tbuckley/cabot-search huggingface dataset:
LDL Cholesterol Upregulates Synthesis of Asymmetrical Dimethylarginine in Human Endothelial Cells
Authors: Rainer H. Böger, Karsten Sydow, Jürgen Borlak, Thomas Thum, Henrike Lenzen, Bibiana Schubert, Dimitrios Tsikas, Stefanie M. Bode-Böger
Journal: Circulation Research (2000)

Abstract —Asymmetrical dimethylarginine (ADMA) is an endogenous nitric oxide synthase inhibitor. It is formed by protein arginine N -methyltransferases (PRMTs), which utilize S -adenosylmethionine as methyl group donor. ADMA plasma concentration is elevated in hypercholesterolemia, leading to endothelial dysfunction and producing proatherogenic changes of endothelial cell function. Four different isoforms of human PRMTs have been identified. Because the release of ADMA from human endothelial cells is increased in the presence of native or oxidized LDL cholesterol, we investigated the potential involvement of PRMT activity and gene expression in this effect. We found that the production of ADMA by human endothelial cells is upregulated in the presence of methionine or homocysteine and inhibited by either of the methyltransferase inhibitors S -adenosylhomocysteine, adenosine dialdehyde, or cycloleucine. This effect is specific for ADMA but not symmetrical dimethylarginine. The upregulation of ADMA release by native and oxidized LDL is abolished by S -adenosylhomocysteine and by the antioxidant pyrrollidine dithiocarbamate. Furthermore, a methyl- 14 C label is transferred from S -adenosylmethionine to ADMA but not symmetrical dimethylarginine, in human endothelial cells. The expression of PRMTs is upregulated in the presence of native or oxidized LDL. Our data suggest that the production of ADMA by human endothelial cells is regulated by S -adenosylmethionine–dependent methyltransferases. This activity is upregulated by LDL cholesterol, which may be due in part to the enhanced gene expression of PRMTs. In concentrations reached by stimulation of methyltransferases (5 to 50 μmol/L), ADMA significantly inhibited the formation of 15 N-nitrite from l -[ guanidino - 15 N 2 ]arginine. These findings suggest a novel mechanism by which ADMA concentration is elevated in hypercholesterolemia, leading to endothelial dysfunction and atherosclerosis. (Circ Res. 2000;87:99-105.)
When a Myocardial Infarction Comes Out of the Not-So-Blue Air
Authors: Annette Peters
Journal: Circulation (2006)

A cute coronary syndromes such as unstable angina or myocardial infarction often develop unexpectedly and severely interrupt a patient's life.Two main pathological processes, atherosclerosis and thrombosis, lead to acute coronary syndromes such as unstable angina and myocardial infarction. 1,2The typical atherosclerotic lesion is a fibrolipid plaque composed of a pool of lipids covered with a connective tissue cap.Although the plaque narrows the coronary arteries, acute coronary syndromes only occur when a plaque erodes, fissures, or ruptures and a thrombus is formed that partially or totally occludes the arteries and impedes blood flow.The sudden onset of the disease has led to research examining triggers of acute coronary syndromes.Among the factors that contribute to acute coronary syndromes in vulnerable patients 1,2 are physical exertion, extreme anger, sexual activity, and drug abuse. 3These factors alter the shear stress at the arterial walls and increase the risk of thrombosis.Triggering of myocardial infarction caused by these stressors occurs within 1 or 2 hours of exposure, and the risk subsides rapidly after this time window.This further emphasizes the transient nature of the risks associated with triggers and distinguishes these factors from those risk factors promoting the gradual development of atherosclerosis over decades.
A meta-analysis of rectal NSAIDs in the prevention of post-ERCP pancreatitis
Authors: B J Elmunzer, A K Waljee, G H Elta, J R Taylor, S M A Fehmi, P D R Higgins
Journal: Gut (2008)

<h3>Background:</h3> Several pharmacological agents for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) have been studied. Clinical trials evaluating the protective effect of non-steroidal anti-inflammatory drugs (NSAIDs) have yielded inconclusive results. <h3>Aim:</h3> To perform a meta-analysis of studies evaluating the effect of prophylactic rectal NSAIDs on PEP. <h3>Methods:</h3> By searching Medline, Embase, meeting abstracts and bibliographies, two independent reviewers systematically identified prospective randomised controlled trials (RCTs) examining the effect of rectally administered prophylactic NSAIDs on the incidence of PEP pancreatitis. A meta-analysis of these clinical trials was performed. <h3>Results:</h3> Four RCTs, enrolling a total of 912 patients, have been published. Meta-analysis of these studies demonstrates a pooled relative risk for PEP after prophylactic administration of NSAIDs of 0.36 (95% CI 0.22 to 0.60); patients who received NSAIDs in the periprocedural period were 64% less likely to develop pancreatitis and 90% less likely to develop moderate to severe pancreatitis. The pooled number needed to treat with NSAIDs to prevent one episode of pancreatitis is 15 patients. No adverse events attributable to the use of NSAIDs were reported in any of the clinical trials. <h3>Conclusion:</h3> In this meta-analysis, prophylactic NSAIDs were effective in preventing PEP. Widespread prophylactic administration of these agents may significantly reduce the incidence of PEP, resulting in major clinical and economic benefit. Given current scepticism regarding the efficacy of any prophylactic medication for ERCP, additional multicentre studies are needed for confirmation prior to widespread adoption of this strategy.
Muscle cells under attack
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

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Autoantigens associated with dermatomyositis are expressed in regenerating muscle cells (brown).Antitumor T cells may confuse regenerating muscle cells for their intended targets and attack them, according to new data from Casciola-Rosen et al. (

[page 591][2]). This
An Endocrinologist-Supported Intervention Aimed at Providers Improves Diabetes Management in a Primary Care Site
Authors: Lawrence S. Phillips, David C. Ziemer, Joyce P. Doyle, Catherine S. Barnes, Paul Kolm, William T. Branch, Jane M. Caudle, Curtiss B. Cook, Virginia G. Dunbar, Imad M. El-Kebbi, Daniel L. Gallina, Risa P. Hayes, Christopher D. Miller, Mary K. Rhee, Dennis M. Thompson, Clyde Watkins
Journal: Diabetes Care (2005)

OBJECTIVE—Management of diabetes is frequently suboptimal in primary care settings, where providers often fail to intensify therapy when glucose levels are high, a problem known as clinical inertia. We asked whether interventions targeting clinical inertia can improve outcomes. RESEARCH DESIGN AND METHODS—A controlled trial over a 3-year period was conducted in a municipal hospital primary care clinic in a large academic medical center. We studied all patients (4,138) with type 2 diabetes who were seen in continuity clinics by 345 internal medicine residents and were randomized to be control subjects or to receive one of three interventions. Instead of consultative advice, the interventions were hard copy computerized reminders that provided patient-specific recommendations for management at the time of each patient’s visit, individual face-to-face feedback on performance for 5 min every 2 weeks, or both. RESULTS—Over an average patient follow-up of 15 months within the intervention site, improvements in and final HbA1c (A1C) with feedback + reminders (ΔA1C 0.6%, final A1C 7.46%) were significantly better than control (ΔA1C 0.2%, final A1C 7.84%, P &amp;lt; 0.02); changes were smaller with feedback only and reminders only (P = NS vs. control). Trends were similar but not significant with systolic blood pressure (sBP) and LDL cholesterol. Multivariable analysis showed that the feedback intervention independently facilitated attainment of American Diabetes Association goals for both A1C and sBP. Over a 2-year period, overall glycemic control improved in the intervention site but did not change in other primary care sites (final A1C 7.5 vs. 8.2%, P &amp;lt; 0.001). CONCLUSIONS—Feedback on performance aimed at overcoming clinical inertia and given to internal medicine resident primary care providers improves glycemic control. Partnering generalists with diabetes specialists may be important to enhance diabetes management in other primary care settings.
Contribution of calpains to myocardial ischaemia/reperfusion injury
Authors: J. Inserte, V. Hernando, D. Garcia-Dorado
Journal: Cardiovascular Research (2012)

Loss of calcium (Ca2+) homeostasis contributes through different mechanisms to cell death occurring during the first minutes of reperfusion. One of them is an unregulated activation of a variety of Ca2+-dependent enzymes, including the non-lysosomal cysteine proteases known as calpains. This review analyses the involvement of the calpain family in reperfusion-induced cardiomyocyte death. Calpains remain inactive before reperfusion due to the acidic pHi and increased ionic strength in the ischaemic myocardium. However, inappropriate calpain activation occurs during myocardial reperfusion, and subsequent proteolysis of a wide variety of proteins contributes to the development of contractile dysfunction and necrotic cell death by different mechanisms, including increased membrane fragility, further impairment of Na+ and Ca2+ handling, and mitochondrial dysfunction. Recent studies demonstrating that calpain inhibition contributes to the cardioprotective effects of preconditioning and postconditioning, and the beneficial effects obtained with new and more selective calpain inhibitors added at the onset of reperfusion, point to the potential cardioprotective value of therapeutic strategies designed to prevent calpain activation.
Association between obstructive sleep apnea and elevated levels of B-type natriuretic peptide in a community based sample of women
Authors: Mirjam Ljunggren, Bertil Lindahl, Jenny Theorell-Haglöw, Eva Lindberg
Journal: European Respiratory Journal (2012)

Background:  Obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular disease and mortality. One contributory factor may be hemodynamic stress due to the negative intrathoracic pressure during each apnea. Type-B Natriuretic Peptide (BNP) is secreted by the cardiac ventricles in response to volume expansion and pressure load and we hypothesized that there would be an association between indices of obstructive sleep apnea in the night and levels of BNP in the morning.   Methods:  From a community-based sample, 349 women underwent full-night polysomnography, anthropometric measurements and answered a questionnaire about medical conditions and current medication. The morning following the polysomnography, blood samples were drawn for analysis of plasma BNP, C-reactive protein, creatinine and hemoglobin.   Results:  There was an increase in mean BNP as the severity of sleep apnea increased, increasing from a mean value of 8.5ng/L among women with an AHI of  30. Elevated BNP levels (>20ng/L) were found in 29.8% of the women, while 70.2% had normal levels. The odds ratio was 2.2 for elevated BNP levels for women with an AHI of 5- 30 after adjustment for age, BMI, systolic blood pressure, antihypertensive drugs and creatinine.   Conclusions:  We found a dose-response relationship between the severity of sleep apnea during the night in women and the levels of BNP in the morning.
Urea synthesis after oral protein ingestion in man.
Authors: R J Rafoth, G R Onstad
Journal: Journal of Clinical Investigation (1975)

In an attempt to assess hepatic functional capacity, hourly urea production, and corresponding serum amino acid concentrations after the ingestion of single protein meals (60, 120, and 240 g of protein) were evaluated in 18 normal subjects and in 8 patients with liver disease. In normal subjects, the relationship between urea production and serum amino acid concentration was linear (urea production in milligram urea nitrogen/kilogram lean body mass/hour = 6.3 times mg amino acid nitrogen/100 ml minus 20.5 SE of the estimate 6.9, r = 0.74, P less than 0.001), and variation of protein intake from 50 to 150 g/day for 3 days before testing did not change this relationship. The patients demonstrated impairment of urea synthesis proportional to the clinical severity of their liver disease. The potential clinical applications of these findings need to be determined.
Clinical measures of disease severity and outcome in psoriasis: a critical appraisal of their quality
Authors: None Ashcroft, None Li Wan Po, None Williams, None Griffiths
Journal: British Journal of Dermatology (1999)

In clinical trials, a wide range of outcome measures has been used to evaluate the severity of psoriasis and its response to treatment. Despite their widespread use, many measures have received little attention with regards to their reliability and validity. Selecting an appropriately developed measurement tool is therefore of critical importance. We conducted a literature survey to examine the status of clinical outcome measures used in psoriasis research. The measures most commonly used were individual sign scores, e.g. for erythema, plaque thickness or scaling, and pooled indices, e.g. the Psoriasis Area and Severity Index. None of these, however, systematically fulfilled all the requirements of a validated instrument for disease assessment. Ideally, a core set of reliable and validated outcome measures for use in all psoriasis clinical trials is needed. Objective instrumental methods should minimise observer variation, but unless a simple non-invasive method can be developed, the uptake of such technology will probably be limited by cost and lack of practicality. Moreover, the translation of instrumental readings into clinically relevant measures is always a major problem, and for none of the methods has there been a robust mapping of instrumental readings on to a clinically meaningful scale. Further research is needed to determine the most appropriate and sensitive parameters to use as surrogate measures for capturing the distress which psoriatic patients feel but which is not measured with sufficient sensitivity or precision with current quality of life or distress questionnaires.
Genetic Markers
Authors: Gary H. Gibbons, Choong Chin Liew, Mark O. Goodarzi, Jerome I. Rotter, Willa A. Hsueh, Helmy M. Siragy, Richard Pratt, Victor J. Dzau
Journal: Circulation (2004)

Cholesterol ester transfer protein LPL Lipoprotein lipase ACE Angiotensin I converting enzyme 1 ATIIR1 Angiotensin II receptor type 1 CBS Cystathionine-synthase GPIIIA Glycoprotein IIIa FGA Fibrinogen ELAM Endothelial leukocyte adhesion molecule-1 Atherothrombosis (angina pectoris) TAFI Thrombin activatable fibrinolysis inhibitor Brugada syndrome SCN5A Sodium channel voltage-gated Calcific aortic valve stenosis VDR Vitamin D receptor Cardiac arrhythmia, inherited SCN5A Sodium channel voltage
Prevalence of asthma-related symptoms and bronchial responsiveness to exercise in children aged 13-14 yrs in Barcelona, Spain
Authors: RM Busquets, JM Anto, J Sunyer, N Sancho, O Vall
Journal: European Respiratory Journal (1996)

It is not clear whether asymptomatic bronchial responsiveness is a risk factor for development of asthma. A cross-sectional study was conducted to determine the prevalence of asthma among schoolchildren from Barcelona (Spain). The association between respiratory symptoms and bronchial responsiveness to exercise was examined. For this study 3,033 schoolchildren aged 13-14 yrs were studied from the general population. Participants answered a respiratory questionnaire and a self-reporting video-questionnaire. A total of 2,842 children underwent bronchial responsiveness testing by exercise challenge. The study was part of the International Study of Asthma and Allergies in Childhood (ISAAC) project. The prevalence of "current asthma" (recent wheezing and bronchial responsiveness to exercise) was 4% and the prevalence of "wheezing only" 10%. A fall in peak expiratory flow rate (PEFR) &gt; or = 15% after exercise testing was found in 324 (11%) children, 29 (9%) of whom presented clinical symptoms of asthma. Bronchial responsiveness to exercise was significantly associated with all items of the asthma questionnaire. The prevalence of asthma-related symptoms in this inner-city area was lower than frequently reported rates in other countries, although the prevalence of exercise-induced bronchoconstriction was relatively high, and threefold greater than in a geographical area in the vicinity of Barcelona. These findings are consistent with the current view that asthma-related symptoms and bronchial responsiveness to exercise have different meanings in a community survey, and that local environmental factors could influence the prevalence of bronchial responsiveness.
H2-M3 Restricted Presentation of a <i>Listeria</i>-derived Leader Peptide
Authors: Michael F. Princiotta, Laurel L. Lenz, Michael J. Bevan, Uwe D. Staerz
Journal: The Journal of Experimental Medicine (1998)

Protective immunity to infection by many intracellular pathogens requires recognition by cytotoxic T lymphocytes (CTLs) of antigens presented on major histocompatibility complex (MHC) class I molecules. To be presented for recognition by pathogen-specific CTLs, these antigens must gain access to the host cell class I processing pathway. In the case of intracellular bacterial pathogens, the majority of bacterial proteins are retained within the bacterial membrane and therefore remain inaccessible to the host cell for antigen processing. We have isolated a CTL clone from a C57BL/6 mouse infected with the intracellular gram-positive bacterium Listeria monocytogenes (LM) and have identified the source of the antigen. Using a genomic expression library, we determined that the clone recognizes an antigenic N-formyl peptide presented by the nonpolymorphic murine MHC class Ib molecule, H2-M3. Several lengths of this peptide were able to sensitize cells for lysis by this CTL clone. The source of this antigenic peptide is a 23-amino acid polypeptide encoded at the start of a polycistronic region. Analysis of mRNA secondary structure of this region suggests that this polypeptide may be a leader peptide encoded by a transcriptional attenuator.
Tybamate—A Perplexing Drug
Authors: KARL RICKELS, PETER HESBACHER, WILLIAM VANDERVORT, FRED PHILLIPS, JAMES HUTCHISON, LESTER SABLOSKY, DONALD LAVAN
Journal: American Journal of Psychiatry (1968)

Tybamate was evaluated in a controlled, double-blind study conducted with 126 anxious neurotic patients seen in general practice. Tybamate produced significantly more improvement than placebo only at the final four-week evaluation. The largest tybamate-placebo differences were observed on measures of somatic manifestations of free anxiety, followed by measures of bound anxiety such as phobic-obsessive-compulsive symptoms. Severity of initial symptomatology was related to the patient's response to tybamate but not to placebo; those patients who were initially sickest improved significantly more than patients who were initially less sick.
Multicolor Flowcytometric Immunophenotyping Is a Valuable Tool for Detection of Intraocular Lymphoma
Authors: Tom Missotten, Dennis Tielemans, Jacolien E. Bromberg, P. Martin van Hagen, Ellen G. van Lochem, Jacques J.M. van Dongen, G. Seerp Baarsma, Anton W. Langerak
Journal: Ophthalmology (2013)
Update on toll-like receptor-directed therapies for human disease
Authors: K. Tse, A. A Horner
Journal: Annals of the Rheumatic Diseases (2007)

Innate responses to microbes are mediated in large part by toll-like receptors (TLRs), which recognise a diverse range of molecules produced by viruses, bacteria and fungi. Great effort has been directed towards translating this knowledge into the development of new therapies for a wide spectrum of diseases, including infectious, malignant, autoimmune and allergic diseases. This review will provide a brief update on completed, ongoing and planned clinical trials of TLR ligand-based therapies for the treatment of diseases in humans.
Spirometry and Health Status Worsen with Weight Gain in Obese Smokers but Improve in Normal-Weight Smokers
Authors: Akshay Sood, Hans Petersen, Paula Meek, Yohannes Tesfaigzi
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

The literature on the effect of obesity and weight gain on respiratory outcomes in smokers is contradictory.To examine the cross-sectional effect of body mass index (BMI) and the longitudinal effect of change in BMI upon spirometry and health status among smokers at risk for and with milder chronic obstructive pulmonary disease (COPD).Participants from the Lovelace Smokers' Cohort were followed for a median period of 6 years, 75% of whom were at risk and 25% of whom had COPD at baseline examination. BMI and gain in BMI were examined as continuous independent variables overall and after stratification into three categories (normal-weight, overweight, and obese) determined on the basis of baseline weight. Spirometry and health status (as assessed by St. George Respiratory Questionnaire total and subscale scores) were dependent variables. Covariates included age, sex, ethnicity, pack-years of smoking, and current smoking status. Cross-sectional analysis used linear and logistic regression; longitudinal analysis used a mixed model approach.In cross-sectional analyses, higher BMI was associated with worse health status among obese smokers but with better health status among normal-weight smokers. In longitudinal analyses, weight gain was associated with a decrease in FEV1 and health status among obese smokers and with an increase in these outcomes among normal-weight smokers.Weight gain affects respiratory outcomes differently between obese and normal-weight smokers. Whereas FEV1 and health status decrease with weight gain among obese smokers, they improve among normal-weight smokers. The nonlinear relationship between weight gain and respiratory outcomes suggests that this effect of excess weight is unlikely to be mechanical alone.