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pubmed_701_10754 | Hydralazine is an antihypertensive drug that elicits andti-nuclear antibodies in patients as an adverse effect. We investigated the ability of hydralazine to promote/stabilize the triplex DNA form of poly(dA).2poly(dT). Under conditions of low ionic strength, the polynucleotide melted as a double helix with a melting temperature (Tm) of 55.3 degrees C. Hydralazine destabilized this duplex form by reducing its Tm to 52.5 degrees C. Spermidine (2.5 microM), a natural polyamine, provoked the triplex form of poly(dA)-.2poly(dT) with two melting transitions, Tm1 of 42.8 degrees C corresponding to triplex-->duplex+single-stranded DNA and Tm2 of 65.4 degrees C, corresponding to duplex melting. Triplex DNA thus formed in the presence of spermidine was further stabilized by hydralazine (250 microM) with a Tm1 of 53.6 degrees C. A similar stabilization effect of hydralazine was found on triplex DNA formed in the presence of 5 mM Mg2+. CD spectra revealed conformational perturbations of DNA in the presence of spermidine and hydralazine. These results support the hypothesis that hydralazine is capable of stabilizing unusual forms of DNA. In contrast with the weak immunogenicity of DNA in its right-handed B-DNA conformation, these unusual forms are immunogenic and have the potential to elicit anti-DNA antibodies. To test this possibility, we analysed sera from a panel of 25 hydralazine-treated patients for anti-(triplex DNA) antibodies using an ELISA. Our results showed that 72% of sera from hydralazine-treated patients contained antibodies reacting toward the triplex DNA. In contrast, there was no significant binding of normal human sera to triplex DNA. Taken together our data indicate that hydralazine and related drugs might exert their action by interacting with DNA and stabilizing higher-order structures such as the triplex DNA. | 10.1042/bj3110183 |
pubmed_26_8034 | Awakening of the Cp one: The bifunctional complex 1 facilitates the interaction with substrates bearing less electrophilic carbon atoms than ketones, epoxides, and imides. The title reaction was applicable to the reduction of Evans' asymmetric alkylation products to the chiral alcohols along with good recovery of the chiral oxazolidinone auxiliary. EWG = electron-withdrawing group. | 10.1002/anie.200805307 |
pubmed_165_2405 | Cognitive and other behavioural characteristics of 3-month-old heterozygous male transgenic mice expressing the 751-amino acid isoform of human amyloid precursor protein (hAPP751) under the control of a neurone-specific enolase promoter, were compared with those of age-matched non-transgenic control males. No difference was found between hAPP751 transgenics and non-transgenic controls in passive avoidance learning, or in motor coordination. Significantly decreased measures were found in the open field test and in cage activity indicative of general hypoactivity in hAPP751 transgenics. In water maze training, hAPP751 males required significantly longer to locate the hidden platform. This was not due to decreased swimming velocity in hAPP751 mice, but rather to increased path lengths. This suggests a purely spatial learning deficit in hAPP751 males even though their performance during a final spatial test, the probe trail that followed water maze training, was indistinguishable from that of controls. Decreased activity and impaired spatial learning were also reported in an independent study of hAPP751-expressing transgenics showing beta-amyloid immunoreactive deposits and altered tau protein. Since such histopathological alterations were not found in the transgenic model analysed in this study, our results indicate that beta-amyloid deposition is not required for the development of behavioural and/or cognitive deficits in hAPP751 transgenic mice. | 10.1097/00001756-199611040-00080 |
pubmed_1095_5250 | A new system has been developed for obtaining electrographic potential through thin underwear inserted between the measuring electrodes and the skin of a neonate or an infant when lying supine. The system is based on capacitive coupling involving the electrode, the underwear, and the skin. Validation of the system revealed the following: (1) the signal detected using the system displayed a periodic waveform synchronized with the simultaneously recorded ECG, even when thin underwear was inserted between the electrode and the skin, (2) the gain of the system when the cloth was inserted decreased as the frequency increased. The present system appears promising for application to bedding as a non-invasive and awareness-free method for ECG monitoring of neonates or infants. However, there is still room for improvement in terms of its practical use, because the high-frequency component of the signal was depressed in comparison with the reference ECG. | 10.1109/IEMBS.2006.260362 |
pubmed_777_1473 | OBJECTIVE
To characterize the isometric contractility of Bufo gastrocnemius ex vivo in light of the rest tension.
METHODS
Bufo gastrocnemius treated with SOD inhibitor and ascorbate was stimulated electrically (12 V DC, 2 ms duration with a 2 s interval) to record the tension within 10 min. Weighted fitting to the relaxation curve of the tension below 90% of the peak tension with a mono-exponential model yielded the rest tension and relaxation rate.
RESULTS
The control gastrocnemius showed monotonic decrease of the rest tension, but treatment with SOD inhibitor and ascorbate resulted in a decrease of the rest tension followed by a fast increase within a 1.0 min contraction. The increase of the rest tension at 7.0 min of contraction of the treated muscle was significantly greater than that of the control muscle. The control muscle showed a monotonic decrease of the relaxation rate in 10 min, whereas treatment with SOD inhibitor and ascorbate produced increased relaxation rate followed by monotonic decrease till a plateau was reached. In the course of the 10 min recording, the relaxation rate of the treated muscle was lower than that of the control after the same duration of contraction.
CONCLUSION
Rest tension is a characteristic index to represent the skeletal muscle contractility. | pubmed_777_1473 |
pubmed_35_9457 | Recent advances in basic and clinical research indicate that interstitial cystitis (IC) is a form of neurogenic inflammation, thereby opening new avenues for research into this painful disease. With this in mind, we have recently developed a rat model of neurogenic inflammation of the bladder produced by a central nervous system viral disease. As in IC, the inflammation in this model develops without direct injury or trauma to the bladder, is non-infectious, and is limited to the bladder. Our most recent studies aimed at further testing the similarity of this animal model to IC by assessing the urine content in histamine with the occurrence of mast cell degranulation in the bladder wall. We further verified for a sex difference in the occurrence of the disease. Our results showed increased levels of urine histamine and mast cell activation during the early stages of the disease. We additionally observed that females had a greater degree of plasma extravasation, while males had a greater cellular infiltration together with worse behavioral signs. Gonadectomy prevented the bladder inflammation altogether in both males and females. These findings further validate our model of neurogenic cystitis to study the neurogenic component of IC. | 10.1007/978-1-4419-8889-8_24 |
pubmed_556_16971 | The Asian citrus psyllid (ACP), Diaphorina citri Kuwayama, is the only natural vector of bacteria responsible for Huanglongbing (HLB), a worldwide destructive disease of citrus. ACP reproduces and develops only on the young leaves of its rutaceous host plants. Olfactory stimuli emitted by young leaves may play an important role in ACP control and HLB detection. In this study, volatile organic compounds (VOCs) from healthy and HLB-infected young leaves of navel orange and pomelo were analyzed by headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS). A total of 36 compounds (including dimers or polymers) were identified and quantified from orange and 10 from pomelo leaves. Some compounds showed significant differences in signal intensity between healthy and HLB-infected leaves and may constitute possible indicators for HLB infection. Principal component analysis (PCA) clearly discriminated healthy and HLB-infected leaves in both orange and pomelo. HS-GC-IMS was an effective method to identify VOCs from leaves. This study may help develop new methods for detection of HLB or find new attractants or repellents of ACP for prevention of HLB. | 10.3390/molecules25184119 |
pubmed_550_10031 | This work reports the results of an environmental survey carried out in an industrial area in the Province of Turin: its main aim is to assess the levels of iron and aluminium in the outside air during the period from July to September to assess the influence of industrial activity (a cast-iron and aluminium foundry) which is interrupted during the month of August, on the level of metals present in the air. Conducting the analysis during this period of time made it possible to avoid the confounding effect of pollution due to domestic central heating. The measurements were taken from nine areas at different distances from the foundry in the area and according to the direction of the prevailing winds, as deduced from the historical data. The results of this survey show a statistically significant difference in iron and aluminium levels in the outside air in the geographic areas between the two main periods examined: during August (no foundry activity) v/s July-September (foundry activity). The values recorded are: Aluminium 0.4+/-0.45 microg/m(3) v/s 1.12+/-1.29 microg/m(3) (p<0.0001); Iron 0.95+/-0.56 microg/m(3) v/s 1.6+/-1.0 microg/m(3) (p<0.0001). There were no statistically significant differences between the nine sampling points from the point of view of the sampling sites, climate conditions and wind directions. We found no correlation with car traffic, in terms of the number of vehicles, and metals. The values of iron tended to be higher in the areas farther away from the foundry site in the areas located along the path of the prevailing winds. | 10.1016/j.jinorgbio.2007.06.012 |
pubmed_1033_3290 | Natural killer (NK), lymphokine-activated killer (LAK) and cytotoxic T lymphocyte (CTL) cells induce target cell death by two main mechanisms, the perforin/granzyme pathway and the Fas-ligand (FasL)/Fas pathway. We have previously found that organophosphorus pesticides significantly inhibit human and murine NK, LAK and CTL activities and that this inhibition is partially mediated by the inhibition of granzymes. We asked here whether organophosphorus pesticides also affect the FasL/Fas pathway by using perforin-knockout (PKO) mice. Thus, we examined the effect that dimethyl 2,2-dichlorovinyl phosphate (DDVP), an organophosphorus pesticide has on NK, CTL and LAK activities of PKO mice in vitro using the Fas antigen-positive YAC-1 cell as a target in the present study. We found that DDVP significantly decreased NK, CTL and LAK activities in a dose-dependent manner, and that the CTL and LAK activities of PKO mice were significantly blocked by anti-FasL antibody, suggesting that DDVP and anti-FasL antibody have the same/similar mechanism of inhibiting LAK and CTL activities. We further found that DDVP decreases the expression of Fas antigen on YAC-1 cells, and the expression of FasL on LAK cells in a dose-dependent manner, respectively. Taken together, these findings indicate that the DDVP-induced inhibition of NK, LAK and CTL activities in PKO mice is mediated by the impairment of the FasL/Fas pathway. | 10.1016/j.tox.2004.05.019 |
pubmed_805_18185 | A comprehensive software system called ANALYZE has been developed which permits detailed investigation and evaluation of 3-D biomedical images. The software can be used with any 2-D or 3-D imaging modality, including x-ray computed tomography, radionuclide emission tomography, ultrasound tomography, magnetic resonance imaging and both light and electron microscopy. The package is unique in its synergistic integration of fully interactive modules for direct display, manipulation and measurement of multidimensional image data. Several original algorithms are included which improve image display efficiency and quality. One of the most versatile and powerful algorithms is interactive volume rendering, which is optimized to be fast without compromising image quality. An important advantage of this technique is to display 3-D images directly from the original data and to provide on-the-fly combinations of selected image transformations and/or volume set operations (union, intersection, difference, etc.). The inclusion of a variety of interactive editing and quantitative mensuration tools significantly extends the usefulness of the software. Any curvilinear path or region-of-interest can be manually specified and/or automatically segmented for numerical determination and statistical analyses of distances, areas, volumes, shapes, densities and textures. ANALYZE is written entirely in "C" and runs on several standard UNIX workstations. It is being used in a variety of applications by over 40 institutions around the world, and has been licensed by Mayo to several imaging companies. The software architecture permits systematic enhancements and upgrades which has fostered development of a readily expandable package. ANALYZE comprises a powerful "visualization workshop" for rapid prototyping of specific application packages, including applications to interactive surgery simulation and radiation treatment planning. ANALYZE offers the potential to accurately and reproducibly examine, from images, the structure and function of any cell, tissue, limb, organ or organ system of the body, much like a surgeon or pathologist might do in real life, but entirely non-invasively, without pain or destruction of tissue. These capabilities promise exciting new insights into the basic processes of life, and major advances in health care delivery through improved diagnosis and treatment of disease. | pubmed_805_18185 |
pubmed_670_15890 | OBJECTIVE
The construction of an indirect calorimeter capable of long-term automated sequential monitoring of multiple patients in adult and pediatric ICUs.
DESIGN
A prototype system utilizing modular engineering principles, including central respiratory mass spectrometer; validation by organic solvent combustion and nitrogen dilution methods, and Tissot spirometer.
SETTING
Surgical and pediatric ICUs in a tertiary care university hospital.
RESULTS
When expired minute volume was measured over a range of 4 to 28 L in six intubated patients, expired minute volume measured by the prototype system demonstrated a correlation coefficient of .998 compared with simultaneous expired minute volume measured by a Tissot spirometer. Organic solvent combustion demonstrated a maximum error of 3.8% for oxygen consumption (VO2) and an average error of 1.73 +/- 1.25% (SEM). The maximum error for the respiratory quotient was 3.0%, with an average error of 1.75 +/- 1.07%. VO2 (predicted) vs. VO2 (measured) demonstrated a correlation coefficient of .997. Validation with the nitrogen dilution method over a range of FIO2 from 0.21 to 0.60 demonstrated a maximum error of 7.9%, with an average error of -1.72 +/- 1.1% (n = 51).
CONCLUSIONS
Indirect calorimetry by means of a shared system for measurements in multiple patients in ICUs is feasible and cost effective utilizing modular principles and a centralized respiratory gas analyzer. | 10.1097/00003246-199107000-00023 |
pubmed_771_1572 | Hyperuricemia is currently recognized as a risk factor for cardiovascular diseases. It has been reported that the angiotensin II-receptor blocker (ARB) losartan decreases serum uric acid level. In this study, the effects of another ARB, irbesartan, on [(14)C]uric acid-transport activity of renal uric acid reabsorptive transporters URAT1 and URATv1 were examined with Xenopus oocytes expressing each transporter. The results showed that irbesartan (100-500 µM) inhibited the uptake of uric acid via both transporters. The inhibitory effects of irbesartan exceeded those of losartan and other ARBs, and the results suggest that irbesartan can reduce serum uric acid level. | 10.1254/jphs.10064sc |
pubmed_230_10361 | Proteins necessary for the normal regulation of the cell cycle include minichromosome maintenance protein 2 (Mcm2) and geminin. These are overexpressed in several premalignant and malignant tumours. The Mcm2/Ki67 ratio can be used to estimate the population of cells that are in early G(1) (licensed to proliferate), and the geminin/Ki67 ratio can determine the relative length of G(1). A high ratio indicates a short G(1) and a high rate of cell proliferation. Mcm2 and geminin have been scarcely explored in oral epithelial dysplasia (OED) and oral squamous-cell carcinoma (OSCC). The purpose of this study was to identify the expression pattern of Mcm2, Ki67 and geminin in normal oral mucosa (NOM), OED and their subsequent OSCC, to determine if expression could help predict the prognosis of OED. Paraffin sections of 41 OED cases that progressed to carcinoma, 40 OED without malignant progression, 38 OSCC and 15 NOM were immunostained with antibodies against Mcm2, geminin and Ki67. Labelling indices (LIs) increased progressively from NOM, OED and OSCC (Mcm2, P<0.001; geminin, P<0.001 and Ki67, P<0.001). In all the OED cases (n=81) the levels of expression of Mcm2 (LI, 73.6), geminin (LI, 24.4) and Ki67 (LI, 44.5) were elevated indicating a constant cell-cycle re-entry. When the OED groups were compared, Mcm2 protein expression was higher in the OED with malignant progression (P=0.04), likewise there was a significant increase in the Mcm2/Ki67 and geminin/Ki67 ratios (P=0.04 and 0.02 respectively). Mcm2 and geminin proteins seem to be novel biomarkers of growth and may be useful prognostic tools for OED. | 10.1038/sj.bjc.6604967 |
pubmed_443_18418 | The effects of the xanthine oxidase/hypoxanthine free radical generating system on endothelium dependent and independent relaxation were compared in aortic rings from New Zealand white rabbits and heterozygous Watanabe heritable hyperlipidemic (WHHL) rabbits with mild atherosclerosis. Studies were carried out in young (3 months) and mature (18 months) animals. Plasma cholesterol levels were significantly higher in both 3 and 18 month WHHL animals. Endothelium independent relaxation to SNP did not differ between groups. However, the attenuation of relaxation to carbachol after xanthine oxidase/hypoxanthine treatment tended to be less in WHHL. This reached significance at 18 but not 3 months. We propose that this could be due to increases in levels of endogenous scavenger enzymes in these WHHL rabbits. | 10.3109/10715769809069277 |
pubmed_783_13217 | There is an increasing body of evidence suggesting that metal homeostasis is dysregulated in the pathology of Alzheimer's disease (AD). Although expression levels of several transporters belonging the SLC30 family, which comprises predominantly zinc transporters, have been studied in the AD brain, SLC30A10 (ZnT10) has not been studied in this context. To determine if dysregulated expression of ZnT10, which may transport both Zn and Mn, could be a factor that contributes to AD, we investigated if there were differences in ZnT10 mRNA levels in specimens of frontal cortex from AD patients and controls and also if brain tissue from the APP/PS1 transgenic (Tg) mouse model showed abnormal levels of ZnT10 mRNA expression. Our results show that ZnT10 is significantly (P<0.01) decreased in the frontal cortex in AD. Furthermore, we observed a significant decrease in ZnT10 mRNA levels in the APP/PS1-Tg mice compared with wild-type controls (P<0.01). Our results suggest that this dysregulation in ZnT10 could further contribute to disease progression. | 10.1371/journal.pone.0065475 |
pubmed_844_15702 | Effects of FTY720 (2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol HCl), a novel immunosuppressant, were examined on neurons and thymocytes respectively dissociated from rat brains and thymus glands using a flow cytometer to see if FTY720 exerts cytotoxic actions not only on spleen cells as previously reported but also on the other cells. FTY720 at a concentration of 10 microM deteriorated almost all of the thymocytes, while it was not the case for brain neurons. FTY720 increased the intracellular concentration of Ca2+ ([Ca2+]i) of thymocytes in both the presence and absence of external Ca2+, although the [Ca2+]i increased by FTY720 in the presence of external Ca2+ was much greater than that in the absence of external Ca2+. Thus, FTY720 may increase the membrane permeability of Ca2+ and release Ca2+ from intracellular Ca2+ stores in thymocytes. Furthermore, the number of thymocytes stained with ethidium, a dye impermeant to intact membranes, time-dependently increased after drug application. Therefore, FTY720 at concentrations of 3 - 10 microM non-specifically increases the membrane permeability of thymocytes, resulting in necrotic cell death, although FTY720 at micromolar concentrations was reported to induce apoptosis of spleen cells. | 10.1254/jjp.76.377 |
pubmed_306_24796 | The calcium-activated small conductance potassium channel SK3 plays an essential role in the regulation of dopamine neuron activity patterns. Here we demonstrate that expression of a human disease-related SK3 mutation (hSK3Δ) in dopamine neurons of mice disrupts the balance between tonic and phasic dopamine neuron activity. Expression of hSK3Δ suppressed endogenous SK currents, reducing coupling between SK channels and NMDA receptors (NMDARs) and increasing permissiveness for burst firing. Consistent with enhanced excitability of dopamine neurons, hSK3Δ increased evoked calcium signals in dopamine neurons in vivo and potentiated evoked dopamine release. Specific expression of hSK3Δ led to deficits in attention and sensory gating and heightened sensitivity to a psychomimetic drug. Sensory-motor alterations and psychomimetic sensitivity were recapitulated in a mouse model of transient, reversible dopamine neuron activation. These results demonstrate the cell-autonomous effects of a human ion channel mutation on dopamine neuron physiology and the impact of activity pattern disruption on behavior. | pubmed_306_24796 |
pubmed_367_1616 | We found that acetaminophen could be effectively transformed and removed from water by laccase-mediated oxidative coupling processes. The removal of acetaminophen followed second-order kinetics with first-order to the concentrations of both the substrate and the enzyme. Mass spectrum analysis demonstrated that polymerization through radical-radical coupling mechanism was the pathway leading to acetaminophen transformation. Coupling products thus formed are believed to be biologically inactive and more readily removable from water. Secondary mass spectra of the dimers in combination with molecular modeling analysis further elucidated that the coupling proceeded via covalent bonding between two molecules at their unsubstituted carbons in benzene rings. These findings demonstrated that laccase-mediated oxidative coupling can potentially serve as an alternative strategy to control certain micropollutants in water/wastewater treatment and reuse. | 10.1021/es9002422 |
pubmed_394_20239 | Tumor angiogenesis is believed to be a prognostic indicator associated with tumor growth and metastasis. Microvessel density (MVD) assessment with common endothelial markers such as CD34 has been found to influence prognosis among endometrial carcinoma patients. The CD105/endoglin antibody has been reported to preferentially bind to proliferated endothelial cells in tissues participating in angiogenesis. The aim of this study was to evaluate the quantification of angiogenesis by assessing MVD in endometrial lesions when comparing the performance of anti-CD34 and anti-CD105 in women with benign and malignant endometrial changes. The study included 58 women (37 postmenopausal) with normal, hyperplastic and malignant endometrium in which preoperative transvaginal sonography was performed. Histological results of the removed endometrium were correlated with MVD assessed in "hot areas" where high densities of microvessels were detected within tumoral tissue. Endometrial cancer was confirmed in 37 women (3 premenopausal). Benign hyperplasia (14 cases), secretory or proliferative endometrium (5 cases) or endometrial atrophy (2 cases) was found in the remaining women. Malignant changes were mostly noted as FIGO stage I and II (28 cases) and had a low (1 or 2) histological grade (29 cases). Median MVD's assessed with CD105 and CD34 were 10.4 and 32.3, respectively. Median MVD assessed with CD34 was almost twice higher in women with endometrial cancer than in women with benign endometrium (CD34 MVD = 41.8 vs. 27.6, p=0.004). In cases of CD105 MVD significant differences between women with benign and malignant endometrial changes were also found (CD105 MVD = 11.8, vs. 6.4; p=0.00007). The menopausal status, but not the clinical stage or histological grading was significantly correlated with both CD34 MVD (p=0.02) and CD105 MVD (p=0.0003). A significant correlation was also found between CD34 and CD105 measured MVD (p=0.000001). In conclusion, transition from endometrial hyperplasia to endometrial cancer appears to be accompanied by microvessel density changes. MVD assessed with both CD34 and CD105 antibodies could be used as a potential prognostic factor in women with endometrial cancer. Our study showed that endoglin, by staining the proliferating microvessels could be more specific and sensitive marker for tumor neoangiogenesis than the more commonly used marker, CD34. | pubmed_394_20239 |
pubmed_425_21806 | BACKGROUND
What type of reconstruction procedure should be applied is one of the important issues in surgery for gastric cancer. We have several options for reconstruction procedure after distal gastrectomy. The Billroth II and Roux-en-Y reconstruction have a duodenal stump while the Billroth I does not have it, which is the biggest structural difference in these procedures. An increase in intraduodenal pressure due to the formation of duodenum stump occasionally causes severe complication such as duodenal stump leakage; however, a duodenal diverticulum perforation after the Roux-en-Y reconstruction has not yet been reported. Herein, we report two cases of a perforated duodenal diverticulum after gastrectomy with the Roux-en-Y reconstruction.
CASE PRESENTATION
The first case was a 66-year-old man who presented to our hospital with an acute onset right-upper-quadrant abdominal pain. He had undergone laparoscopic distal gastrectomy with the Roux-en-Y reconstruction for the early gastric cancer 15 months before. A large periampullary diverticulum had been detected during the checkup before the gastrectomy. Abdominal contrast-enhanced CT showed a retroperitoneal fluid collection with gas present at the second part of the duodenum. Therefore, a perforated duodenal diverticulum with abdominal abscess was diagnosed, and an emergency laparotomy was performed. Pancreaticoduodenectomy was performed because of severe duodenal inflammation and surrounding tissue damage. The second case was a 52-year-old man who had undergone open distal gastrectomy for locally advanced gastric cancer. Multiple non-ampullary duodenal diverticula had also been identified during the preoperative checkup. On the 2nd postoperative day, he presented with a sudden-onset abdominal pain with peritoneal irritation signs, and intestinal fluid was identified through the intraperitoneal drainage tube placed in a suprapancreatic site during his previous gastrectomy. Therefore, an emergency laparotomy was performed. During laparotomy, a perforated diverticulum at the second part of the duodenum was detected. The perforated duodenum diverticulum was directly sutured with drainage of the retroperitoneal space.
CONCLUSIONS
It is necessary to recognize that the Roux-en-Y reconstruction after gastrectomy for gastric cancer patients with duodenal diverticulum might cause a perforation of the diverticulum. | 10.1186/s40792-019-0738-y |
pubmed_1065_5058 | The extent to which bovine cytochrome c oxidase (COX) dimerizes in nondenaturing detergent environments was assessed by sedimentation velocity and equilibrium. In contrast to generally accepted opinion, the COX dimer is difficult to maintain and is the major oligomeric form only when COX is solubilized with a low concentration of dodecylmaltoside, i.e., approximately 1 mg/mg protein. The dimer form is intrinsically unstable and dissociates into monomers with increased detergent concentration, i.e., >5 mg/mg protein. The structure of the solubilizing detergent, however, greatly alters detergent effectiveness by inducing either monomerization or aggregation. Triton X-100 is most effective at solubilizing COX, but it destabilizes COX dimers, even at low concentration. Undecylmaltoside, decylmaltoside, and octaethyleneglycolmonododecyl ether (C(12)E(8)) are less effective at solubilizing COX. Each prevents COX aggregation at high detergent concentration, but also destabilizes the COX dimer. Other detergents, e.g., Tween 20, sodium cholate, sodium deoxycholate, CHAPS, or CHAPSO, are completely ineffective COX solubilizers and do not prevent aggregation even at 10-40 mg/mL. The transition from dimers to monomers depends on many factors other than detergent structure and concentration, e.g., protein concentration, phospholipid content and pH. We conclude that the intrinsic dimeric structure of COX can be maintained only after solubilization with low concentrations of dodecylmaltoside at near neutral pH, and even then precautions must be taken to prevent its dissociation into monomers. | 10.1021/bi000884z |
pubmed_323_3654 | A 3-year-old English Setter dog was presented for an acute onset of coughing. Tracheobronchoscopic examination allowed localization and removal of one grass awn foreign body. A second migrated grass awn was suspected to be present in the left caudal lung lobe. Transesophageal ultrasound revealed an area of pulmonary consolidation in the dorsomedial portion of left caudal lobe and a linear hyperechoic structure consistent with a grass awn foreign body within the area of consolidation. Transesophageal ultrasonography was also used to provide anatomical landmarks that facilitated successful thoracoscopic removal of the foreign body. | 10.1111/vru.12088 |
pubmed_559_14955 | OBJECTIVE
To determine the effect of the initial metabolic imbalance and its restoration after insulin therapy on adiponectin and acylated ghrelin levels in children with type 1 diabetes mellitus (T1DM).
STUDY DESIGN
Twenty prepubertal children with newly diagnosed T1DM were prospectively studied at diagnosis and after 1 and 4 months of therapy. Body mass index (BMI) and serum levels of adiponectin, resistin, total and acylated ghrelin, leptin, tumor necrosis factor alpha (TNF-alpha), and interleukin-6 (IL-6) were determined. The control group comprised 40 healthy prepubertal children.
RESULTS
BMI was decreased at diagnosis, normalized at 1 month, and remained so thereafter. Adiponectin levels at diagnosis were similar to controls, increasing significantly after 1 month and normalizing at 4 months. Acylated ghrelin levels were lower at diagnosis, with a significant increase at 1 month and normalizing at 4 months. Resistin levels were normal at all time points. Leptin levels were decreased, while TNF-alpha and IL-6 were increased at diagnosis and normalized at 1 month.
CONCLUSIONS
These findings suggest that BMI is not the main predictor of acylated ghrelin or adiponectin levels in newly diagnosed T1DM subjects and that these peptides may play an important role in the metabolic adaptation in this disease. | 10.1530/eje.1.02273 |
pubmed_147_17232 | Mycoplasma hyopneumoniae is the etiological agent of swine enzootic pneumonia (EP), a disease that affects swine production worldwide. Vaccination is the most cost-effective strategy for the control and prevention of the disease. Despite efforts to control M. hyopneumoniae infection, significant economic losses in pig production continue to occur. The results of genome-based research have the potential to help understand the biology and pathogenesis of M. hyopneumoniae, and contribute to the development of more effective vaccines and diagnostic tests. In this review, the characteristics of M. hyopneumoniae related to pathogenesis and control measures will be discussed. Special emphasis will be placed on vaccination strategies that have been proposed with the use of reverse vaccinology approaches. | pubmed_147_17232 |
pubmed_329_7938 | OBJECTIVE
Vascular restenosis remains a major obstacle to long-term success after vascular intervention. Circulating progenitor cells have been implicated in restenosis, and yet it has remained unclear if these cells, particularly nonendothelial progenitors, have an active role in this pathologic process. We hypothesized that circulating CD34(+)/c-kit(+) progenitors would increase after vascular injury, mirrored by changes in the injury signal, stromal cell-derived factor 1α (sdf1α). We further postulated that an antibody-based depletion would mitigate progenitor surge and, in turn, reduce restenosis in a murine model.
METHODS
C57BL6 mice underwent wire injury of the femoral artery and were compared with mice with sham surgery and vessel ligation by flow cytometry as well as by sdf1α enzyme-linked immunosorbent assay of peripheral blood. Next, injured C57BL6 mice treated with a depleting antibody toward the progenitor marker sca-1 or with an isotype control were compared in terms of sdf1α as well as enumeration of progenitors. At 28 days, restenosis was quantified between sca-1- and isotype-treated animals.
RESULTS
Wire injury generated an increase in sdf1α as well as a surge of CD34(+)/c-kit(+) progenitors relative to nonsurgical controls (P = .005). Treatment with sca-1 antibody ablated the peripheral surge compared with isotype-treated, injured animals (P = .02), and sca progenitor depletion reduced the 28-day intima to media ratio in a statistically significant fashion compared with either nontreated (P = .04) or isotype-treated (P = .036) animals.
CONCLUSIONS
Our study has demonstrated that sca-1 antibody reduces both progenitor surge and vascular restenosis after endoluminal vascular injury in a murine model. This suggests that circulating progenitors play an active role in restenotic disease. | pubmed_329_7938 |
pubmed_35_12637 | The properties of an acid rain episode that could influence the germination of pollen in corn, Zea mays L., were evaluated by treating silks with a simulated acid rain and measuring the subsequent germination of pollen on the silks. The data indicated that acid rain creates an inhospitable environment for pollen germination on the silk surface. Reduced germination appeared directly related to the acidity of the rain, but not the sulphate concentration. Rinsing silks with a pH 5.6 rain after treatment with a pH 2.6 rain did not increase pollen germination above that on silks treated only with a pH 2.6 rain, suggesting the reduced germination was due to physical and/or chemical modifications of the silk surface and not to residual acid on the tissue. Pollen germination on silks was inhibited even when silk tissue was exposed to a simulated rain of pH 2.6 for <1.5min. | 10.1016/0269-7491(87)90031-5 |
pubmed_218_9915 | Leukocyte function associated antigen-1 (LFA-1) is a primary cell adhesion molecule of leukocytes required for mediating cellular transmigration into sites of inflammation via the vascular endothelium. A cyclic peptide, cIBR, possesses high affinity for LFA-1, and conjugation to the surface of poly(DL-lactic-co-glycolic acid) nanoparticles can specifically target and deliver the encapsulated agents to T cells expressing LFA-1. The kinetics of targeted nanoparticle uptake by acute lymphoblastic leukemia T cells was investigated by flow cytometry and microscopy and compared to untargeted nanoparticles. The specificity of targeted nanoparticles binding to the LFA-1 integrin was demonstrated by competitive inhibition using free cIBR peptide or using the I domain of LFA-1 to inhibit the binding of targeted nanoparticles. The uptake of targeted nanoparticles was concentration and energy dependent. The cIBR-conjugated nanoparticles did not appear to localize with lysosomes whereas untargeted nanoparticles were detected in lysosomes in 6 h and steadily accumulated in lysosomes for 24 h. Finally, T-cell adhesion to epithelial cells was inhibited by cIBR nanoparticles. Thus, nanoparticles displaying the cIBR ligand may offer a useful targeted drug delivery system as an alternative treatment of inflammatory diseases involving transmigration of leukocytes. | 10.1021/mp900185u |
pubmed_396_11755 | OBJECTIVE
The objective of this study is to report a series of patients with adenomatous ductal proliferation of the salivary gland and to investigate the nature and histogenesis of this process.
STUDY DESIGN
The histologic and immunohistochemical studies of 13 patients with adenomatous ductal proliferation of the salivary gland were performed.
RESULTS
Ten cases coexisted with other diseases, such as salivary gland tumor or chronic parotitis. Most of the lesions were limited to 1 or 2 lobules and showed prominent ductal proliferation with some acinar cell complexes. The proliferative ducts had a compact growth pattern with little stroma. Dedifferentiation of acinar cells, identified by the loss of their secretory granules and appearing similar to intercalated duct epithelium, was seen in the early stages of adenomatous ductal proliferation.
CONCLUSION
Acinar cells play a role in the histogenesis of salivary gland tumors because acinar cells clearly participate in the formation of the proliferative ducts. | 10.1067/moe.2001.110419 |
pubmed_542_3139 | Selected papillary squamous tumors of the upper aerodigestive tract (UADT) mucosa in adult patients do not have well-defined histologic criteria and the clinical behavior is poorly understood. To better characterize this spectrum of neoplasms, UADT papillary neoplasms were evaluated by routine histology, determination of cellular DNA content using Feulgen-stained tissue sections, and the typing of human papillomavirus (HPV) by in situ hybridization. Solitary papillomas were studied in two patients; there was no recurrence in either case, both had normal DNA content, and one was typed as HPV-6 while the other was typed as HPV-11. Seven adult patients with recurrent papillomatosis and at least one biopsy with dysplasia/atypia were identified (mean age at diagnosis, 13.3 years; mean age at last contact, 42.7 years). Six of seven patients had abnormal DNA cellular content in foci of epithelial atypia. In all biopsies evaluated, the papillomas of the seven patients were consistently typed as either HPV-6 or HPV-11. Six patients with malignant papillary neoplasms also had abnormal DNA cellular content, but none revealed evidence of HPV type 6, 11, 16, or 18 by in situ hybridization of tissue sections. In many of the recurrent papillomas, the degree of epithelial atypia encountered was pronounced and was commonly misdiagnosed as carcinoma in situ or papillary carcinoma. The aneuploid DNA content of these foci of atypia reflected the abnormal cellular appearance and partially explained the overdiagnosis of malignancy. However, none of the seven patients were treated for malignant disease and none progressed to invasive carcinoma, with an average follow-up period of almost 30 years. We conclude that histologic and cytologic atypia in HPV-containing papillomatosis may be appreciable. The aneuploid DNA content may represent premalignant conditions and the patient may be at an increased risk for the subsequent development of squamous cancer. However, none of the seven patients with recurrent papillomatosis developed any evidence of malignancy. In addition, none of the patients with papillary carcinomas had previous recurrent papillomatosis. | 10.1016/s0046-8177(88)80231-4 |
pubmed_454_3771 | OBJECTIVES
To implement a Learning Bridge tool to improve educational outcomes for pharmacy students as well as for preceptors and faculty members.
DESIGN
Pharmacy faculty members collaborated to write 9 case-based assignments that first-year pharmacy (P1) students worked with preceptors to complete while at experiential sites.
ASSESSMENT
Students, faculty members, and preceptors were surveyed about their perceptions of the Learning Bridge process. As in our pilot study,(1) the Learning Bridge process promoted student learning. Additionally, the Learning Bridge assignments familiarized preceptors with the school's P1 curriculum and its content. Faculty teamwork also was increased through collaborating on the assignments.
CONCLUSIONS
The Learning Bridge assignments provided a compelling learning environment and benefited students, preceptors, and faculty members. | 10.5688/ajpe75346 |
pubmed_609_8174 | Alveolar echinococcosis is a rare parasitic disease caused by the intrahepatic growth of Echinococcus multilocularis larvae. Secondary localizations can be observed; pulmonary metastases are the most frequent and are observed in 22% of patients. Other extrahepatic localizations are less frequent. We describe two patients with abdominal skin involvement. To our knowledge, this has never before been reported. In both patients, the liver lesion was located in the left lobe, and larvae probably spread to the skin via the falciform ligament. In one patient albendazole therapy was effective. | 10.1016/s0190-9622(96)90068-7 |
pubmed_135_15489 | Objective: Transcription elongation factor 1 (TCERG1) is a nuclear protein consisted of multiple protein structural domains that plays an important role in regulating the transcription, extension, and splicing regulation of RNA polymerase II. However, the prognostic and immunological role of TCERG1 in human cancer remains unknown. In this study, we analyzed the expression of TCERG1 gene in hepatocellular carcinoma (HCC) patients, its clinical significance, and its possible prognostic value by bioinformatics. Methods: RNA sequencing data and clinicopathological characteristics of patients with HCC were collected from TCGA and CCLE databases. The Wilcoxon rank-sum test was used to analyze the expression of TCERG1 in HCC tissues and normal tissues. The protein levels of TCERG1 between normal and liver cancer tissues were analyzed by the Human Protein Atlas Database (HPA) (www.proteinatlas.org). Validation was performed using the Gene Expression Omnibus (GEO) dataset of 167 samples. The expression of TCERG1 in HCC cells were verified by qRT-PCR, and CCK-8, scratch assay and Transwell assay were performed to detect cell proliferation, migration and invasion ability. According to the median value of TCERG1 expression, patients were divided into high and low subgroups. Logistic regression, GSEA enrichment, TME, and single-sample set gene enrichment analysis (ssGSEA) were performed to explore the effects of TCERG1 on liver cancer biological function and immune infiltrates. TCERG1 co-expression networks were studied through the CCLE database and the LinkedOmics database to analyze genes that interact with TCERG1. Results: The expression levels of TCERG1 in HCC patient tissues were significantly higher than in normal tissues. Survival analysis showed that high levels of TCERG1 expression were significantly associated with low survival rates in HCC patients. Multifactorial analysis showed that high TCERG1 expression was an independent risk factor affecting tumor prognosis. This result was also verified in the GEO database. Cellular experiments demonstrated that cell proliferation, migration and invasion were inhibited after silencing of TCERG1 gene expression. Co-expression analysis revealed that CPSF6 and MAML1 expression were positively correlated with TCERG1. GSEA showed that in samples with high TCERG1 expression, relevant signaling pathways associated with cell cycle, apoptosis, pathways in cancer and enriched in known tumors included Wnt signaling pathway, Vegf signaling pathway, Notch signaling pathway, MAPK signaling pathway and MTOR pathways. The expression of TCERG1 was positively correlated with tumor immune infiltrating cells (T helper two cells, T helper cells). Conclusion: TCERG1 gene is highly expressed in hepatocellular carcinoma tissues, which is associated with the poor prognosis of liver cancer, and may be one of the markers for the diagnosis and screening of liver cancer and the prediction of prognosis effect. At the same time, TCERG1 may also become a new target for tumor immunotherapy. | 10.3389/fgene.2022.959832 |
pubmed_11_17363 | Information-theoretic secrecy is combined with cryptographic secrecy to create a secret-key exchange protocol for wireless networks. A network of transmitters, which already have cryptographically secured channels between them, cooperate to exchange a secret key with a new receiver at a random location, in the presence of passive eavesdroppers at unknown locations. Two spatial point processes, homogeneous Poisson process and independent uniformly distributed points, are used for the spatial distributions of transmitters and eavesdroppers. We analyse the impact of the number of cooperating transmitters and the number of eavesdroppers on the area fraction where secure communication is possible. Upper bounds on the probability of existence of positive secrecy between the cooperating transmitters and the receiver are derived. The closeness of the upper bounds to the real value is then estimated by means of numerical simulations. Simulations also indicate that a deterministic spatial distribution for the transmitters, for example, hexagonal and square lattices, increases the probability of existence of positive secrecy capacity compared to the random spatial distributions. For the same number of friendly nodes, cooperative transmitting provides a dramatically larger secrecy region than cooperative jamming and cooperative relaying. | 10.1155/2014/760175 |
pubmed_975_1666 | MAP kinase activity is necessary for growth factor induction of neurite outgrowth in PC12 cells. Although NGF and EGF both stimulate MAP kinase activity, EGF does not stimulate neurite extension. We report that EGF, in combination with KCl, stimulates neurite outgrowth in PC12 cells. This phenomenon was independent of intracellular Ca2+ increases and not due to enhancement of MAP kinase activity over that seen with EGF alone. However, EGF plus KCl increased intracellular cAMP, and other cAMP elevating agents acted synergistically with EGF to promote neurite outgrowth. Stimulation of neurite outgrowth by cAMP and EGF was blocked by inhibitors of transcription suggesting that synergistic regulation of transcription by the cAMP and MAP kinase pathways may stimulate neurite growth. | 10.1083/jcb.130.3.701 |
pubmed_968_21173 | Diabetes mellitus is a severe condition in which the pancreas produces inadequate insulin or the insulin generated is ineffective for utilisation by the body; as a result, insulin therapy is required for control blood sugar levels in patients having type 1 diabetes and is widely recommended in advanced type 2 diabetes patients with uncontrolled diabetes despite dual oral therapy, while subcutaneous insulin administration using hypodermic injection or pump-mediated infusion is the traditional route of insulin delivery and causes discomfort, needle phobia, reduced adherence, and risk of infection. Therefore, transdermal insulin delivery has been extensively explored as an appealing alternative to subcutaneous approaches for diabetes management which not only is non-invasive and easy, but also avoids first-pass metabolism and prevents gastrointestinal degradation. Microneedles have been commonly investigated in human subjects for transdermal insulin administration because they are minimally invasive and painless. The different types of microneedles developed for the transdermal delivery of anti-diabetic drugs are discussed in this review, including solid, dissolving, hydrogel, coated, and hollow microneedles. Numerous microneedle products have entered the market in recent years. But, before the microneedles can be effectively launched into the market, a significant amount of investigation is required to address the numerous challenges. In conclusion, the use of microneedles in the transdermal system is an area worth investigating because of its significant benefits over the oral route in the delivery of anti-diabetic medications and biosensing of blood sugar levels to assure improved clinical outcomes in diabetes management. | 10.1007/s11356-021-17346-0 |
pubmed_106_4925 | Automated external defibrillators, or AEDs, will automatically analyze a patient's ECG and, if needed, deliver a defibrillating shock to the heart. We sometimes refer to these devices as AED-only devices or stand-alone AEDs. The basic function of AEDs is similar to that of defibrillator/monitors, but AEDs lack their advanced capabilities and generally don't allow manual defibrillation. A device that functions strictly as an AED is intended to be used by basic users only. Such devices are often referred to as public access defibrillators. In this Evaluation, we present our findings for a newly evaluated model, the Zoll AED Plus. We also summarize our findings for the previously evaluated model that is still on the market and describe other AEDs that are also available but that we haven't evaluated. We rate the models collectively for first-responder use and public access defibrillation (PAD) applications. | pubmed_106_4925 |
pubmed_546_10184 | To assess the role of prefrontal cortex in retrieval and address the controversy about whether prefrontal retrieval operations are engaged only following successful retrieval, we recorded event-related brain potentials during two recognition tests with differing demands on retrieval effort. Both tests included object drawings that were (1) identical to those studied, (2) the same but with altered aspect ratios, and (3) previously unseen. Instructions were to respond "old" only if drawings were not modified (specific test) or regardless of modifications (general test). Frontal potentials were enhanced during the specific relative to the general test for all three types of drawings. We conclude that these potentials reflected differential engagement of strategic retrieval, that this function relied on left prefrontal cortex, and that it was not contingent on successful retrieval. | 10.1016/s0896-6273(00)80714-x |
pubmed_940_13103 | Del(22q11) is a common microdeletion syndrome with an extremely variable phenotype. Besides classical manifestations, such as velocardiofacial (Shprintzen) or DiGeorge syndromes, del(22q11) syndrome may be associated with unusual but probably causally related anomalies that expand its phenotype and complicate its recognition. We report here three children with the deletion and a chronic, erosive polyarthritis resembling idiopathic cases of juvenile rheumatoid arthritis (JRA). Patient 1, born in 1983, initially presented with developmental delay, facial dysmorphism, velopharyngeal insufficiency, and severe gastro-oesophageal reflux requiring G tube feeding. From the age of 3 years, he developed JRA, which resulted in severe restrictive joint disease, osteopenia, and platyspondyly. Patient 2, born in 1976, had tetralogy of Fallot and peripheral pulmonary artery stenosis. She developed slowly, had mild dysmorphic facial features, an abnormal voice, and borderline intelligence. JRA was diagnosed at the age of 5 years. The disorder followed a subacute course, with relatively mild inflammatory phenomena, but an extremely severe skeletal involvement with major osteopenia, restrictive joint disease (bilateral hip replacement), and almost complete osteolysis of the carpal and tarsal bones with phalangeal synostoses, leading to major motor impairment and confinement to a wheelchair. Patient 3, born in 1990, has VSD, right embryo-toxon, bifid uvula, and facial dysmorphism. She developed JRA at the age of 1 year. She is not mentally retarded but has major speech delay secondary to congenital deafness inherited from her mother. In the three patients, a del(22q11) was shown by FISH analysis. These observations, and five other recently published cases, indicate that a JRA-like syndrome is a component of the del(22q11) spectrum. The deletion may be overlooked in those children with severe, chronic inflammatory disorder. | 10.1136/jmg.35.11.943 |
pubmed_901_6612 | The stroke blood volume and the MBV were determined by tetrapolar rheocardiography at rest and under the effect of muscular exertion in neurosurgical patients (35), in surgical patients (20) and in a control group of healthy subjects (10). A Soviet device, the Ppigamma2-02 tetrapolar rheocardiograph was employed. The method of tetrapolar rheocardiography is simple, atraumatic and provides for prolonged continuous recording. It is sufficiently precise as a method of indirect determination of the minute volume: comparison with data of the radioisotope method shows the precision of tetrapolar rheocardiography to be +/- 5.5%. Its main disadvantage consists in the difficult calculation of MBV in deep, frequent and irregular respiration when the rheocardiogram waves are sharply distorted. | pubmed_901_6612 |
pubmed_710_15542 | BACKGROUND
Women living in rural areas face unique challenges in achieving a heart-healthy lifestyle that are related to multiple levels of the social-ecological framework. The purpose of this study was to evaluate changes in diet and physical activity, which are secondary outcomes of a community-based, multilevel cardiovascular disease risk reduction intervention designed for women in rural communities.
METHODS
Strong Hearts, Healthy Communities was a six-month, community-randomized trial conducted in 16 rural towns in Montana and New York, USA. Sedentary women aged 40 and older with overweight and obesity were recruited. Intervention participants (eight towns) attended twice weekly exercise and nutrition classes for 24 weeks (48 total). Individual-level components included aerobic exercise, progressive strength training, and healthy eating practices; a civic engagement component was designed to address social and built environment factors to support healthy lifestyles. The control group (eight towns) attended didactic healthy lifestyle classes monthly (six total). Dietary and physical activity data were collected at baseline and post-intervention. Dietary data were collected using automated self-administered 24-h dietary recalls, and physical activity data were collected by accelerometry and self-report. Data were analyzed using multilevel linear regression models with town as a random effect.
RESULTS
At baseline, both groups fell short of meeting many recommendations for cardiovascular health. Compared to the control group, the intervention group realized significant improvements in intake of fruit and vegetables combined (difference: 0.6 cup equivalents per day, 95% CI 0.1 to 1.1, p = .026) and in vegetables alone (difference: 0.3 cup equivalents per day, 95% CI 0.1 to 0.6, p = .016). For physical activity, there were no statistically significant between-group differences based on accelerometry. By self-report, the intervention group experienced a greater increase in walking MET minutes per week (difference: 113.5 MET-minutes per week, 95% CI 12.8 to 214.2, p = .027).
CONCLUSIONS
Between-group differences in dietary and physical activity behaviors measured in this study were minimal. Future studies should consider how to bolster behavioral outcomes in rural settings and may also continue to explore the value of components designed to enact social and environmental change.
TRIAL REGISTRATION
clinicaltrials.gov Identifier: NCT02499731. Registered 16 July 2015. | 10.1186/s12966-019-0852-z |
pubmed_459_284 | Starting from the structural analogy between bromo-ergocryptine (Parlodel) and dihydroergocryptine caffeine (Vasobral), as well as with dihydroergotoxine (Hydergine), the authors decided to test the efficacy of the last two products in inhibiting post-partum physiological milk secretion. Twelve patients will be treated with either one of the two products, with a clinical and biological efficacy (serum prolactin level assay) which is comparable to that found in the literature regarding Parlodel. This study confirm the results obtained in a study of the inhibition of hyper-prolactinemia of other origin, by the same authors. | pubmed_459_284 |
pubmed_297_24434 | Therapy of Burkholderia pseudomallei acute infections is largely limited to a few β-lactam antibiotics such as ceftazidime or meropenem. Although relatively rare, resistance emergence during therapy leads to treatment failures with high mortality rates. In the absence of acquired external resistance determinants in B. pseudomallei emergence of β-lactam resistance is invariably caused by mutational modification of genomically encoded factors. These include the deletion of the ceftazidime target penicillin-binding protein 3 or amino acid changes in the Class A PenA β-lactamase that expand its substrate spectrum, as well as penA gene duplication and amplification or its overexpression via transcriptional up-regulation. Evidence is presented that penA is co-transcribed with the upstream nlpD1 gene, that the transcriptional terminator for nlpD1 serves as a penA attenuator and that generation of a new promoter immediately upstream of the terminator/attenuator by a conserved G to A transition leads to anti-termination and thus constitutive PenA expression and extended β-lactam resistance. Further evidence obtained with the extensively β-lactam resistant clinical isolate Bp1651 shows that in addition to PenA overexpression and structural mutations other adaptive mechanisms contribute to intrinsic and acquired B. pseudomallei β-lactam resistance. | 10.1038/s41598-018-28843-7 |
pubmed_828_7540 | Borate saline buffer (0.1 M, pH 8.45) solubilized proteins from almond, Brazil nut, cashew nut, hazelnut, macadamia, pine nut, pistachio, Spanish peanut, Virginia peanut, and soybean seeds were prepared from the corresponding defatted flour. The yield was in the range from 10.6% (macadamia) to 27.4% (almond). The protein content, on a dry weight basis, of the lyophilized preparations ranged from 69.23% (pine nut) to 94.80% (soybean). Isolated proteins from Brazil nut had the lightest and hazelnut the darkest color. Isolated proteins exhibited good solubility in aqueous media. Foaming capacity (<40% overrun) and stability (<1 h) of the isolated proteins were poor to fair. Almond proteins had the highest viscosity among the tested proteins. Oil-holding capacity of the isolated proteins ranged from 2.8 (macadamia) to 7 (soybean) g of oil/g of protein. Least gelation concentrations (% w/v) for almond, Brazil nut, cashew, hazelnut, macadamia, pine nut, pistachio, Spanish peanut, Virginia peanut, and soybean were, respectively, 6, 8, 8, 12, 20, 12, 10, 14, 14, and 16. | 10.1021/jf1002446 |
pubmed_225_8367 | The human hepatoma cell line, Hep3B, synthesizes large quantities of erythropoietin (Epo) mRNA and protein in a regulated manner in response to hypoxia and cobaltous chloride (CoCl2). To further understand the regulation of Epo gene expression, we studied the effects of hypoxia and CoCl2 on the rate of Epo gene transcription. While Northern blot analyses showed that steady-state Epo mRNA levels increase more than 50-fold in response to hypoxia or CoCl2, nuclear run-off experiments demonstrated only a 10-fold increase in Epo gene transcription in response to these stimuli. In the presence of either actinomycin D (Act D) or cycloheximide, the stability of biologically functional Epo mRNA was much greater than that observed in the absence of these agents and much greater than that which has been reported in vivo. These findings suggest that the stability of Epo mRNA is modulated by the transcription and translation of rapidly turning over gene product(s). Thus, Epo mRNA levels are determined by both the rate of gene transcription and posttranscriptional events. These experiments demonstrate a potential pitfall in estimating mRNA half-lives based on Act D chase experiments alone. | pubmed_225_8367 |
pubmed_873_7038 | BACKGROUND
Anastomotic leakage (AL) is the most serious and common complication of surgery for rectal cancer, and associated risk factors remain unknown despite developments in laparoscopic surgery. The present study aimed to determine risk factors for AL after laparoscopic anterior resection (AR) of rectal cancer.
METHODS
This retrospective cohort study extracted information from a prospective database of all consecutive colorectal resections that proceeded at Nippon Medical School Hospital between January 2011 and December 2015 (n = 865). We identified 154 patients with rectal cancer treated by elective laparoscopic AR with anastomosis using primary double-stapling. Clinical variables and comorbidity, habits, and surgery-related variables were assessed by univariate and multivariate analyses to determine preoperative risk factors for clinical AL.
RESULTS
The overall rate of clinical AL was 11.7% (18 of 154 patients), and 5 (27.8%) of 18 patients required revised laparotomy. Data from males were analyzed because AL occurred only in males. Univariate analysis of male patients (n = 100) significantly associated preoperative creatinine values (p = 0.03) and a history of ischemic heart disease (IHD) (p = 0.012) with AL. The frequency of AL tended to increase (p = 0.06) when patients had low AR (p = 0.06) and transanal drainage. Having AL significantly prolonged hospital stays compared with patients without leakage (36.2 vs. 11.1 days; p < 0.01). Multivariate analysis identified a history of IHD (odds ratio [OR], 4.73; 95% confidence interval [CI], 1.27-17.5; p = 0.025] as an independent risk factor for AL.
CONCLUSIONS
Male sex and a history of IHD are possible risk factors for AL after elective laparoscopic rectal cancer surgery. | 10.1186/s12876-018-0846-3 |
pubmed_64_17913 | Failure is a major element that causes deterioration, which in turn affects the serviceability of long span bridges. Currently, the Bayesian network, which relates to probability statistics, is widely used for evaluating fatigue failure reliability. In particular, Bayesian network can not only calculate the fatigue failure at the system level, but also deduce the fatigue failure at the weld level. In this study, a system-level fatigue reliability evaluation model of a bridge deck (BD), which is seen as a parallel system, is proposed based on the Bayesian network. A fatigue probability reliability model of the BD was derived using the master S-N curve. In addition, the Monte Carlo (MC) method was applied to solve the multi-dimensional and complex analytical expressions in the Bayesian network. The applicability of the proposed model was demonstrated by three numerical case studies. | 10.3390/ma14061411 |
pubmed_346_10574 | F-actin affinity chromatography and immunological techniques are used to identify actin-binding proteins in purified Dictyostelium discoideum plasma membranes. A 17-kD integral glycoprotein (gp17) consistently elutes from F-actin columns as the major actin-binding protein under a variety of experimental conditions. The actin-binding activity of gp17 is identical to that of intact plasma membranes: it resists extraction with 0.1 N NaOH, 1 mM dithiothreitol (DTT); it is sensitive to ionic conditions; it is stable over a wide range of pH; and it is eliminated by proteolysis, denaturation with heat, or treatment with DTT and N-ethylmaleimide. gp17 may be responsible for much of the actin-binding activity of plasma membranes since monovalent antibody fragments (Fab) directed primarily against gp17 inhibit actin-membrane binding by 96% in sedimentation assays. In contrast, Fab directed against cell surface determinants inhibit binding by only 0-10%. The actin-binding site of gp17 appears to be located on the cytoplasmic surface of the membrane since Fab against this protein continue to inhibit 96% of actin-membrane binding even after extensive adsorption against cell surfaces. gp17 is abundant in the plasma membrane, constituting 0.4-1.0% of the total membrane protein. A transmembrane orientation of gp17 is suggested since, in addition to the cytoplasmic localization of the actin-binding site, extracellular determinants of gp17 are identified. gp17 is surface-labeled by sulfo-N-hydroxy-succinimido-biotin, a reagent that cannot penetrate the cell membrane. Also, gp17 is glycosylated since it is specifically bound by the lectin, concanavalin A. We propose that gp17 is a major actin-binding protein that is important for connecting the plasma membrane to the underlying microfilament network. Therefore, we have named this protein "ponticulin" from the Latin word, ponticulus, which means small bridge. | 10.1083/jcb.105.4.1741 |
pubmed_840_7488 | Sodium hypochlorite (bleach) is routinely used in hospitals and health care facilities for surface sterilization; however, the mechanism of action by which this disinfectant kills and the extent to which Pseudomonas aeruginosa is resistant to sodium hypochlorite have not been elucidated. Consequently, nosocomial infections from P. aeruginosa result in considerable casualties and economic hardship. We report the genome-wide transcriptome response of P. aeruginosa to sodium hypochlorite-induced oxidative stress via the use of DNA microarrays. In addition to a general oxidative stress response, our data revealed a downregulation of virtually all genes related to oxidative phosphorylation and electron transport and an upregulation of many organic sulfur transport and metabolism genes. | 10.1007/s00253-006-0644-7 |
pubmed_866_26191 | Research has developed various solutions in order for computers to recognize hand gestures in the context of human machine interface (HMI). The design of a successful hand gesture recognition system must address functionality and usability. The gesture recognition market has evolved from touchpads to touchless sensors, which do not need direct contact. Their application in textiles ranges from the field of medical environments to smart home applications and the automotive industry. In this paper, a textile capacitive touchless sensor has been developed by using screen-printing technology. Two different designs were developed to obtain the best configuration, obtaining good results in both cases. Finally, as a real application, a complete solution of the sensor with wireless communications is presented to be used as an interface for a mobile phone. | 10.3390/s19235068 |
pubmed_1061_10442 | Hydrogen sulphide (H2S) is an endogenous gasotransmitter, largely known as a pleiotropic mediator endowed with antioxidant, anti-inflammatory, pro-autophagic, and neuroprotective properties. Moreover, a strong relationship between H2S and aging has been recently identified and consistently, a significant decline of H2S levels has been observed in patients affected by Alzheimer's disease (AD). On this basis, the use of H2S-donors could represent an exciting and intriguing strategy to be pursued for the treatment of neurodegenerative diseases (NDDs). In this work, we designed a small series of multitarget molecules combining the rivastigmine-scaffold, a well-established drug already approved for AD, with sulforaphane (SFN) and erucin (ERN), two natural products deriving from the enzymatic hydrolysis of glucosinolates contained in broccoli and rocket, respectively, endowed both with antioxidant and neuroprotective effects. Notably, all new synthetized hybrids exhibit a H2S-donor profile in vitro and elicit protective effects in a model of LPS-induced microglia inflammation. Moreover, a decrease in NO production has been observed in LPS-stimulated cells pre-treated with the compounds. Finally, the compounds showed neuroprotective and antioxidant activities in human neuronal cells. The most interesting compounds have been further investigated to elucidate the possible mechanism of action. | 10.1016/j.ejmech.2019.111745 |
pubmed_764_19342 | The interaction between beta-cyclodextrin and five mono- and disubstituted benzenes in water was investigated by means of molecular dynamics. The trajectories were calculated for each system, imposing a 1:1 host-guest stoichiometry with 512 water molecules. Periodic boundary conditions were adopted. The results account for the formation of stable adducts and the predicted geometry agrees with experimental circular dichroism data. | 10.1016/S1093-3263(97)00001-6 |
pubmed_310_22950 | Systemically administered cholinomimetics or cholinesterase inhibitors can depress behavior in humans and animals, whereas antimuscarinic agents reverse this effect or even produce euphoria. Although these effects have been well documented, the specific brain regions that mediate them remain largely unknown. In the present experiments, muscarinic agonists and antagonists were locally injected into the nucleus accumbens of female Sprague-Dawley rats to test for their effects on behavioral depression in the Porsolt swim test and locomotor activity. Local, microinjections of the drugs in the accumbens elicited behaviors that were similar to the systemic effects reported in other studies. Injection of the non-specific agonist arecoline (40 and 80 microg) dose-dependently inhibited swimming and escape behavior. This may be mediated in part by accumbens M1 receptors because blocking these receptors with the specific antagonist pirenzepine (17.5 and 35.0 microg) did the opposite by increasing swimming. Gallamine (0.13, 0.44, and 0.88 microg), an antagonist at M2 receptors, dose-dependently decreased swimming. Two-way microdialysis suggested that this was in part due to the release of ACh by blocking M2 autoreceptors. Scopolamine, a mixed M1/M2 receptor antagonist, also released ACh but did not decrease swimming, probably because the M1 receptors were blocked; the drug (1.0 microg) increased swimming time, much like pirenzepine. With the exception of arecoline, none of the drugs significantly affected locomotor activity in a photocell cage. Arecoline (40 microg), which had decreased swimming, reduced activity. The present study suggests that muscarinic receptors in the nucleus accumbens can control immobility in the Porsolt swim test. The onset of immobility may depend on the activation of post-synaptic M1 receptors. | 10.1016/s0306-4522(01)00133-6 |
pubmed_1000_2567 | We carried out clinical and bacteriological studies on clavulanic acid/amoxicillin and amoxicillin in pediatric sinusitis at 11 general practice settings. The results are summarized as follows. 1. The major isolated organisms from content of middle meatus were Streptococcus pneumoniae 32.2%, Haemophilus influenzae 32.0% and Moraxella subgenus Branhamella catarrhalis 25.1%. Similar results were observed for the major isolates from nasopharynx. 2. 62.1% of S. pneumoniae isolated were drug resistant S. pneumoniae (PISP, PRSP) and they were increasing year by year. 3. Drug resistant S. pneumoniae was isolated from 38.6% of all cases. 4. Regarding MIC90, CVA/AMPC showed superior antimicrobial activity against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella subgenus Branhamella catarrhalis. 5. The clinical efficacy, bacteriological efficacy and utility of CVA/AMPC-treated group were 78%, 58% and 72.8%, respectively, and they were significantly superior to AMPC-treated group. 6. Adverse reactions were observed in 11.2% of CVA/AMPC group, involving diarrhea and stool loose and there was no statistical deference from those of AMPC group. | pubmed_1000_2567 |
pubmed_336_4940 | Renal transplantation is potentially curative in renal failure, but long-term efficacy is limited by untreatable chronic rejection. Endothelial damage contributes to chronic rejection and is potentially repairable by circulating endothelial progenitor cells (EPC). The frequency and function of EPC are variably influenced by end-stage renal failure (ESRF). Here, we isolated and functionally characterized the late outgrowth EPC (LO-EPC) from ESRF patients to investigate their potential for endothelial repair. Patients with ESRF generated more LO-EPC colonies than healthy controls and had higher plasma levels of IL-1rα, IL-16, IL-6, MIF, VEGF, Prolactin, and PLGF. Patients' LO-EPC displayed normal endothelial cell morphology, increased secretion of PLGF, MCP-1, and IL-1β, and normal network formation in vitro and in vivo. They demonstrated decreased adhesion to extracellular matrix. Integrin gene profiles and protein expression were comparable in patients and healthy volunteers. In some patients, mesenchymal stem cells (MSC) were co-isolated and could be differentiated into adipocytes and osteocytes in vitro. This is the first study to characterize LO-EPC from patients with ESRF. Their behavior in vitro reflects the presence of elevated trophic factors; their ability to proliferate in vitro and angiogenic function makes them candidates for prevention of chronic rejection. Their impaired adhesion and the presence of MSC are areas for potential therapeutic intervention. | 10.1111/tri.12277 |
pubmed_957_24455 | BACKGROUND
In-stent stenosis (ISS) is a delayed complication that can occur after pipeline embolization device use when treating intracranial aneurysms (IAs).
OBJECTIVE
To assess the incidence, predictors, and outcomes of ISS.
METHODS
This was a retrospective, multicenter, observational study. All patient data were collected from a PLUS registry study. We collected data from patients with IA who completed digital subtraction angiography at follow-up and divided patients into "non-ISS," "mild ISS," or "severe ISS" groups. Multivariate logistic regression analysis was conducted to determine predictors of ISS.
RESULTS
A total of 1171 consecutive patients with 1322 IAs participated in this study. Angiographic follow-up was available for 662 patients with 728 IAs, and the mean follow-up time was 9 months. ISS was detected in 73 cases (10.03%), including 61 mild ISS cases and 12 severe ISS cases. Univariate and multivariable analysis demonstrated that current smoking history (mild ISS: OR 2.15, 95% CI 1.122-4.118, P = .021; severe ISS: OR 5.858, 95% CI 1.186-28.93, P = .030) and cerebral atherosclerosis (mild ISS: OR 5.694, 95% CI 3.193-10.15, P = .001; severe ISS: OR 6.103, 95% CI 1.384-26.91, P = .017) were independent predictors of ISS. Compared with the other groups, the severe ISS group had higher rate of ischemic stroke (33.3%).
CONCLUSION
ISS occurs in approximately 10.03% of cases at a mean follow-up of 9 months. Statistically, current smoking history and cerebral atherosclerosis are the main predictors of ISS. Severe ISS may be associated with higher risk of neurological ischemic events in patients with IA after pipeline embolization device implantation. | 10.1227/neu.0000000000002142 |
pubmed_431_13065 | The goal of this study was to develop a novel cooking method for fried meat products, to improve their nutritional value, and to provide superior taste and texture. We used the fat derived from each individual meat source during radiant heat roasting (alternate roasting with its own fat: AROF) without deep-fat frying (DFF), first without any air flow and subsequently with an exposure to air flow. We then compared these roasted chicken samples to breaded fried chicken samples that were deep-fat fried in 3 types of fat: soybean oil (SB), partially hydrogenated soybean oil (PSB), and lard. The final fat contents of both the skin and lean parts of the AROF samples of chicken were less than half of those of the DFF groups. The total trans-fatty acids (TFA) contents were significantly lower in the AROF samples compared to the DFF samples. The cholesterol levels of the samples did not show any significant differences among the tested groups, except for the sample fried in lard, which was significantly higher. Moreover, the sensory evaluation results showed that the crispy texture of the AROF samples was not significantly different from that of the DFF samples (P < 0.05); the AROF samples had higher scores for the characteristic fried flavor and for overall acceptability (P < 0.05). This study shows the potential value of products prepared by AROF, which can successfully replace DFF methods used for chicken and other meat products and improve their nutritional value. | 10.1111/j.1750-3841.2008.00731.x |
pubmed_959_25259 | Macrophages are phagocytic sentinel cells of the immune system that are central to both innate and adaptive immune responses and serve as the first line of defense against pathogenic insults to tissues. In the tumor microenvironment, tumor-derived factors induce monocyte polarization towards a pro-tumor phenotype. The pro-tumor macrophages regulate key steps in tumorigenicity including tumor growth, angiogenesis, immune suppression, and metastasis. Macrophage infiltration in solid tumors correlates with poor prognosis and resistance to chemotherapy in most cancers. Here in this review, we will shed light on tumor-associated macrophages (TAMs) in regulating tumorigenicity and TAMs as a prognostic biomarker. Also, we will review the recent advances in targeting TAMs to increase the prognosis of cancer patients. | 10.1007/s12282-021-01231-2 |
pubmed_722_9746 | Understanding the factors related to invasive exotic species distributions at broad spatial scales has important theoretical and management implications, because biological invasions are detrimental to many ecosystem functions and processes. Housing development facilitates invasions by disturbing land cover, introducing nonnative landscaping plants, and facilitating dispersal of propagules along roads. To evaluate relationships between housing and the distribution of invasive exotic plants, we asked (1) how strongly is housing associated with the spatial distribution of invasive exotic plants compared to other anthropogenic and environmental factors; (2) what type of housing pattern is related to the richness of invasive exotic plants; and (3) do invasive plants represent ecological traits associated with specific housing patterns? Using two types of regression analysis (best subset analysis and hierarchical partitioning analysis), we found that invasive exotic plant richness was equally or more strongly related to housing variables than to other human (e.g., mean income and roads) and environmental (e.g., topography and forest cover) variables at the county level across New England. Richness of invasive exotic plants was positively related to area of wildland-urban interface (WUI), low-density residential areas, change in number of housing units between 1940 and 2000, mean income, plant productivity (NDVI), and altitudinal range and rainfall; it was negatively related to forest area and connectivity. Plant life history traits were not strongly related to housing patterns. We expect the number of invasive exotic plants to increase as a result of future housing growth and suggest that housing development be considered a primary factor in plans to manage and monitor invasive exotic plant species. | 10.1890/09-2168.1 |
pubmed_886_10551 | SIGA Technologies, Inc. is a small biotech company committed to developing novel products for the prevention and treatment of serious viral diseases, with an emphasis on products to combat outbreaks that could result from bioterrorism. With government support, SIGA has developed the necessary infrastructure to successfully advance new antiviral drugs from the discovery stage through to licensing. Currently, there is a need to develop safe and effective inhibitors for poxvirus-induced diseases such as smallpox caused by variola, which is a potential biological warfare agent. Likewise emerging zoonotic infections due to cowpox virus and monkeypox virus require the development of effective countermeasures. Tecovirimat, also known as ST-246, has shown efficacy in all small animal and nonhuman primate prophylaxis and therapeutic efficacy models of poxvirus-induced disease tested to date. Phase I clinical trials and new drug application-enabling toxicology studies have been completed with tecovirimat. A phase II clinical study is being run and SIGA has initiated commercial scale-up manufacturing and preparation for the pivotal safety and efficacy studies. SIGA is committed to getting approval for tecovirimat and supplying it to the Strategic National Stockpile, the Department of Defense and global health authorities. | 10.1358/dot.2010.46.2.1437244 |
pubmed_869_13995 | We have designed and synthesized four compounds integrating luminescent and photochromic components in their molecular skeletons. Two of them combine a nitrospiropyran photochrome with either one or two naphthalene fluorophores and can be prepared in three synthetic steps. The other two consist of a nitrospiropyran photochrome and a benzophenone phosphore connected by either ether or ester linkages and can be prepared in six or five, respectively, synthetic steps. The luminescent components of these assemblies are expected to transfer energy intramolecularly to the photochromic species upon excitation and encourage their photoisomerization. Consistently, the phosphorescence of the benzophenone units and the fluorescence of the naphthalene components are effectively quenched when these species are connected covalently to a nitrospiropyran. Nonetheless, the photoisomerization of the photochrome becomes significantly less efficient after the covalent attachment to the luminescent partner. The fraction of incident radiations absorbed by either the benzophenone or the naphthalene fragment does not promote the isomerization of the photochromic appendage. Instead, irreversible transformations occur upon irradiation of the luminophore-photochrome assemblies. Thus, the covalent attachment of a benzophenone or a naphthalene to a nitrospiropyran is not a viable strategy to improve the photocoloration efficiency of the photochromic component. Even although the very same luminophores are known to sensitize intermolecularly the isomerization of nitrospiropyrans, the transition to covalent luminophore-photochrome assemblies tends to promote degradation, rather than sensitization, upon irradiation. | 10.1021/jo062004d |
pubmed_170_20492 | We examined the cognitive processes that might account for the impact of cross-group friendship on novel intergroup situations. Study 1 demonstrated that closeness with outgroup members predicts an association of the outgroup with the self, both in terms of the group itself and the personality traits stereotypically associated with the group. In Studies 2 and 3, we manipulated the accessibility of either a same-group friendship or cross-group friendship. Participants who described a cross-group friend exhibited a greater association of the friend's ethnicity with the self, and this association mediated the effects of friendship accessibility on positive expectations for intergroup contact (Study 2) and adaptive hormonal responses during a real interaction with a novel outgroup member (Study 3). These findings imply that cross-group friendship improves novel intergroup experiences to the degree that outgroups become associated with the self. | 10.1037/a0017880 |
pubmed_22_960 | We propose a comprehensive delayed HBV model, which not only considers the immune response to both infected cells and viruses and a time delay for the immune system to clear viruses but also incorporates an exposed state and the proliferation of hepatocytes. We prove the positivity and boundedness of solutions and analyze the global stability of two boundary equilibria and then study the local asymptotic stability and Hopf bifurcation of the positive (infection) equilibrium and also the stability of the bifurcating periodic solutions. Moreover, we illustrate how the factors such as the time delay, the immune response to infected cells and viruses, and the proliferation of hepatocytes affect the dynamics of the model by numerical simulation. | 10.1155/2017/7805675 |
pubmed_482_11296 | BACKGROUND
Primary small bowel non-Hodgkin's lymphoma is a rare disease representing 2% of small intestine malignancies. There is limited data delineating the optimal treatment for these heterogeneous tumors. We aim to examine relationships between different treatment modalities and surgical outcomes in patients with small bowel lymphoma.
MATERIALS AND METHODS
Patients diagnosed with stage I-III small bowel lymphoma in 2004-2015 who underwent surgery were identified in the National Cancer Database. Two cohorts were created based on systemic chemotherapy treatment status. The primary outcome was overall survival. An adjusted Cox proportional hazards model was used to evaluate the impact of treatment strategy on survival.
RESULTS
2283 patients met inclusion criteria Of these patients, 826 patients (36%) underwent surgical resection alone, and 1457 patients (64%) underwent resection with systemic chemotherapy. Chemotherapy was associated with improved overall survival in unadjusted (5-year overall survival, 55% versus 70%) and adjusted analysis (HR 0.54, 95% CI 0.47-0.63, p < 0.001).
DISCUSSION
Patients with small bowel lymphoma have a low five-year overall survival after surgery. Chemotherapy is associated with improved survival, although one third of patients do not receive this therapy. Several other clinical factors are identified that are also associated with overall survival, including histology subtype, margin status, age, and medical comorbidities. This information can help with prognostication and potentially aid in treatment decision-making. | 10.1007/s11605-020-04730-3 |
pubmed_491_2324 | AIM
In this study we investigated the frequency and characteristics of pulmonary manifestations in a group of patients with Behcet's disease (BD) who were admitted to Cairo University Hospital.
METHODS
Fifteen patients were included in our study, 14 men (93.3%) and one woman (6.66%).Their mean age was 30.06 ± 9.8 years and the mean age of onset of BD was 23.7 ± 5.54 years. All patients were subjected to full history taking, clinical examination, plain chest X-ray and helical computed tomography (CT) study of the chest.
RESULTS
Pulmonary involvements were detected in 11 patients with BD, 73.3% of cases: 10 men (90.9%) and one woman (9.09%).Their mean age was 28.8 ± 8.07, the mean age of onset of BD was 23.2 ± 5.59 years and the mean disease duration until lung manifestations appear was 3.7 ± 4.8 years. The main pulmonary and constitutional symptoms in these 11 patients were as follows: dyspnea 81.8%, cough 63.6%, weight loss 63.6%, chest tightness 54.5%, hemoptysis 45%, massive hemoptysis 27.2%, fever 36.3% and expectoration 36.3. Analysis of both vascular and parenchymal lung lesions in helical CT scan in the 11 patients with BD were as follows: pulmonary artery aneurysm (PAA) occurred in 5/11 patients (45.4%), pulmonary nodules occurred in 3/11 patients (27.2%), pleural effusion occurred in 3/11 patients (27.2%), pulmonary embolism and infarction occurred in 1/11 patients (9.09%) and pneumonitis occurred in 1/11 patients (9.09%).
CONCLUSION
The higher frequency of pulmonary manifestations in our patients (73.3%) and the higher frequency of PAA (33.3%) could be related to the fact that this study was conducted on a group of patients who were admitted to the hospital with more severe illnesses. | 10.1111/1756-185X.12626 |
pubmed_965_1546 | BACKGROUND
Carbon dioxide (CO2) insufflation during colonoscopy was reported to reduce pain, but data are limited. The objective of this randomized controlled trial was to assess the effect of CO2 insufflation on pain during and after colonoscopy.
METHODS
Patients were randomized into CO2 insufflation (CO2i) or air insufflation (AIRi) groups. Pain during and after the examination were recorded using a visual analogue scale. Other outcomes included the caecal intubation rate, time to reach the caecum and complication. With questionnaire, patients' satisfaction and acceptance of the procedure were assessed.
RESULTS
Over a 4-month period, 96 patients were recruited. The caecal intubation rate was 96 and 98% in the CO2i group and the AIRi group, respectively. No complication occurred in the CO2i group whereas one patient from the AIRi group developed late haemorrhage after polypectomy. Patients in the CO2i group had a lower pain score during (P < 0.01) and 30 min after (P = 0.02) the examination. Significantly more patients in the CO2i group reported the examination as painless (visual analogue scale 0) during the procedure (45 vs 14%, P < 0.01) and 30 min after (70 vs 51%, P = 0.04). In both groups, high satisfaction scores were recorded. Most patients (93% for the CO2i group and 98% for the AIRi group) would accept another colonoscopy if indicated.
CONCLUSION
Insufflation with CO2 during colonoscopy results in less pain during and after the examination. Because of better tolerance, colonoscopy with CO2 insufflation might gain wide acceptance in the community to be used as a screening tool. | 10.1111/j.1445-2197.2008.04683.x |
pubmed_92_2935 | A simple, rapid and robust liquid chromatography-tandem mass spectrometry was established and validated for simultaneous quantifications of three pyranocoumarins (praeruptorin A-C) in rat plasma. Following a single-step liquid-liquid extraction, the analytes were separated on a reversed-phase C18 column with a mobile phase consisting of methanol and 10 mM ammonium acetate solution (70 : 30, v/v) at a constant flow rate of 0.3 mL/min. The linear calibration curves were obtained over the concentration ranges 2.93-1470 ng/mL for praeruptorin A, 1.47-734 ng/mL for praeruptorin B and 2.00-1000 ng/mL for praeruptorin C. The within-batch accuracy was -8.6 to 7.5% for praeruptorin A, -9.5 to 12.0% for praeruptorin B and -10.5 to 12.5% for praeruptorin C, respectively. The between-batch accuracy was -3.5 to 1.4% for praeruptorin A, -8.7 to 3.4% for praeruptorin B and -6.0 to 4.3% for praeruptorin C, respectively. The within-batch and between-batch precisions were ≤13.1 and ≤8.2%, respectively. This method is suitable to simultaneously determine the three pyranocoumarins in plasma and thus to investigate the pharmacokinetics of the pyranocoumarins of Peucedanum praeruptorum in rats. | 10.1093/chromsci/bmu077 |
pubmed_271_19320 | We investigated the optical, electrical, structural, and surface properties of roll-to-roll [R2R] sputter-grown flexible IZO/Ag/IZO/Ag [IAIA] multilayer films on polyethylene terephthalate substrates as a function of the top indium zinc oxide [IZO] thickness. It was found that the optical transmittance of the IAIA multilayer was significantly influenced by the top IZO layer thickness, which was grown on identical AIA multilayers. However, the sheet resistance of the IAIA multilayer was maintained between the range 5.01 to 5.1 Ω/square regardless of the top IZO thickness because the sheet resistance of the IAIA multilayer was mainly dependent on the thickness of the Ag layers. Notably, the optimized IAIA multilayer had a constant resistance change (ΔR/R0) under repeated outer bending tests with a radius of 10 mm. The mechanical integrity of the R2R-sputtered IAIA multilayer indicated that hybridization of an IZO and Ag metal layer is a promising flexible electrode scheme for the next-generation flexible optoelectronics. | 10.1186/1556-276X-7-67 |
pubmed_229_18187 | The following paper is the manuscript of an oral presentation during the annual GPOH meeting on May 22nd, 2000 in Berlin. Following her experiences as a member of the psychosocial care team of a children's cancer unit the author discusses the emotional impact of stemcell or bone marrow transplantation in children. Psychosocial care is identified as a way to support children emotionally during a situation of existential crisis, and to help them share their inner feelings and experiences. | 10.1055/s-2001-16857 |
pubmed_1025_8852 | A retrospective case-note study was undertaken to look at recorded details relating to information/advice given to women prior to or at the time of their gynaecological surgery with regard to possible effects of menopause/menopausal symptoms or advice given about hormone replacement therapy. | 10.1258/mi.2011.011019 |
pubmed_552_17417 | The clonal cell line HT29-D4 is able to differentiate by two different ways: i) by replacing glucose by galactose in the culture medium; ii) by addition of suramin (a drug known to interfere with the growth promoting activity of growth factors) in the medium. In both cases the transition in the organization of the cell monolayer occurred without cell loss. The two ways (i.e., glucose starvation or suramin addition) lead to polarized cells which generate electrically active cell monolayers (Fantini et al., Biol. Cell 65, 163-169 (1989) and this paper). Yet several important differences can be observed at the morphological or at the electrophysiological levels. 1) The suramin-treated cells (HT29-D4-S cells) organized into monolayers of high (40-50 microns) columnar cells while glucose-starved cells (HT29-D4-Gal cells) were rather cuboidal (20-25 microns). 2) HT29-D4-S cells were highly polarized; the nucleus was rejected at the basal side of the cell and lysosomes in the upper part of the cytoplasm. Numerous lipid-like droplets surrounded with glycogen were observed underneath the nucleus. HT29-D4-Gal cells never presented such a degree of organization. 3) The transepithelial resistance and the potential difference of HT29-D4-S monolayers reached values significantly higher than those for HT29-D4-Gal monolayers, reflecting a higher degree of organization. Specific proteins such as sucrase-isomaltase, alkaline phosphatase and carcinoembryonic antigen were localized exclusively on the apical membrane while human lymphocyte antigen (HLA) class I molecules were restricted to the basolateral membrane for both HT29-D4-S and HT29-D4-Gal cells. The present data demonstrate that the same cells can generate a different degree of cellular organization according to the experimental conditions of cell growth, the most elaborate state of differentiation being obtained in the presence of suramin. | pubmed_552_17417 |
pubmed_189_249 | OBJECTIVES
We sought to describe the course and correlates of psychological distress in frontline healthcare workers (FHCWs) during the COVID-19 pandemic in New York City (NYC).
METHODS
A prospective cohort study of FHCWs at the Mount Sinai Hospital was conducted during the initial 2020 surge (T1) and 7 months later (T2). Psychological distress [i.e., positive screen for pandemic-related post-traumatic stress disorder (PTSD), major depressive disorder (MDD), and/or generalized anxiety disorder (GAD)], occupational and personal exposures to COVID-19, coping strategies, and psychosocial characteristics were assessed. Four courses of psychological distress response were identified: no/minimal, remitted, persistent, and new-onset. Multinomial logistic regression and relative importance analyses were conducted to identify factors associated with courses of distress.
RESULTS
Of 786 FHCWs, 126 (16.0%) FHCWs had persistent distress; 150 (19.1%) remitted distress; 35 (4.5%) new-onset distress; and 475 (60.4%) no/minimal distress. Relative to FHCWs with no/minimal distress, those with persistent distress reported greater relationship worries [19.8% relative variance explained (RVE)], pre-pandemic burnout (18.7% RVE), lower dispositional optimism (9.8% RVE), less emotional support (8.6% RVE), and feeling less valued by hospital leadership (8.4% RVE). Relative to FHCWs with remitted symptoms, those with persistent distress reported less emotional support (29.7% RVE), fewer years in practice (28.3% RVE), and psychiatric history (23.6% RVE).
CONCLUSIONS
One-fifth of FHCWs in our study experienced psychological distress 7 months following the COVID-19 surge in NYC. Pandemic-related worries, pre-pandemic burnout, emotional support, and feeling valued by leaders were linked to persistent distress. Implications for prevention, treatment, and organizational efforts to mitigate distress in FHCWs are discussed. | 10.1007/s00420-022-01832-0 |
pubmed_188_117 | BACKGROUND
Pregnenolone sulfate (PregS), an endogenous neurosteroid, which negatively and positively modulates gamma amino butyric acid subunit A (GABAA) and N-methyl D-aspartate (NMDA) receptors (R) respectively, among other potential neuroplastic changes on synaptic processes, has shown some beneficial effects on treating cognitive impairment associated with schizophrenia (CIAS) and negative symptoms. Lurasidone (Lur), an atypical antipsychotic drug (AAPD), and tandospirone (Tan), a 5-HT1A R partial agonist, have also been reported to improve cognitive or negative symptoms, or both, in some schizophrenia patients.
METHODS
We tested whether PregS, by itself, and in combination with Lur or Tan could rescue persistent deficits produced by subchronic treatment with the NMDAR antagonist, phencyclidine (PCP)-in episodic memory, executive functioning, and social behavior, using novel object recognition (NOR), operant reversal learning (ORL), and social interaction (SI) tasks, in male C57BL/6 J mice.
RESULTS
PregS (10, but not 3 mg/kg) significantly rescued subchronic PCP-induced NOR and SI deficits. Co-administration of sub-effective doses (SEDs) of PregS (3 mg/kg) + Lur (0.1 mg/kg) or Tan (0.03 mg/kg) rescued scPCP-induced NOR and SI deficits. Further, PregS (30, but not 10 mg/kg) rescued PCP-induced ORL deficit, as did the combination of SED PregS (10 mg/kg) +SED Lur (1 mg/kg) or Tan (1 mg/kg).
CONCLUSION
PregS was effective alone and as adjunctive treatment for treating two types of cognitive impairments and negative symptoms in this schizophrenia model. Further study of the mechanisms by which PregS alone and in combination with AAPDs and 5-HT1A R partial agonists, rescues the deficits in cognition and SI in this preclinical model is indicated. | 10.1016/j.bbr.2018.05.005 |
pubmed_675_25541 | CCTV plays a prominent role in public security, health and safety. Monitoring large arrays of CCTV camera feeds is a visually and cognitively demanding task. Arranging the scenes by geographical proximity in the surveilled environment has been recommended to reduce this demand, but empirical tests of this method have failed to find any benefit. The present study tests an alternative method for arranging scenes, based on psychological principles from literature on visual search and scene perception: grouping scenes by semantic similarity. Searching for a particular scene in the array-a common task in reactive and proactive surveillance-was faster when scenes were arranged by semantic category. This effect was found only when scenes were separated by gaps for participants who were not made aware that scenes in the multiplex were grouped by semantics (Experiment 1), but irrespective of whether scenes were separated by gaps or not for participants who were made aware of this grouping (Experiment 2). When target frequency varied between scene categories-mirroring unequal distributions of crime over space-the benefit of organising scenes by semantic category was enhanced for scenes in the most frequently searched-for category, without any statistical evidence for a cost when searching for rarely searched-for categories (Experiment 3). The findings extend current understanding of the role of within-scene semantics in visual search, to encompass between-scene semantic relationships. Furthermore, the findings suggest that arranging scenes in the CCTV control room by semantic category is likely to assist operators in finding specific scenes during surveillance. | 10.1186/s41235-021-00277-2 |
pubmed_258_8087 | BACKGROUND
Adult studies have demonstrated within-season declines in influenza vaccine effectiveness (VE); data in children are limited.
METHODS
We conducted a prospective, test-negative study of children 6 months-17 years hospitalized with acute respiratory illness at 7 pediatric medical centers during the 2015-2016 through 2019-2020 influenza seasons. Case-patients were children with an influenza-positive molecular test matched by illness onset to influenza-negative control-patients. We estimated VE [100% x (1 - odds ratio)] by comparing the odds of receipt of ≥1 dose of influenza vaccine ≥14 days before illness onset among influenza-positive children to influenza-negative children. Changes in VE over time between vaccination date and illness onset date were estimated using multivariable logistic regression.
RESULTS
Of 8,430 children, 4,653 (55%) received ≥1 dose of influenza vaccine. On average, 48% were vaccinated through October and 85% through December each season. Influenza vaccine receipt was lower in case-patients than control-patients (39% vs. 57%, p < 0.001); overall VE against hospitalization was 53% (95% CI: 46%-60%). Pooling data across 5 seasons, the odds of influenza-associated hospitalization increased 4.2% (-3.2%-12.2%) per month since vaccination, with an average VE decrease of 1.9% per month (n = 4,000, p = 0.275). Odds of hospitalization increased 2.9% (95% CI: -5.4%-11.8%) and 9.6% (95% CI: -7.0%-29.1%) per month in children ≤8 years (n = 3,084) and 9-17 years (n = 916), respectively. These findings were not statistically significant.
CONCLUSIONS
We observed minimal, not statistically significant within-season declines in VE. Vaccination following current ACIP guidelines for timing of vaccine receipt remains the best strategy for preventing influenza-associated hospitalizations in children. | 10.1093/cid/ciac577 |
pubmed_898_13654 | BACKGROUND
Renal transplantation in developing countries like India is largely live donor transplantation. Cadaveric transplantation comprises <2% of all transplants in India.
METHODS
Ninety-two cadaveric renal transplantations were included. Various donor and recipient characteristics were analysed along with graft and patient survival, using Kaplan-Meier method.
RESULTS
The mean age of the recipients was 35.5 ± 10.9 years while that of cadaver was 43.9 ± 17.0 years. Proportion of females among recipients was 47.8% while that of donors was 34.8%. The most common underlying pathology was chronic glomerulonephritis (44.6%). Antithymocyte globulin was used as induction in 84.8% of cases. Tacrolimus-based triple-drug regimen was most commonly used as maintenance (80.4%). The mean follow-up time was 39.02 ± 28.24 months. The most common cause of death was sepsis (47%). More than 50% deaths (9/17) occurred within first 3 years, while 61.5% of graft loss occurred 5 years after transplantation. The mean graft survival time was 81.6 months (95% confidence interval [CI]: 72.8-90.4). Cumulative proportion of graft survival was 91.6% at 3 years and 77.1% at 5 years. Although females have better mean graft survival time (91.6 vs 73.5 months), it was not a significant difference as shown by log-rank test (p value = 0.062). Pretransplant haemodialysis has no significant effect on graft loss, but patients on peritoneal dialysis have significantly higher odds of graft loss (odds: 4.86, p value < 0.05 [0.018]). The mean patient survival time was 99.5 months (95% CI: 84.0-114.9). Cumulative proportion of patient survival was 83.3% at 3 years and 70.8% at 5 years.
CONCLUSION
Graft and patient survival rate of cadaveric transplant at our centre was satisfactory. There is need to sensitise and augment the rate of cadaveric transplantation to increase the donor pool. | 10.1016/j.mjafi.2018.08.011 |
pubmed_468_9729 | OBJECTIVES
Human coronary bare-metal stents (BMS) and drug-eluting stents (DES) from autopsy cases with implant duration >30 days were examined for the presence of neointimal atherosclerotic disease.
BACKGROUND
Neointimal atherosclerotic change (neoatherosclerosis) after BMS implantation is rarely reported and usually occurs beyond 5 years. The incidence of neoatherosclerosis after DES implantation has not been reported.
METHODS
All available cases from the CVPath stent registry (n = 299 autopsies), which includes a total of 406 lesions-197 BMS, 209 DES (103 sirolimus-eluting stents [SES] and 106 paclitaxel-eluting stents [PES])-with implant duration >30 days were examined. Neoatherosclerosis was recognized as clusters of lipid-laden foamy macrophages within the neointima with or without necrotic core formation.
RESULTS
The incidence of neoatherosclerosis was significantly greater in DES lesions (31%) than BMS lesions (16%; p < 0.001). The median stent duration with neoatherosclerosis was shorter in DES than BMS (DES, 420 days [interquartile range [IQR]: 361 to 683 days]; BMS, 2,160 days [IQR: 1,800 to 2,880 days], p < 0.001). Unstable lesions characterized as thin-cap fibroatheromas or plaque rupture were more frequent in BMS (n = 7, 4%) than in DES (n = 3, 1%; p = 0.17), with relatively shorter implant durations for DES (1.5 ± 0.4 years) compared to BMS (6.1 ± 1.5 years). Independent determinants of neoatherosclerosis identified by multiple logistic regression included younger age (p < 0.001), longer implant durations (p < 0.001), SES usage (p < 0.001), PES usage (p = 0.001), and underlying unstable plaques (p = 0.004).
CONCLUSIONS
Neoatherosclerosis is a frequent finding in DES and occurs earlier than in BMS. Unstable features of neoatherosclerosis are identified for both BMS and DES with shorter implant durations for the latter. The development of neoatherosclerosis may be yet another rare contributing factor to late thrombotic events. | 10.1016/j.jacc.2011.01.011 |
pubmed_337_11220 | Enhanced glycolysis in cancer cells presents a target for chemotherapy. Previous studies have indicated that proliferation of cancer cells can be inhibited by treatment with phenformin and with an inhibitor of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB) namely 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO). In the present work, the action of two inhibitors that are effective at lower concentrations than 3PO, namely 1-(3-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one (PQP) and 1-(4-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one (PFK15) were investigated. The inhibitors of lactate dehydrogenase (LDHA) studied in order of half-maximal inhibitory concentrations were methyl 1-hydroxy-6-phenyl-4-(trifluoromethyl)-1H-indole-2-carboxylate (NHI-2) < isosafrole < oxamate. In colonic and bladder cancer cells, additive growth inhibitory effects were seen with the LDHA inhibitors, of which NHI-2 was effective at the lowest concentrations. Growth inhibition was generally greater with PFK15 than with PQP. The increased acidification of the culture medium and glucose uptake caused by phenformin was blocked by combined treatment with PFKFB3 or LDHA inhibitors. The results suggest that combined treatment with phenformin and inhibitors of glycolysis can cause additive inhibition of cell proliferation and may mitigate lactic acidosis caused by phenformin when used as a single agent. | pubmed_337_11220 |
pubmed_840_12284 | Glycogen storage diseases (GSDs) are characterized by abnormal inherited glycogen metabolism in the liver, muscle, and brain and divided into types 0 to X. GSD type I, glucose 6-phosphatase system, has types Ia, Ib, Ic, and Id, glucose 6-phosphatase, glucose 6-phosphate translocase, pyrophosphate translocase, and glucose translocase deficiencies, respectively. GSD type II is caused by defective lysosomal alpha-glucosidase (GAA), subdivided into 4 onset forms. GSD type III, amylo-1,6-glucosidase deficiency, is subdivided into 6 forms. GSD type IV, Andersen disease or amylopectinosis, is caused by deficiency of the glycogen-branching enzyme in numerous forms. GSD type V, McArdle disease or muscle phosphorylase deficiency, is divided into 2 forms. GSD type VI is characterized by liver phosphorylase deficiency. GSD type VII, phosphofructokinase deficiency, has 2 subtypes. GSD types VIa, VIII, IX, or X are supposedly caused by tissue-specific phosphorylase kinase deficiency. GSD type 0, glycogen synthase deficiency, is divided into 2 subtypes. | 10.1016/j.spen.2006.06.007 |
pubmed_282_14564 | OBJECTIVE
Gestational diabetes mellitus (GDM) is a metabolic disorder that shares pathophysiologic features with type 2 diabetes mellitus. The aim of this study was to investigate the association of the polymorphisms fat mass and obesity-associated (FTO) rs1421085, leptin receptor (LEPR) rs1137100, rs1137101, peroxisome proliferator-activated receptor gamma (PPARg) rs1801282, and transcription factor 7-like 2 (TCF7L2) rs7901695 with GDM.
SUBJECTS AND METHODS
252 unrelated Euro-Brazilian pregnant women were classified into two groups according to the 2015 criteria of the American and Brazilian Diabetes Association: healthy pregnant women (n = 125) and pregnant women with GDM (n = 127), matched by age. The polymorphisms were genotyped using fluorescent probes (TaqMan®).
RESULTS
All groups were in Hardy-Weinberg equilibrium. The genotype and allele frequencies of the studied polymorphisms did not show significant differences between the groups (P > 0.05). In the healthy and GDM groups, the C allele frequencies (95% CI) of the FTO rs1421085 polymorphism were 36.8% [31-43%] and 35.0% [29-41%]; the G allele frequencies (95% CI) of the LEPR rs1137100 polymorphism were 24.8% [19-30%] and 22.8% [18-28%]; the G allele frequencies (95% CI) of the LEPR rs1137101 polymorphism were 43.6% [37-50%] and 42.9% [37-49%]; the G allele frequencies (95% CI) of the PPARg rs1801282 polymorphism were 7.6% [4-11%] and 8.3% [5-12%]; and the C allele frequencies (95% CI) of the TCF7L2 rs7901695 polymorphism were 33.6% [28-39%] and 39.0% [33-45%], respectively.
CONCLUSION
The studied polymorphisms were not associated with GDM in a Brazilian population. | 10.1590/2359-3997000000258 |
pubmed_140_3683 | G protein-coupled receptors (GPCRs) not only exist as monomers but also as homomers and heteromers in which allosteric receptor-receptor interactions take place, modulating the functions of the participating GPCR protomers. GPCRs can also form heteroreceptor complexes with ionotropic receptors and receptor tyrosine kinases modulating their function. Furthermore, adaptor proteins interact with receptor protomers and modulate their interactions. The state of the art is that the allosteric receptor-receptor interactions are reciprocal, highly dynamic and substantially alter the signaling, trafficking, recognition and pharmacology of the participating protomers. The pattern of changes appears to be unique for each heteromer and can favor antagonistic or facilitatory interactions or switch the G protein coupling from e.g., Gi/o to Gq or to beta-arrestin signaling. It lends a new dimension to molecular integration in the nervous system. Future direction should be aimed at determining the receptor interface involving building models of selected heterodimers. This will make design of interface-interfering peptides that specifically disrupt the heterodimer possible. This will help to determine the functional role of the allosteric receptor-receptor interactions as well as the integration of signals at the plasma membrane by the heteroreceptor complexes, vs. integration of the intracellular signaling pathways. Integration of signals also at the plasma membrane seems crucial in view of the hypothesis that learning and memory at a molecular level takes place by reorganization of homo and heteroreceptor complexes in the postsynaptic membrane. Homo and heteroreceptor complexes are in balance with each other, and their disbalance is linked to disease. Targeting heteroreceptor complexes represents a novel strategy for the treatment of brain disorders. | 10.3389/fnmol.2019.00230 |
pubmed_249_9663 | OBJECTIVES AND DESIGN
Actin is the dominating protein in mammalian cells, including muscle cells, and is released into the circulation after tissue injury. Gc-globulin, one of the proteins in the Extracellular Actin Scavenger System (EASS) is responsible for the clearance of actin from the circulation. Clinical studies show that plasma levels of Gc-globulin are reduced in situations with tissue death, and that the degree of reduction correlates with development of organ dysfunction and survival. The purpose of the present study was to describe the serial changes in Gc-globulin after a standardized surgical procedure resulting in major muscle injury, comparing changes in Gc-globulin with changes in other acute phase proteins.
MATERIAL AND METHODS
Twelve patients who underwent posterolateral lumbar fusion from L4 or L5 to sacrum were included in the study. Peripheral venous blood samples were obtained before surgery and on day 1, 3, 5, 12, 21, and 28 after surgery. Serum samples were analyzed for total Gc-globulin (Gc(total)), percentage of Gc-globulin complexed with actin (GC(complexed)), albumin, orosomucoid, haptoglobin, transferrin and creatin phosphokinase (CK).
RESULTS
Gc(total) decreased to 87% of pre-operative values on day one. Thereafter the levels increased to a maximum of 135% of pre-operative values on day five, approaching baseline values towards the end of the observation period. Compared to this, changes in GC(complexed) displayed a mirror-like time-course, with levels of Gc(total) and GC(complexed) being significantly inversely correlated on day one (P < 0.05). Levels of albumin remained below pre-operative values the first three weeks post-operatively, reaching baseline at the end of the observation period (P < 0.05).
CONCLUSION
The initial changes in Gc-globulin can be explained by increased release of actin from injured muscle tissue. Subsequently Gc-globulin displays characteristics of a so-called positive acute phase reactant, supporting previous in vitro studies, and clinical studies after minor surgery. In spite of genetic linkage and structural homology Gc-globulin and albumin are regulated differently after surgical trauma. | 10.1007/s000110050722 |
pubmed_403_24161 | Alzheimer's Disease (AD) is becoming more prevalent as the population lives longer. For individuals over 60 years of age, the prevalence of AD is estimated at 40.19% across the world. Regarding the cognitive decline caused by the disease, mitogen-activated protein kinases (MAPK) pathways such as the c-Jun N-terminal kinase (JNK) pathway are involved in the progressive loss of neurons and synapses, brain atrophy, and augmentation of the brain ventricles, being activated by synaptic dysfunction, oxidative stress, and excitotoxicity. Nowadays, AD symptoms are manageable, but the disease itself remains incurable, thus the inhibition of JNK3 has been explored as a possible therapeutic target, considering that JNK is best known for its involvement in propagating pro-apoptotic signals. This review aims to present biological aspects of JNK, focusing on JNK3 and how it relates to AD. It was also explored the recent development of inhibitors that could be used in AD treatment since several drugs/compounds in phase III clinical trials failed. General aspects of the MAPK family, therapeutic targets, and experimental treatment in models are described and discussed throughout this review. | 10.3390/ijms21249677 |
pubmed_17_491 | The complement system plays a complex role in transplantation, beginning with effects on reperfusion injury and continuing with stimulation of the adaptive immune response. Recent evidence has emphasised the importance of the late components of the complement cascade in the mediation of post-ischaemic damage, which are apparently triggered by the classical, alternative or lectin pathways of complement activation, depending on the organ affected. In studies of renal allograft rejection, the local synthesis of complement component C3 seems to influence the T-cell response more strongly than circulating complement protein, raising the possibility that there is co-operation between locally derived C3 and antigen presentation in the graft. Class switching of alloantibody to a high-affinity IgG response is also highly dependent on C3. In addition, the finding that capillary-bound C4d is a robust marker for humoral rejection has started a new investigation into the significance of alloantibodies in acute and chronic allograft rejection. There are several selective and nonselective inhibitors suitable for clinical development; clearly it is time for more concerted effort to evaluate their role in clinical transplantation. | 10.1016/s0952-7915(03)00100-6 |
pubmed_365_10988 | Human Chr 2p13-14 and homologous regions on mouse Chrs 6 and 11 have been subjects of previous studies because they comprise the loci for several neuromuscular diseases. Here we report on high-resolution mapping of 55 STS and EST loci on human Chr 2p13.3 and of 47 markers on the corresponding region on proximal mouse Chr. 11. The maps comprise several known genes, MEIS1/Meis1, RAB1a/Rab1a, MDH1/Mor2, OTX1/Otx1, and REL on human 2p13.3 and mouse Chr 11, respectively, as well as the wobbler (wr) critical region of the mouse. Whereas a perfect correspondence was found in most of the 4-Mb region, a small rearrangement was discovered around the OTX1/Otx1 locus. The detailed STS and EST transcript maps of these regions and a further narrowing down of the mouse wr critical region to the interval between D11Mit79 and D11Mit19 allow for the selection of positional candidate genes for wr, and the exclusion of others. | 10.1007/s003359900890 |
pubmed_986_11924 | Cytological hybridization in situ and karyotypic analysis have been used to investigate positional changes in rDNA, and morphological changes in rDNA-bearing chromosomes, in a series of cell lines established from patients with various proliferative disorders. Characteristic features of chromosomes in these cell lines include extreme differences in the number of rRNA genes per locus, translocations involving rDNA, and distinct rearrangements of a large portion of the rDNA complex to a q-terminal position on acrocentric chromosomes. | 10.1016/0165-4608(82)90016-4 |
pubmed_453_18466 | Precise diagnosis of well-differentiated hepatocellular carcinoma (HCC) is sometimes difficult to establish. Telomerase activity was examined by telomeric-repeat-amplification protocol (TRAP) in 37 HCC nodules smaller than 3 cm in diameter, including 24 fine-needle-aspiration biopsy specimens, 22 non-tumor chronic-liver-disease tissues (9 chronic hepatitis and 13 liver cirrhosis) and 3 normal liver tissues. Telomerase activity was assayed by serially diluted samples and quantitated by using an internal telomerase assay standard (ITAS). Telomerase activity was detected in all HCC and in 11 of 22 non-tumor chronic-liver-disease tissues. Normal liver samples had undetectable telomerase activity. Cut-off level of telomerase activity for its practical usage in HCC diagnosis was tentatively set for 0.6 microg liver protein/assay at 10-cell equivalent activity of a gastric-cancer cell line, MKN-1. This level was twice the highest activity in non-tumor chronic liver disease therefore, telomerase activity in all non-tumor liver samples was below this level. The telomerase-positive incidence exceeding this cut-off level was 73% (11/15) in well-differentiated HCC, 94% (16/17) in moderately differentiated HCC and 100% (5/5) in poorly differentiated HCC. Well-differentiated HCC showed low positivity by other diagnostic markers. 21% by AFP, 0% by PIVKA-II and 13% by angiography. The detection of telomerase activity may thus be a useful additional tool for precise and early diagnosis of small differentiated HCC, even when diagnosis is inconclusive by conventional techniques. | 10.1002/(sici)1097-0215(19970422)74:2<141::aid-ijc1>3.0.co;2-z |
pubmed_517_5695 | The role of human chondrocytes in the pathogenesis of cartilage degradation in rheumatic joint diseases has presently gained increasing interest. An active chondrocyte participation in local inflammation may play a role in the initiation and progression of inflammatory joint diseases and in a disruption of cartilage repair mechanisms resulting in cartilage degradation. In the present study, we hypothesized that inflammatory synovial fluid triggers human chondrocytes to actively take part in inflammatory processes in rheumatic joint diseases. Primary human chondrocytes were incubated in synovial fluids gained from patients with rheumatoid arthritis, psoriasis arthritis and reactive arthritis. The detection of vital cell numbers was determined by using Casy Cell Counter System. Apoptosis was measured by Annexin-V and 7AAD staining. Cytokine and chemokine secretion was determined by a multiplex suspension array. Detection of vital cells showed a highly significant decrease in chondrocyte numbers. Flow cytometry demonstrated a significant increase in apoptotic chondrocytes after the incubation. An active secretion of cytokines such as MCP-1 and MIF by chondrocytes was observed. The inflammatory synovial fluid microenvironment mediates apoptosis and cell death of chondrocytes. Moreover, in terms of cytokine secretion, it also induces an active participation of chondrocytes in ongoing inflammation. | 10.1007/s12026-011-8247-5 |
pubmed_1138_10458 | Rab escort proteins (REPs) bind to newly synthesized Rab proteins and remain bound during and after the attachment of a geranylgeranyl (GG) group by the catalytic component of the Rab GG transferase. Transfer of the GG group is absolutely dependent on the participation of a REP. REP-1, the first characterized REP, is produced by a gene on the X chromosome that is defective in patients with choroideremia, a form of retinal degeneration. Cremers et al. (Cremers, F.P.M., Molloy, C. M., van de Pol, D. J. R., van den Hurk, J. A. J. M., Bach, I., Geurts van Kessel, A. H. M., and Ropers, H.-H. (1992) Hum. Mol. Genet. 1, 71-75) isolated a related gene, designated choroideremia-like, which encodes a protein that closely resembles REP-1. In the current studies, we produced REP-1 and REP-2 by recombinant DNA methods and showed that both proteins were approximately equal in facilitating the attachment of GG groups to several Rab proteins, including Rab1A, Rab5A, and Rab6. However, REP-2 was only 25% as active as REP-1 in supporting GG attachment to Rab3A and Rab3D. The low activity toward Rab3A was increased to that of Rab1A when the COOH-terminal 12 amino acids of Rab3A were replaced with the corresponding residues of Rab1A. We suggest that REP-2 substitutes for the absent function of REP-1 in nonretinal cells of patients with choroideremia, thus preventing cellular dysfunction throughout the body. In the retina, REP-2 may be only partially effective, leading eventually to retinal degeneration and blindness. | pubmed_1138_10458 |
pubmed_929_255 | A target induced recycling amplification method for the detection of cellular microRNA is reported based on strand displacement polymerization and nicking endonuclease mediated cleavage. Moreover, by utilizing silver nanoparticle-based solid-state Ag/AgCl reaction, ultrahigh sensitivity is achieved with powerful discriminating towards the identification of target microRNA. The limit of detection is as low as 70 am. This method also allows the detection of cellular microRNA by lysing cells, thus making it a powerful tool for microRNA expression profiling and disease diagnosis. | 10.1002/cplu.201500249 |
pubmed_909_8272 | Mast cells (MCs) are active participants in blood coagulation and innate and acquired immunity. This review focuses on the development of mouse and human MCs, as well as the involvement of their granule serine proteases in inflammation and the connective tissue remodeling that occurs during the different phases of the healing process of wounded skin and other organs. The accumulated data suggest that MCs, their tryptases, and their chymases play important roles in tissue repair. While MCs initially promote healing, they can be detrimental if they are chronically stimulated or if too many MCs become activated at the same time. The possibility that MCs and their granule serine proteases contribute to the formation of keloid and hypertrophic scars makes them potential targets for therapeutic intervention in the repair of damaged skin. | pubmed_909_8272 |
pubmed_937_17846 | OBJECTIVE
To investigate the effect of mitogen-activated protein kinase (MAPK) signal cascade in the non-estrogen antagonistic mechanism of tamoxifen (TAM).
METHODS
Human breast cancer cells MCF-7 were cultured. TAM, PD98075, inhibitor of MAPK kinase (MEK), or TAM + PD98075 was added into the culture media, followed by methyl thiazolyl tetrazolium (MTT) and DMSO. Then the 542nm absorption value was measured and the growth curve was drawn. Western blot was used to measure the expression of p-extracellular signal-regulated kinase (ERK) in MCF-7 cells. Flow cytometry was applied to analyze the cell cycle and apoptosis.
RESULTS
The optical density representing the relative expression of p-ERK was lower successively in the control, TAM, PD09875, and TAM + PD09875 groups. The apoptotic rate of MCF-7 cells was 6.44%, 8.3%, 36.5% and 53.5% in the control, PD98075, TAM, and TAM + PG98075 groups respectively The rate of cells in G(0)G(1) phase was 74.25%, 79.76%, 84.02%, and 95.82% in those groups respectively. Ther rate o cells in S phase was 21.03%, 15.22%, 11.43%, and 2.22% respectively in those groups. The rate of cells in G(2)M phase was 4.71%, 5.02%, 4.52%, and 1.96% respectively in those groups.
CONCLUSION
MAPK signal transduction pathway plays a certain role in the non-estrogen antagonistic mechanism of tamoxifen. | pubmed_937_17846 |
pubmed_202_19009 | The kinetics of the binding of mebendazole (MBZ) to tubulin from the third-stage (L3) larvae of the parasitic nematode, Haemonchus contortus, have been characterized. In partially purified preparations, the association of [3H]MBZ to nematode tubulin was rapid, k1 = (2.6 +/- 0.3) x 10(5) M-1 min-1, but dissociation was slow, k-1 = (1.58 +/- 0.02) x 10(-3) min-1. The affinity constant (K(a)) for the interaction, determined by the ratio k1/k-1, was (1.6 +/- 0.2) x 10(8) M-1. Similar results were obtained with crude cytosolic fractions. In equilibrium studies, performed with partially purified nematode tubulin under similar conditions, a K(a) of (5.3 +/- 1.6) x 10(6) M-1 was obtained. The best estimate for the K(a) of the MBZ-nematode tubulin interaction is considered to be the 'kinetic' value determined from the ratio of rate constants. The slow dissociation of MBZ from nematode tubulin, which contrasts with the rapid dissociation of MBZ from mammalian tubulin, supports the hypothesis that the selective toxicity of the benzimidazole anthelmintics results from a difference between the affinities of mammalian and nematode tubulins for these drugs. | 10.1016/0020-7519(92)90051-l |
pubmed_83_18675 | Cold plasma technology is an emerging tool facilitating the spatially controlled delivery of a multitude of reactive species (ROS) to the skin. While the therapeutic efficacy of plasma treatment has been observed in several types of diseases, the fundamental consequences of plasma-derived ROS on skin physiology remain unknown. We aimed to bridge this gap since the epidermal skin barrier and perfusion plays a vital role in health and disease by maintaining homeostasis and protecting from environmental damage. The intact skin of SKH1 mice was plasma-treated in vivo. Gene and protein expression was analyzed utilizing transcriptomics, qPCR, and Western blot. Immunofluorescence aided the analysis of percutaneous skin penetration of curcumin. Tissue oxygenation, perfusion, hemoglobin, and water index was investigated using hyperspectral imaging. Reversed-phase liquid-chromatography/mass spectrometry was performed for the identification of changes in the lipid composition and oxidation. Transcriptomic analysis of plasma-treated skin revealed modulation of genes involved in regulating the junctional network (tight, adherence, and gap junctions), which was confirmed using qPCR, Western blot, and immunofluorescence imaging. Plasma treatment increased the disaggregation of cells in the stratum corneum (SC) concomitant with increased tissue oxygenation, gap junctional intercellular communication, and penetration of the model drug curcumin into the SC preceded by altered oxidation of skin lipids and their composition in vivo. In summary, plasma-derived ROS modify the junctional network, which promoted tissue oxygenation, oxidation of SC-lipids, and restricted penetration of the model drug curcumin, implicating that plasma may provide a novel and sensitive tool of skin barrier regulation. | 10.1016/j.freeradbiomed.2020.09.026 |
pubmed_213_1182 | Four mg of lorazepam was given intravenously 5 min prior to thiopental anaesthesia in 5 clinically healthy dogs weighing 14 +/- 2 kg and aged about 10-12 months. Animals required only 7.0 +/- 1.5 ml of 5% thiopental sodium to achieve surgical anaesthesia which lasted about 30.4 +/- 3.3 minutes. There was adequate muscle relaxation and loss of pedal and palpebral reflexes. Five min after administration of lorazepam, there was no appreciable change in various cardiopulmonary dynamics. However, there was moderate arterial hypertension, tachycardia and arterial hypoxemia 15 min after the onset of the thiopental anaesthesia. There was no respiratory depression. The lorazepam-thiopental combination was also attempted in 16 clinical cases varying from repair of fractures of long bones (9), mammary tumour (2), ear haematoma (1), ear cropping (1), tail gangrene (2) and rectal prolapse (1). This combination of anaesthesia proved extremely useful for orthopaedic surgery as the muscle relaxation was adequate and reduction of the fractured ends was comparatively easier. | 10.1111/j.1439-0442.1989.tb00788.x |
pubmed_884_10079 | Refering to a case report of five patients with atrial myxoma the symptoms, diagnosis, and therapy of this disease were described. In one case a biatrial tumor was found. In four cases atrial myxoma imitated a mitral-valve disease. An elevated BSR was found in all patients. The non invasive diagnostic procedure of ultrasound-echocardiography led in the last two cases to the correct diagnosis before heart-catheterization. The diagnosis was ascertained in all cases by angiocardiography. If left atrial tumor is suspected transpulmonary laevocardiography can be considered as a save diagnostic procedure better than the direct injection into the left atrium after transseptal puncture. Even the left ventricular angiogram in right anterior oblique position led in four of the five cases to the diagnosis of left atrial tumor. Coronary-angiography was performed in three patients and revealed pathologic atrial vessels in all three cases. Immediate operation is the indicated therapy. Two of the five patients were reviewed over a eight year period after operation without any signs of recurrence of the tumor. | pubmed_884_10079 |
pubmed_970_4370 | Riparian buffer systems (RBS) are considered a best management practice (BMP) in agricultural landscapes to intercept soil nitrogen (N) and phosphorus (P) leaching and surface runoff into aquatic ecosystems. However, these environmental benefits could be offset by increased greenhouse gas (GHG) emissions, including nitrous oxide (N2O). The main sources of N2O in soil are linked to processes which are mediated by soil microbial communities. These microorganisms play crucial roles in N-cycling and in the reduction of nitrate to N2, and N2O gases. This study was conducted to determine the abundance and diversity of microbial communities and functional genes associated with N-cycling and their influence on N2O emissions in different riparian land-use: undisturbed natural forest (UNF), rehabilitated site (RH), grass buffer (GRB), and an adjacent agricultural land (AGR). Soil was sampled concurrently with N2O emissions on July 13, 2017. DNA was extracted and used to target key N-cycling genes for N-fixation (nifH), nitrification: (amoA), and denitrification (nirS, nirK, and nosZ) via quantitative PCR, and for high throughput sequencing of total bacterial and fungal communities. Non-metric multidimensional scaling (NMDS) was used to examine microbial community composition and indicated significant differences in bacterial (p < 0.001) and fungal (p < 0.0085) communities between sites. Bacterial abundance differed significantly (p = 0.0005) between RBS and AGR sites with the highest populations occurring in the UNF (2.1 × 1010 copies g-1 dry soil), and lowest in AGR (5.3 × 109 copies g-1 dry soil). However, the AGR site had the highest ammonia-oxidizing bacteria (AOB) abundance, indicating that nitrification is highest at this site. The abundance of the nosZ gene was highest in RH and GRB demonstrating the capacity for complete denitrification at these sites, lowering measured N2O. These results suggest N-cycling microbial community dynamics differ among RBS and are influencing N2O emissions in the sites investigated. | 10.1016/j.scitotenv.2020.138148 |
pubmed_898_5958 | Objective of the study was to determine the correlation between plasma levels of galectin-3 and aldosterone and the dependence of their levels on different clinical characteristics in patients of young and middle age with stage 2 arterial hypertension. 160 male and female patients (80 persons of each gender) with stage 2 hypertension, regardless of the degree, and 27 relatively healthy persons were examined by determining the levels of galectin-3 and aldosterone in blood serum of the main and control groups of the examined persons. The absence of a statistically significant correlation (n=27, R=-0.28, p=0.16) between galectin-3 and aldosterone levels in generally healthy individuals was proved, and the presence of a direct correlation of the average strength between the level of neurohormones (n=160, R=0.64, p<0.0001) in patients of young and middle age with stage 2 hypertension was shown. In addition, the fact of fundamental differences in the nature of associations distribution with the similar level of galectin-3 and aldosterone was demonstrated: in patients with stage 2 and 3 AH as compared to patients with stage 1 AH; in patients with abdominal obesity as compared to patients with normal weight; in patients with dyslipidemia as compared to normal level of proatherogenic lipids. Positive correlation between association with a high level of galectin-3 and aldosterone with the presence of dyslipidemia (R=0.24, p=0.03), high degree of AH (R=0.30, p=0.01), an increase in the total number of risk factors (R=0.45, p<0.0001) and abdominal obesity (R=0.72, p<0.0001) was determined. | pubmed_898_5958 |
pubmed_542_7070 | Progressive myopia may result from an inherited biomechanical weakness of the sclera that allows it to stretch (creep) in response to stress. Increased intraocular pressure could be the mediator of stress produced by the inclined head position and the accommodation/convergence aspects of near work. This paper reviews data that relate to this hypothesis including work on sclera, intraocular pressure, animal models of myopia, and attempts at human treatment. Although the weight of evidence appears to support the proposed notion, no firm conclusion can be drawn due to imperfections in the design of prior studies. A future research agenda is proposed, including a controlled clinical trial of pharmacologically sustained ocular hypotension in young progressive myopes. | 10.1111/j.1755-3768.1988.tb02685.x |
pubmed_361_12320 | Four different methods for the determination of the total serum IgE in children with atopic diseases have been compared. The three ELISA tests and radiosorbent test (PRIST) have shown satisfactory correlation, though in several cases diagnostically significant discrepancies have been observed. An ELISA system has been developed and proved to be highly sensitive in the detection of the total serum IgE (0.3 ng IgE per 1 ml of the sample). | pubmed_361_12320 |
pubmed_1038_11874 | The present study compared the validity of visual estimations of percent fat (% fat) in lean males (mean +/- SD = 9.6 +/- 2.3 % fat) to the validity of bioelectrical impedance analysis (BIA) and skinfold equations. Thirty-five Caucasian male volunteers (mean +/- SD = 23 +/- 5 yr; range = 19-40) served as subjects. Visual estimations of % fat were performed by two experienced male raters. The validity (compared to underwater weighing) for each procedure was determined by examining the constant error (CE), standard error of the estimate (SEE), r, and total error (TE). The results indicated that rater 1 (TE = 2.3% fat) could visually estimate % fat as accurately as the skinfold equations (TE = 2.4% fat). However, based on low TE, SEE, and CE values as well as considerable variability (mean difference = 2.7% fat) between the % fat estimates of the two raters, skinfold equations are recommended over visual inspection and BIA (TE = 5.0% fat) for estimating % fat in lean males. | pubmed_1038_11874 |
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