tbuckley/cabot-search huggingface dataset:
Effects of fasting on insulin binding, glucose transport, and glucose oxidation in isolated rat adipocytes: relationships between insulin receptors and insulin action.
Authors: J M Olefsky
Journal: Journal of Clinical Investigation (1976)

Insulin binding, glucose transport, and glucose oxidation were studied in isolated adipocytes obtained from fasting rats. Fasting led to an increase in the overall binding affinity for insulin, while the number of receptor sites per cell remained constant. Glucose oxidation was markedly attenuated during fasting. Basal rates of oxidation decreased by about 50%, while insulin-stimulated rates decreased 6 to 10-fold. Glucose transport was assessed by measuring initial uptake rate of 2-deoxy-glucose. Fasting led to a 40-50% decrease in the apparent maximal transport capacity (Vmax) of 2-deoxy-glucose uptake with no change in apparent Km. A progressive decrease in basal and insulin-stimulated rates of 2-deoxy-glucose uptake was seen from 24-72 h of starvation and a significant correlation (r=0.85, P less than 0.001) existed between basal and maximal insulin-stimulated uptake rates in individual animals. When 2-deoxy-glucose uptake was plotted as a function of insulin bound, due to the decrease in maximal uptake capacity, cells from fasting animals took up less hexose for any amount of insulin bound. When the insulin bound was plotted as a function of the percent insulin effect on uptake, control cells and cells from 24-h-fasted rats gave comparable results, while cells from 48- and 72-h-fasted animals still took up less hexose for any amount of bound insulin. The effects of fasting on 3-O-methyl glucose uptake were comparable to the 2-deoxy-glucose data. In conclusion: (a) insulin binding is increased during fasting due to an increased overall binding affinity with no change in receptor number; (b) glucose oxidation is severely impaired during fasting; (c) 2-deoxy-glucose uptake decreases with fasting due to a decrease in maximal transport capacity (Vmax) with no change in Km; (d) the decrease in glucose oxidation is much greater than the decrease in glucose transport, indicating impaired intracellular oxidative metabolism; and (e) coupling between insulin receptors and the glucose transport system is normal after 24 h of fasting but is impaired at 48 and 72 h.
Genetic Suppression of Inflammation Blocks the Tumor-Promoting Effects of TGF-β in Gastric Tissue
Authors: Mitsuhiko Ota, Masahito Horiguchi, Victoria Fang, Kotaro Shibahara, Kyuichi Kadota, Cynthia Loomis, Michael Cammer, Daniel B. Rifkin
Journal: Cancer Research (2014)

Abstract The contributions of TGF-β signaling to cancer are complex but involve the inflammatory microenvironment as well as cancer cells themselves. In mice encoding a TGF-β mutant that precludes its binding to the latent TGF-β binding protein (Tgfb1−/C33S), we observed multiorgan inflammation and an elevated incidence of various types of gastrointestinal solid tumors due to impaired conversion of latent to active TGF-β1. By genetically eliminating activators of latent TGF-β1, we further lowered the amount of TGF-β, which enhanced tumor frequency and multiorgan inflammation. This model system was used to further investigate the relative contribution of TGF-β1 to lymphocyte-mediated inflammation in gastrointestinal tumorigenesis. Toward this end, we generated Tgfb1−/C33S;Rag2−/− mice that lacked adaptive immune function, which eliminated tumor production. Analysis of tissue from Tgfb1−/C33S mice indicated decreased levels of P-Smad3 compared with wild-type animals, whereas tissue from Tgfb1−/C33S;Rag2−/− mice had normal P-Smad3 levels. Inhibiting the inflammatory response normalized levels of interleukin (IL)-1β and IL-6 and reduced tumor cell proliferation. In addition, Tgfb1−/C33S;Rag2−/− mice exhibited reduced paracrine signaling in the epithelia, mediated by hepatocyte growth factor produced by gastric stroma. Together, our results indicate that many of the responses of the gastric tissue associated with decreased TGF-β1 may be directly or indirectly affected by inflammatory processes, which accompany loss of TGF-β1, rather than a direct effect of loss of the cytokine. Cancer Res; 74(9); 2642–51. ©2014 AACR.
Cytomegalovirus Immune Globulin Prophylaxis in Liver Transplantation
Authors: D R Snydman, B G Werner, N N Dougherty, J Griffith, R H Rubin, J L Dienstag, R H Rohrer, R Freeman, R Jenkins, W D Lewis, S Hammer, E O'Rourke, G F Grady, K Fawaz, M M Kaplan, M A Hoffman, A T Katz, M Doran
Journal: Annals of Internal Medicine (1993)

To study the effect of cytomegalovirus immune globulin (CMVIG) on prevention of cytomegalovirus (CMV) disease and its complications in patients receiving liver transplants.Randomized, multicenter, placebo-controlled, double-blind trial.Four university-affiliated transplant centers in Boston (Boston Center for Liver Transplantation).One hundred forty-one liver transplant recipients completed the study.CMVIG or placebo (1% albumin) given in a dose of 150 mg/kg body weight within 72 hours of the transplant, then at weeks 2, 4, 6, and 8, and at 100 mg/kg at weeks 12 and 16.Patients were observed for 1 year after transplantation for the development of CMV infection, disease, pneumonia, as well as for opportunistic fungal infections, graft survival, and mortality. Weekly cultures were taken of urine, buffy coat, and throat wash for CMV for 2 months, then monthly, and at any clinical illness.Using a Cox proportional hazards model, CMVIG was shown to reduce severe CMV-associated disease (multi-organ CMV disease, CMV pneumonia, or invasive fungal disease associated with CMV infection) from 26% to 12% (relative risk, 0.39; 95% CI, 0.17 to 0.89). When we controlled for the use of monoclonal antibodies to T cells (OKT3), CMVIG use was still protective (relative risk, 0.39; CI, 0.17 to 0.90). Rates of CMV disease were reduced from 31% to 19% (relative risk, 0.56; CI, 0.3 to 1.1) in CMVIG recipients although no effect on rates of CMV infection, graft survival, or patient survival at 1 year were shown. When we controlled for the urgency of transplantation and OKT3 use, a reduction in CMV disease (relative risk, 0.22; CI, 0.06 to 0.81) was shown for globulin recipients for all serologic groups except for the highest risk group (the CMV-seropositive donor, CMV-seronegative group).CMVIG reduced the rate of severe CMV-associated disease in patients undergoing orthotopic liver transplantation. No effect of CMVIG on CMV donor-positive, recipient-negative liver transplant recipients was shown, suggesting a need for additional prophylactic strategies.
TRAPID: an efficient online tool for the functional and comparative analysis of de novo RNA-Seq transcriptomes
Authors: Michiel Van Bel, Sebastian Proost, Christophe Van Neste, Dieter Deforce, Yves Van de Peer, Klaas Vandepoele
Journal: Genome biology (2013)

Abstract Transcriptome analysis through next-generation sequencing technologies allows the generation of detailed gene catalogs for non-model species, at the cost of new challenges with regards to computational requirements and bioinformatics expertise. Here, we present TRAPID, an online tool for the fast and efficient processing of assembled RNA-Seq transcriptome data, developed to mitigate these challenges. TRAPID offers high-throughput open reading frame detection, frameshift correction and includes a functional, comparative and phylogenetic toolbox, making use of 175 reference proteomes. Benchmarking and comparison against state-of-the-art transcript analysis tools reveals the efficiency and unique features of the TRAPID system. TRAPID is freely available at http://bioinformatics.psb.ugent.be/webtools/trapid/ .
Vascular Endothelial Growth Factor in Human Preterm Lung
Authors: PATRIK LASSUS, ARI RISTIMÄKI, OLAVI YLIKORKALA, LASSE VIINIKKA, STURE ANDERSSON
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Endothelial cell damage is characteristic for respiratory distress syndrome and development of chronic lung disease. Vascular endothelial growth factor (VEGF) is an endothelial mitogen that takes part in the growth and repair of vascular endothelial cells. We measured VEGF in 189 tracheal aspirate samples (TAF), and in 24 plasma samples from 44 intubated preterm infants (gestational age, 27.3 ± 2.0 wk; birth weight, 962 ± 319 g) during their first postnatal week. VEGF in TAF increased from 25 ± 12 pg/ml (mean ± SEM) on Day 1 to 526 ± 120 pg/ml on Day 7 (mean concentrations, 106 ± 25 pg/ml on Days 1 to 3 and 342 ± 36 pg/ml on Days 4 to 7). In plasma, mean concentration of VEGF during the first week was 48 ± 6 pg/ml, with no increase observed. In TAF, higher VEGF was found in patients born to mothers with premature rupture of the membranes, or chorionamnionitis, whereas preeclampsia of the mother was associated with lower VEGF (all p < 0.05). In TAF, no correlations existed between VEGF and gestational age or birth weight, but a correlation existed between lecithin/sphengomyelin ratio and VEGF (p < 0.05). During Days 4 to 7 patients developing bronchopulmonary dysplasia (BPD) had lower VEGF in TAF than did those surviving without BPD (235 ± 31 versus 383 ± 50; p < 0.05). VEGF increased rapidly in the lungs of the preterm infant during the first days of life. VEGF may be indicative of pulmonary maturity and may participate in pulmonary repair after acute lung injury.
Spontaneous seroclearance of hepatitis B seromarkers and subsequent risk of hepatocellular carcinoma
Authors: Jessica Liu, Hwai-I Yang, Mei-Hsuan Lee, Sheng-Nan Lu, Chin-Lan Jen, Richard Batrla-Utermann, Li-Yu Wang, San-Lin You, Chuhsing K Hsiao, Pei-Jer Chen, Chien-Jen Chen
Journal: Gut (2013)

<h3>Background and aims</h3> The associations between long-term risk of hepatocellular carcinoma (HCC) and spontaneous seroclearance of HBV e antigen (HBeAg), HBV DNA and HBV surface antigen (HBsAg) have never been examined by a prospective study using serially measured seromarkers. This study aimed to assess the importance of spontaneous HBeAg, HBV DNA and HBsAg seroclearance in the prediction of HCC risk. <h3>Methods</h3> This study included 2946 HBsAg seropositive individuals who were seronegative for antibodies against HCV and free of liver cirrhosis. Serial serum samples collected at study entry and follow-up health examinations were tested for HBeAg, HBV DNA and HBsAg. Cox proportional hazards models were used to calculate the HRs of developing HCC after seroclearance of HBV markers. <h3>Results</h3> The HR (95% CI) of developing HCC after seroclearance of HBeAg, HBV DNA and HBsAg during follow-up was 0.63 (0.38 to 1.05), 0.24 (0.11 to 0.57) and 0.18 (0.09 to 0.38), respectively, after adjustment for age, gender and serum level of alanine aminotransferase at study entry. High HBV DNA levels at the seroclearance of HBeAg (mean±SD, 4.35±1.64 log10 IU/mL) may explain the non-significant association between HBeAg seroclearance and HCC risk. Among HBeAg seronegative participants with detectable serum HBV DNA at study entry, the lifetime (30–75-years-old) cumulative incidence of HCC was 4.0%, 6.6% and 14.2%, respectively, for those with seroclearance of both HBV DNA and HBsAg, seroclearance of HBV DNA only, and seroclearance of neither. <h3>Conclusions</h3> Spontaneous seroclearance of HBV DNA and HBsAg are important predictors of reduced HCC risk.
Smoke-free Legislation and Hospitalizations for Childhood Asthma
Authors: Daniel Mackay, Sally Haw, Jon G. Ayres, Colin Fischbacher, Jill P. Pell
Journal: New England Journal of Medicine (2010)

Previous studies have shown that after the adoption of comprehensive smoke-free legislation, there is a reduction in respiratory symptoms among workers in bars. However, it is not known whether respiratory disease is also reduced among people who do not have occupational exposure to environmental tobacco smoke. The aim of our study was to determine whether the ban on smoking in public places in Scotland, which was initiated in March 2006, influenced the rate of hospital admissions for childhood asthma.Routine hospital administrative data were used to identify all hospital admissions for asthma in Scotland from January 2000 through October 2009 among children younger than 15 years of age. A negative binomial regression model was fitted, with adjustment for age group, sex, quintile of socioeconomic status, urban or rural residence, month, and year. Tests for interactions were also performed.Before the legislation was implemented, admissions for asthma were increasing at a mean rate of 5.2% per year (95% confidence interval [CI], 3.9 to 6.6). After implementation of the legislation, there was a mean reduction in the rate of admissions of 18.2% per year relative to the rate on March 26, 2006 (95% CI, 14.7 to 21.8; P<0.001). The reduction was apparent among both preschool and school-age children. There were no significant interactions between hospital admissions for asthma and age group, sex, urban or rural residence, region, or quintile of socioeconomic status.In Scotland, passage of smoke-free legislation in 2006 was associated with a subsequent reduction in the rate of respiratory disease in populations other than those with occupational exposure to environmental tobacco smoke. (Funded by NHS Health Scotland.)
Sperm Proteomics Reveals Intensified Selection on Mouse Sperm Membrane and Acrosome Genes
Authors: Steve Dorus, Elizabeth R. Wasbrough, Jennifer Busby, Elaine C. Wilkin, Timothy L. Karr
Journal: Molecular Biology and Evolution (2010)

Spermatozoa are a focal point for the impact of sexual selection due to sperm competition and sperm-female interactions in a wide range of sexually reproducing organisms. In-depth molecular investigation of the ramifications of these selective regimes has been limited due to a lack of information concerning the molecular composition of sperm. In this study, we utilize three previously published proteomic data sets in conjunction with our whole mouse sperm proteomic analysis to delineate cellular regions of sperm most impacted by positive selection. Interspecific analysis reveals robust evolutionary acceleration of sperm cell membrane genes (which include genes encoding acrosomal and sperm cell surface proteins) relative to other sperm genes, and evidence for positive selection in approximately 22% of sperm cell membrane components was obtained using maximum likelihood models. The selective forces driving the accelerated evolution of these membrane proteins may occur at a number of locations during sperm development, maturation, and transit through the female reproductive tract where the sperm cell membrane and eventually the acrosome are exposed to the extracellular milieu and available for direct cell-cell interactions.
Avoidance of Transient Cardiomyopathy in Cardiomyocyte-Targeted Tamoxifen-Induced MerCreMer Gene Deletion Models
Authors: Norimichi Koitabashi, Djahida Bedja, Ari L. Zaiman, Yigal M. Pinto, Manling Zhang, Kathleen L. Gabrielson, Eiki Takimoto, David A. Kass
Journal: Circulation Research (2009)

Cardiac myocyte targeted MerCreMer transgenic mice expressing tamoxifen-inducible Cre driven by the α-myosin heavy chain promoter are increasingly used to control gene expression in the adult heart. Here, we show tamoxifen-mediated MerCreMer (MCM) nuclear translocation can induce severe transient dilated cardiomyopathy in mice with or without loxP transgenes. The cardiomyopathy is accompanied by marked reduction of energy/metabolism and calcium-handling gene expression (eg, PGC1-α, peroxisome proliferator-activated α, SERCA2A), all fully normalized with recovery. MCM-negative/flox-positive controls display no dysfunction with tamoxifen. Nuclear Cre translocation and equally effective gene knockdown without cardiomyopathy is achievable with raloxifene, suggesting toxicity is not simply from Cre. Careful attention to controls, reduced tamoxifen dosing and/or use of raloxifene is advised with this model.
The composition of hepatic and gallbladder bile in patients with gallstones
Authors: C. Mackay, J. N. Crook, D. C. Smith, R. A. McAllister
Journal: Gut (1972)

Bile specimens were obtained from 17 patients with gallstones and 21 patients with duodenal ulcer. The specimens were obtained from the former by needle aspiration of the gallbladder and common bile duct at operation and from the latter by duodenal intubation. The concentrations of bile salt, phospholipid, and cholesterol were measured. Gallbladder bile from gallstone patients contained significantly more cholesterol than did ;duodenal' bile from duodenal ulcer patients. Hepatic bile from gallstone patients contained significantly more cholesterol than did gallbladder bile from the same patients. When the data were plotted on triangular coordinates the relative composition lay within the zone of cholesterol solubility in all 21 ulcer patients. The relative composition of hepatic bile lay outside the zone of cholesterol solubility in five gallstone patients, at the limits of cholesterol solubility in a further three, and within the micellar zone in the remaining nine patients. This suggests that supersaturation of hepatic bile with cholesterol is not the sine qua non for the production of cholesterol gallstones.
Analysis of naturally occurring delayed-type hypersensitivity reactions in leprosy by in situ hybridization.
Authors: C L Cooper, C Mueller, T A Sinchaisri, C Pirmez, J Chan, G Kaplan, S M Young, I L Weissman, B R Bloom, T H Rea
Journal: The Journal of Experimental Medicine (1989)

Analysis of tissue lesions of the major reactional states of leprosy was undertaken to study the immune mechanisms underlying regulation of cell-mediated immunity and delayed-type hypersensitivity (DTH) in man. In situ hybridization hybridization of reversal reaction biopsy specimens for INF-gamma mRNA expression revealed a 10-fold increase in specific mRNA-containing cells over that observed in unresponsive lepromatous patients. Expression of huHF serine esterase, a marker for T cytotoxic cells, were fourfold increased in reversal reaction and tuberculoid lesions above that detected in unresponsive lepromatous individuals. Immunohistology of reversal reactions confirmed a selective increase of Th and T cytotoxic cells in the cellular immune response. Of interest, the microanatomic location of these serine esterase mRNA-containing cells was identical to the distribution of CD4+ cells. Analysis of erythema nodosum leprosum (ENL) lesions revealed differences in the underlying immune processes in comparison with reversal reaction lesions. Although phenotypic Th cells predominated in ENL lesions, IFN-gamma and serine esterase gene expression were markedly reduced. We suggest that reversal reactions represent a hyperimmune DTH response characterized by a selective increase of CD4+ IFN-gamma producing cells and T cytotoxic cells, which result in the clearing of bacilli and concomitant tissue damage. In contrast, ENL reactions may be viewed as a transient diminution of Ts cells and activity leading to a partial and transient augmentation in cell-mediated immunity, perhaps sufficient to result in antibody and immune complex formation, but insufficient to clear bacilli from lesions.
Regional left ventricular function assessed by contrast angiography in acute myocardial infarction.
Authors: M Rigaud, P Rocha, J Boschat, J C Farcot, J Bardet, J P Bourdarias
Journal: Circulation (1979)

The relationship of segmental left ventricular (LV) wall motion abnormalities to LV function 2-6 days after acute transmural myocardial infarction (MI) was investigated in 45 patients by quantitative contrast ventriculography. Patients were divided into four classes according to the MIRU criteria. Segmental wall motion was assessed by determining the percentage of systolic shortening (deltaS) along nine hemiaxes and the extent of akinetic or dyskinetic abnormally contracting segments (% ACS) expressed as a percentage of end-diastolic perimeter. When compared with that in 17 normal control-subjects, the LV end-diastolic volume was increased only in patients in class III and class IV; the LV end-systolic volume increased progressively from normal through class IV. Ejection fraction had a negative linear correlation with %ACS (r = 0.97). The size of ACS was larger in anterior (34 +/- 14%) than in inferior MIs (23 +/- 7%), resulting in greater LV dysfunction. However, for a comparable size of ACS, infarct location alone did not influence LV function parameters. In the noninfarcted zone, deltaS was increased when the size of ACS was less than 25% and reduced when the size of ACS was greater than 25%. Thus, the size of ACS is a major determinant of LV dysfunction in acute MI. The compensatory mechanisms operate either through an augmented mechanical function of residual myocardium when the infarct is small, or through the Frank-Starling mechanism when the infarct is large.
Effort thrombosis of the upper extremity in a young sportsman: Paget–Schroetter syndrome
Authors: Graham Roche-Nagle, Ronan Ryan, Mary Barry, David Brophy
Journal: British Journal of Sports Medicine (2007)

Paget-Schroetter syndrome is the spontaneous thrombosis of the axillary/subclavian vein. A 16-year-old male presented with acute onset of right upper limb swelling after vigorous weight training. A venogram confirmed the diagnosis of Paget–Schroetter syndrome. He was started on intravenous thrombolytics followed by oral anticoagulation therapy. His symptoms resolved and he was symptom free at six-month follow-up. Thrombolytics and anticoagulation is the most widely accepted first-line therapy for this syndrome. Defining any anatomical anomaly as the predisposing factor in this condition is essential in the selection of which patients will benefit from thoracic outlet decompression.
Mitogen-Activated Protein Kinase Phosphorylation in Kidneys of βs Sickle Cell Mice
Authors: MILITZA KIROYCHEVA, FAYYAZ AHMED, GILLIAN M. ANTHONY, CSABA SZABO, GARRY J. SOUTHAN, NORMAN BANK
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Previous studies in β s sickle cell mice demonstrated renal immunostaining for nitrotyrosine, which is putative evidence of peroxynitrite (ONOO - ) formation. ONOO - is known to nitrate tyrosine residues of various enzymes, thereby interfering with phosphorylation and inactivating them. The present study examined the state of phosphorylation of mitogen-activated protein (MAP) kinase signal transduction enzymes, i.e. , p38, c-Jun NH 2 -terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). Western blot performed with antibodies directed against specific phosphorylated threonine/tyrosine residues of these enzymes demonstrated reduced phosphorylation of renal p38 and a trend toward reduced phosphorylation of ERK. In contrast, phosphorylation of renal JNK was markedly increased compared with normal mice. The abundance of MAP kinase phosphatase-1 (MKP-1), a key upstream enzyme that modulates phosphorylation of MAP kinases, was not different in β s versus normal mice. To determine whether nitration of tyrosine by ONOO - was responsible for reduced phosphorylation of p38 and ERK, mercaptoethylguanidine (MEG), a compound known to reduce inducible isoform of nitric oxide synthase activity and to scavenge ONOO - , was administered to β s mice for 5 d. MEG was found to restore phosphorylation of p38 and ERK toward normal levels. These observations provide evidence that ONOO - (or closely related reaction products of NO) contributes to dephosphorylation of p38 and ERK, and presumably reduces activity of these enzymes. The increased phosphorylation of JNK, which suggests activation of this signaling pathway by extracellular stress signals, may play a role in apoptosis in the kidneys of these mice. The changes in phosphorylation of MAP kinase pathways found in this study could have important consequences for regulation of nuclear transcription factors, and thus renal function and pathology in sickle cell kidneys.