tbuckley/cabot-search huggingface dataset:
Endogenous fibroblast growth factor-2 mediates cytotoxicity in experimental mesangioproliferative glomerulonephritis.
Authors: J Floege, M Burg, C Hugo, K L Gordon, H Van Goor, M Reidy, W G Couser, K M Koch, R J Johnson
Journal: Journal of the American Society of Nephrology (1998)

Fibroblast growth factor-2 (FGF-2) is released from mesangial cells in experimental mesangioproliferative glomerulonephritis induced with anti-Thy 1.1 antibody. To investigate the functional role of released FGF-2, rats received either neutralizing anti-FGF-2 IgG or a functional peptide antagonist of FGF-2 (FGF119-126) before or shortly after induction of anti-Thy 1.1 nephritis. In additional experiments, rats were treated with bolus injections of FGF-2 from 2 to 6 h after disease induction. The data showed that anti-FGF-2 therapy led to significant reductions of early mesangial cell injury (mesangiolysis, microaneurysm formation) and the subsequent mesangioproliferative changes (glomerular de novo expression of alpha-smooth muscle actin, mesangial cell proliferation, matrix accumulation, and platelet influx). Conversely, injections of FGF-2 augmented both mesangial injury and the subsequent mesangioproliferative changes. Studies on the mechanisms underlying the amplification of mesangial cell injury by FGF-2 showed that anti-FGF-2 therapy reduced cell death at 2 and 8 h after disease induction by 58 and 54%, respectively. This was associated with significant reductions in the number of glomerular H2O2- and OH -producing cells, as well as reduced glomerular production of nitric oxide. These data suggest that release of constitutively expressed FGF-2 after immune-mediated cell injury contributes to glomerular cell damage and thus identify FGF-2 as a novel mediator of cytotoxicity.
Axonal Ion Channel Dysfunction in<i>C9orf72</i>Familial Amyotrophic Lateral Sclerosis
Authors: Nimeshan Geevasinga, Parvathi Menon, James Howells, Garth A. Nicholson, Matthew C. Kiernan, Steve Vucic
Journal: JAMA Neurology (2014)

IMPORTANCEAbnormalities of axonal excitability characterized by upregulation of persistent sodium (Na + ) conductances and reduced potassium (K + ) currents have been reported in sporadic amyotrophic lateral sclerosis (SALS) phenotypes and linked to the development of clinical features such as fasciculations and neurodegeneration.OBJECTIVE To investigate whether abnormalities of axonal ion channel function, particularly upregulation of persistent Na + conductances and reduced K + currents, form the pathophysiological basis of chromosome 9 open reading frame 72 (c9orf72) familial amyotrophic lateral sclerosis (FALS). DESIGN, SETTING, AND PARTICIPANTSThis was a prospective study.Clinical and functional assessment, along with motor-nerve excitability studies, were undertaken in 10 clinically affected patients with c9orf72 FALS, 9 asymptomatic c9orf72 mutation carriers, and 21 patients with SALS from 3 hospitals and 2 outpatient clinics.MAIN OUTCOMES AND MEASURES Axonal excitability variables were measured in patients with c9orf72 ALS and results compared with matched patients with SALS and healthy control participants.RESULTS Strength-duration time constant (τ SD ) was significantly increased in the patients with c9orf72 FALS and those with SALS (mean [SD], c9orf72 FALS: 0.50 [0.02] milliseconds; SALS: 0.52 [0.02] milliseconds; P < .01)when compared with control participants (mean [SD], 0.44 [0.01] milliseconds).In contrast, there were no significant changes of τ SD in asymptomatic c9orf72 mutation carriers (P = .42).An accompanying increase in depolarizing threshold electrotonus at 90 to 100 milliseconds (TEd 90-100 milliseconds) was also evident in the c9orf72 FALS (P < .05)and SALS (P < .01)cohorts.Mathematical modeling suggested that an increase in persistent Na + conductances, along with reduced K + currents, best explained the changes in axonal excitability.Importantly, these abnormalities in axonal excitability correlated with the motor amplitude (τ SD : R = -0.38,P < .05 and TEd 90-100 milliseconds: R = -0.44,P < .01),muscle weakness (TEd 90-100 milliseconds: R = -0.32,P < .05),and the ALS Functional Rating Scale (TEd 90-100 milliseconds: R = -0.34,P < .05). CONCLUSIONS AND RELEVANCEFindings from the present study establish that upregulation of persistent Na + conductances and reduced K + currents were evident in both c9orf72 FALS and SALS cohorts, and these changes in axonal excitability were associated with motor neuron degeneration.
SOAPfuse: an algorithm for identifying fusion transcripts from paired-end RNA-Seq data
Authors: Wenlong Jia, Kunlong Qiu, Minghui He, Pengfei Song, Quan Zhou, Feng Zhou, Yuan Yu, Dandan Zhu, Michael L Nickerson, Shengqing Wan, Xiangke Liao, Xiaoqian Zhu, Shaoliang Peng, Yingrui Li, Jun Wang, Guangwu Guo
Journal: Genome biology (2013)

Abstract We have developed a new method, SOAPfuse, to identify fusion transcripts from paired-end RNA-Seq data. SOAPfuse applies an improved partial exhaustion algorithm to construct a library of fusion junction sequences, which can be used to efficiently identify fusion events, and employs a series of filters to nominate high-confidence fusion transcripts. Compared with other released tools, SOAPfuse achieves higher detection efficiency and consumed less computing resources. We applied SOAPfuse to RNA-Seq data from two bladder cancer cell lines, and confirmed 15 fusion transcripts, including several novel events common to both cell lines. SOAPfuse is available at http://soap.genomics.org.cn/soapfuse.html .
Effect of High-Protein Diet on Pyrimidine Synthesis and Response to PALA in Mouse Tissues
Authors: D. W. Zaharevitz, M. F. Grubb, R. Hyman, C. Chisena, R. L. Cysyk
Journal: JNCI Journal of the National Cancer Institute (1993)

High-protein diets have been found to protect mice from the lethal effects of cytotoxic pyrimidine analogues and to reduce the toxicity of the antipyrimidine fluorouracil (5-FU), but the biochemical explanation for these effects is not known. PALA potentiates the chemotherapeutic efficacy of 5-FU, and each of the two agents can produce dose-limiting intestinal toxic effects. We have shown that intraperitoneal infusion of ammonium chloride stimulates intestinal de novo pyrimidine synthesis. This stimulation with excess ammonia, which can also result from high-protein intake, is dependent on the presence of carbamoyl phosphate synthetase I, an enzyme in the liver and intestine but not in most tumors. These findings suggest that a high-protein diet can stimulate pyrimidine synthesis in the liver and intestine but leave it unchanged in tumor tissue.The purpose of this study was to determine whether varying dietary protein causes pharmacologically relevant and preferential changes in de novo pyrimidine synthesis.Mice were fed diets containing 18%, 35%, or 50% casein. Dietary effects on de novo pyrimidine synthesis were measured in the intestine, liver, and B16 mouse melanoma in mice treated with PALA and in untreated mice. De novo synthesis was measured by infusion of [15N]alanine into intact animals, determination of 15N incorporation into uracil by use of gas chromatography-mass spectrometry, and calculation of the fraction of the uracil nucleotide pool formed by de novo synthesis.In mice on a 50% casein diet (high protein), de novo pyrimidine synthesis increased substantially in the liver and intestine, compared with synthesis in mice receiving 18% casein. Increase in pyrimidine synthesis in B16 tumor tissue was negligible. The high-protein diet protected the intestine and liver from depletion of uracil nucleotide pools by PALA, and toxicity in tumor-free animals was reduced, as determined by mortality after PALA treatment. Sensitivity of the B16 tumor to the biochemical and cytotoxic effects of PALA was not diminished.We propose that the basis for these effects of a high-protein diet is the generation of excess carbamoyl phosphate in tissues containing carbamoyl phosphate synthetase I. This carbamoyl phosphate can stimulate de novo pyrimidine synthesis and compete with drugs that interact with enzymes of the de novo pathway, thereby selectively protecting the liver and intestine.These data provide a biochemical explanation for reported effects of high-protein diet on toxicity of antipyrimidines like 5-FU. Studies are underway to determine if stimulation of pyrimidine synthesis by excess ammonia improves therapy with 5-FU alone or combined with PALA.
Temporal Variability and Predictors of Urinary Bisphenol A Concentrations in Men and Women
Authors: Shruthi Mahalingaiah, John D. Meeker, Kimberly R. Pearson, Antonia M. Calafat, Xiaoyun Ye, John Petrozza, Russ Hauser
Journal: Environmental Health Perspectives (2007)

BackgroundBisphenol A (BPA) is used to manufacture polymeric materials, such as polycarbonate plastics, and is found in a variety of consumer products. Recent data show widespread BPA exposure among the U.S. population.ObjectiveOur goal in the present study was to determine the temporal variability and predictors of BPA exposure.MethodsWe measured urinary concentrations of BPA among male and female patients from the Massachusetts General Hospital Fertility Center.ResultsBetween 2004 and 2006, 217 urine samples were collected from 82 subjects: 45 women (145 samples) and 37 men (72 samples). Of these, 24 women and men were partners and contributed 42 pairs of samples collected on the same day. Ten women became pregnant during the follow-up period. Among the 217 urine samples, the median BPA concentration was 1.20 μg/L, ranging from below the limit of detection (0.4 μg/L) to 42.6 μg/L. Age, body mass index, and sex were not significant predictors of urinary BPA concentrations. BPA urinary concentrations among pregnant women were 26% higher (–26%, +115%) than those among the same women when not pregnant (p &gt; 0.05). The urinary BPA concentrations of the female and male partner on the same day were correlated (r = 0.36; p = 0.02). The sensitivity of classifying a subject in the highest tertile using a single urine sample was 0.64.ConclusionWe found a nonsignificant increase in urinary BPA concentrations in women while pregnant compared with nonpregnant samples from the same women. Samples collected from partners on the same day were correlated, suggesting shared sources of exposure. Finally, a single urine sample showed moderate sensitivity for predicting a subject’s tertile categorization.
Ibuprofen does not affect serum electrolyte concentrations after an ultradistance run * COMMENTARY
Authors: Charles L Dumke, David C Nieman, Kevin Oley, Robert H Lind
Journal: British Journal of Sports Medicine (2007)

Objective: To determine the effects of ibuprofen on serum electrolyte concentrations after a 160 km running race. Methods: Twenty nine subjects (mean (SD) age 47.9 (7.4) years) ingested 600 mg ibuprofen the day before, and 1200 mg ibuprofen during, a 160 km competitive trail running race (approximately every 4 h in 200 mg doses). Twenty five control subjects (mean (SD) age 46.8 (10.3) years) avoided ingestion of ibuprofen before or during the race. Blood was drawn on the day before the race and immediately after the race. Serum biochemical profiles were analysed by a clinical laboratory. Significant effects of treatment and time were determined with a general linear model with repeated measures. Results: Subjects in the two groups did not differ by age, training volume, race experience, body mass index, body fat, or finishing time (25.8 (3.3) vs 25.6 (3.9) h). Body weight did not change significantly over the race (measured before, mid-race (90 km), and after). Ibuprofen ingestion did not significantly affect any of the serum markers including creatine kinase (p = 0.16). A significant decrease in serum sodium (p = 0.006), potassium (p = 0.001), chloride (p&lt;0.001), calcium (p&lt;0.001), albumin (p&lt;0.001) and globulin (p&lt;0.001) was observed after the race. Increases were seen in creatine kinase (p&lt;0.001), creatinine (p&lt;0.001), blood urea nitrogen (p&lt;0.001), uric acid (p&lt;0.001) and glucose (p&lt;0.001) as the result of the race. Conclusions: These data suggest that the non-specific cyclo-oxygenase inhibitor, ibuprofen, does not alter serum electrolyte concentrations during ultradistance running. However, the stress of ultradistance running appears to be related to significant changes in certain serum markers.
CD8+ Regulatory T Cells Induced by T Cell Vaccination Protect Against Autoimmune Nephritis
Authors: Yuan Min Wang, Geoff Yu Zhang, Min Hu, Tania Polhill, Andrew Sawyer, Jimmy Jianheng Zhou, Mitsuru Saito, Debbie Watson, Huiling Wu, Ya Wang, Xin Maggie Wang, Yiping Wang, David C.H. Harris, Stephen I. Alexander
Journal: Journal of the American Society of Nephrology (2012)

Autoreactive T cells play a pivotal role in the pathogenesis of autoimmune kidney disease. T cell vaccination (TCV) may limit autoimmune disease and induce CD8+ regulatory T cells (Tregs). We used Heymann nephritis (HN), a rat model of human membranous nephritis, to study the effects of TCV on autoimmune kidney disease. We harvested CD4+ T cells from renal tubular antigen (Fx1A) -immunized rats and activated these cells in vitro to express the MHC Class Ib molecule Qa-1. Vaccination of Lewis rats with these autoreactive Fx1A-induced T cells protected against HN, whereas control-primed T cells did not. Rats that underwent TCV had lower levels of proteinuria and serum creatinine and significantly less glomerulosclerosis, tubular damage, and interstitial infiltrates. Furthermore, these rats expressed less IFN-γ and IL-6 in splenocytes, whereas the numbers of Tregs and the expression of Foxp3 were unchanged. In vitro cytotoxicity assays showed CD8+ T cell-mediated elimination of Qa-1-expressing CD4+ T cells. In vivo, TCV abrogated the increase in Qa-1-expressing CXCR5+ TFH cells observed in HN compared with controls. Taken together, these results suggest that TCV protects against autoimmune kidney disease by targeting Qa-1-expressing autoreactive CD4+ cells.
Effects of high intensity canoeing training on fibre area and fibre type in the latissimus dorsi muscle.
Authors: S J Baker, L Hardy
Journal: British Journal of Sports Medicine (1989)

A high intensity short duration exercise training programme was undertaken by nine subjects on three occasions each week for nine weeks. Muscle samples from the latissimus dorsi were taken by needle biopsy, at rest, before and after training. The results revealed that there was no change in either Type I or Type II muscle fibre distribution following training. Type I fibre area did not alter significantly as a result of the training stress. Mean cross-sectional area of Type II fibres was 82 per cent greater post-training than pre-training.
Physical and sexual abuse histories among children with borderline personality disorder
Authors: S J Goldman, E J D'Angelo, D R DeMaso, E Mezzacappa
Journal: American Journal of Psychiatry (1992)

The purpose of the study was to determine whether a history of physical or sexual abuse is more common in children with borderline personality disorder than in other children evaluated in the same outpatient psychiatric clinic.The authors contrasted rates of abuse in 44 children diagnosed with borderline personality disorder and in 100 comparison children.The borderline personality disorder group had a significantly greater prevalence of physical and combined physical/sexual abuse. Sexual abuse rates alone did not differ significantly between groups.The finding of greater abuse in the group with borderline personality disorder supports the hypothesis that a history of trauma is associated with the disorder.
RNA Interference (RNAi)-Based Therapeutics: Delivering on the Promise?
Authors: Maggie L. Bobbin, John J. Rossi
Journal: The Annual Review of Pharmacology and Toxicology (2016)

A resurgence in clinical trials using RNA interference (RNAi) occurred in 2012. Although there were initial difficulties in achieving efficacious results with RNAi without toxic side effects, advances in delivery and improved chemistry made this resurgence possible. More than 20 RNAi-based therapeutics are currently in clinical trials, and several of these are Phase III trials. Continued positive results from these trials have helped bolster further attempts to develop clinically relevant RNAi therapies. With a wide variety of disease targets to choose from, the first RNAi therapeutic to be clinically approved is not far off. This review covers recently established and completed clinical trials.
Developmental Stage, Phenotype, and Migration Distinguish Naive- and Effector/Memory-like CD4+ Regulatory T Cells
Authors: Jochen Huehn, Kerstin Siegmund, Joachim C.U. Lehmann, Christiane Siewert, Uta Haubold, Markus Feuerer, Gudrun F. Debes, Joerg Lauber, Oliver Frey, Grzegorz K. Przybylski, Uwe Niesner, Maurus de la Rosa, Christian A. Schmidt, Rolf Bräuer, Jan Buer, Alexander Scheffold, Alf Hamann
Journal: The Journal of Experimental Medicine (2004)

Regulatory T cells (Tregs) fulfill a central role in immune regulation. We reported previously that the integrin αEβ7 discriminates distinct subsets of murine CD4+ regulatory T cells. Use of this marker has now helped to unravel a fundamental dichotomy among regulatory T cells. αE−CD25+ cells expressed L-selectin and CCR7, enabling recirculation through lymphoid tissues. In contrast, αE-positive subsets (CD25+ and CD25−) displayed an effector/memory phenotype expressing high levels of E/P-selectin–binding ligands, multiple adhesion molecules as well as receptors for inflammatory chemokines, allowing efficient migration into inflamed sites. Accordingly, αE-expressing cells were found to be the most potent suppressors of inflammatory processes in disease models such as antigen-induced arthritis.
The use of the tumour necrosis factor antagonist infliximab in heart transplant recipients: two case reports
Authors: S Metyas, D La, D G Arkfeld
Journal: Annals of the Rheumatic Diseases (2007)

Inflammatory cytokines, such as tumour necrosis factor alpha (TNF-α), have been implicated in the pathophysiology of heart failure, leading to the hypothesis that TNF inhibition might improve the symptoms of patients with moderate-to-severe cardiac symptoms. Recent data from the Anti-TNF Therapy Against Congestive Heart failure (ATTACH) pilot study, however, suggested that infliximab, a chimeric monoclonal antibody against TNF-α, not only failed to produce clinical benefits, but given at higher doses (10 mg/kg) was associated with a worsening of cardiac symptoms. Conversely, two large-scale trials, RECOVER and RENAISSANCE, examined the effects of infliximab and etanercept in over 2000 patients with heart failure, finding no …
Control of cytoplasmic and nuclear protein kinase A by phosphodiesterases and phosphatases in cardiac myocytes
Authors: Zeineb Haj Slimane, Ibrahim Bedioune, Patrick Lechêne, Audrey Varin, Florence Lefebvre, Philippe Mateo, Valérie Domergue-Dupont, Matthias Dewenter, Wito Richter, Marco Conti, Ali El-Armouche, Jin Zhang, Rodolphe Fischmeister, Grégoire Vandecasteele
Journal: Cardiovascular Research (2014)

AimsThe cAMP-dependent protein kinase (PKA) mediates β-adrenoceptor (β-AR) regulation of cardiac contraction and gene expression. Whereas PKA activity is well characterized in various subcellular compartments of adult cardiomyocytes, its regulation in the nucleus remains largely unknown. The aim of the present study was to compare the modalities of PKA regulation in the cytoplasm and nucleus of cardiomyocytes.
Psychological and behavioural reactions to the bombings in London on 7 July 2005: cross sectional survey of a representative sample of Londoners
Authors: G James Rubin, Chris R Brewin, Neil Greenberg, John Simpson, Simon Wessely
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objectives</b> To assess the impact of the bombings in London on 7 July on stress levels and travel intentions in London9s population. <b>Design</b> A cross sectional telephone survey using random digit dialling was conducted to contact a representative sample of adults. Respondents were asked to participate in an interview enquiring about current levels of stress and travel intentions. <b>Setting Interviews</b> took place between 18 and 20 July. <b>Participants</b> 1010 participants (10% of the eligible people we contacted) completed the interviews. <b>Main outcome measures</b> Main outcomes were presence of substantial stress, measured by using an identical tool to that used to assess the emotional impact of 11 September 2001 in the US population, and intention to travel less on tubes, trains, and buses, or into central London, once the transport network had returned to normal. <b>Results</b> 31% of Londoners reported substantial stress and 32% reported an intention to travel less. Among other things, having difficulty contacting friends or family by mobile phone (odds ratio 1.7, 95% confidence interval 1.1 to 2.7), having thought you could have been injured or killed (3.8, 2.4 to 6.2), and being Muslim (4.0, 2.5 to 6.6) were associated with a greater presence of substantial stress, whereas being white (0.3, 0.2 to 0.4) and having previous experience of terrorism (0.6, 0.5 to 0.9) were associated with reduced stress. Only 12 participants (1%) felt that they needed professional help to deal with their emotional response to the attacks. <b>Conclusions</b> Although the psychological needs of those intimately caught up in the attacks will require further assessment, we found no evidence of a widespread desire for professional counselling. The attacks have inflicted disproportionately high levels of distress among non-white and Muslim Londoners.
Comment on Shore et al. Association Between Hyperglycemia at Admission During Hospitalization for Acute Myocardial Infarction and Subsequent Diabetes: Insights From the Veterans Administration Cardiac Care Follow-up Clinical Study. Diabetes Care 2014;37:409–418
Authors: Luigi Meloni, Roberta Montisci, Massimo Ruscazio
Journal: Diabetes Care (2014)

We read with great interest the recently published article by Shore et al. (1) that addresses the important issue of admission hyperglycemia during hospitalization for acute myocardial infarction (AMI). The authors measured the prevalence of admission hyperglycemia in a very large cohort of AMI patients without known diabetes and examined its association with new evidence of diabetes in the 6 months following hospitalization. Diagnostic codes for diabetes, outpatient prescriptions for glucose-lowering medications, and/or HbA1c ≥6.5% during or after the index hospitalization were used for …