tbuckley/cabot-search huggingface dataset:
Impact of hepatitis B virus basic core promoter mutations on T cell response to an immunodominant HBx-derived epitope
Authors: Silvina Laura Malmassari, Qiang Deng, Hélène Fontaine, Dianne Houitte, François Rimlinger, Valérie Thiers, Bernard Maillere, Stanislas Pol, Marie‐Louise Michel
Journal: Hepatology (2007)

The hepatitis B X (HBx) protein is a crucial component in HBV infection in vivo and has been implicated in HCC. In this study, we aimed to detect and characterize peripheral HBx-specific T cells in chronically infected patients at the inactive carrier state of the disease. HBx-specific IFN-γ–secreting T cells were found in 36 of 52 patients (69%), and 78% (28/36) of responding patients had T cells targeting epitopes in the carboxy-terminal part of HBx. IL-10 secretion after the stimulation of T cells with HBx-derived peptides was weak or undetectable. IFN-γ–secreting T cells recognized a previously unknown immunodominant CD4+ T cell epitope, HBx 126–140 (EIRLKVFVLGGCRHK), in 86% (24 of 28) of patients. This peptide bound several HLA-DR molecules (HLA-DRB1*0101, HLA-DRB1*0401, HLA-DRB1*1301, and HLA-DRB5*0101). Its coding sequence overlaps a domain of the HBV genome encompassing the basic core promoter (BCP) region. Taking into account the selection of viral core promoter mutants during HBV infection, we found that HBV variants with BCP mutations were present in patient sera. We further demonstrated that these viral mutant sequences activated T cells specific for the immunodominant epitope only weakly, if at all. This is the first study linking BCP mutations and HBx-specific T cell responses. Conclusion: Wild-type and variant peptides may represent potential tools for monitoring the HBV-specific T cell responses involved in sequence evolution during disease progression. Finally, the degenerate HLA-DR binding of this promiscuous, immunodominant peptide would make it a valuable component of vaccines for protecting large and ethnically diverse patient populations. (HEPATOLOGY 2007;45:1199–1209.)
Prognostic value of anti-ADAMTS13 antibody features (Ig isotype, titer, and inhibitory effect) in a cohort of 35 adult French patients undergoing a first episode of thrombotic microangiopathy with undetectable ADAMTS13 activity
Authors: Silvia Ferrari, Friedrich Scheiflinger, Manfred Rieger, Geert Mudde, Martine Wolf, Paul Coppo, Jean-Pierre Girma, Elie Azoulay, Christian Brun-Buisson, Fadi Fakhouri, Jean-Paul Mira, Eric Oksenhendler, Pascale Poullin, Eric Rondeau, Nicolas Schleinitz, Benoit Schlemmer, Jean-Louis Teboul, Philippe Vanhille, Jean-Paul Vernant, Dominique Meyer, Agnès Veyradier
Journal: Blood (2006)
Effect of Variations of Plasma Sodium Concentration on the Adrenal Response to Angiotensin II
Authors: JOHN R. BLAIR-WEST, JOHN P. COGHLAN, DEREK A. DENTON, JAMES R. GODING, MARELYN WINTOUR, R. DOUGLAS WRIGHT
Journal: Circulation Research (1965)

The secretion rate of aldosterone was increased by infusion of valine-5-angiotensin II into the adrenal arterial blood supply of sheep. The dimensions of the increase in aldosterone output were inversely related to the control plasma concentration. This high aldosterone secretion was reduced substantially by concurrent adrenal infusion of concentrated NaCl solution which increased plasma sodium concentration by approximately 10 meq/liter. The reduction of aldosterone secretion occurred within 20 minutes. Angiotensin II infusion did not increase the secretion rates of cortisol or corticosterone. The significance of the finding that environmental sodium concentration has different effects on the aldosterone-stimulating action and the pressor action of angiotensin II is discussed.
Secondary Care Team of the Year: The magic of teamwork
Authors: T. Delamothe
Journal: BMJ (2011)

This year’s judges for the award for secondary care team of the year were looking for initiatives in secondary care that improved patient outcomes. The winning team needed to have identified a clinical need, produced measurable improvements in outcomes that mattered to patients, and showed that a team was responsible for achieving the goal. The award was restricted to UK based secondary care teams whose initiatives had been evaluated since June 2009.

Despite these onerous entry requirements we received 47 entries from around the country. Three entries were shortlisted for consideration by our judging panel: John Black, president of the Royal College of Surgeons; Bernard Crump, chief executive of the NHS Institute for Innovation and Improvement; and Jane Dacre, director of medical education, UCL Medical School. Two of the three teams had extended their activities beyond their original “patch.” The teams comprised members from many different professional silos and straddled the boundaries between primary care, secondary care, and the community—a testament to what is possible in the unreformed NHS.

Immunisation of infants prevents 95% of perinatal transmission …
Cellular Basis for the Brugada Syndrome and Other Mechanisms of Arrhythmogenesis Associated With ST-Segment Elevation
Authors: Gan-Xin Yan, Charles Antzelevitch
Journal: Circulation (1999)

Background —The Brugada syndrome is characterized by marked ST-segment elevation in the right precordial ECG leads and is associated with a high incidence of sudden and unexpected arrhythmic death. Our study examines the cellular basis for this syndrome. Methods and Results —Using arterially perfused wedges of canine right ventricle (RV), we simultaneously recorded transmembrane action potentials from 2 epicardial and 1 endocardial sites, together with unipolar electrograms and a transmural ECG. Loss of the action potential dome in epicardium but not endocardium after exposure to pinacidil (2 to 5 μmol/L), a K + channel opener, or the combination of a Na + channel blocker (flecainide, 7 μmol/L) and acetylcholine (ACh, 2 to 3 μmol/L) resulted in an abbreviation of epicardial response and a transmural dispersion of repolarization, which caused an ST-segment elevation in the ECG. ACh facilitated loss of the action potential dome, whereas isoproterenol (0.1 to 1 μmol/L) restored the epicardial dome, thus reducing or eliminating the ST-segment elevation. Heterogeneous loss of the dome caused a marked dispersion of repolarization within the epicardium and transmurally, thus giving rise to phase 2 reentrant extrasystole, which precipitated ventricular tachycardia (VT) and ventricular fibrillation (VF). Transient outward current ( I to ) block with 4-aminopyridine (1 to 2 mmol/L) or quinidine (5 μmol/L) restored the dome, normalized the ST segment, and prevented VT/VF. Conclusions —Depression or loss of the action potential dome in RV epicardium creates a transmural voltage gradient that may be responsible for the ST-segment elevation observed in the Brugada syndrome and other syndromes exhibiting similar ECG manifestations. Our results also demonstrate that extrasystolic activity due to phase 2 reentry can arise in the intact wall of the canine RV and serve as the trigger for VT/VF. Our data point to I to block (4-aminopyridine, quinidine) as an effective pharmacological treatment.
THE REACTION OF THE CONTENT OF THE GASTRO-INTESTINAL TRACT
Authors: FRANK C. MANN
Journal: JAMA (1930)

The various digestive enzymes that are poured into the gastro-intestinal tract require different chemical reactions of the gastro-intestinal content for optimal activity. These reactions vary from one definitely acid for the stomach to one neutral or slightly alkaline for the remaining portion of the gastro-intestinal tract. The changes in reaction of the gastro-intestinal content as it passes through the gastro-intestinal tract, necessitated because of the needs of the various enzymes, have formed the basis for many physiologic problems and have offered the possibility for the development of certain pathologic conditions. The actual changes in the acidity of the gastro-intestinal content at various portions of the gastro-intestinal tract and following various diets are in themselves of considerable physiologic value. The mechanism whereby the changes are graded as the content passes, for instance, from the acid secretion in the stomach to the neutral or alkaline secretion in the duodenum also raises problems
C1q/Tumor Necrosis Factor–Related Protein-9, a Novel Adipocyte-Derived Cytokine, Attenuates Adverse Remodeling in the Ischemic Mouse Heart via Protein Kinase A Activation
Authors: Yang Sun, Wei Yi, Yuexing Yuan, Wayne Bond Lau, Dinghua Yi, Xiaoliang Wang, Yajing Wang, Hui Su, Xiaoming Wang, Erhe Gao, Walter J. Koch, Xin-Liang Ma
Journal: Circulation (2013)

Background— C1q/tumor necrosis factor–related protein-9 (CTRP9) is a newly identified adiponectin paralog with established metabolic regulatory properties. However, the role of CTRP9 in postmyocardial infarction remodeling remains completely unknown. This study determined whether CTRP9 may regulate cardiac remodeling after acute myocardial infarction (AMI) and elucidated the underlying mechanisms. Methods and Results— Male adult mice were subject to AMI by left anterior descending coronary artery ligation or sham surgery and treated with saline (vehicle) or globular CTRP9 via peritoneal implant osmotic pumps for 6 weeks. H9C2 cardiac cell lines were used in vitro for determining underlying mechanisms. Adipocyte CTRP9 expression and plasma CTRP9 levels were both significantly reduced after AMI. Compared with vehicle, CTRP9 treatment improved animal survival rate ( P &lt;0.05), restored cardiac function ( P &lt;0.05), attenuated adverse remodeling ( P &lt;0.01), and ameliorated cardiomyocyte apoptosis and fibrosis after AMI ( P &lt;0.01). Among the multiple antiremodeling molecules determined, AMP-activated protein kinase, protein kinase A (PKA), and Akt were significantly activated in CTRP9-treated heart. Surprisingly, CTRP9 remains cardioprotective in mice with cardiomyocyte-specific overexpression of a mutant AMP-activated protein kinase α2 subunit (AMPK-DN). Additional in vitro experiments demonstrated that administration of either PKA inhibitor or PKA-specific small interfering RNA virtually abolished the antiapoptotic effect of CTRP9 ( P &lt;0.05), whereas inhibition of Akt is less effective in blocking CTRP9 cardioprotection. Finally, CTRP9 phosphorylates BCL-2-associated agonist of cell death at its multiple antiapoptotic sites, an effect blocked by PKA inhibitor. Conclusions— We demonstrate that adipokine CTRP9 attenuates adverse cardiac remodeling after AMI, largely via a PKA-dependent pathway.
A CASE OF TRANSVERSE MYELITIS WITH AN UNUSUAL FORM OF DESCENDING DEGENERATION IN THE POSTERIOR COLUMNS.
Authors: JOHN K. MITCHELL
Journal: JAMA (1898)

seems to be progressing in exactly the same way.In this child also there is absolutely no increase of temperature.These nerve cells are simply poisoned by some ptomain, some toxin, and they do not present any structural changes any more than they would with aconite or strychnia poisoning.Dr. Spiller-In regard to Dr. Patrick's statement, I would say that one case of asthenic bulbar paralysis has been reported in which lesions were found.Landry's paralysis is probably due to different causes and different lesions.
Mepolizumab, a humanized anti–IL-5 mAb, as a treatment option for severe nasal polyposis
Authors: Philippe Gevaert, Nicholas Van Bruaene, Tom Cattaert, Kristel Van Steen, Thibaut Van Zele, Frederic Acke, Natalie De Ruyck, Katrien Blomme, Ana R. Sousa, Richard P. Marshall, Claus Bachert
Journal: Journal of Allergy and Clinical Immunology (2011)
Changing color of antiepileptic pills raises risk of patients' non-adherence, study shows
Authors: S. Mayor
Journal: BMJ (2013)

Changing the color of antiepileptic tablets is associated with an increased risk of patients with seizure disorder stopping taking them as prescribed, a US study has found.1

Researchers analyzed a national database of prescription records of patients with health insurance who started taking an antiepileptic drug between 2001 and 2006. They identified 11 472 patients as being “non-persistent,” defined as failing to fill a prescription within five days of the date required to take the drug as prescribed.

They assessed changes in pill color and shape of generic drugs dispensed in the two refills before patients became non-persistent and compared them with 50 050 controls who had no …
An epidemiological study of ulcerative colitis and regional enteritis in the Oxford area.
Authors: J G Evans, E D Acheson
Journal: Gut (1965)

Kinder Morgan Energy Partners (KMP) and Kinder Morgan Management (KMR) issue two separate securities that provide essentially identical cash flows. There are, however, minor distinctions between the securities in regard to the form of payout, taxation, control rights, and liquidity. Cornell studies the variation over time in the relative valuation of KMP and KMR to gain insight into the impact of those distinctions on asset pricing. The surprising result of this study is the discovery of a significant and continuing price differential between the two securities, but none of the distinctions between the two securities explains the price differential’s level or its variation over time. <b>TOPICS:</b>Exchanges/markets/clearinghouses, in markets, financial crises and financial market history
A safe technique for removing a malpositioned covered biliary self-expandable metal stent
Authors: J. Koornstra, H. van Dullemen, R. Weersma
Journal: Endoscopy (2008)

Self-expandable metal stents (SEMS) represent the preferred palliative management of malignant biliary strictures [1]. They are relatively easy to insert and provide immediate drainage of the biliary tract. Removal of a SEMS, sometimes considered necessary because of occlusion or malposition, can be technically challenging [2]. In this report, we present a safe and easy method of removing a malpositioned biliary SEMS.
Contribution of Impaired Myocardial Insulin Signaling to Mitochondrial Dysfunction and Oxidative Stress in the Heart
Authors: Sihem Boudina, Heiko Bugger, Sandra Sena, Brian T. O'Neill, Vlad G. Zaha, Olesya Ilkun, Jordan J. Wright, Pradip K. Mazumder, Eric Palfreyman, Timothy J. Tidwell, Heather Theobald, Oleh Khalimonchuk, Benjamin Wayment, Xiaoming Sheng, Kenneth J. Rodnick, Ryan Centini, Dong Chen, Sheldon E. Litwin, Bart E. Weimer, E. Dale Abel
Journal: Circulation (2009)

Background— Diabetes-associated cardiac dysfunction is associated with mitochondrial dysfunction and oxidative stress, which may contribute to left ventricular dysfunction. The contribution of altered myocardial insulin action, independent of associated changes in systemic metabolism, is incompletely understood. The present study tested the hypothesis that perinatal loss of insulin signaling in the heart impairs mitochondrial function. Methods and Results— In 8-week-old mice with cardiomyocyte deletion of insulin receptors (CIRKO), inotropic reserves were reduced, and mitochondria manifested respiratory defects for pyruvate that was associated with proportionate reductions in catalytic subunits of pyruvate dehydrogenase. Progressive age-dependent defects in oxygen consumption and ATP synthesis with the substrate glutamate and the fatty acid derivative palmitoyl-carnitine were observed. Mitochondria also were uncoupled when exposed to palmitoyl-carnitine, in part as a result of increased reactive oxygen species production and oxidative stress. Although proteomic and genomic approaches revealed a reduction in subsets of genes and proteins related to oxidative phosphorylation, no reductions in maximal activities of mitochondrial electron transport chain complexes were found. However, a disproportionate reduction in tricarboxylic acid cycle and fatty acid oxidation proteins in mitochondria suggests that defects in fatty acid and pyruvate metabolism and tricarboxylic acid flux may explain the mitochondrial dysfunction observed. Conclusions— Impaired myocardial insulin signaling promotes oxidative stress and mitochondrial uncoupling, which, together with reduced tricarboxylic acid and fatty acid oxidative capacity, impairs mitochondrial energetics. This study identifies specific contributions of impaired insulin action to mitochondrial dysfunction in the heart.
Slide Atlas of Clinical Endocrinology
Authors: Frederick G. Berlinger
Journal: JAMA (1995)

The format of the<i>Slide Atlas of Clinical Endocrinology</i>consists of 10 units, each containing a written text in a spiral notebook with numerous large illustrations of the 35-mm slides associated with each unit—60 to 91 slides per unit, 765 in all. Whether it is possible to reduce all of clinical endocrinology into even this large number of slides is open to question. One doubts that even such a large volume of slides can adequately cover all that the title implies. The units are large, heavy, cumbersome, and difficult to store. They appear intended for teachers who would use the slides in a lecture format. At $1000 it is hard to imagine that there will be a large call for such a collection. The slides are of excellent photographic quality, as are the illustrations within the text.
Illinois Society for Prevention of Consumption.
Authors: Liston H. Montgomery
Journal: JAMA (1899)

Chicago, June, 28. 1899. <h3>To the Editor:</h3> —One week ago there was organized in this city a society having for its object, as its name indicates, the prevention of tuberculosis. Relative to this topic and apropos of it is what theJournaland theAmerican Medical Associationhas advocated for several years, viz., that the United States Government should have a department of public health and a competent scientific physician as medical secretary of the same. In this respect the Government is behind the times. At the Columbus meeting of theAssociation, Dr. Joseph M. Mathews, in his presidential address, among other things stated, "That it was incumbent upon theAssociationas far scientific investigation can do so, to eliminate tuberculosis from the land, a disease so dreaded in character that is actually does remove yearly one-seventh of the population of the universe." I have often thought that statistics are
Childhood epidermolysis bullosa acquisita
Authors: P. INAUEN, TH. HUNZIKER, H. GERBER, L. BRUCKNER-TUDERMAN, L.R. BRAATHEN
Journal: British Journal of Dermatology (1994)

We report a 6-year-old boy suffering from acquired epidermolysis bullosa, who presented with extensive lesions of the mucous membranes and disseminated, herpetiform and 'cluster of jewels'-like vesicles and bullae arising on erythematous plaques. Direct immunofluorescence showed linear deposits of IgG and C3 at the epidermal basement membrane zone. Indirect immunofluorescence demonstrated circulating autoantibodies (titre 1:128-1:256) directed at the blister floor of human NaCl-split skin, and reacting specifically with collagen VII of the anchoring fibrils, as demonstrated by immunoblotting. The disease was controlled with a combination of dapsone and prednisone. This case demonstrates the importance of modern immunological techniques in classifying childhood autoimmune bullous diseases, as precise diagnosis is important in determining an appropriate therapeutic regimen.
Clinical Implications of the DREAM Study
Authors: Mayer B. Davidson
Journal: Diabetes Care (2007)

In response to an article (1) published in 2003 demonstrating that both diet and exercise as well as pioglitazone reduced insulin resistance in upper-body obese, sedentary, nondiabetic individuals, I wrote an editorial (2) discussing whether the treatment of insulin resistance independent of any effect on glycemia could be beneficial for reducing the risk of cardiovascular disease (CVD). At that time, evidence for a beneficial effect rested on surrogate end points and intermediate outcomes of CVD. The final sentence in the editorial was, “If the ongoing clinical trials demonstrate a reduction in hard clinical events, difficult decisions will need to be made.” Although thiazolidinediones (TZDs) continued to lower many of the surrogate risk factors associated with and early manifestations of CVD (e.g., endothelial dysfunction, intima medial thickness of carotid arteries) in subsequent studies, the effect on preventing hard clinical outcomes in the first clinical trial reported was less robust than many had anticipated (3). Now the Diabetes Reduction Assessment with Rampipril and Rosiglitazone Medication (DREAM) study (4) has been published, raising the question of treating nondiabetic individuals with a TZD, to reduce the risk of developing type 2 diabetes rather than CVD.

The DREAM study (4) randomized over 5,000 individuals with impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG) to receive either 8 mg rosiglitazone or placebo over a median of 3 years. There was an ∼60% less chance of those receiving the TZD to develop diabetes compared with those receiving the placebo. For every 1,000 subjects with IFG and/or IGT given rosiglitazone, 144 would be prevented from developing diabetes. There would be, however, four to five excess cases (i.e., over what would have occurred if a TZD had not been given) of heart failure. In addition to the small increase in heart failure, the cost of the TZD …
Cancer trends in England and Wales
Authors: H. O Dickinson
Journal: BMJ (2000)

Papers p 895 

Cancer is among the three leading causes of death in England and Wales at all ages except for preschool children.1 Survival from almost all cancers is better in affluent areas than in deprived ones, for a variety of reasons.2 In July 1999 the government set a “tough” target: “to reduce the death rate from cancer in people under 75 years by at least a fifth (20%) by 2010 [compared with 1997]—saving up to 100 000 lives.”3 Unfortunately the basis of the target has not yet been published. During 1985-98 the death rate from cancer fell by 16% in people under 75.1 Although there is no reason to assume a similar trend will apply to the comparable period 1997-2010 without assessing the effects of the ageing population, the increasing risk of cancer with age, and the changing risk in different periods, this trend suggests that the government is off to a flying start and its target …
Large-Scale Quarantine Following Biological Terrorism in the United States
Authors: Joseph Barbera, Anthony Macintyre, Larry Gostin, Tom Inglesby, Tara O'Toole, Craig DeAtley, Kevin Tonat, Marci Layton
Journal: JAMA (2001)

Concern for potential bioterrorist attacks causing mass casualties has increased recently. Particular attention has been paid to scenarios in which a biological agent capable of person-to-person transmission, such as smallpox, is intentionally released among civilians. Multiple public health interventions are possible to effect disease containment in this context. One disease control measure that has been regularly proposed in various settings is the imposition of large-scale or geographic quarantine on the potentially exposed population. Although large-scale quarantine has not been implemented in recent US history, it has been used on a small scale in biological hoaxes, and it has been invoked in federally sponsored bioterrorism exercises. This article reviews the scientific principles that are relevant to the likely effectiveness of quarantine, the logistic barriers to its implementation, legal issues that a large-scale quarantine raises, and possible adverse consequences that might result from quarantine action. Imposition of large-scale quarantine—compulsory sequestration of groups of possibly exposed persons or human confinement within certain geographic areas to prevent spread of contagious disease—should not be considered a primary public health strategy in most imaginable circumstances. In the majority of contexts, other less extreme public health actions are likely to be more effective and create fewer unintended adverse consequences than quarantine. Actions and areas for future research, policy development, and response planning efforts are provided.