tbuckley/cabot-search huggingface dataset:
DOES NEW-ONSET AF LEAD TO CONGESTIVE HEART FAILURE AND VICE VERSA IN HYPERTENSIVE PATIENTS?
Authors: Casper N. Bang, Anders Greve, Sverre Kjeldsen, Bjorn Dahlof, Lars Kober, Richard Devereux, Peter Okin, Kristian Wachtell
Journal: Journal of the American College of Cardiology (2014)
Genetic Factors in Alzheimer's Disease
Authors: Thomas D. Bird
Journal: New England Journal of Medicine (2005)

Nearly 100 years ago, Alois Alzheimer described the clinical and pathological characteristics of a 50-year-old woman with the dementing illness that now bears his name.1 She had no family history of dementia. It soon became established dogma that Alzheimer's disease was a rare, noninherited cause of presenile dementia.The past 25 years have seen an astounding confluence of seven new observations that have resulted in fundamental changes in our understanding of this important disease. First, Alzheimer's disease is by far the most common cause of dementia. Second, the major pathological component of the disease is the accumulation of a form . . .
Transcutaneous assessment of renal function in conscious rats with a device for measuring FITC-sinistrin disappearance curves
Authors: Daniel Schock-Kusch, Qing Xie, Yury Shulhevich, Juergen Hesser, Dzmitry Stsepankou, Maliha Sadick, Stefan Koenig, Friederike Hoecklin, Johannes Pill, Norbert Gretz
Journal: Kidney International (2011)
Circulating Adhesion Molecules in Cystic Fibrosis
Authors: VIRGINIA DE ROSE, ALESSANDRO OLIVA, BARBARA MESSORE, BIANCA GROSSO, CINZIA MOLLAR, ERNESTO POZZI
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

A marked influx of inflammatory cells occurs into the airways of patients with cystic fibrosis (CF), which may contribute to the development of lung injury. Leukocyte–endothelial adhesion molecules play a crucial role in the recruitment of inflammatory cells, and soluble forms of these molecules have been shown to increase in several inflammatory diseases. By using a capture ELISA, we determined serum levels of soluble ICAM-1 (sICAM-1), E-selectin (sE-selectin), and VCAM-1 (sVCAM-1) in patients with CF, in stable clinical conditions (n = 29, mean age: 25.8 ± 1.5 yr), and healthy control subjects (n = 12, mean age: 27.6 ± 1.5 yr). Clinical, spirometric, microbiological, and hematological assessments were made in all subjects. sICAM-1 and sE-selectin concentrations, but not sVCAM-1 levels were significantly increased in CF patients as compared with normal subjects (both p < 0.001). sICAM-1 levels were inversely related to FEV1 values (r = − 0.519, p = 0.004) and Schwachman score (r = − 0.405, p = 0.03) in CF patients. In 7 of 29 CF patients, soluble adhesion molecule levels were determined not only at the time of stable clinical conditions, but also before and after antibiotic treatment for a pulmonary exacerbation. sICAM-1 and sE-selectin levels increased in all patients at the time of the exacerbation, compared with levels at the time of stable conditions (p < 0.02 for both comparisons); antibiotic treatment induced a significant decrease of both circulating adhesion molecules (p < 0.02). The elevated serum levels of sICAM-1 and sE-selectin in CF patients, even when they are clinically stable, may reflect the marked and persistent inflammatory process in the disease.
Angiotensin II Upregulates Toll-Like Receptor 4 on Mesangial Cells
Authors: Gunter Wolf, Jürgen Bohlender, Tzvetanka Bondeva, Thierry Roger, Friedrich Thaiss, Ulrich O. Wenzel
Journal: Journal of the American Society of Nephrology (2006)

Angiotensin II (AngII) mediates proinflammatory properties by activating NF-kappaB transcription factor nuclear translocation and inducing the expression of chemokines. For examination of whether AngII modulates the expression of Toll-like receptor 4 (TLR4), a key element of the innate immune system that senses LPS, mouse mesangial cells (MMC) were treated with AngII. AngII upregulated TLR4 mRNA and protein in MMC, and this effect was mediated through AngII type 1 receptors. Reporter gene experiments indicate that an activating protein-1 (AP-1) as well as an E-26 specific sequence (Ets) binding site in the TLR4 promoter are responsible for the AngII-stimulated transcriptional activity of the TLR4 gene. Preincubation of MMC with AngII enhanced LPS-induced NF-kappaB activation and chemokine expression. Immunohistochemical analyses revealed that double-transgenic rats that overexpressed human renin and angiotensinogen expressed higher levels of glomerular TLR4 compared with normal Sprague-Dawley rats. In vivo, infusion with AngII but not with norepinephrine into rats for 7 d also enhanced glomerular NF-kappaB activation after systemic application of LPS, suggesting that the effects are independent of concomitantly induced hypertension. Together, these observations suggest that AngII leads to an activation of the innate immune system by a novel mechanism involving the upregulation of TLR4. Our data contribute to a better understanding of how exogenous infections may trigger renal autoimmune processes, particularly in pathophysiologic situations with high renal AngII concentrations. Because TLR4 binds endogenous ligands (e.g., extracellular matrix components) in addition to microbial products, AngII-mediated upregulation of TLR4 also could be relevant for the development of inflammation in many noninfectious renal diseases.
Points from Letters: Strengthening General Practice
Authors: M. J. Leverton
Journal: BMJ (1971)

Analyzer.The conditions remained identical apart from increased concentration of indicator enzymes.3Normal ranges were determined for each system on blood drawn from healthy volunteers.The results are given in the Table .The range for asparate amino- transferase was much narrower with the LKB instrument, the upper limit of normal falling by 8 units.This was due to the standard deviation being virtually halved, since the mean was similar to the previous value.Instrument No.
Acquired resistance to Borrelia burgdorferi infection in the rabbit. Comparison between outer surface protein A vaccine- and infection-derived immunity.
Authors: D M Foley, Y P Wang, X Y Wu, D R Blanco, M A Lovett, J N Miller
Journal: Journal of Clinical Investigation (1997)

Intradermal inoculation of the rabbit with Borrelia burgdorferi, sensu lato, results in the consistent development of erythema migrans (EM), dermal infection, and visceral dissemination of the spirochete. Within 5 mo, EM as well as dermal and visceral infection are cleared and the animals exhibit immunity to reinfection. This study compares infection-derived immunity with acquired resistance resulting from the administration of a lipidated recombinant outer surface protein A (OspA) vaccine presently undergoing human trial. 4 of 11 OspA vaccinated rabbits, challenged intradermally at each of 10 sites with 10(5) low passage B. burgdorferi, developed EM as well as dermal and disseminated infection. After identical challenge, 2 of the 11 infection-immune rabbits developed a dermal infection, but not EM or disseminated infection. Further, ELISA anti-OspA titers did not correlate with the status of immunity for either OspA vaccinated or infection-immune rabbits. Prechallenge ELISA anti-OspA titers were relatively low in the infection-immune group. This study demonstrates that a state of partial immunity to experimental Lyme disease may result that could potentially mask infection. Further, our data strongly suggest that immunogen(s) other than OspA is/are responsible for stimulating acquired resistance in the infection-immune rabbit.
Photochemically Altered Air Pollution Mixtures and Contractile Parameters in Isolated Murine Hearts before and after Ischemia
Authors: Rachel McIntosh-Kastrinsky, David Diaz-Sanchez, Kenneth G. Sexton, Corey M. Jania, Jose Zavala, Stephen L. Tilley, Ilona Jaspers, M. Ian Gilmour, Robert B. Devlin, Wayne E. Cascio, Haiyan Tong
Journal: Environmental Health Perspectives (2013)

The cardiopulmonary effects of the individual criteria air pollutants have been well investigated, but little is known about the cardiopulmonary effects of inhaled multipollutant mixtures that more realistically represent environmental exposures.We assessed the cardiopulmonary effects of exposure to photochemically altered particle-free multipollutant mixtures.We exposed mice to filtered air (FA), multipollutant mixtures, or ozone (O3) for 4 hr in a photochemical reaction chamber. Eight hours after exposure, we assessed cardiac responses using a Langendorff preparation in a protocol consisting of 20 min of global ischemia followed by 2 hr of reperfusion. Cardiac function was assessed by measuring the index of left-ventricular developed pressure (LVDP) and contractility (dP/dt) before ischemia. On reperfusion after ischemia, recovery of postischemic LVDP and size of infarct were examined. We used bronchoalveolar lavage (BAL) cell counts to assess lung inflammation.Exposure to the multipollutant mixtures decreased LVDP, baseline rate of left ventricular contraction (dP/dtmaximum), and baseline rate of left ventricular relaxation (dP/dtminimum) compared with exposure to FA. Exposure to O3 also decreased heart rate and dP/dtminimum. Time to ischemic contracture was prolonged in the multipollutant-mixture group relative to that in the FA group. Mice in the multipollutant-mixture group had better recovery of postischemic LVDP and smaller infarct size. Exposure to multipollutant mixtures and to O3 exposure increased numbers of macrophages in the BAL fluid.Exposure to photochemically altered urban air pollution appears to affect cardiac mechanics in isolated perfused hearts. Inhalation of acute multipollutant mixtures decreases LVDP and cardiac contractility in isolated non-ischemic murine hearts, prolongs ischemic contracture, increases postischemic recovery of LVDP, and reduces infarct size.
Role of Small-Conductance Calcium-Activated Potassium Channels in Atrial Electrophysiology and Fibrillation in the Dog
Authors: Xiao-Yan Qi, Jonas G. Diness, Bianca J.J.M. Brundel, Xiao-Bo Zhou, Patrice Naud, Chia-Tung Wu, Hai Huang, Masahide Harada, Mona Aflaki, Dobromir Dobrev, Morten Grunnet, Stanley Nattel
Journal: Circulation (2013)

Background— Recent evidence points to functional Ca 2+ -dependent K + (SK) channels in the heart that may govern atrial fibrillation (AF) risk, but the underlying mechanisms are unclear. This study addressed the role of SK channels in atrial repolarization and AF persistence in a canine AF model. Methods and Results— Electrophysiological variables were assessed in dogs subjected to atrial remodeling by 7-day atrial tachypacing (AT-P), as well as controls. Ionic currents and single-channel properties were measured in isolated canine atrial cardiomyocytes by patch clamp. NS8593, a putative selective SK blocker, suppressed SK current with an IC 50 of ≈5 μmol/L, without affecting Na + , Ca 2+ , or other K + currents. Whole-cell SK current sensitive to NS8593 was significantly larger in pulmonary vein (PV) versus left atrial (LA) cells, without a difference in SK single-channel open probability ( P o ), whereas AT-P enhanced both whole-cell SK currents and single-channel P o . SK-current block increased action potential duration in both PV and LA cells after AT-P; but only in PV cells in absence of AT-P. SK2 expression was more abundant at both mRNA and protein levels for PV versus LA in control dogs, in both control and AT-P; AT-P upregulated only SK1 at the protein level. Intravenous administration of NS8593 (5 mg/kg) significantly prolonged atrial refractoriness and reduced AF duration without affecting the Wenckebach cycle length, left ventricular refractoriness, or blood pressure. Conclusions— SK currents play a role in canine atrial repolarization, are larger in PVs than LA, are enhanced by atrial-tachycardia remodeling, and appear to participate in promoting AF maintenance. These results are relevant to the potential mechanisms underlying the association between SK single-nucleotide polymorphisms and AF and suggest SK blockers as potentially interesting anti-AF drugs.
Myocardial Tc-99m MDP Uptake on a Bone Scan in Senile Systemic Amyloidosis with Cardiac Involvement
Authors: İLKNUR AK, ERKAN VARDARELİ, OĞUZ ERDİNĈ, EMİNE KASAPOĞLU, NECMİ ATA
Journal: Clinical Nuclear Medicine (2000)

A Tc-99m MDP bone scan showed diffuse myocardial uptake in a 61-year-old man who reported progressive glove- and stocking-like parasthesias. Results of complete blood counts, thyroid and liver function tests, tumor markers, electrolytes, and electrocardiography were normal. Electromyelographic findings revealed bilateral sensorimotor peripheral polyneuropathy in both upper and lower extremities. Monoclonal immunoglobulin light chains were not detected in serum or urine by immunoelectrophoresis. Amyloid deposition was noted on the histologic analyses of rectal biopsy samples. Results of immunohistochemical staining were positive. There were no clinical signs of cardiac functional impairment. Follow-up investigations did not reveal any other site of amyloid deposition, and the only symptoms were peripheral neuropathy.
1012-103 Blood pressure changes do not influence the beneficial effects of carvedilol compared to metoprolol in the patients with heart failure: Results from COMET (carvedilol or metoprolol European trial)
Authors: Marco Metra, Andrea Di Lenarda, Peter Hanrath, Michel Komajda, Beatrix Lutiger, John G Cleland, Willem J Remme, Armin Scherhag, Andrew Charlesworth, Karl Swedberg, Christian Torp-Pedersen
Journal: Journal of the American College of Cardiology (2004)
Recent progress in understanding apolipoprotein B.
Authors: S G Young
Journal: Circulation (1990)

For the past 5 years, investigators from many different laboratories have contributed to a greatly increased understanding of two very important lipid-carrying proteins in plasma--apo B-100 and apo B-48. Apo B-100, an extremely large protein composed of 4,536 amino acids, is synthesized by the liver and is crucial for the assembly of triglyceride-rich VLDL particles. Apo B-100 is virtually the only protein of LDL, a cholesteryl ester-enriched class of lipoproteins that are metabolic products of VLDL. The apo B-100 of LDL serves as a ligand for the LDL receptor-mediated uptake of LDL particles by the liver and extrahepatic tissues. The LDL receptor-binding region of apo B-100 is located in the carboxyterminal portion of the molecule, whereas its lipid-binding regions appear to be broadly dispersed throughout its length. Apo B-48 contains the amino-terminal 2,152 amino acids of apo B-100 and is produced by the intestine as a result of editing of a single nucleotide of the apo B mRNA, which changes the codon specifying apo B-100 amino acid 2,153 to a premature stop codon. Apo B-48 has an obligatory structural role in the formation of chylomicrons; therefore, its synthesis is essential for absorption of dietary fats and fat-soluble vitamins. Both apo B-48 and apo B-100 are encoded on chromosome 2 by a single gene that contains 29 exons and 28 introns. An elevated level of apo B-100 in the plasma is a potent risk factor for developing premature atherosclerotic disease. In the past 3 years, many different apo B gene mutations that affect the concentrations of both apo B and cholesterol in the plasma have been characterized. A missense mutation in the codon for apo B-100 amino aid 3,500 is associated with hypercholesterolemia. This mutation results in poor binding of apo B-100 to the LDL receptor, thereby causing the cholesteryl ester-enriched LDL particles to accumulate in the plasma. This disorder is called familial defective apo B-100, and it is probably a cause of premature atherosclerotic disease. Familial hypobetalipoproteinemia is a condition associated with abnormally low levels of apo B and cholesterol; affected individuals may actually have a reduced risk of atherosclerotic disease.(ABSTRACT TRUNCATED AT 400 WORDS)
Developing clinical guidelines: a challenge to current methods
Authors: Rosalind Raine, Colin Sanderson, Nick Black
Journal: BMJ (2005)

Current methods for producing clinical guidelines are cumbersome and not always reliable.Could a more streamlined approach improve coverage and make decisions more transparent?Clinical guidelines are rarely based solely on research evidence.In most cases they also incorporate the consensus views of experts.Despite recognition of the need for rigour in developing a consensus, current approaches often lack sufficient transparency, fail to make clear what influence the level of resources in the health system has, lack sufficient reliability, and will never achieve comprehensive and timely coverage of the whole range of health care.We propose a new approach that we believe will be more cost effective and that could meet these challenges. Need for consensusMost professional societies and national agencies in North America, Australia, and Europe recognise that guidelines cannot be based on research evidence alone.To paraphrase the philosopher David Hume: "ought" statements such as guidelines cannot be constructed from "is" statements such as research evidence. 1 The conversion from is to ought inevitably introduces value judgments about underlying goals and, in this context, somewhat subjective assessments of the quality of the research evidence and its relevance for particular patients and settings.The recognised need to go beyond the often limited research evidence has led to the use of expert consensus in developing guidelines.The assumption is that the views of a group have greater validity and reliability than the judgment of an individual.In addition, formal or structured methods for developing a consensus have advantages over informal committees: they should offer more transparent ways of synthesising individual judgments, can reduce the influence of dominating personalities and "group think," and can provide valuable information on the extent and reasons for differences of opinion. 2 Since there can be no standard for checking the validity of a consensus based guideline, we must ensure that the way consensus is developed, in particular who to involve and how to structure the process, is as rigorous as possible.Despite rapid growth in the use of formal methods for developing consensus throughout the world, 3 several challenges remain.
National Patterns of Use and Effectiveness of Angiotensin-Converting Enzyme Inhibitors in Older Patients With Heart Failure and Left Ventricular Systolic Dysfunction
Authors: Frederick A. Masoudi, Saif S. Rathore, Yongfei Wang, Edward P. Havranek, Jeptha P. Curtis, JoAnne Micale Foody, Harlan M. Krumholz
Journal: Circulation (2004)

Although ACE inhibitors are underprescribed for heart failure, factors associated with their use are not well described. Furthermore, the effectiveness of ACE inhibitors has been questioned in some populations, potentially contributing to underuse. Our objectives were to assess the correlates of ACE inhibitor use and the relationship between ACE inhibitor prescription and mortality in older patients with heart failure.We studied a national sample aged > or =65 years who had survived hospitalization for heart failure between April 1998 and March 1999 or July 2000 and June 2001, restricting the analysis to patients with left ventricular systolic dysfunction and without a documented contraindication to use of ACE inhibitors (n=17 456). Factors associated with ACE inhibitor prescription at discharge and the relationship between ACE inhibitor prescription and death within 1 year were assessed with hierarchical logistic models. Secondary analyses assessed therapeutic substitution with angiotensin receptor blockers (ARBs). ACE inhibitors were prescribed to only 68% of this ideal cohort, and 76% received either an ACE inhibitor or an ARB. Patient, physician, and hospital factors were weak predictors of prescription, except for serum creatinine (RR for 133 to 221 micromol/L=0.87, 95% CI 0.85 to 0.89; RR for > or =222 micromol/L=0.53, 95% CI 0.49 to 0.57 compared with < or =132 micromol/L). ACE inhibitor prescription was associated with lower crude 1-year mortality (33.0% versus 42.1%, P<0.001), lower risk of death after adjustment (RR 0.86, 95% CI 0.82 to 0.90), and lower mortality regardless of patient gender, age, race, or serum creatinine level.ACE inhibitors were widely underprescribed despite evidence of a favorable impact on survival in a broad range of patients with heart failure. These results emphasize the importance of ongoing efforts to translate clinical trial results into practice.
Intestinal heat shock protein 110 regulates expression of CD1d on intestinal epithelial cells
Authors: Sean P. Colgan, Richard S. Pitman, Takashi Nagaishi, Atsushi Mizoguchi, Emiko Mizoguchi, Lloyd F. Mayer, Ling Shao, R. Balfour Sartor, John R. Subjeck, Richard S. Blumberg
Journal: Journal of Clinical Investigation (2003)

CD1d is expressed on the surface of professional and nonprofessional APCs, including intestinal epithelial cells (IECs), for a role in the presentation of glycolipid-based antigens to subsets of T cells. The mechanisms that regulate CD1d expression in any cell type are unknown. To investigate the possibility that expression of CD1d is influenced by exogenous factors present within the intestinal lumen, CD1d expression was analyzed in several IEC lines after culturing in the presence of lumenal contents (LC) of the normal human intestine. Exposure of the colon-derived cell lines T84, HT-29, and Caco-2 to soluble LC resulted in a marked induction of CD1d expression as determined by RT-PCR, confocal microscopy, cell surface ELISA, and Western blot analysis. Similarly, exposure of human IECs to LC isolated from mice bred in both specific pathogen–free and germfree conditions also resulted in the induction of CD1d expression, with the maximum CD1d-inducing activity observed in the small intestine. Biochemical and biophysical characterization of the human CD1d-inducing activity identified heat shock protein 110 (Hsp110) as a major functional component of the LC that contributes to CD1d surface regulation, and immunolocalization studies revealed Hsp110 expression in subsets of human IECs in vivo. These data support the presence of a novel autocrine pathway of CD1d regulation by Hsp110.
Virus specific antibodies in multiple sclerosis.
Authors: K B Fraser, M Haire, J H Millar
Journal: BMJ (1972)

hibitor and Fast Red TR salt solution in 3% aqueous dupanol as colour index.The results are summarized in the Table.Number IAbnor-Genetic Disorder Exam-mal ined Cases % i-thalassaemia trait .. 156 27 17-3 Hb A, increased (>335%) 156 25 16-0 g I thal.(Hb F > 5%) 156 2 1-3 -6-PD deficiency . . . . . . . . .
Immunofluorescence studies on eosinophilic granulocytes
Authors: P.J.M. BERRETTY, R.H. CORMANE
Journal: British Journal of Dermatology (2006)

Immunofluorescence techniques were used to find out whether immunoglobulins (Ig) and complement (C3) determinants are present on the membrane of eosinophilic granulocytes in atopic patients and in patients with an allergic contact dermatitis. Normal healthy individuals served as controls. The studies were performed with eosinophilic granulocytes in suspension and in thin cell layers. The demonstration of the presence of cytoplasmic Ig and C3 in eosinophilic granulocytes was carried out in skin specimens taken 20-30 min after injection of the antigen and in specimens taken from positive patch tests 48 h after application of the antigen. No immunoglobulins or C3 determinants could be demonstrated on the membrane of eosinophilic granulocytes in the patients or the healthy controls, when the suspension methods were used. However, in thin cell layers and in skin sections the eosinophilic granulocytes showed a positive fluorescence of the cytoplasm after having been exposed to various conjugates and a FITC solution. It is concluded that the commonly used immunofluorescence techniques tend to give non-specific staining results, most likely due to reactivity of the FITC marker of the conjugates with basic proteins present in the cytoplasm of the eosinophilic granulocyte.