tbuckley/cabot-search huggingface dataset:
B cell activation. III. B cell plasma membrane depolarization and hyper-Ia antigen expression induced by receptor immunoglobulin cross-linking are coupled.
Authors: J G Monroe, J C Cambier
Journal: The Journal of Experimental Medicine (1983)

We report investigation of the relationship between ligand-induced B cell plasma membrane depolarization and increased expression of membrane-associated, I-A subregion encoded (mI-A) antigens. Results demonstrate that equal frequencies of B cells are stimulated to undergo membrane depolarization and to increase mI-A expression in response to mitogen, anti-Ig, and thymus-independent (TI) or thymus-dependent (TD) antigens. Further, a cause-and-effect relationship between these two events is suggested by results that demonstrate that inhibition of anti-Fab--induced depolarization by valinomycin also inhibits the subsequent increase in mI-A antigen expression and "passive" (non-ligand-mediated) depolarization of murine B cells by K+ results in hyper-mI-A antigen expression. Based upon these results we hypothesize that antigen-mediated receptor cross-linking results in signal transduction via membrane depolarization, which is resultant in increased mI-A antigen synthesis and cell surface expression. This increase in mI-A antigen density may render the B cell more receptive to subsequent interaction with I-region-restricted helper T cells.
Defects in the CD19 complex predispose to glomerulonephritis, as well as IgG1 subclass deficiency
Authors: Nicolas Vince, David Boutboul, Gael Mouillot, Nicolas Just, Maria Peralta, Jean-Laurent Casanova, Mary Ellen Conley, Jean-Christophe Bories, Eric Oksenhendler, Marion Malphettes, Claire Fieschi
Journal: Journal of Allergy and Clinical Immunology (2010)
Regional Variation in Spending and Survival for Older Adults With Advanced Cancer
Authors: Gabriel A. Brooks, Ling Li, Dhruv B. Sharma, Jane C. Weeks, Michael J. Hassett, K. Robin Yabroff, Deborah Schrag
Journal: JNCI Journal of the National Cancer Institute (2013)

BackgroundMedicare spending varies substantially across the United States. We evaluated the association between mean regional spending and survival in advanced cancer.
Elevated calcium and activation of trypsinogen in rat pancreatic acini
Authors: T W Frick, C Fernández-del-Castillo, D Bimmler, A L Warshaw
Journal: Gut (1997)

Background —Acute pancreatitis associated with hypercalcaemia has been described in humans and experimental animals. It has been demonstrated that calcium dose dependently accelerates trypsinogen activation, and it is generally believed that ectopic activation of digestive enzymes is an early event in the pathophysiology of acute pancreatitis. Aims and methods —Trypsinogen activation peptide (TAP) was measured in isolated rat pancreatic acini exposed to elevated extracellular calcium in order to investigate the association between calcium and trypsinogen activation in living cells. TAP was determined in the culture medium either before (extracellular compartment) or after (intracellular compartment) cell homogenisation. Results —Neither secretory stimulation nor elevated calcium alone caused an increase in TAP levels. Maximal cerulein or carbachol stimulation superimposed on high medium calcium, however, significantly increased intracellular trypsinogen activation twofold. This increase was inhibited by either N G -monomethyl- l -arginine ( l -NMMA) or verapamil. A cinar cell morphology and function remained intact as demonstrated by electron microscopy and secretagogue dose-response studies. Conclusions —These results support the hypothesis that increased intracellular trypsinogen activation is an early step in the pathogenesis of hypercalcaemia induced pancreatitis. The model may have a bearing on other types of pancreatitis as elevated cytosolic calcium is thought to be an early event in the pathogenesis of acute pancreatitis in general.
Adherence to medication in patients with psoriasis: a systematic literature review
Authors: R.J. Thorneloe, C. Bundy, C.E.M. Griffiths, D.M. Ashcroft, L. Cordingley
Journal: British Journal of Dermatology (2012)

Psoriasis is associated with considerable physical and psychological morbidity. Optimal use of psoriasis treatments can limit the physical manifestations of psoriasis and help improve quality of life, but nonadherence is common. Smoking, obesity and excessive alcohol consumption are prevalent in this population. A systematic review of adherence to medication and recommendations for lifestyle change in psoriasis was undertaken, with a critical appraisal of the quality of the selected studies. Electronic searches from inception to March 2012 (PubMed, Web of Science and Embase) were conducted. Twenty-nine studies were included; however, none examined adherence to advice about lifestyle change. Studies using a dichotomous classification of adherence tended to report suboptimal adherence, with 21·6-66·6% of patients classed as adherent. No consistent pattern of results emerged for sociodemographical, disease and lifestyle factors as determinants of adherence. However, some treatment factors were associated with adherence. While mixed findings were reported for quality of life as a determinant of adherence, psychological factors (psychological distress and patient satisfaction with care and therapy) were associated with adherence. Only tentative conclusions can be made for determinants of adherence because the methodological quality of many of the included studies limits conclusions. There is a need for improved quality of research and reporting in this area, and this review provides a platform from which future research within this area should progress, along with suggested research recommendations.
Mycobacteria and sarcoidosis
Authors: O. M. Kon, R. M. du Bois
Journal: Thorax (1997)

Background.Acid fast cell wall deficient forms (CWDF) of bacteria have been grown from blood, bronchial washings, and ocular anterior chamber fluid from patients with sarcoidosis.A monoclonal antibody raised against Mycobacterium tuberculosis whole cell antigen (H37RV) was used to characterise further CWDF grown from the blood of patients with sarcoidosis.Methods.Blood from 20 patients with active sarcoidosis and from 20 controls was cultured using methods favourable for the growth of CWDF.Isolates were further characterised by indirect fluorescent antibody analysis using a monoclonal antibody highly reactive with M tuberculosis.Results.CWDF were grown from the blood of 19 of 20 subjects with sarcoidosis.All isolates stained positively with the monoclonal antibody and with a modified Kinyoun stain.No organisms were grown from the blood of controls.Conclusions.These data demonstrate that CWDF can be grown from the blood of nearly all patients with active sarcoidosis.The results confirm that the organisms are mycobacterial in origin and are similar, if not identical, to M tuberculosis.Their role in the pathogenesis of sarcoidosis is unknown.(Thorax 1996;51:530-3) LEARNING POINTS * The aetiology of sarcoidosis is stilluncertain.* There is accumulating evidence for the role of mycobacteria in patients with sarcoidosis.* The finding of cell wall deficient forms goes some way to explaining previous conflicting data on the role of mycobacteria in sarcoidosis.* Use of molecular biological techniques may be helpful in further characterising whether these organisms are atypical or tuberculous mycobacteria.* An appreciation of the epidemiological and genetic basis of the susceptibility to cell wall deficient forms (CWDF) would support their role in the aetiology of sarcoidosis.
Activity patterns, blood lactate concentrations and ratings of perceived exertion during a professional singles tennis tournament
Authors: Alberto Mendez-Villanueva, Jaime Fernandez-Fernandez, David Bishop, Benjamin Fernandez-Garcia, Nicolas Terrados
Journal: British Journal of Sports Medicine (2007)

To examine the game characteristics and physiological (ie, blood lactate concentration) and perceptual (ie, rating of perceived exertion, RPE) responses during actual tennis competition in professional performers.Eight trained and internationally ranked (Association of Tennis Professionals rankings) male tennis players were studied during singles matches (best of three sets) played on an outdoor clay court surface during a professional, invitational tournament. Blood lactate concentrations (n = 53) and RPE (n = 113) were determined at selected change-overs during the game. The variables describing the characteristics of the matches, (a) duration of rallies (DRs); (b) rest time (RT); (c) effective playing time (EPT); and (d) shots per rally (SR), were determined from video recordings.The mean (SD) values for the match-play activity variables were DR 7.5 (7.3) s, RT 16.2 (5.2) s, EPT 21.5 (4.9%), SR 2.7 (2.2) shots. Average blood lactate concentration and RPE values were 3.8 (2.0) mmol/l and 13 (2). Blood lactate concentrations and RPE values were significantly higher (p<0.01) in service games than in receiving games. Both blood lactate concentration and RPE values were significantly correlated with SR and DR (r = 0.80 to 0.28; p<0.001).Blood lactate concentrations and RPE were found to be influenced by the characteristics of the match and the playing situation (ie, serving or returning). These specific situations might be used to alter the overload training stimulus during tennis on-court practice.
Enhanced Gene Transfer and Oncolysis of Head and Neck Cancer and Melanoma Cells by Fiber Chimeric Oncolytic Adenoviruses
Authors: P. Seshidhar Reddy, Shanthi Ganesh, De-Chao Yu
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The purpose of this study was to evaluate a fiber knob replacement strategy to improve infectivity and efficacy of Ad5 fiber chimeric oncolytic viruses for treatment of melanoma and head and neck cancers (HNC). Experimental Design: Adenoviral receptors and transduction levels were used to determine the level of infectivity of fiber-modified, green fluorescent protein–expressing, replication-deficient viruses in a panel of melanoma and HNC cell lines in vitro. Virus yield and cytotoxicity assays were used to determine the tumor specificity and virus replication-mediated cytotoxicity of the fiber-modified oncolytic viruses in the same panel of melanoma and HNC in vitro. Xenograft tumor models were used to assess the antitumor activity of those fiber-modified chimeric viruses compared with the parental virus. Results: Marker gene expression following gene transfer of the fiber chimeric vectors in melanoma and HNC cell lines was ∼10-fold higher than that obtained with parental Ad5 vector. The fiber chimeric oncolytic variants mediated killing of melanoma and HNC cells that was 2- to 576-fold better than with the parental virus. In addition, fiber chimeric variants produced 2- to 7-fold more progeny virus in tumor cells than the parental virus. Moreover, a high multiplicity of infection was needed for the fiber chimeric viruses to produce cytotoxicity in normal cells. A significantly stronger antitumor response and survival advantage were shown in the tested melanoma and HNC xenograft models following i.t. injections. Conclusions: In vitro and in vivo studies showed the improved transduction, replication, cytotoxicity, antitumor efficacy, and survival advantage in melanoma and HNC tumor models, suggesting a potential use of these oncolytic agents for the treatment of melanoma and HNCs.
Traditional Cardiovascular Disease Risk Factors in Dialysis Patients Compared with the General Population
Authors: J. Craig Longenecker, Josef Coresh, Neil R. Powe, Andrew S. Levey, Nancy E. Fink, Alice Martin, Michael J. Klag
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Although atherosclerotic cardiovascular disease (ASCVD) risk in end-stage renal disease (ESRD) is 5 to 30 times that of the general population, few data exist comparing ASCVD risk factors among new dialysis patients to the general population. This cross-sectional study of 1041 dialysis patients describes the prevalence of ASCVD risk factors at the beginning of ESRD compared with estimates of ASCVD risk factors in the adult US population derived from the Third National Health and Nutrition Examination (NHANES III). CHOICE Study participants had a high prevalence of diabetes (54%), hypertension (96%), left ventricular hypertrophy by electrocardiogram (EKG) criteria (22%), low physical activity (80%), hypertriglyceridemia (36%), and low HDL cholesterol (33%). CHOICE participants were more likely to be older, black, and male than NHANES III participants. After adjustment for age, race, gender, and ASCVD (defined as myocardial infarction, revascularization procedure, stroke, carotid endarterectomy, and amputation in CHOICE; and as myocardial infarction and stroke in NHANES III), the prevalence of diabetes, hypertension, left ventricular hypertrophy by EKG, low physical activity, low HDL cholesterol, and hypertriglyceridemia were still more common in CHOICE participants. Smoking, obesity, hypercholesterolemia, and high LDL cholesterol, however, were less common in CHOICE than NHANES III participants. The projected 5-yr ASCVD risk based on the Framingham Risk Equation among those older than 40 yr without ASCVD was higher in CHOICE Study participants (13%) than in the NHANES III participants (6%). In summary, many ASCVD risk factors are more prevalent in ESRD than in the general population and may explain some, but probably not all, of the increased ASCVD risk in ESRD.
Arterial stiffness in patients with COPD: the role of systemic inflammation and the effects of pulmonary rehabilitation
Authors: Lowie E.G.W. Vanfleteren, Martijn A. Spruit, Miriam T.J. Groenen, Piet L.B. Bruijnzeel, Ziad Taib, Erica P.A. Rutten, Jos Op ‘t Roodt, Marco A. Akkermans, Emiel F.M. Wouters, Frits M.E. Franssen
Journal: European Respiratory Journal (2013)

Clear evidence for an association between systemic inflammation and increased arterial stiffness in patients with chronic obstructive pulmonary disease (COPD) is lacking. Moreover, the effects of pulmonary rehabilitation on arterial stiffness are not well studied. We aimed to 1) confirm increased arterial stiffness in COPD; 2) evaluate its correlates including systemic inflammation; and 3) study whether or not it is influenced by pulmonary rehabilitation. Aortic pulse-wave velocity (APWV) was determined in 168 healthy volunteers, and APWV and inflammatory markers were determined in 162 COPD patients during baseline evaluation of a pulmonary rehabilitation programme. A complete post-pulmonary rehabilitation dataset was collected in 129 patients. It was found that APWV was increased in COPD patients when compared with controls, blood pressure and age predicted baseline APWV, and systemic inflammatory markers were not independently related to APWV. Although baseline APWV was predictive for the change in APWV after pulmonary rehabilitation (r= -0.77), on average APWV did not change (10.7±2.7 versus 10.9±2.5 m·s −1 ; p=0.339). Arterial stiffness in COPD is not related to systemic inflammation and does not respond to state-of-the-art pulmonary rehabilitation. These results emphasise the complexity of cardiovascular risk and its management in COPD.
Recognition of multiple peptide cores by a single T cell receptor.
Authors: N K Nanda, K K Arzoo, H M Geysen, A Sette, E E Sercarz
Journal: The Journal of Experimental Medicine (1995)

We present evidence that a single T cell clone can recognize at least five different overlapping peptides, each with its distinct core structure, in the context of the same major histocompatibility complex (MHC) molecule. Distinct core residues are crucial for triggering the T cell receptor (TCR) in each case. These results suggest that the TCR (a) has multiple sets of contact residues for alternative peptide-MHC ligands, the binding to any one of which can trigger the cell; and/or (b) is able to attach to the peptide-MHC complex in more than one orientation. In this sense, the TCR is a multisubsite structure capable of being stimulated by a variety of peptide ligands associated with the same MHC molecules.
Explaining the Decrease in U.S. Deaths from Coronary Disease, 1980–2000
Authors: Earl S. Ford, Umed A. Ajani, Janet B. Croft, Julia A. Critchley, Darwin R. Labarthe, Thomas E. Kottke, Wayne H. Giles, Simon Capewell
Journal: New England Journal of Medicine (2007)

Mortality from coronary heart disease in the United States has decreased substantially in recent decades. We conducted a study to determine how much of this decrease could be explained by the use of medical and surgical treatments as opposed to changes in cardiovascular risk factors.We applied a previously validated statistical model, IMPACT, to data on the use and effectiveness of specific cardiac treatments and on changes in risk factors between 1980 and 2000 among U.S. adults 25 to 84 years old. The difference between the observed and expected number of deaths from coronary heart disease in 2000 was distributed among the treatments and risk factors included in the analyses.From 1980 through 2000, the age-adjusted death rate for coronary heart disease fell from 542.9 to 266.8 deaths per 100,000 population among men and from 263.3 to 134.4 deaths per 100,000 population among women, resulting in 341,745 fewer deaths from coronary heart disease in 2000. Approximately 47% of this decrease was attributed to treatments, including secondary preventive therapies after myocardial infarction or revascularization (11%), initial treatments for acute myocardial infarction or unstable angina (10%), treatments for heart failure (9%), revascularization for chronic angina (5%), and other therapies (12%). Approximately 44% was attributed to changes in risk factors, including reductions in total cholesterol (24%), systolic blood pressure (20%), smoking prevalence (12%), and physical inactivity (5%), although these reductions were partially offset by increases in the body-mass index and the prevalence of diabetes, which accounted for an increased number of deaths (8% and 10%, respectively).Approximately half the decline in U.S. deaths from coronary heart disease from 1980 through 2000 may be attributable to reductions in major risk factors and approximately half to evidence-based medical therapies.
Intracoronary Infusion of Reduced Glutathione Improves Endothelial Vasomotor Response to Acetylcholine in Human Coronary Circulation
Authors: Kiyotaka Kugiyama, Masamichi Ohgushi, Takeshi Motoyama, Osamu Hirashima, Hirofumi Soejima, Kenji Misumi, Michihiro Yoshimura, Hisao Ogawa, Seigo Sugiyama, Hirofumi Yasue
Journal: Circulation (1998)

Background —Oxygen free radicals have been shown to cause endothelial vasomotor dysfunction. This study examined the effect of reduced glutathione (GSH), an antioxidant, on human coronary circulation. Methods and Results —Responses of epicardial diameter and blood flow of the left anterior descending coronary artery to intracoronary infusion of acetylcholine (ACh, 50 μg/min) were measured by quantitative coronary angiography and Doppler flow-wire technique, respectively, before and during combined intracoronary infusion of GSH (50 mg/min) or saline in 26 subjects with no significant coronary stenosis. GSH infusion suppressed the constrictor response of epicardial diameter to ACh and enhanced the increase in blood flow response to ACh. Furthermore, GSH potentiated the coronary dilator effect of nitroglycerin. A beneficial effect of GSH on the epicardial diameter response to ACh was observed in a subgroup of subjects with ≥1 coronary risk factors but not in a subgroup without risk factors. Saline infusion did not have any effects. Conclusions —The results indicate that GSH improved coronary endothelial vasomotor function, particularly in subjects with coronary risk factors, and it potentiated the vasodilator effect of nitroglycerin in human coronary arteries.
Population Genomics and Transcriptional Consequences of Regulatory Motif Variation in Globally Diverse Saccharomyces cerevisiae Strains
Authors: Caitlin F. Connelly, Daniel A. Skelly, Maitreya J. Dunham, Joshua M. Akey
Journal: Molecular Biology and Evolution (2013)

Noncoding genetic variation is known to significantly influence gene expression levels in a growing number of specific cases; however, the patterns of genome-wide noncoding variation present within populations, the evolutionary forces acting on noncoding variants, and the relative effects of regulatory polymorphisms on transcript abundance are not well characterized. Here, we address these questions by analyzing patterns of regulatory variation in motifs for 177 DNA binding proteins in 37 strains of Saccharomyces cerevisiae. Between S. cerevisiae strains, we found considerable polymorphism in regulatory motifs across strains (mean π = 0.005) as well as diversity in regulatory motifs (mean 0.91 motifs differences per regulatory region). Population genetics analyses reveal that motifs are under purifying selection, and there is considerable heterogeneity in the magnitude of selection across different motifs. Finally, we obtained RNA-Seq data in 22 strains and identified 49 polymorphic DNA sequence motifs in 30 distinct genes that are significantly associated with transcriptional differences between strains. In 22 of these genes, there was a single polymorphic motif associated with expression in the upstream region. Our results provide comprehensive insights into the evolutionary trajectory of regulatory variation in yeast and the characteristics of a compendium of regulatory alleles.
Cyclosporin A inhibits CD40 ligand expression in T lymphocytes.
Authors: R Fuleihan, N Ramesh, A Horner, D Ahern, P J Belshaw, D G Alberg, I Stamenkovic, W Harmon, R S Geha
Journal: Journal of Clinical Investigation (1994)

The ligand for CD40 is expressed on activated T lymphocytes and delivers contact-dependent activation signals to B lymphocytes. The mechanisms regulating CD40 ligand gene expression are largely unknown. Optimal expression of CD40 ligand required activation of protein kinase C and a rise in intracellular calcium concentration. CD40 ligand expression was inhibited by pretreatment of T cells with cyclosporin A. Cyclosporin A analogues inhibited CD40 ligand expression with a potency mirroring the ability of each compound to inhibit calcineurin activity, indicating that calcineurin plays a key role in CD40 ligand gene expression. Cyclosporin A inhibited IL-4-driven CD40 ligand-dependent IgE isotype switching in PBMC but did not inhibit IgE synthesis induced by CD40 mAb plus IL-4. PBMC derived from transplant patients receiving cyclosporin A failed to express CD40 ligand upon stimulation. These results suggest that patients receiving cyclosporin A may be deficient in CD40 ligand-dependent T cell help.