pubmed_960_22830 | Cross-species chromosome painting with probes derived from flow-sorted dog and human chromosomes was used to construct a high-resolution comparative map for the pig. In total 98 conserved autosomal segments between pig and dog were detected by probes specific for the 38 autosomes and X Chromosome of the dog. Further integration of our results with the published human--dog and cat--dog comparative maps, and with data from comparative gene mapping, increases the resolution of the current pig--human comparative map. It allows for the conserved syntenies detected in the pig, human, and cat to be aligned against the putative ancestral karyotype of eutherian mammals and for the history of karyotype evolution of the pig lineage to be reconstructed. Fifteen fusions, 17 fissions, and 23 inversions are required to convert the ancestral mammalian karyotype into the extant karyotype of the pig. | 10.1007/s00335-004-2391-3 |
pubmed_854_3020 | Thyroid stunning is usually defined as the inhibition or suppression of iodide trapping by remnant thyroid tissue or by functioning metastases following a diagnostic dose of 131I. The risk of stunning increases progressively with larger doses. Because the threshold above which this effect occurs in thyroid remnants seems to be between 37 MBq and 111 MBq of 131I, therapeutic 131I doses of 3.7 GBq may cause stunning. We describe stunning of papillary thyroid cancer lung and bone metastases after a therapeutic dose of 131I (3.7 GBq). A T1 bone metastasis and bilateral lung metastases were diagnosed by post-therapeutic dose whole-body scan. Nuclear MRI detected another lesion at T4, whose 131I fixation was not obvious. An additional 0.7 GBq were given after recombinant TSH, 37 days after the therapeutic dose; 24 h later, uptake by the lung and T1 metastases had disappeared, but trapping was again seen 6 months later on the post-therapeutic scan. This re-appearance is evidence in favour of the transitory and reversible character of stunning, and confirms its correspondence to the decreased ability of viable thyroid cells to trap iodine and not to their destruction. A better understanding of stunning would make it possible, in the event of rapidly progressing disease and in conjunction with recombinant thyroid stimulating hormone (TSH), to give several therapeutic doses of 131I in close succession without each dose hampering the effectiveness of the subsequent one. | 10.1259/bjr/92548685 |
pubmed_752_9291 | Social relationships are fundamental to animals living in complex societies. The extent to which individuals base their decisions around their key social relationships, and the consequences this has on their behavior and broader population level processes, remains unknown. Using a novel experiment that controlled where individual wild birds (great tits, Parus major) could access food, we restricted mated pairs from being allowed to forage at the same locations. This introduced a conflict for pair members between maintaining social relationships and accessing resources. We show that individuals reduce their own access to food in order to sustain their relationships and that individual foraging activity was strongly influenced by their key social counterparts. By affecting where individuals go, social relationships determined which conspecifics they encountered and consequently shaped their other social associations. Hence, while resource distribution can determine individuals' spatial and social environment, we illustrate how key social relationships themselves can govern broader social structure. Finally, social relationships also influenced the development of social foraging strategies. In response to forgoing access to resources, maintaining pair bonds led individuals to develop a flexible "scrounging" strategy, particularly by scrounging from their pair mate. This suggests that behavioral plasticity can develop to ameliorate conflicts between social relationships and other demands. Together, these results illustrate the importance of considering social relationships for explaining behavioral variation due to their significant impact on individual behavior and demonstrate the consequences of key relationships for wider processes. | pubmed_752_9291 |
pubmed_340_18529 | Recent data from literature report that reactive oxygen species (ROS) seem to play a crucial role in the etiology of both types I and II diabetes. This may render diabetic individuals more prone to oxidative injury when challenged with hypoxic stress. It is in fact well known that many diabetic complications cause ischaemic episodes, with a consequent reduction in oxygen supply to various tissues and organs. To check this hypothesis, in this work we tested type I diabetic individuals' antioxidant capability towards a hypoxic-mediated oxidative challenge. In particular, spontaneously diabetic and age-matched non-diabetic biobreeding (BB) Wistar rats were submitted to chronic normobaric hypoxia, and the response of antioxidant enzymes, as well as redox-sensitive transcription factor NF-kappaB and p53, were monitored. Results show that diabetic subjects present a dramatic enhancement in the major antioxidant enzymes activities, thus supporting the notion of diabetes-related changes in cellular redox status. This allows diabetic individuals to counteract hypoxia-mediated oxidative challenge better than the non-diabetic counterpart. Also the behaviour of both the redox-sensitive nuclear transcription factor NF-kappaB and p53 protein in response to hypoxic stimulation seems to support the hypothesis of a better ROS scavenging efficiency in diabetics under hypoxic conditions. In conclusion, high levels of antioxidant enzymatic defences in diabetic BB rats reflect a positive adaptive response able to assure an efficient protection not only against chronic, diabetes-mediated reactive oxygen species (ROS) overproduction, but also versus further oxidative damage. | 10.1016/j.biocel.2006.06.011 |
pubmed_733_554 | Allergic disease is a common cause of morbidity, particularly in young children. The prevalence of allergic disease has increased in the last 20 y in most countries. The sequential order of occurrence of allergy is food hypersensitivity, gastrointestinal manifestations, atopic eczema, asthma and hay fever. A variety of factors increase the risk of allergic disease, for example hereditary predisposition, exposure to 'allergenic' foods and environmental triggers such as house dust mites and tobacco in early life. Prolonged breast feeding, the use of a partial whey hydrolysed formula, delayed introduction of certain 'allergenic foods', and avoidance of inhalant allergens reduces the incidence of eczema and asthma, especially in high-risk infants. These preventive measures are extremely cost-effective and should be adopted widely at the community level. | 10.1038/sj.ejcn.1601487 |
pubmed_1122_12097 | BACKGROUND: To determine the efficacy and dose-response of the new angiotensin II receptor antagonist eprosartan, we conducted a 4-week, double-blind, randomized, multicenter study in 114 men with essential hypertension using trough clinic and ambulatory blood pressure measurements.METHODS: Patients were included if the seated diastolic blood pressure was between 95 and 115 mmHg inclusive and 0-12 h diastolic blood pressure was at least 87 mmHg. The effects of twice daily eprosartan at 50, 100, 150 and 200 mg were compared with those of placebo. RESULTS: At trough, the clinic diastolic blood pressure was reduced significantly only by the 200 mg dose compared with placebo (mean placebo-subtracted change -6.0 mmHg, 95% confidence intervals -10.5, -1.5, P = 0.001). In contrast, the 12 h mean reduction in diastolic blood pressure was significant for both the 150 mg dose (mean change -5.3 mmHg, 95% confidence intervals -10.2, -0.1, P = 0.0075) and the 200 mg dose (mean change -5.5 mmHg, 95% confidence intervals -10.3, -0.6, P = 0.0049). Similar trends were observed for the systolic pressure and mean changes in 24 h pressures. Eprosartan significantly reduced adjusted mean daytime (0-12 h after dose) diastolic ambulatory pressure linearly with dose. CONCLUSION: These data demonstrate increased sensitivity of the ambulatory blood pressure over the research clinic blood pressure in evaluating the efficacy of the new antihypertensive agent eprosartan. Additionally, these findings demonstrate that higher doses of this drug will be necessary in future studies. | pubmed_1122_12097 |
pubmed_200_19793 | Darier's disease is a rare autosomal dominant genodermatosis. It has an estimated prevalence of 1 in 55,000 to 100,000 individuals, regardless of gender. It is characterized by multiple keratotic papules on the seborrheic areas of the trunk, scalp, forehead and flexures, and the clinical picture is worsened by heat, sun exposure, perspiration and mechanical trauma. Histopathology observed loss of epithelial adhesion and abnormal keratinization. About 10% of cases present in the localized form of the disease. We report a case of segmental Darier's Disease Type I and discuss the main characteristics of this condition. | pubmed_200_19793 |
pubmed_328_5678 | OBJECTIVE
To investigate the relationship between baseline snoring sound energy (SSE) and disease severity, changes in SSE after adenotonsillectomy, and the predictors of surgical success in children with obstructive sleep apnoea (OSA).
DESIGN
Prospective cohort study.
SETTING
Tertiary referral medical centre.
PARTICIPANTS
Thirty-two children with OSA whose apnoea-hypopnoea index ≥5 or apnoea-hypopnoea index ≥1.5 with OSA comorbidities were recruited. Patients with complicated OSA were excluded. All participants underwent snoring sound analysis, polysomnography, and adenotonsillectomy.
MAIN OUTCOME MEASURES
Snoring sound energy and apnoea-hypopnoea index were assessed at baseline and 6 months after adenotonsillectomy. Surgical success was defined as a postoperative apnoea-hypopnoea index <1.5.
RESULTS
The median age, body mass index, and apnoea-hypopnoea index was 9 years, 19.0 kg/m2 , and 13.2 events/h, respectively. Multivariate logistic regression showed that a baseline tonsil size of IV (odds ratio 15.7 [95% CI: 1.5-166.3]) and SSE of 801-1000 Hz > 21.9 dB (odds ratio 32.3 [95% CI: 2.6-396.6]) were significantly related to severe OSA. Following adenotonsillectomy, apnoea-hypopnoea index decreased significantly (P < 0.001). SSE of 41-200 Hz, 201-400 Hz and 801-1000 Hz also decreased significantly (P = 0.04, 0.01 and 0.006, respectively). Baseline SSE of 801-1000 Hz < 8.5 dB significantly predicted surgical success (odds ratio 11.0 [95% CI: 1.4-85.2]).
CONCLUSIONS
Our findings suggest the potential utility of SSE of 801-1000 Hz to screen for severe OSA, predict surgical success and assess therapeutic outcomes. Specific baseline SSE may represent a potential biomarker for childhood OSA. | 10.1111/coa.13231 |
pubmed_955_4605 | The dodecapeptide Boc-(Ala-Leu-Aib)4-OMe crystallized with two independent helical molecules in a triclinic cell. The two molecules are very similar in conformation, with a 3(10)-helix turn at the N-terminus followed by an alpha-helix, except for an elongated N(7)...O(3) distance in both molecules. All the helices in the crystal pack in a parallel motif. Eleven water sites have been found in the head-to-tail region between the apolar helices that participate in peptide-water hydrogen bonds and a network of water-water hydrogen bonds. The crystal parameters are as follows: 2(C58H104N12O15)+ca. 10H2O, space group P1 with a = 12.946(2), b = 17.321(3), c = 20.465(4) A, alpha = 103.12(2), beta = 105.63(2), gamma = 107.50(2) degrees, Z = 2, R = 10.9% for 5152 data observed > 3 sigma (F), resolution 1.0 A. In contrast to the shorter sequences [Karle et al. (1988) Proc. Natl. Acad. Sci. USA 85, 299-303] and Boc-(Ala-Leu-Aib)2-OMe [Karle et al. (1989) Biopolymers 28, 773-781], no insertion of a water molecule into the helix is observed. However, the elongated N---O distance between Ala7 NH and Aib3 CO in both molecules (molecule A, 3.40 A; molecule B, 3.42 A) is indicative of an incipient break in the helices. | 10.1111/j.1399-3011.1994.tb00187.x |
pubmed_597_25138 | The benefit of providing learners control over their repetition schedule during multi-task learning has been limited to adult samples. Recently, differences in self-controlled strategies, such as frequent requests for knowledge of results by children (10 years) compared to adults have been reported. The purpose of the present experiment was to assess the benefits of a self-controlled repetition schedule during multi-task learning for children compared to adults. Twenty-four children (M age = 11.7 yr., SD = 2.0) and 24 adults (M age = 22.0 yr., SD = 2.2) completed 36 acquisition (12 per sequence) and 12 retention trials (4 per sequence) over two days for a key-pressing task. Half the adults (n = 12) and half the children (n = 12) chose the order in which to practice the three sequences during acquisition. The remaining participants practiced under the repetition schedule of a self-controlled counterpart. The dependent variables were the total time to complete the trial and the success of the motor trial (successful or unsuccessful). No differences were observed in the total number of times participants switched from one sequence to another in acquisition for the children and adults in the self-controlled condition. In retention, the proportion of error trials did not differ between the children and adults. The main effect for self-controlled vs yoked conditions indicated superior learning for the self-controlled conditions independent of age. | 10.2466/23.22.PMS.116.3.741-749 |
pubmed_405_5942 | Fusarium disease causes considerable losses in the cultivation of Piper nigrum, the black pepper used in the culinary world. Brazil was the largest producer of black pepper, but in recent years has lost this hegemony, with a significant reduction in its production, due to the ravages produced by the Fusarium solani f. sp. piperis, the fungus which causes this disease. Scientific research seeks new alternatives for the control and the existence of other Piper species in the Brazilian Amazon, resistant to disease, are being considered in this context. The main constituents of the oil of Piper divaricatum are methyleugenol (75.0%) and eugenol (10.0%). The oil and these two main constituents were tested individually at concentrations of 0.25 to 2.5 mg/mL against F. solani f. sp. piperis, exhibiting strong antifungal index, from 18.0% to 100.0%. The 3D structure of the β-glucosidase from Fusarium solani f. sp. piperis, obtained by homology modeling, was used for molecular docking and molecular electrostatic potential calculations in order to determine the binding energy of the natural substrates glucose, methyleugenol and eugenol. The results showed that β-glucosidase (Asp45, Arg113, Lys146, Tyr193, Asp225, Trp226 and Leu99) residues play an important role in the interactions that occur between the protein-substrate and the engenol and methyleugenol inhibitors, justifying the antifungal action of these two phenylpropenes against Fusarium solani f. sp. piperis. | 10.3390/molecules191117926 |
pubmed_171_15355 | Ticks are known vectors of transmission for a number of infectious viral diseases from wild or domestic animals to humans. Many tick-borne diseases cause severe clinical syndromes such as encephalitis or hemorrhagic fever. Animal carriers of enzootic diseases are often asymptomatic. Within the framework of a program to monitor emerging viral diseases in Southeast Asia, identification of ticks capable of transmitting diseases from animals to man is a prerequisite for epidemiologic study to assess the risk of tick-borne disease. The purpose of this report is to provide an update on the situation based on a study of tick fauna in the central plain area of Thailand and on current knowledge about tick-borne arboviruses in Asia. In addition to an exhaustive inventory of ticks found in Thailand, this study describes the viruses with pathogenic potential that ticks are known to carry and transmit to man. A perusal of the literature allowed initial assessment of the risk for introduction and spread of ticks by bird hosts in Southeast Asia as well as of associated virus. | pubmed_171_15355 |
pubmed_551_21739 | Abundance of duck adipocyte fatty acid-binding protein (A-FABP) mRNA was detected in this study by quantitative real-time PCR. The results showed that duck A-FABP gene was expressed in muscular tissues and many organs, except pancreas, lung, and kidney, and highly expressed in adipose tissues, especially in sebum. The expression of A-FABP and adipocyte differentiation-related genes was upregulated by oleic acid, and the A-FABP knockdown suppressed the oleic acid-stimulated expression of these genes in the cultured duck adipocytes, indicating A-FABP might play an important role in duck adipocyte differentiation. | 10.3382/ps.2012-02149 |
pubmed_90_448 | The paper contains the results of light microscopical, electron microscopical and histochemical examinations of chronic otitis media, with and without cholesteatoma, with special focus on the problems regarding bone resorption. It is demonstrated that bone resorption takes place without the presence of cholesteatoma itself, even though the magnitude of resorption is higher in the cases with cholesteatoma. It is demonstrated that there is always a layer of subepithelial granulation tissue between the cholesteatoma membrane and the underlying bone. The picture in the resorbing zone is dominated by mononuclear histiocyte like cells, containing dense cytoplasmatic bodies, called lysosomes, and it is demonstrated that the marker enzyme for acid hydrolases, the acid phosphatase, is present in large quantities, both in the histiocytes, as well as spread along the bony surface. It is concluded that a possible mechanism for bone resorption is performed by the acid hydrolases, contained in the histiocytes, working at acid pH. It is noteworthy that the multinucleated osteoclast is not demonstrated in the resorbing margin of bone and that the picture is dominated by capillary proliferation, indicating that ischemia does not play a role in bone resorption. On the contrary, this is in the author's opinion caused by inflammation and hyperemia. The various factors influencing bone resorption in general and in chronic otitis media are discussed and a new model for studying cholesteatoma pathology in the middle ear is presented. | 10.1111/j.1365-2273.1981.tb01529.x |
pubmed_517_13912 | Functionalized microcarriers or hollow capsules transporting active agents offer the opportunity for drug delivery inside cells. A promising application of these drug delivery systems is the direct transport as well as the release of immobilized antiinflammatory substances (AIS) into polymorphonuclear leukocytes (PMNs), which play a key role in the course of inflammatory processes. The intended delivery of AIS into the inflamed tissue could alleviate tissue destruction taking place during chronic inflammation, as well as facilitate the termination of these processes. In this study, the capability of functionalized CaCO(3) microcarriers as AIS transporter system targeted at PMNs is investigated. The time-dependent interaction of protamine sulfate and dextran sulfate multilayer-coated 5 μm ± 1 μm CaCO(3) carriers with PMNs, in comparison with the usage of SiO(2) carriers as monodisperse model system of defined sizes (1, 3, and 5 μm), reveals a sufficient carrier/cell interaction and uptake for coincubation periods between 2 and 24 h. Furthermore, the microcarriers are exposed to an environment simulating primary granule/phagosomal conditions after phagocytosis by means of PMN stimulation. The incubation of CaCO(3) microcarriers with cell supernatant demonstrates a partial multilayer decomposition (three to five layers) within 24 h, allowing the gradual release of AIS within the short PMN life span. This observation suggests a potential application for this drug delivery system inside immunologically active cells and may open the way to new alternatives in the treatment of chronic processes. | 10.1002/cyto.a.21145 |
pubmed_311_6091 | BACKGROUND
This study assessed the feasibility of near-infrared fluorescence imaging with indocyanine green (ICG) to identify the parathyroid glands (PGs) intraoperatively and to assess their perfusion after thyroid resection.
METHODS
Patients undergoing elective thyroidectomy were enrolled in this prospective study. An intravenous bolus of 7.5 mg ICG was administered twice: the first bolus to identify the PGs before resection of the thyroid and the second to assess vascularization of the PGs after resection.
RESULTS
A total of 30 operations in 26 patients were included. In 17 surgeries (56.7%), fluorescence imaging was of added value, especially to confirm the presence of a suspected PG. No intraoperative or postoperative complications occurred because of the use of ICG.
CONCLUSION
Near-infrared fluorescence imaging with the use of ICG for intraoperative identification of the PGs and the assessment of its vascularization is feasible and safe and can provide more certainty about the location of the PGs. | 10.1002/hed.25451 |
pubmed_229_20642 | This work focuses on microparticles as potential antigen delivery systems to target professional antigen-presenting cells. Surface modified polystyrene microparticles were administered to human-derived macrophages (MPhis) and dendritic cells (DCs) in vitro to evaluate the phagocytosis activity of each cell type. To discriminate between internalised particles and those closely attached to the outside of the cells, particle internalisation was verified by confocal laser scanning microscopy. Especially positively charged particles tend to stick to the outer cell membrane and may lead to false positive results when measured by conventional microscopy. In contrast, fluorescence microscopy in combination with an extracellular fluorescence quenching agent (trypan blue) allows the unequivocal assessment of particle uptake for screening purposes. For this assay, the fluorescent label needs to be in direct contact to the quenching agent and cannot be localised inside the particle core. Different types of microparticles varying in size, surface-material and zeta potential resulted in vast differences regarding their uptake by MPhis and DCs as well as the maturation of DCs. Negatively-charged carboxylated and bovine serum albumin-coated particles were phagocytosed by MPhis to a relatively small extent. Interestingly, phagocytosis of these particles was still significantly lower in DCs while positively charged poly-L-lysine (PLL) coated particles induced high phagocytosis activity in both cell types. By comparing our results with literature data, we conclude that phagocytosis activity of DCs and MPhis largely depends on particle size and surface charge and is also influenced by the character of bulk and coating material. PLL can be directed to DCs and MPhis with comparable efficiency and, in addition, induce maturation of DCs. | 10.1016/s0168-3659(01)00412-6 |
pubmed_934_5033 | AIMS
Type 2 diabetes mellitus is an independent risk factor for the development of heart failure. To better understand the mechanism by which this occurs, we investigated cardiac structure, function, and perfusion in patients with and without diabetes.
METHODS AND RESULTS
Sixty-five patients with no stenosis >30% on invasive coronary angiography were categorized into diabetes (19) and non-diabetes (46) which was further categorized into prediabetes (30) and controls (16) according to the American Diabetes Association guidelines. Each patient underwent comprehensive cardiovascular magnetic resonance assessment. Left-ventricular (LV) mass, relative wall mass (RWM), Lagrangian circumferential strain, LV torsion, and myocardial perfusion reserve (MPR) were calculated. LV mass was higher in diabetics than non-diabetics (112.8 ± 39.7 vs. 91.5 ± 21.3 g, P = 0.01) and in diabetics than prediabetics (112.8 ± 39.7 vs. 90.3 ± 18.7 g, P = 0.02). LV torsion angle was higher in diabetics than non-diabetics (9.65 ± 1.90 vs. 8.59 ± 1.91°, P = 0.047), and MPR was lower in diabetics than non-diabetics (2.10 ± 0.76 vs. 2.84 ± 1.25 mL/g/min, P = 0.01). There was significant correlation between MPR and early diastolic strain rate (r = -0.310, P = 0.01) and LV torsion (r = -0.306, P = 0.01). In multivariable linear regression analysis, non-diabetics waist-hip ratio, but not body mass index, had a significant association with RWM (Beta = 0.34, P = 0.02).
CONCLUSION
Patients with diabetes have increased LV mass, LV torsion, and decreased MPR. There is a significant association between decreased MPR and increased LV torsion suggesting a possible mechanistic link between microvascular disease and cardiac dysfunction in diabetes. | 10.1093/ehjci/jeu142 |
pubmed_330_15862 | Matrix metalloproteinase-9 (MMP-9) plays an important role in the invasion and metastasis of cancer cells. In this study, we examined the inhibitory effect of bee venom (BV) and its major peptides, melittin and apamin, on PMA-induced invasion induced by MMP-9 expression in Caki-1 renal cancer cells. BV and melittin, but not apamin, significantly suppressed PMA-induced invasion by inhibiting MMP-9 expression in Caki-1 cells. Furthermore, as evidenced by MMP-9 promoter assays, melittin inhibited MMP-9 gene expression by blocking the PMA-stimulated activations of activator protein-1 (AP-1) and nuclear factor-kappa B (NF-kappaB). In addition, melittin suppressed the PMA-induced phosphorylations of ERK and JNK mitogen-activated protein kinases, upstream factors involved in Ap-1 and NF-kappaB. These results suggest that the suppression of MMP-9 expression contributes to the anti-tumor properties of melittin. | 10.1007/s10059-010-0028-9 |
pubmed_65_5103 | OBJECTIVE
To determine whether brimonidine 0.2% can control intraocular pressure (IOP) spikes as well as apraclonidine 1.0% can in those patients undergoing argon laser trabeculoplasty (ALT).
DESIGN
Prospective, randomized, double-masked, clinical trial.
PARTICIPANTS
A total of 56 eyes of 41 patients with open-angle glaucoma or ocular hypertension were entered in the study; 46 eyes of 41 patients were eventually used for the final analysis.
INTERVENTION
Patients were randomized to receive either brimonidine 0.2% or apraclonidine 1.0% before and after 360 degrees ALT. Both patient and physician were masked as to which agent each patient received.
MAIN OUTCOME MEASURES
Intraocular pressure measurements were recorded before surgery and at 1, 2, and 4 hours after surgery. The difference between the preoperative IOP (baseline) and the highest recorded postoperative IOP was recorded as the maximum IOP change. The mean of the maximum IOP change for each group was analyzed using a two-sample, one-tailed t test.
RESULTS
The mean of the maximum IOP change in the brimonidine 0.2% group was -2.6+/-3.6 mmHg, and the mean for the apraclonidine 1.0% group was -2.3+/-3.7 mmHg (P = 0.8). No patient had a pressure spike greater than 10 mmHg.
CONCLUSIONS
Brimonidine 0.2% appears to be as effective as apraclonidine 1.0% in preventing IOP spikes after argon laser trabeculoplasty. | 10.1016/S0161-6420(99)90420-7 |
pubmed_43_15135 | Cigarette smoking is disproportionately high among sexual minority populations, but it is unclear whether these disparities exist among race/ethnicity subgroups. This study examined trends in sexual orientation disparities in cigarette smoking by race/ethnicity. Data are from the 2014-2019 Behavioral Risk Factor Surveillance System (N = 1,194,768). Trend analyses compared cigarette smoking by race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, non-Hispanic other) and sexual orientation (straight, lesbian or gay, bisexual, something else/don't know/refused). Multivariable analyses examined associations between sexual orientation and cigarette use for each race/ethnicity, controlling for other sociodemographic characteristics. Between 2014 and 2019, lesbian or gay, and bisexual populations consistently had higher smoking rates than straight populations, which held across race/ethnicity. Among non-Hispanic White adults, lesbians (OR = 1.51, 95% CI = 1.29, 1.76), bisexual females (OR = 1.56, 95% CI = 1.39, 1.75), gay (OR = 1.38, 95% CI = 1.22, 1.55), and bisexual males (OR = 1.22, 95% CI = 1.04, 1.43) had higher odds of smoking compared those self-identifying as straight. Among non-Hispanic Black adults, lesbians (OR = 1.90, 95% CI =1.33, 2.73) and bisexual females (OR = 1.85, 95% CI =1.42, 2.41) were more likely to currently smoke. Among Hispanic adults, those self-identifying as lesbian or gay (OR = 1.58, 95% CI = 1.19, 2.09) or bisexual (OR = 2.40, 95% CI = 1.88, 3.07) were more likely to currently smoke, though the associations were not significant in Hispanic males. Disparities in cigarette smoking by race/ethnicity and sexual orientation suggest that aggregating these groups mask important differences and limit efforts to target those most at risk. | 10.1016/j.ypmed.2021.106760 |
pubmed_689_13500 | Cobalt is essential to the metabolism of all animals due to its key role in cobalamin, also known as vitamin B12, the primary biological reservoir of cobalt as an ultra-trace element. Current cancer treatment strategies, including chemotherapy and radiotherapy, have been seriously restricted by their side effects and low efficiency for a long time, which urges us to develop new technologies for more effective and much safer anticancer therapies. Novel nanotechnologies, based on different kinds of functional nanomaterials, have been proved to act as effective and promising strategies for anticancer treatment. Based on the important biological roles of cobalt, cobalt oxide nanoparticles (NPs) have been widely developed for their attractive biomedical applications, especially their potential for anticancer treatments due to their selective inhibition of cancer cells. Thus, more and more attention has been attracted to the preparation, characterization and anticancer investigation of cobalt oxide nanoparticles in recent years, which is expected to introduce novel anticancer treatment strategies. In this review, we summarize the synthesis methods of cobalt oxide nanoparticles to discuss the advantages and restrictions for their preparation. Moreover, we emphatically discuss the anticancer functions of cobalt oxide nanoparticles as well as their underlying mechanisms to promote the development of cobalt oxide nanoparticles for anticancer treatments, which might finally benefit the current anticancer therapeutics based on functional cobalt oxide nanoparticles. | 10.3390/pharmaceutics13101599 |
pubmed_646_19512 | BACKGROUND
Urtica dioica agglutinin (UDA), a monomeric lectin extracted from stinging nettle rhizomes, is specific for saccharides containing N-acetylglucosamine (GlcNAc). The lectin behaves as a superantigen for murine T cells, inducing the exclusive proliferation of Vbeta8.3(+) lymphocytes. UDA is unique among known T cell superantigens because it can be presented by major histocompatibility complex (MHC) molecules of both class I and II.
RESULTS
The crystal structure of UDA has been determined in the ligand-free state, and in complex with tri-acetylchitotriose and tetra-acetylchitotetraose at 1.66 A, 1.90 A and 1.40 A resolution, respectively. UDA comprises two hevein-like domains, each with a saccharide-binding site. A serine and three aromatic residues at each site form the principal contacts with the ligand. The N-terminal domain binding site can centre on any residue of a chito-oligosaccharide, whereas that of the C-terminal domain is specific for residues at the nonreducing terminus of the ligand. We have shown previously that oligomers of GlcNAc inhibit the superantigenic activity of UDA and that the lectin binds to glycans on the MHC molecule. We show that UDA also binds to glycans on the T cell receptor (TCR).
CONCLUSIONS
The presence of two saccharide-binding sites observed in the structure of UDA suggests that its superantigenic properties arise from the simultaneous fixation of glycans on the TCR and MHC molecules of the T cell and antigen-presenting cell, respectively. The well defined spacing between the two binding sites of UDA is probably a key factor in determining the specificity for Vbeta8.3(+) lymphocytes. | 10.1016/s0969-2126(00)00142-8 |
pubmed_733_22838 | OBJECTIVE
To describe a new syndrome of X-linked myoclonic epilepsy with generalized spasticity and intellectual disability (XMESID) and identify the gene defect underlying this disorder.
METHODS
The authors studied a family in which six boys over two generations had intractable seizures using a validated seizure questionnaire, clinical examination, and EEG studies. Previous records and investigations were obtained. Information on seizure disorders was obtained on 271 members of the extended family. Molecular genetic analysis included linkage studies and mutational analysis using a positional candidate gene approach.
RESULTS
All six affected boys had myoclonic seizures and TCS; two had infantile spasms, but only one had hypsarrhythmia. EEG studies show diffuse background slowing with slow generalized spike wave activity. All affected boys had moderate to profound intellectual disability. Hyperreflexia was observed in obligate carrier women. A late-onset progressive spastic ataxia in the matriarch raises the possibility of late clinical manifestations in obligate carriers. The disorder was mapped to Xp11.2-22.2 with a maximum lod score of 1.8. As recently reported, a missense mutation (1058C>T/P353L) was identified within the homeodomain of the novel human Aristaless related homeobox gene (ARX).
CONCLUSIONS
XMESID is a rare X-linked recessive myoclonic epilepsy with spasticity and intellectual disability in boys. Hyperreflexia is found in carrier women. XMESID is associated with a missense mutation in ARX. This disorder is allelic with X-linked infantile spasms (ISSX; MIM 308350) where polyalanine tract expansions are the commonly observed molecular defect. Mutations of ARX are associated with a wide range of phenotypes; functional studies in the future may lend insights to the neurobiology of myoclonic seizures and infantile spasms. | 10.1212/wnl.59.3.348 |
pubmed_482_13664 | Tumor-associated antigen (TAA) T-cell receptor (TCR) gene-engineered T cells exhibit great potential in antitumor immunotherapy. Considering the high costs and low availability of patient-derived peripheral blood T cells, substantial efforts have been made to explore alternatives to natural T cells. We previously reported that enforced expression of Hoxb5 converted B cells into induced T (iT) cells in vivo Here, we successfully regenerated naive OT1 (major histocompatibility complex I restricted ovalbumin antigen) iT cells (OT1-iT) in vivo by expressing Hoxb5 in pro-pre-B cells in the OT1 transgenic mouse. The OT1-iT cells can be activated and expanded in vitro in the presence of tumor cells. Particularly, these regenerated OT1-iT cells effectively eradicated tumor cells expressing the TAA (ovalbumin) both in vitro and in vivo This study provides insights into the translational applications of blood lineage-transdifferentiated T cells in immunotherapy. | 10.1136/jitc-2019-000498 |
pubmed_64_517 | Heat shock instantly reprograms transcription. Whether gene and enhancer transcription fully recover from stress and whether stress establishes a memory by provoking transcription regulation that persists through mitosis remained unknown. Here, we measured nascent transcription and chromatin accessibility in unconditioned cells and in the daughters of stress-exposed cells. Tracking transcription genome-wide at nucleotide-resolution revealed that cells precisely restored RNA polymerase II (Pol II) distribution at gene bodies and enhancers upon recovery from stress. However, a single heat exposure in embryonic fibroblasts primed a faster gene induction in their daughter cells by increasing promoter-proximal Pol II pausing and by accelerating the pause release. In K562 erythroleukemia cells, repeated stress refined basal and heat-induced transcription over mitotic division and decelerated termination-coupled pre-mRNA processing. The slower termination retained transcripts on the chromatin and reduced recycling of Pol II. These results demonstrate that heat-induced transcriptional memory acts through promoter-proximal pause release and pre-mRNA processing at transcription termination. | 10.1016/j.molcel.2021.03.007 |
pubmed_1090_11054 | A gas chromatographic-mass spectrometric procedure is described for the identification and differentiation of sedative-hypnotics and their metabolites in urine. The following 24 barbiturates and thirteen other hypnotics could be detected: acecarbromal, allobarbital, amobarbital, aprobarbital, barbital, brallobarbital, bromisoval, (sec)butabarbital, butalbital, butobarbital, carbromal, clomethiazole, crotylbarbital, cyclobarbital, cyclopentobarbital, diethylallylacetamide, dipropylbarbital, glutethimide, guaifenesin, ethinamate, heptabarbital, hexobarbital, meprobamate, methaqualone, metharbital, methohexital, methylphenobarbital, methyprylone, pentobarbital, phenobarbital, propallylonal, pyrithyldione, secobarbital, thiobutabarbital, thiopental, vinbarbital and vinylbital. The procedure presented is integrated in a general screening procedure (general unknown analysis) for several groups of drugs detecting over 300 drugs and over 1000 of their metabolites. It includes cleavage of conjugates by acid hydrolysis, isolation by liquid-liquid extraction, derivatization by acetylation, separation by capillary gas chromatography, and identification by computerized mass spectrometry. Using mass chromatography with the selected ions m/z 83, 117, 141, 167, 169, 207, 221 and 235, the presence of barbiturates, other hypnotics and/or their metabolites was indicated. The identity of positive signals in the reconstructed mass chromatograms was confirmed by a visual or computerized comparison of the stored full mass spectra with the reference spectra. The sample preparation, mass chromatograms, reference mass spectra and gas chromatographic retention indices are documented. | 10.1016/s0378-4347(00)82334-8 |
pubmed_894_3988 | A case is reported of a 33-year-old man with hepatocellular carcinoma associated with familial polyposis of the colon. During subtotal colectomy for diffuse colonic polyposis, a small tumor was excised from the right lobe of the liver. Histologic examination revealed hepatocellular carcinoma. The association of primary hepatoma in familial polyposis of the colon is very rare. However, it is well known that familial polyposis of the colon has a potent oncogenicity not only in the colon but also in the extracolonic organs. The hepatoma may also be one of the extracolonic malignant manifestations in this inherited disease. | 10.1007/BF02556528 |
pubmed_748_19465 | The purpose of this study was to identify the number of hospitals employing nurses and radiographers formally to undertake radiographic interpretation of trauma images and to compare the education undertaken by these professionals and any limitations imposed. A cross-sectional questionnaire survey of nurse and radiographer managers responsible for Accident and Emergency services within National Health Service hospitals in the UK was undertaken in January 2002. A total of 526 questionnaires were distributed. Response rates of 75.3% (n=198/263) and 69.2% (n=182/263) were received from radiographer and nurse managers, respectively. 96 nurse managers (52.7%, n=96/182) indicated that nurses within their departments were formally interpreting radiographs as part of their extended role whereas only 68 radiography managers (34.3%, n=68/198) indicated that radiographers were undertaking this role. Education to support radiographic interpretation varied markedly with 92.6% (n=63/68) of radiographers having undertaken a postgraduate qualification in image interpretation. In contrast, nurse education at all levels was more generic to the nursing role. The range of examinations which nurses and radiographers were permitted to interpret also varied markedly. Radiographic interpretation is undertaken by both nurses and radiographers. However, there is interprofessional and intraprofessional inconsistency in the range of examinations they are permitted to interpret and the level of education provided to support this role. Consequently, it can be surmised that national variation in service delivery and quality exists and a review of current service delivery strategies is recommended. | 10.1259/bjr/53007610 |
pubmed_924_17623 | BACKGROUND
Treatment group imbalances in baseline stroke severity in the NINDS intravenous t-PA for acute stroke treatment trial led to controversy regarding the efficacy of tissue plasminogen activator (t-PA) in the treatment of acute ischemic stroke.
PURPOSE
Describe the steps used to independently re-evaluate this trial.
METHODS
NIH appointed an independent multidisciplinary committee that gained access to the original data. We undertook analyses of t-PA efficacy accounting for this imbalance, as well as analyses to identify subgroups that experienced additional harm or benefit from t-PA. Analyses of time from stroke onset to treatment (OTT), blood pressure, and intracerebral hemorrhage are given as illustrations.
RESULTS
Despite subgroup imbalances in baseline stroke severity, when t-PA was administered to acute ischemic stroke patients according to study protocol, there was a statistically significant and clinically important benefit of t-PA treatment resulting in a higher likelihood of having a favorable clinical outcome at 3 months. Moreover, we were unable to identify subgroups of patients between which t-PA treatment effect differed, albeit these analyses had low power. These data failed to support the NINDS investigators' conclusion that effect of t-PA therapy diminished with increasing values of OTT within the protocol-specified 3 h time limit. In addition, the blood pressure measurements were highly variable and inconsistently determined so as to be too unreliable for inclusion in analysis.
CONCLUSION
With new NIH requirements for data-sharing, the frequency of re-analysis of clinical trial data may increase substantially. This re-evaluation provides a blueprint for future re-evaluations of other trials. These best practices include re-analysis of the study data, after suitable replication, by an independent multidisciplinary committee, including a skilled statistical programmer analyst. Primary investigators should address significant errors determined in such re-analyses. | 10.1177/1740774508094404 |
pubmed_240_18719 | Specific conditions of the honeybee life honeybee life require the presence of effective mechanisms of antiinfectious protection whose one of the most important components are defensins--the family of antimicrobial peptides. In the honeybee, defensins are present in the form of two different peptides--defensin 1 and 2 that are similar between each other only by 55.8 %. Defensin 1 synthesized in salivary glands plays an important role in social immunity, whereas defensin 2 synthesized by cells of lat body and lymph is an important factor in the system of the honeybee individual immunity. Defensins are inducible, are controlled by interaction of Toll and Imd signal pathways and have a large specter of antimicrobial action. | pubmed_240_18719 |
pubmed_572_23300 | A microcapsule-type self-healing protective coating with secondary crack preventing capability has been developed using a silanol-terminated polydimethylsiloxane (STP)/dibutyltin dilaurate (DD) healing agent. STP undergoes condensation reaction in the presence of DD to give a viscoelastic substance. STP- and DD-containing microcapsules were prepared by in-situ polymerization and interfacial polymerization methods, respectively. The microcapsules were characterized by Fourier-transform infrared (FT-IR) spectroscopy, optical microscopy, and scanning electron microscopy (SEM). The microcapsules were integrated into commercial enamel paint or epoxy coating formulations, which were applied on silicon wafers, steel panels, and mortar specimens to make dual-capsule self-healing protective coatings. When the STP/DD-based coating was scratched, self-healing of the damaged region occurred, which was demonstrated by SEM, electrochemical test, and water permeability test. It was also confirmed that secondary crack did not occur in the healed region upon application of vigorous vibration to the self-healing coating. | 10.3390/ma10020114 |
pubmed_940_14325 | OBJECTIVE
Temporary covering of a defect of the soft tissues with a silicon sheet after fasciotomy in the treatment of compartment syndrome.
DESIGN
Retrospective study.
SETTING
University Hospital, Tübingen.
PATIENTS
From January 1991 to June 1996, open fasciotomy was performed a total of 18 times on 17 patients with compartment syndrome. In 17 of the 18 cases acute vascular ischemia was the cause of the compartment syndrome.
INTERVENTIONS
For the 18 necessary fasciotomies, a silicon sheet was temporarily used to cover the defect of the soft tissue temporarily a total of 9 times. The silicon sheet was gradually drawn together and the wound was finally closed with a secondary suture.
RESULTS
In 6 of the 9 cases a secondary suture could be performed without any difficulties after the swelling had subsided, and a meshgraft covering was not necessary. Only one patient suffered from wound infection because the silicon sheet had not been sutured correctly. In the other cases there was no sign of infection. The wound dressing was changed painlessly and furthermore, an improved cosmetic result was observed.
CONCLUSIONS
There are considerable advantages in the use of a silicon sheet as a temporary covering for the defect of the soft tissues in the treatment of compartment syndrome: lower costs because of shorter hospitalisation and the dressing change is practically painless. A reduced risk of infection and improved cosmetic results are further advantages of this method. | pubmed_940_14325 |
pubmed_948_2966 | Three members of a family developed eosinophilic myelomeningoencephalitis following ingestion of Pila snails. They were father, daughter and son and had similar clinical presentations. Two days after ingestion of snails, they developed a generalized itchy maculopapular rash followed by myalgia, marked paresthesia, fever and headache. Two days later there was weakness of the extremities which was progressive in severity involving the legs more than the arms. They later developed urine retention and cloudiness of consciousness. Two patients progressed to coma, one of whom died after 3 weeks and the other died at home 9 months after the onset. Autopsy of the fatal case revealed multiple tracks and cavities with the presence of Angiostrongylus cantonensis in the brain and various levels of the spinal cord. | pubmed_948_2966 |
pubmed_343_12724 | Snapping scapula syndrome manifests as an audible or palpable crackling during the sliding movements of the scapula over the rib cage, often perceived during physical or professional activities. It can be caused by morphological alteration of the scapula and rib cage, by an imbalance in periscapular musculature forces (dyskinesia), or by neoplasia (bone tumors or soft tissue tumors). In this pictorial essay, we review the main causes of snapping scapula syndrome, exemplified by a collection of didactic cases. | 10.1590/0100-3984.2017.0226 |
pubmed_173_18485 | Both inhibitor of growth 4 (ING4) and phosphatase and tensin homolog (PTEN) have been shown to be strong candidate tumor suppressors. However, the combined efficacy of ING4 and PTEN for human gastric cancer remains to be determined. In this report, we constructed a multiple promoter expression cassette-based recombinant adenovirus coexpressing ING4 and PTEN (AdVING4/PTEN), assessed the combined effects of AdVING4/PTEN on gastric cancer using wild-type p53 AGS and SNU-1 human gastric cancer cell lines, and elucidated its underlying mechanisms. We found that AdVING4/PTEN-induced synergistic growth inhibition and apoptosis in vitro AGS or SNU-1 tumor cells and in vivo AGS xenografted tumors subcutaneously inoculated in athymic BALB/c nude mice. Mechanistically, AdVING4/PTEN exhibited an enhanced effect on upregulation of p53, Ac-p53 (K382), P21, Bax, PUMA, Noxa, cleaved Caspase-9, cleaved Caspase-3 and cleaved PARP as well as downregulation of Bcl-2 in vitro and in vivo. In addition, AdVING4/PTEN synergistically downregulated tumor vessel CD34 expression and reduced microvessel density, and additively inhibited vascular endothelial growth factor (VEGF) expression in vivo. The synergistic tumor suppression elicited by AdVING4/PTEN was closely associated with the synergistic induction of apoptosis possibly via enhancement of endogenous p53 responses through cooperatively facilitating p53's stability and acetylation, and the synergistic inhibition of tumor angiogenesis probably via overlapping reduction of VEGF through cooperatively downregulating hypoxia inducible factor-1α's level and transcription activity. Thus, our results indicate that cancer gene therapy combining ING4 and PTEN may constitute a novel and effective therapeutic modality for human gastric cancer and other cancers. | 10.1038/cgt.2015.59 |
pubmed_753_6003 | Acute hematometra, also termed the postabortal syndrome or redo syndrome, is a rare immediate complication of suction curettage characterized by severe lower abdominal cramping in association with an enlarged and markedly tender uterus. We describe the transvaginal sonographic features of this syndrome. | 10.1002/jcu.20795 |
pubmed_762_13539 | Arabidopsis TOM1 (AtTOM1) and TOM2A (AtTOM2A) are integral membrane proteins genetically identified to be necessary for efficient intracellular multiplication of tobamoviruses. AtTOM1 interacts with the helicase domain polypeptide of tobamovirus-encoded replication proteins and with AtTOM2A, suggesting that both AtTOM1 and AtTOM2A are integral components of the tobamovirus replication complex. We show here that AtTOM1 and AtTOM2A proteins tagged with green fluorescent protein (GFP) are targeted to the vacuolar membrane (tonoplast)-like structures in plant cells. In subcellular fractionation analyses, GFP-AtTOM2A, AtTOM2A and its tobacco homolog NtTOM2A were predominantly fractionated to low-density tonoplast-rich fractions, whereas AtTOM1-GFP, AtTOM1 and its tobacco homolog NtTOM1 were distributed mainly into the tonoplast-rich fractions and partially into higher-buoyant-density fractions containing membranes from several other organelles. The tobamovirus-encoded replication proteins were co-fractionated with both NtTOM1 and viral RNA-dependent RNA polymerase activity. The replication proteins were also found in the fractions containing non-membrane-bound proteins, but neither NtTOM1 nor the polymerase activity was detected there. These observations suggest that the formation of tobamoviral RNA replication complex occurs on TOM1-containing membranes and is facilitated by TOM2A. | 10.1093/emboj/cdg033 |
pubmed_591_20469 | BACKGROUND
Genetically caused neurological disorders of the central nervous system (CNS) are mostly characterized by poor or even fatal clinical outcome and few or no causative treatments are available. Often, these disorders are associated with low-grade, disease-promoting inflammation, another feature shared by progressive forms of multiple sclerosis (PMS). We previously generated two mouse lines carrying distinct mutations in the oligodendrocytic PLP1 gene that have initially been identified in patients diagnosed with MS. These mutations cause a loss of PLP function leading to a histopathological and clinical phenotype common to both PMS and genetic CNS disorders, like hereditary spastic paraplegias. Importantly, neuroinflammation promotes disease progression in these models, suggesting that pharmacological modulation of inflammation might ameliorate disease outcome.
METHODS
We applied teriflunomide, an approved medication for relapsing-remitting MS targeting activated T-lymphocytes, in the drinking water (10 mg/kg body weight/day). Experimental long-term treatment of PLP mutant mice was non-invasively monitored by longitudinal optical coherence tomography and by rotarod analysis. Immunomodulatory effects were subsequently analyzed by flow cytometry and immunohistochemistry and treatment effects regarding neural damage, and neurodegeneration were assessed by histology and immunohistochemistry.
RESULTS
Preventive treatment with teriflunomide attenuated the increase in number of CD8+ cytotoxic effector T cells and fostered the proliferation of CD8+ CD122+ PD-1+ regulatory T cells in the CNS. This led to an amelioration of axonopathic features and neuron loss in the retinotectal system, also reflected by reduced thinning of the innermost retinal composite layer in longitudinal studies and ameliorated clinical outcome upon preventive long-term treatment. Treatment of immune-incompetent PLP mutants did not provide evidence for a direct, neuroprotective effect of the medication. When treatment was terminated, no rebound of neuroinflammation occurred and histopathological improvement was preserved for at least 75 days without treatment. After disease onset, teriflunomide halted ongoing axonal perturbation and enabled a recovery of dendritic arborization by surviving ganglion cells. However, neither neuron loss nor clinical features were ameliorated, likely due to already advanced neurodegeneration before treatment onset.
CONCLUSIONS
We identify teriflunomide as a possible medication not only for PMS but also for inflammation-related genetic diseases of the nervous system for which causal treatment options are presently lacking. | 10.1186/s12974-018-1228-z |
pubmed_178_11789 | The expression of myeloid and megakaryocytic markers of differentiation has been studied in one K-562 cell subline, in its clones, and in the original cell line. Cytotoxicity, electron microscopy, immunofluorescence studies with a panel of polyclonal and monoclonal antibodies, and radioimmunoassays were performed on K-562 cells before and after induction with hemin, sodium butyrate, and 12-O-tetradecanoylphorbol-13-acetate. Myeloid membrane markers were present in all K-562 cell lines. Only the early granulopoietic cell surface markers were expressed in 75 to 95% of the cells, while none of the late membrane markers was detected. In contrast, neither the early (myeloperoxidase) nor late (lactoferrin) cytoplasmic markers were present. Thus, K-562 cells showed a membrane phenotype similar to that of a normal or leukemic promyelocyte but lacking myeloperoxidase. Membrane megakaryocytic markers, such as platelet glycoprotein IIIa and platelet peroxidase, were also detected in K-562 cells. However, some other early megakaryocytic markers, such as platelet glycoprotein lb, Factor VIII-R-Ag, and platelet Factor 4, could not be detected by fluorescent labeling. Cloning of the cell line did not result in the selection of a unipotential cell line. These results could be explained by the expression of multilineage markers in a single cell. In all of the cell lines and clones, hemin slightly increased the expression of the myeloid membrane markers without any modification of the megakaryocytic markers. Sodium butyrate and 12-O-tetradecanoylphorbol-13-acetate diminished most of the myeloid markers and very significantly increased the expression of the megakaryocytic markers. | pubmed_178_11789 |
pubmed_612_16101 | The mycobacterial membrane protein large 3 (MmpL3) transporter is essential and required for shuttling the lipid trehalose monomycolate (TMM), a precursor of mycolic acid (MA)-containing trehalose dimycolate (TDM) and mycolyl arabinogalactan peptidoglycan (mAGP), in Mycobacterium species, including Mycobacterium tuberculosis and Mycobacterium smegmatis. However, the mechanism that MmpL3 uses to facilitate the transport of fatty acids and lipidic elements to the mycobacterial cell wall remains elusive. Here, we report 7 structures of the M. smegmatis MmpL3 transporter in its unbound state and in complex with trehalose 6-decanoate (T6D) or TMM using single-particle cryo-electron microscopy (cryo-EM) and X-ray crystallography. Combined with calculated results from molecular dynamics (MD) and target MD simulations, we reveal a lipid transport mechanism that involves a coupled movement of the periplasmic domain and transmembrane helices of the MmpL3 transporter that facilitates the shuttling of lipids to the mycobacterial cell wall. | 10.1371/journal.pbio.3001370 |
pubmed_1055_15724 | Menstrual cycle-dependent changes have been reported for a variety of functions, including cognition, attention, emotion, inhibition, and perception. For several of these functions, an effect of hormonal contraceptives has also been discussed. Cognitive, attentional, emotional, inhibitory, and perceptual functions have been linked to distinct intrinsic connectivity networks during the resting state. However, changes in resting-state connectivity across the menstrual cycle phase and due to hormonal contraceptive use have only been investigated in two selected networks and without controlling for the type of hormonal contraceptives. In the present study, we demonstrate menstrual cycle and hormonal contraceptive-dependent changes in several intrinsic connectivity networks, including networks that have been related to emotion processing, olfaction, audition, vision, coordination, and two lateralized frontoparietal networks related to a variety of cognitive functions. These changes parallel behavioral changes in the functions associated with these networks. Changes in connectivity and changes in behavior occur during the same cycle phases. Furthermore, hormonal contraceptive-dependent effects were observed in the same networks and same target sites as menstrual cycle-related changes and were dependent on the androgenicity of the progestin component contained in the hormonal contraceptive. | 10.1089/brain.2015.0407 |
pubmed_512_18074 | BACKGROUND
Mycobacterial infection is the most common cause of cervical granuloma, implicating either a tuberculous or a non-tuberculous mycobacterium (NTM). NTM is a ubiquitous organism, found in soil, water, food, etc. The most frequently implicated is Mycobacterium avium-intracellular. Most authors agree that NTM is increasingly isolated, due to a decrease in vaccination rates. Initial diagnosis is difficult and management is not clearly codified.
METHODS
A retrospective study conducted in the University Hospital of Nantes, France, between 2005 and 2014, included all patients treated for head and neck NTM lymphadenitis. The research was conducted on the database of the institution's bacteriology department. Population, history, symptoms and diagnostic features were noted. Treatment, surgical complications, adverse reactions to antibiotics, patient adherence, antibiotic therapy duration, time to remission and prognosis were analyzed.
RESULTS
Between 2005 and 2014, 30 patients were diagnosed with head and neck NTM lymphadenitis: 17 female, 13 male; mean age at diagnosis, 4.5 years. Locations were submandibular (n=16), parotid, (n=7), cervical (n=5), parapharyngeal (n=4) and, for 1 patient, in the auricle concha. Eight patients received first-line surgical treatment, which was effective in 75% of cases, 2 patients requiring additional antibiotic therapy. Twenty-two patients were treated with first-line antibiotherapy, which was effective in 90% of cases. There were no relapses at a mean 32 weeks' follow-up.
CONCLUSIONS
Total resection of all affected nodes and infiltrated subcutaneous fatty tissue is the treatment of choice. Drug therapy (including at least a macrolide) seems indicated only in case of incomplete resection or if surgery would entail functional and/or esthetic risk. Increased incidence, since BCG vaccination was stopped, will continue to confront the practitioner with an infantile disease in which management must be multidisciplinary. | pubmed_512_18074 |
pubmed_125_18459 | BACKGROUND
Compressive optic neuropathy is the most common indication for transsphenoidal surgery for pituitary adenomas. Optical coherence tomography (OCT) is a useful visual assessment tool for predicting postoperative visual field recovery.
OBJECTIVE
To analyze visual parameters and their association based on long-term follow-up.
METHODS
Only pituitary adenoma patients with abnormal visual field defects were selected. A total of 188 eyes from 113 patients assessed by visual field index (VFI) and 262 eyes from 155 patients assessed by mean deviation (MD) were enrolled in this study. Postoperative VFI, MD, and retinal nerve fiber layer (RNFL) thickness were evaluated and followed up. After classifying the patients into normal (>5%) and thin (<5%) RNFL groups, we investigated whether preoperative RNFL could predict visual field outcomes. We also observed how RNFL changes after surgery on a long-term basis.
RESULTS
Both preoperative VFI and MD had a linear proportional relationship with preoperative RNFL thickness. Sustained improvement of the visual field was observed after surgery in both groups, and the degree of improvement over time in each group was similar. RNFL thickness continued to decrease until 36 mo after surgery (80.2 ± 13.3 μm to 66.6 ± 11.9 μm) while visual field continued to improve (VFI, 61.8 ± 24.5 to 84.3 ± 15.4; MD, -12.9 ± 7.3 dB to -6.3 ± 5.9 dB).
CONCLUSION
Patients with thin preoperative RNFL may experience visual recovery similar to those with normal preoperative RNFL; however, the probability of normalized visual fields was not comparable. RNFL thickness showed a strong correlation with preoperative visual field defect. Long-term follow-up observation revealed a discrepancy between anatomic and functional recovery. | 10.1093/neuros/nyaa318 |
pubmed_147_20778 | BACKGROUND
Some individuals with bipolar disorder have cognitive deficits even when euthymic. In previous studies, we found an association between elevated levels of C-reactive protein (CRP), a marker of inflammation, and reduced cognitive functioning in schizophrenia. This issue has not been examined in bipolar disorder.
METHODS
We measured the levels of high sensitivity CRP in serum samples from 107 individuals with bipolar disorder. Cognitive functioning was measured with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Trail Making Test Part A and WAIS Information and Letter Number Sequencing. We estimated the odds of RBANS scores <=70 for participants whose CRP levels were above the 75th and the 90th percentile of the level of non-psychiatric controls. We also examined the association between cognitive scores and CRP levels. Covariates included demographic factors, mood symptom severity, cigarette smoking status, and body mass index.
RESULTS
There was a significantly increased odds of low RBANS total score for individuals who had a CRP level higher than the 90th percentile (OR=4.32, p=.018) and the 75th percentile (OR=3.07, p=.04)) of the control group. There was an inverse relationship between CRP levels and performance on RBANS total (t=-2.48, p=.015); RBANS immediate memory (t=-2.16, p=.033); RBANS attention (t=-2.18, p=.032); RBANS language (t=-2.13, p=.036); Trail Making A (t=-2.39, p=.019).
LIMITATIONS
Factors which we did not measure such as diet, allergen exposure, and underlying autoimmune disorders may contribute to CRP levels.
CONCLUSIONS
Inflammation may play a major role in the cognitive deficits associated with bipolar disorder. | pubmed_147_20778 |
pubmed_695_16366 | BACKGROUND
Vulvar carcinoma is a rare gynecological malignancy. The most commonly used staging system for vulvar cancer is the 2009 International Federation of Gynecology and Obstetrics (FIGO) staging system. Nevertheless, it does not incorporate many indispensable prognostic parameters, which prominently influence vulvar cancer patient survival. Thus, the development of a prediction model for evaluating survival prognosis in postoperative vulvar squamous cell cancer patients is of vital importance.
METHODS
Data from 2,166 patients with pathologically confirmed diagnosis of vulvar squamous cell carcinoma from 2004 to 2015 were acquired from the Surveillance, Epidemiology, and End Results (SEER) database. Thirty percent of the patients were randomly assigned to the validation group, and the remainder were used to develop the nomogram. Parameters that significantly correlated with overall survival (OS) were used to create the nomogram. Concordance index (C-index), calibration curve, and decision curve analysis (DCA) were used to assess the predictive accuracy and discriminability of the nomogram model. Additionally, the C-index and DCA of the nomogram and the FIGO staging system were compared.
RESULTS
Following multivariate analysis of the training cohort, independent factors for OS, including race, age at diagnosis, marital status, FIGO stage, tumor diameter, and lymph node ratio (LNR), were included in the nomogram model. The calibration curve indicated a high correlation between the nomogram-predicted and observed survival probability. The C-index of the nomogram in the training cohort was 0.772 (95% CI: 0.752-0.792), statistically superior to the C-index value of the FIGO staging system (0.676, 95% CI: 0.654-0.698). In DCA, compared to the FIGO staging system, this nomogram showed a greater net benefit and a wider range of threshold probability. Results were verified by an internal validation cohort.
CONCLUSIONS
Our nomogram, based on LNR, showed superior prognostic predictive accuracy compared with the FIGO staging system for predicting OS in postoperative vulvar squamous cell carcinoma patients. | 10.21037/atm-20-3240 |
pubmed_85_23274 | We performed a study to investigate whether contamination of hemostasis samples with a glucose-containing solution might generate spurious results in rotational thromboelastometry (ROTEM) tests.Venous blood was taken from 12 healthy volunteers and divided into 4 specimen bottles, which were contaminated with different concentrations (0%, 5%, 10%, and 20%) of glucose solution.Significant lengthening of INTEMCT was observed in the 10% and 20% groups compared with baseline values (7.7% and 9%, P = 0.041 and P = 0.037, respectively). INTEMCFT increased by 20.1% in the 20% group (P = 0.005). INTEMα-angle and INTEMMCF decreased by 3.9% and 2.7%, respectively, in the 20% group (P = 0.010 and P = 0.049, respectively). EXTEMCFT was prolonged significantly, by 10.2%, 15.5%, and 25.6%, in the 5%, 10%, and 20% groups, respectively (P = 0.004, P < 0.001, and P < 0.001, respectively). EXTEMα-angle decreased significantly by 1.9%, 3.2%, and 4.0% in the 5%, 10%, and 20% groups, respectively (P = 0.014, P = 0.001, and P = 0.005, respectively). EXTEMMCF decreased by 3.4% in the 20% group (P = 0.023). FIBTEMMCF decreased by 9.2% and 17.5% in the 10% and 20% groups, respectively (P = 0.019 and P = 0.021, respectively). A significant correlation was observed between standard glucose solution contamination in the specimens and percentage variation of EXTEMCFT, EXTEMMCF, and FIBTEMMCF.To obtain accurate data from the ROTEM test regarding the hemostatic status of patients, specimens with suspected or known contamination should not be analyzed. | 10.1097/MD.0000000000004703 |
pubmed_539_20197 | The molecular changes associated with the transition of melanoma cells from radial growth phase (RGP) to vertical growth phase [(VGP), metastatic phenotype] are not very well defined. We previously demonstrated that expression of the cell-surface adhesion molecule MCAM/MUC18 correlates directly with the metastatic potential of human melanoma cells. In addition, the progression of human melanoma towards the metastatic phenotype is associated with loss of expression of the tyrosine-kinase receptor c-KIT. In this review, I will summarize our recent studies demonstrating that the expression of both genes is regulated by the AP-2 transcription factor. Moreover, we have observed a loss of AP-2 expression in metastatic melanoma cells. Re-expression of AP-2 in the highly metastatic A375SM cells decreased their tumorigenicity and inhibited their metastatic potential in nude mice. MCAM/MUC18 mRNA and protein expression was significantly down-regulated while c-KIT expression was up-regulated in the AP-2-transfected cells. To further investigate the role of AP-2 in the progression of human melanoma, we attempted to inactivate AP-2 in primary cutaneous melanoma by using a dominant-negative AP-2, or the AP-2B gene. Expression of AP-2B in SB-2 cells augmented their tumorigenicity in nude mice, and upregulated MMP-2 expression and activity. As AP-2 also regulates other genes that are involved in the progression of human melanoma such as E-cadherin, p21/WAF-1, HER2/neu, Bcl-2, FAS/APO-1, IGF-R-1, VEGF and the thrombin receptor (PAR-1), we therefore propose that loss of AP-2 is a crucial event in the development of malignant melanoma. In addition, the transition of melanoma cells from RGP to VGP is also associated with over-expression of the transcription factors CREB and ATF-1. The notion that the balance between AP-2 and CREB/ATF-1 expression determines the progression of melanoma cells towards the metastatic phenotype will be discussed. | 10.1034/j.1600-0749.2001.140202.x |
pubmed_360_2790 | A case of contact dermatitis produced on the face of patient after the application of an oxygen mask is described. This paper includes the results of epicutaneous tests, the identification of the possible etiological agent and chromatographic analysis of the samples sterilized by ethylene oxide. | 10.1111/j.1600-0536.1981.tb04045.x |
pubmed_552_18468 | We developed a new 8F catheter-introducer system designed for simultaneous insertion of two catheters into each internal iliac artery via a single puncture. This introducer has a common distal limb and a pair of proximal limbs connected in a Y-shaped fashion. Each of the proximal limbs has its own check valve and flushing side arm, through which one can pass two catheters separately. We succeeded in placing each of two catheters at desired sites in three cases of pelvic angiography. This system will be of great help in pelvic angiography and infusion-chemotherapy when bilateral catheterization is required. | pubmed_552_18468 |
pubmed_179_862 | INTRODUCTION
Pharmacological treatment of chronic obstructive pulmonary disease in Spain is usually chosen according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) or Spanish guidelines for chronic obstructive pulmonary disease (GesEPOC). The main objective of this study was to evaluate the degree of concordance between treatment for newly diagnosed chronic obstructive pulmonary disease patients according to GOLD and GesEPOC.
MATERIAL AND METHODS
Simulation study. The following variables were used: FEV1%, exacerbations, dyspnoea at first evaluation, blood eosinophilia, personal history of asthma, and degree of bronchodilator reversibility. Four investigators classified and assigned a treatment to each patient (2 using GOLD criteria and the other 2 using GesEPOC). Global Kappa index was calculated.
RESULTS
The database included 467 patients. Agreement between treatment decided using GOLD and GesEPOC was poor (Kappa: 0.17, 95% CI: 0.12-0.23).
CONCLUSION
There is a poor agreement between GOLD and GesEPOC recommendations for initial chronic obstructive pulmonary disease treatment. | 10.1016/j.rceng.2021.01.009 |
pubmed_302_5175 | Atherosclerosis is a generalized vascular disease. There are methods to investigate the development of atherosclerosis. Doppler ultrasonography is a noninvasive and safe method. By this method we can see and measure the first stage of atherosclerosis development--thickening of intima-media complex. Measuring intima-media thickness of common carotid artery may be used as an indicator of generalized atherosclerosis. Intima-media thickness is also used to study progression of atherosclerosis and its possible regression during therapy. | pubmed_302_5175 |
pubmed_975_822 | Variability in airway conductance (Gaw) and lung volume (TGV) was studied in 26 subjects with moderately severe asthma during a 9-week period. Specific airway conductance (SGaw) was calculated as Gaw:TGV. There was considerable inter-individual variability in airway conductance, and a smaller variability in TGV. Airway conductance (SGaw) showed an eight-fold difference and TGV a three-fold difference between smallest and largest values. The intra-individual variability was less, with a range of +/- 55% (SGaw) and +/- 12% (TGV) of the grand mean, respectively. The error of the method contributed only marginally to the variations in airway conductance. These data for spontaneous variability of conductance facilitate, for example, the assessment of the clinical importance of changes in lung function seen after exposure to air pollutants in chamber studies. Furthermore, the substantial inter-individual variability in conductance argues against comparing samples of asthmatic subjects in polluted and non-polluted areas, and in favour of prospective studies of cohorts of subjects with asthma. | 10.1111/j.1475-097x.1995.tb00512.x |
pubmed_110_10730 | Doctors often lack the knowledge and skills to identify and assess those who drink to excess and are unsure of what their preventive and educational role should be. As part of a prospective study of early identification and intervention with general hospital patients who drink to excess, we were interested to discover whether brief education about alcohol-related problems and training in the use of a quick and efficient alcohol screening questionnaire would improve doctors' alcohol history-taking and thus their identification of those at risk. The case notes of every fifth admission to orthopaedic and medical wards at the York District Hospital were studied before and after doctor education. Recorded information on both alcohol and tobacco increased over the period reviewed, reflecting perhaps doctors' growing awareness of the health-threatening aspects of these drugs. While there was no major change in doctors' alcohol history-taking, with two thirds of case notes making no mention, or only vague mention, of alcohol, there was a significant post-education increase in the number of patients for whom detailed drinking histories were recorded, but no significant changes in tobacco histories. Small but significant improvements such as these are important in view of the size of the medical problems arising from the use of alcohol. | 10.1111/j.1365-2923.1988.tb00800.x |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.