tbuckley/cabot-search huggingface dataset:
Does neuroinflammation fan the flame in neurodegenerative diseases?
Authors: Tamy C Frank-Cannon, Laura T Alto, Fiona E McAlpine, Malú G Tansey
Journal: Molecular Neurodegeneration (2009)

While peripheral immune access to the central nervous system (CNS) is restricted and tightly controlled, the CNS is capable of dynamic immune and inflammatory responses to a variety of insults. Infections, trauma, stroke, toxins and other stimuli are capable of producing an immediate and short lived activation of the innate immune system within the CNS. This acute neuroinflammatory response includes activation of the resident immune cells (microglia) resulting in a phagocytic phenotype and the release of inflammatory mediators such as cytokines and chemokines. While an acute insult may trigger oxidative and nitrosative stress, it is typically short-lived and unlikely to be detrimental to long-term neuronal survival. In contrast, chronic neuroinflammation is a long-standing and often self-perpetuating neuroinflammatory response that persists long after an initial injury or insult. Chronic neuroinflammation includes not only long-standing activation of microglia and subsequent sustained release of inflammatory mediators, but also the resulting increased oxidative and nitrosative stress. The sustained release of inflammatory mediators works to perpetuate the inflammatory cycle, activating additional microglia, promoting their proliferation, and resulting in further release of inflammatory factors. Neurodegenerative CNS disorders, including multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), tauopathies, and age-related macular degeneration (ARMD), are associated with chronic neuroinflammation and elevated levels of several cytokines. Here we review the hallmarks of acute and chronic inflammatory responses in the CNS, the reasons why microglial activation represents a convergence point for diverse stimuli that may promote or compromise neuronal survival, and the epidemiologic, pharmacologic and genetic evidence implicating neuroinflammation in the pathophysiology of several neurodegenerative diseases.
Scotland's drinking laws set for reform to stem alcohol problems
Authors: B. Christie
Journal: BMJ (2003)

Scotland's drinking laws should be reformed, says a new report, which recommends the abolition of fixed opening hours, a crackdown on cheap drink promotions, and moves to make pubs more child friendly.

The recommendations of the review team, led by Sheriff Principal Gordon Nicholson, follow concern about increasing health problems that are related to alcohol. Binge drinking, which is being encouraged by cheap drink promotions, is highlighted as a particular problem in the report. …
Pathogen Virulence Impedes Mutualist-Mediated Enhancement of Host Juvenile Growth via Inhibition of Protein Digestion
Authors: Berra Erkosar, Gilles Storelli, Mélanie Mitchell, Loan Bozonnet, Noémie Bozonnet, François Leulier
Journal: Cell Host & Microbe (2015)

The microbial environment impacts many aspects of metazoan physiology through largely undefined molecular mechanisms. The commensal strain Lactobacillus plantarumWJL (LpWJL) sustains Drosophila hormonal signals that coordinate systemic growth and maturation of the fly. Here we examine the underlying mechanisms driving these processes and show that LpWJL promotes intestinal peptidase expression, leading to increased intestinal proteolytic activity, enhanced dietary protein digestion, and increased host amino acid levels. LpWJL-mediated peptidase upregulation is partly driven by the peptidoglycan recognition and signaling cascade PGRP-LE/Imd/Relish. Additionally, this mutualist-mediated physiological benefit is antagonized upon pathogen infection. Pathogen virulence selectively impedes LpWJL-mediated intestinal peptidase activity enhancement and juvenile growth promotion but does not alter growth of germ-free animals. Our study reveals the adaptability of host physiology to the microbial environment, whereby upon acute infection the host switches to pathogen-mediated host immune defense at the expense of mutualist-mediated growth promotion.
Cellular Cardiomyoplasty of Cardiac Fibroblasts by Adenoviral Delivery of <i>MyoD</i> Ex Vivo: An Unlimited Source of Cells for Myocardial Repair
Authors: Sharon Etzion, Israel M. Barbash, Micha S. Feinberg, Parvin Zarin, Liron Miller, Esther Guetta, Radka Holbova, Robert A. Kloner, Laurence H. Kedes, Jonathan Leor
Journal: Circulation (2002)

The muscle-specific MyoD family of transcription factors function as master genes that are able to prompt myogenesis in a variety of cells. The purpose of our study was to determine whether MyoD could induce primary cardiac fibroblasts, isolated from infarcted myocardium or pericardium, to undergo myogenic conversion in a clinically relevant approach.Primary rat fibroblasts from 7-day-old infarcted myocardium or normal pericardium were transfected by an E1/E3-deleted adenoviral vector carrying both a human MyoD cDNA driven by a CMV promoter and a green fluorescent protein (GFP) reporter gene driven by a second CMV promoter. Expression of MyoD caused myogenic differentiation of cultured fibroblasts, as defined by elongation and fusion into multinucleated myotubes, typical cross striation as identified by electron microscopy, and positive immunostaining for sarcomeric actin, fast myosin heavy chain (MHC), and actinin. The myogenic cells (1.5x10(6)) were transplanted into the infarcted myocardium 7 days after coronary artery occlusion. By 1 month after transplantation, the converted fibroblasts gave rise to a cluster of myogenic cells that in a few hearts occupied a large part of the scar with positive immunostaining for the myogenic proteins fast-MHC and sarcomeric actin. A few cells expressed the gap junction protein connexin 43 in a disorganized manner. There was no positive staining in the control hearts treated with injections of untreated fibroblasts or culture medium.Our work shows that it is possible to exploit the unique capacity of MyoD to activate myogenesis in fibroblasts ex vivo and to create a vast source of autologous myogenic cells for transplantation.
Observational study of upper gastrointestinal haemorrhage in elderly patients given selective cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs
Authors: Muhammad Mamdani, Paula A Rochon, David N Juurlink, Alex Kopp, Geoffrey M Anderson, Gary Naglie, Peter C Austin, Andreas Laupacis
Journal: BMJ (2002)

To compare rates of upper gastrointestinal haemorrhage among elderly patients given selective cyclo-oxygenase-2 (COX 2) inhibitors and non-selective non-steroidal anti-inflammatory drugs (NSAIDs).Observational cohort study.Administrative data from Ontario, Canada, used from 17 April 2000 to 31 March 2001 to identify population based, NSAID-naive cohorts of patients.Subjects aged > or =66 years who started taking non-selective NSAIDs (n=5391), diclofenac plus misoprostol (n=5087), rofecoxib (n=14 583), or celecoxib (n=18 908) and a randomly selected control cohort not exposed to NSAIDs (n=100 000).Rate ratios of hospital admission for upper gastrointestinal haemorrhage in each drug cohort with adjustment for potential confounders.Relative to controls, the multivariate model revealed an increased short term risk of upper gastrointestinal haemorrhage for users of non-selective NSAIDs (adjusted rate ratio 4.0 (95% confidence intervals 2.3 to 6.9)), diclofenac plus misoprostol (3.0 (1.7 to 5.6)), and rofecoxib (1.9 (1.3 to 2.8)) but not celecoxib (1.0 (0.7 to 1.6)). Relative to celecoxib, significantly higher risks of upper gastrointestinal haemorrhage were observed for non-selective NSAIDs (4.4 (2.3 to 8.5)), diclofenac plus misoprostol (3.2 (1.6 to 6.5)), and rofecoxib (1.9 (1.2 to 2.8)). Relative to rofecoxib, non-selective NSAID users were at significantly higher risk of upper gastrointestinal haemorrhage (1.9 (1.0 to 3.5)).This population based observational study found a lower short term risk of upper gastrointestinal haemorrhage for selective COX-2 inhibitors compared with non-selective NSAIDs.
Targeting Phosphoinositide-3-Kinase-δ with Theophylline Reverses Corticosteroid Insensitivity in Chronic Obstructive Pulmonary Disease
Authors: Yasuo To, Kazuhiro Ito, Yasuo Kizawa, Marco Failla, Misako Ito, Tadashi Kusama, W. Mark Elliott, James C. Hogg, Ian M. Adcock, Peter J. Barnes
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Patients with chronic obstructive pulmonary disease (COPD) show a poor response to corticosteroids. This has been linked to a reduction of histone deacetylase-2 as a result of oxidative stress and is reversed by theophylline.To determine the role of phosphoinositide-3-kinase-delta (PI3K-δ) on the development of corticosteroid insensitivity in COPD and under oxidative stress, and as a target for theophylline.Corticosteroid sensitivity was determined as the 50% inhibitory concentration of dexamethasone on tumor necrosis factor-α-induced interleukin-8 release in peripheral blood mononuclear cells from patients with COPD (n = 17) and compared with that of nonsmoking (n = 8) and smoking (n = 7) control subjects. The effect of theophylline and a selective PI3K-δ inhibitor (IC87114) on restoration of corticosteroid sensitivity was confirmed in cigarette smoke-exposed mice.Peripheral blood mononuclear cells of COPD (50% inhibitory concentration of dexamethasone: 156.8 ± 32.6 nM) were less corticosteroid sensitive than those of nonsmoking (41.2 ± 10.5 nM; P = 0.018) and smoking control subjects (47.5 ± 19.6 nM; P = 0.031). Corticosteroid insensitivity and reduced histone deacetylase-2 activity after oxidative stress were reversed by a non-selective PI3K inhibitor (LY294002) and low concentrations of theophylline. Theophylline was a potent selective inhibitor of oxidant-activated PI3K-δ, which was up-regulated in peripheral lung tissue of patients with COPD. Furthermore, cells with knock-down of PI3K-δ failed to develop corticosteroid insensitivity with oxidative stress. Both theophylline and IC87114, combined with dexamethasone, inhibited corticosteroid-insensitive lung inflammation in cigarette-smoke-exposed mice in vivo.Inhibition of oxidative stress dependent PI3K-δ activation by a selective inhibitor or theophylline provides a novel approach to reversing corticosteroid insensitivity in COPD.
Identifying biological themes within lists of genes with EASE
Authors: Douglas A Hosack, Glynn Dennis, Brad T Sherman, H Clifford Lane, Richard A Lempicki
Journal: Genome biology (2003)

EASE is a customizable software application for rapid biological interpretation of gene lists that result from the analysis of microarray, proteomics, SAGE and other high-throughput genomic data. The biological themes returned by EASE recapitulate manually determined themes in previously published gene lists and are robust to varying methods of normalization, intensity calculation and statistical selection of genes. EASE is a powerful tool for rapidly converting the results of functional genomics studies from 'genes' to 'themes'.
The 0.1% of the Population With Glucokinase Monogenic Diabetes Can Be Recognized by Clinical Characteristics in Pregnancy: The Atlantic Diabetes in Pregnancy Cohort
Authors: Ali J. Chakera, Gill Spyer, Nicola Vincent, Sian Ellard, Andrew T. Hattersley, Fidelma P. Dunne
Journal: Diabetes Care (2014)

Identifying glucokinase monogenic diabetes (GCK-MODY) in pregnancy is important, as management is different from management for other forms of gestational diabetes mellitus (GDM) and there is no increased maternal risk of type 2 diabetes. We calculated the population prevalence of GCK-MODY in pregnancy and determined the clinical characteristics that differentiate pregnant women with GCK-MODY from those with GDM.We calculated the population prevalence of GCK-MODY in pregnancy by testing a subset of patients from the population-based Atlantic Diabetes in Pregnancy (Atlantic DIP) study (n = 5,500). We sequenced for GCK mutations in 247 women with a fasting glucose ≥5.1 mmol/L and 109 randomly selected control subjects with normal fasting glucose. Using data from the cases found and 40 previously identified GCK-MODY pregnancies, we analyzed whether clinical criteria could be used to differentiate GCK-MODY from GDM.Four women with fasting glucose ≥5.1 mmol/L were diagnosed with GCK-MODY. No cases were identified with normal fasting glucose. The population prevalence of GCK-MODY is 1.1 in 1,000 (95% CI 0.3-2.9 in 1,000) and prevalence in GDM is 0.9% (95% CI 0.3-2.3). Fasting glucose and BMI significantly differentiate GCK-MODY from GDM (P < 0.0001). Combined criteria of BMI <25 kg/m(2) and fasting glucose ≥5.5 mmol/L has a sensitivity 68%, specificity 96%, and number needed to test of 2.7 women with GDM to find one case of GCK-MODY.Our large population cohort of pregnant women tested estimates the population prevalence of GCK-MODY of 1.1 in 1,000. We have shown routine clinical criteria that can identify which women should be tested for GCK-MODY in pregnancy.
Measurement of synovial lining volume by magnetic resonance imaging of the knee in chronic synovitis
Authors: G. Clunie, M. A Hall-Craggs, M. N Paley, A. King, I. D Wilkinson, P. J Ell, J. C W Edwards
Journal: Annals of the Rheumatic Diseases (1997)

Current methods of monitoring chronic synovitis in a single joint rely on clinical examination derived indices, such as the detection of synovial thickening. This study aimed to develop a reproducible method for quantifying the volume of synovial lining in chronic synovitis using contrast enhanced magnetic resonance (MR) imaging.The knees of 18 patients with chronic synovitis were examined (34 studies). A 2D T1 weighted FLASH sequence was used to evaluate the temporal enhancement of synovial structures after intravenous contrast. Synovial lining volume was calculated from subtraction of pre and post-enhancement 3D T1 weighted MP RAGE images with thresholding and pixel counting. Eleven patients were examined before and after intra-articular glucocorticoid (mean interval 14 weeks) and MR data compared with changes in clinical examination derived indices of disease activity.Synovial lining volume varied from 52-267 ml. The coefficient of variation in volume calculation was 3.5% for a single observer and was 3.8% for two observers. Synovial lining volume was quantified in all patients where synovial lining thickening could not be detected clinically. A decrease in synovial lining volume of > 40% was associated with an improvement in synovial lining thickening, detected clinically. Decreases in synovial lining volume were quantified by MR in two of three patients where changes in clinical examination derived indices were inconsistent.A reproducible method of estimating the volume of synovial lining in patients with chronic synovitis has been developed. MR measurement of synovial lining volume may quantify changes in chronic synovitis that remain unidentified by clinical measures.
Hydrolase activities in the rat aorta. II. Effects of hypertension alone and in combination with diabetes mellitus.
Authors: H Wolinsky, L Capron, S Goldfischer, F Capron, B Coltoff-Schiller, L E Kasak
Journal: Circulation Research (1978)

Hypertension is an important risk factor for atherosclerosis and often occurs in association with diabetes mellitus. Specific activities of hydrolases in homogenates of aortas from rats with renal-clip hypertension, normotension following a period of hypertension, and hypertension combined with streptozotocin-induced diabetes mellitus were measured. Enzymes included: neutral alpha-glucosidase, and lysosomal N-acetyl-beta-glucosaminidase, beta-galactosidase, cathepsin C, acid alpha-glucosidase, and acid cholesteryl esterase. After 6 or 12 weeks of hypertension, specific activities of all enzymes measured were significantly increased, levels ranging from 24% above normal for cathepsin C to 351% above normal for N-acetyl-beta-glucosaminidase. Six weeks of normotension following 6 weeks of hypertension resulted in restoration to normal of four of the six enzyme activities; the remaining two enzymes were significantly below normal levels. Combined hypertension and diabetes mellitus showed smooth muscle cell levels of four of the five hydrolases measured to be significantly lower than those present with hypertension alone. In every instance, histochemical studies of aortas showed acid phosphatase and N-acetyl-beta-glucosaminidase activities which corresponded to the biochemical findings. These findings indicate profound and discrete effects of two clinical risk factors on vascular smooth muscle cell lysosomes.
Calcium-accumulating properties of subcellular fractions of bovine vascular smooth muscle.
Authors: G D Ford, M L Hess
Journal: Circulation Research (1975)

This study examined the calcium transport properties of two subcellular fractions of bovine aorta obtained by differential centrifugation. The vesicular fraction had a high-affinity (Km = 1.05 X 10(-6)M) calcium transport mechanism which could be potentiated by using the calcium-precipitating anion, oxalate. The mitochondria-enriched fraction's calcium transport system had a lower affinity for calcium than did that of the vesicular fraction. The calcium capacity of the vesicular fraction was determined by comparing the steady-state calcium uptake in the presence of oxalate in the whole homogenate with the same uptake by the vesicular fraction alone. A calcium capacity of about 100 mumoles Ca2+/kg aorta was obtained. It is concluded that the vesicular fraction has all of the properties of a major site of subcellular calcium regulation in vascular smooth muscle.
12-lead ECG in the athlete: physiological versus pathological abnormalities
Authors: D Corrado, A Biffi, C Basso, A Pelliccia, G Thiene
Journal: British Journal of Sports Medicine (2009)

Participation in sports activity and regular physical training is associated with physiological structural and electrical changes in the heart (athlete’s heart) that enable sustained increases in cardiac output for prolonged periods. Cardiovascular remodelling in the conditioned athlete is often associated with ECG changes. In rare cases, abnormalities of an athlete’s ECG may reflect an underlying heart disease which puts the athlete at risk of arrhythmic cardiac arrest during sport. It is mandatory that ECG abnormalities resulting from intensive physical training and those of a potential cardiac pathology are properly defined. This article provides a modern approach to interpreting 12-lead ECGs of athletes based on recently published new findings. The main objective is to distinguish between physiological adaptive ECG changes and pathological ECG abnormalities. The most important aims are to prevent physiological changes in the athlete being erroneously attributed to heart disease, or signs of life-threatening cardiovascular conditions being dismissed as a normal variant of athlete’s heart. As pathological ECG abnormalities not only cause alarm but also require action with additional testing to exclude (or confirm) the suspicion of a lethal cardiovascular disorder, appropriate interpretation of an athlete’s ECG will prevent unnecessary distress and also result in considerable cost saving in the context of a population-based preparticipation screening programme.
Diagnostic impact and sensitivity of skin biopsies in Sneddon's syndrome. A report of 15 cases
Authors: J. Wohlrab, M. Fischer, M. Wolter, W.C. Marsch
Journal: British Journal of Dermatology (2001)

Journal Article Diagnostic impact and sensitivity of skin biopsies in Sneddon's syndrome. A report of 15 cases Get access J. Wohlrab, J. Wohlrab Department of Dermatology and Venereology, Martin Luther University Halle‐Wittenberg, Ernst‐Kromayer‐Str. 5–6, D‐06097 Halle (Saale), Germany Johannes Wohlrab. E‐mail: johannes.wohlrab@medizin.uni‐halle.de Search for other works by this author on: Oxford Academic Google Scholar M. Fischer, M. Fischer Department of Dermatology and Venereology, Martin Luther University Halle‐Wittenberg, Ernst‐Kromayer‐Str. 5–6, D‐06097 Halle (Saale), Germany Search for other works by this author on: Oxford Academic Google Scholar M. Wolter, M. Wolter Department of Dermatology and Venereology, Johann Wolfgang Goethe University, Frankfurt (Main), Germany Search for other works by this author on: Oxford Academic Google Scholar W.C. Marsch W.C. Marsch Department of Dermatology and Venereology, Martin Luther University Halle‐Wittenberg, Ernst‐Kromayer‐Str. 5–6, D‐06097 Halle (Saale), Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 145, Issue 2, 1 August 2001, Pages 285–288, https://doi.org/10.1046/j.1365-2133.2001.04348.x Published: 01 August 2001
Clinical, Echocardiographic, and Hemodynamic Evidence of Cardiac Tamponade Caused by Large Pleural Effusions
Authors: Linda M. Kaplan, Scott K. Epstein, Steven L. Schwartz, Qi-Ling Cao, Natesa G. Pandian
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Large pleural effusions are typically associated with dyspnea and potential respiratory compromise. Experimental evidence suggests that with large effusions, increased intrapleural pressure may be transmitted to the pericardial space, resulting in impaired cardiac filling and reduced stroke volume. We report two cases in which large pleural collections were complicated by hypotension. The effusions were due to an infected right hepatic hydrothorax (Case 1) and a left malignant effusion (Case 2). Echocardiography demonstrated right and left ventricular diastolic collapse, respectively, confirming a diagnosis of cardiac tamponade. Large volume thoracentesis resulted in immediate hemodynamic improvement as demonstrated by a reduction in right ventricular and atrial pressures (Case 1) and echocardiographic resolution of left ventricular diastolic collapse (Case 2). These cases establish that large pleural effusions can cause hemodynamically significant cardiac tamponade. In addition, they illustrate how the demonstration of cardiac compressive physiology can significantly alter the therapeutic approach to large pleural effusions.