tbuckley/cabot-search huggingface dataset:
Mitochondrial Damage Mediates Genotoxicity of Arsenic in Mammalian Cells
Authors: Su-Xian Liu, Mercy M. Davidson, Xiuwei Tang, Winsome F. Walker, Mohammad Athar, Vladimir Ivanov, Tom K. Hei
Journal: Cancer Research (2005)

Abstract Arsenic is an important environmental carcinogen that affects millions of people worldwide through contaminated water supplies. For decades, arsenic was considered a nongenotoxic carcinogen. Using the highly sensitive AL mutation assay, we previously showed that arsenic is, indeed, a potent gene and chromosomal mutagen and that its effects are mediated through the induction of reactive oxygen species. However, the origin of these radicals and the pathways involved are not known. Here we show that mitochondrial damage plays a crucial role in arsenic mutagenicity. Treatment of enucleated cells with arsenic followed by rescue fusion with karyoplasts from controls resulted in significant mutant induction. In contrast, treatment of mitochondrial DNA–depleted (ρ0) cells produced few or no mutations. Mitochondrial damage can lead to the release of superoxide anions, which then react with nitric oxide to produce the highly reactive peroxynitrites. The mutagenic damage was dampened by the nitric oxide synthase inhibitor, NG-methyl-l-arginine. These data illustrate that mitochondria are a primary target in arsenic-induced genotoxic response and that a better understanding of the mutagenic/carcinogenic mechanism of arsenic should provide a basis for better interventional approach in both treatment and prevention of arsenic-induced cancer.
Clopidogrel Inhibition of Stent, Graft, and Vascular Thrombogenesis With Antithrombotic Enhancement by Aspirin in Nonhuman Primates
Authors: Laurence A. Harker, Ulla M. Marzec, Andrew B. Kelly, Nicolas R. F. Chronos, I. Birgitta Sundell, Stephen R. Hanson, J.-M. Herbert
Journal: Circulation (1998)

A recent study showed that clopidogrel reduces thrombo-occlusive complications in patients with symptomatic atherosclerosis more effectively than aspirin.The effects of clopidogrel and aspirin have been compared, singly and in combination, for measurements of 111In-labeled platelets and 125I-labeled fibrin deposition in baboon models of arterial thrombosis and related to platelet aggregation and expression of activation epitopes induced by ADP, collagen, and thrombin receptor agonist peptide (TRAP) and to template bleeding times (BTs). Low-dose oral clopidogrel (0.2 mg. kg-1. d-1) produced cumulative (1) intermediate decreases in 111In-platelet and 125I-fibrin deposition for segments of prosthetic vascular graft, deployed endovascular metallic stents, and endarterectomized aorta (P<0.009 in all cases); (2) elimination of ADP-induced platelet aggregation (P<0.001); (3) modest inhibition of collagen-induced platelet aggregation (P<0.01); (4) no reduction in TRAP-induced platelet aggregation; and (5) minimal prolongation of BTs (P=0.03). High-dose oral clopidogrel (>/=2 mg/kg) produced the same effects within 3 hours. The effects of clopidogrel dissipated over 5 to 6 days. Aspirin 10 mg. kg-1. d-1 alone did not decrease 111In-platelet and 125I-fibrin deposition on segments of vascular graft but detectably decreased 111In-platelet and 125I-fibrin accumulation on stents (P<0.01), minimally inhibited ADP- and collagen-induced platelet aggregation (P<0.05 in both cases), and minimally prolonged BTs (P=0.004). Within 3 hours of aspirin administration, the antithrombotic effects of acute high-dose or chronic low-dose clopidogrel were substantially enhanced, and BTs were modestly prolonged without inhibiting platelet aggregation induced by TRAP (P<0.001 in all cases compared with clopidogrel alone).Clopidogrel produces irreversible, dose-dependent, intermediate reduction in thrombosis that is substantially enhanced by the addition of aspirin. The effects of combining aspirin and clopidogrel need to be evaluated in patients at risk of vascular thrombosis.
BIOCHEMICAL STUDY OF CELLULAR ANTIGEN-ANTIBODY REACTION IN TISSUE CULTURE
Authors: Akira Tokuda, Hideo Hayashi, Kinishiro Matsuba
Journal: The Journal of Experimental Medicine (1960)

Decrease in the protease activity of the culture fluid observed at later stages of the antigen-antibody reaction is believed to be due to the release of an inhibitor by the cells. The inhibitor was submitted to partial purification: it is heat-stable, non-precipitated by trichloracetic acid and non-dialyzable. It inhibits certain cellular and tissue proteases and papain but is inactive against trypsin. It is suggested that the balance between protease and anti-protease released may determine the intensity, extent, and duration of certain sensitization phenomena.
Purification and properties of an extracellular blastogen produced by group A streptococci.
Authors: E D Gray
Journal: The Journal of Experimental Medicine (1979)

An extracellular product of group A streptococci which induces lymphocyte blastogenesis has been purified to homogeneity by DEAE-cellulose and CM-cellulose chromatography. The protein, termed streptococcal blastogen A, has a mol wt of approximately or equal to 17,500 and is inactivated by protease treatment and by heating at 100 degrees C. The purified blastogen gave rise to multiple protein bands on nondenaturing polyacrylamide gel electrophoresis, only two of which possessed blastogenic activity. Treatment of the protein with dithiothreitol before electrophoresis resulted in the apparent conversion of the multiple forms to a single active species. Blastogen A differs in electrophoretic mobility from the streptococcal pyrogenic exotoxins and its lymphocyte stimulating activity is not inhibited by rabbit antisera to the exotoxins. An enzyme immunoassay has been developed to measure human antibodies against blastogen A. A selection of sera with varying levels of anti-DNase B contained antiblastogen A-IgG.
Development of a Type 2 Diabetes Risk Model From a Panel of Serum Biomarkers From the Inter99 Cohort
Authors: Wolfgang Rathmann, Bernd Kowall, Matthias B. Schulze
Journal: Diabetes Care (2010)

Kolberg et al. (1) report from the Inter99 cohort that a risk score incorporating six biomarkers (adiponectin, C-reactive protein, ferritin, interleukin-2 receptor A, glucose, and insulin) is useful in the prediction of type 2 diabetes and could be recommended as a tool for identification of high-risk individuals. So far, however, there is little evidence that a procedure based partly on nonroutinely measured biomarkers is superior to risk scores based on personally known variables or on routinely measured clinical data.

An area under the receiver operating characteristic curve (AROC) of 0.76 is reported by the investigators, indicating a rather moderate diagnostic accuracy of the …
Evidence for Mitochondrial K <sup>+</sup> Channels and Their Role in Cardioprotection
Authors: Brian O’Rourke
Journal: Circulation Research (2004)

Twenty years after the discovery of sarcolemmal ATP-sensitive K + channels and 12 years after the discovery of mitochondrial K ATP (mitoK ATP ) channels, progress has been remarkable, but many questions remain. In the case of the former, detailed structural information is available, and it is well accepted that the channel couples bioenergetics to cellular electrical excitability; however, in the heart, a clear physiological or pathophysiological role has yet to be defined. For mitoK ATP , structural information is lacking, but there is abundant evidence linking the opening of the channel to protection against ischemia-reperfusion injury or apoptosis. This review updates recent progress in understanding the physiological role of mitoK ATP and highlights outstanding questions and controversies, with the intent of stimulating additional investigation on this topic.
THE NATURE OF THE HYPERGLYCEMIA ASSOCIATED WITH ANAPHYLACTIC SHOCK IN THE DOG
Authors: Isolde T. Zeckwer, J. Ernest Nadler
Journal: The Journal of Experimental Medicine (1929)

1. Nine unoperated dogs snowed a rise of blood sugar dunng anaphylactic shock. In six of these dogs the rise was 60 mg. or over. 2. Six dogs in which one adrenal had long previously been extirpated and the opposite splanchnic nerve cut, showed a low preliminary level of blood sugar, and a relative rise of blood sugar during anaphylaxis, but of less degree than in the unoperated animals. In no case was it greater than 52 mg. 3. Anoxemia did not appear to be a complicating factor, as evidenced by determination of the oxygen content of the arterial blood before and during shock. 4. The rise in blood sugar, which occurs in spite of the loss of adrenal activity, is probably due to the venous stasis of the liver seen in anaphylaxis in the dog, because this rise in blood sugar can be simulated in a normal non-sensitized dog by mechanically constricting the hepatic veins for a brief interval. 5. There are, therefore, probably two factors responsible for the hyperglycemia associated with anaphylaxis in the dog, sympathetic stimulation by way of the splanchnic nerves involving the activity of the adrenals, and glycogenolysis resulting directly from venous stasis of the liver.
European standards for lung function testing: 1993 update.
Authors: G Laszlo
Journal: Thorax (1993)

European standards for lung function testing: 1993 updateThe first report of the working party on standardisation of lung function tests set up by the European Community for Steel and Coal was published in 1983.1This document describes in detail most of the available tests of lung mechanics and carbon monoxide transfer, with detailed recommendations as to how they should be performed.An original feature was the compilation of summary equations based on pooled results from a num- ber of series of reference values in normal subjects, calcu- lated from the published regression equations.These recommendations have been re-examined by a new working party, again led by its scientific secretary Philip Quanjer.This group has re-examined the assump- tions of the 1983 document and has updated it with numerous fresh references.The whole work has now
Dexamethasone in the prophylaxis of radiation-induced pain flare after palliative radiotherapy for bone metastases: a double-blind, randomised placebo-controlled, phase 3 trial
Authors: Edward Chow, Ralph M Meyer, Keyue Ding, Abdenour Nabid, Pierre Chabot, Philip Wong, Shahida Ahmed, Joda Kuk, A Rashid Dar, Aamer Mahmud, Alysa Fairchild, Carolyn F Wilson, Jackson S Y Wu, Kristopher Dennis, Michael Brundage, Carlo DeAngelis, Rebecca K S Wong
Journal: The Lancet Oncology (2015)
A renin inhibitor from rabbit kidney: conversion of a large inactive renin to a smaller active enzyme.
Authors: B J Leckie, A McConnell
Journal: Circulation Research (1975)

Renin in extracts of frozen rabbit kidney exists in two forms: active (molecular weight about 37,000) and inactive (molecular weight about 55,000) renin. The inactive form becomes active after exposure to pH 2.5 at 4 degrees C. If extracts are chromatographed on DEAE cellulose, the inactive renin dissociates into active renin plus a renin inhibitor (molecular weight about 13,000). The inhibitor recombines with active renin if the two are incubated together at 37 degrees C. The inhibitor is destroyed by acid treatment at pH 2.5 at 4 degrees C. We conclude that the activation of inactive renin is due to destruction of the inhibitor by acid. The inactive material may be a renin proenzyme or a storage form of active renin combined with inhibitor.
Developing Evidence-Based Clinical Practice Guidelines: Lessons Learned by the US Preventive Services Task Force
Authors: S H Woolf, C G DiGuiseppi, D Atkins, D B Kamerow
Journal: Annual Review of Public Health (1996)

In recent decades, there has been remarkable growth in scientific research examining the multiple ways in which racism can adversely affect health. This interest has been driven in part by the striking persistence of racial/ethnic inequities in health and ...Read More
Prediction and Genetic Demonstration of a Role for Activator E2Fs in Myc-Induced Tumors
Authors: Kenichiro Fujiwara, Inez Yuwanita, Daniel P. Hollern, Eran R. Andrechek
Journal: Cancer Research (2011)

Advances in genomic signatures have begun to dissect breast cancer heterogeneity and application of these signatures will allow the prediction of which pathways are important in tumor development. Here we used genomic signatures to predict involvement of specific E2F transcription factors in Myc-induced tumors. We genetically tested this prediction by interbreeding Myc transgenics with mice lacking various activator E2F alleles. Tumor latency decreased in the E2F1 mutant background and significantly increased in both the E2F2 and E2F3 mutants. Investigating the mechanism behind these changes revealed a reduction in apoptosis in the E2F1 knockout strain. E2F2 and E2F3 mutant backgrounds alleviated Myc proliferative effects on the pregnant mammary gland, reducing the susceptible tumor target population. Gene expression data from tumors revealed that the E2F2 knockout background resulted in fewer tumors with EMT, corresponding with a reduction in probability of Ras activation. In human breast cancer we found that a low probability of E2F2 pathway activation was associated with increased relapse-free survival time. Together these data illustrate the predictive utility of genomic signatures in deciphering the heterogeneity within breast cancer and illustrate the unique genetic requirements for individual E2Fs in mediating tumorigenesis in both mouse models and human breast cancer.
Evidence for in vivo synergism between docetaxel and gemcitabine in patients with metastatic breast cancer
Authors: A. Alexopoulos, D. Tryfonopoulos, M.V. Karamouzis, G. Gerasimidis, I. Karydas, K. Kandilis, J. Stavrakakis, H. Stavrinides, C. Georganta, A. Ardavanis, G. Rigatos
Journal: Annals of Oncology (2003)
Activation of DeltaF508 CFTR in a cystic fibrosis respiratory epithelial cell line by 4-phenylbutyrate, genistein and CPX
Authors: C. Andersson, G.M. Roomans
Journal: European Respiratory Journal (2000)

The cellular basis of cystic fibrosis (CF) is a defect in a cyclic adenosine monophosphate (cAMP)-activated chloride channel (CF transmembrane conductance regulator) in epithelial cells that leads to decreased chloride ion transport and impaired water transport across the cell membrane. This study investigated whether it was possible to activate the defective chloride channel in cystic fibrosis respiratory epithelial cells with 4-phenylbutyrate (4PBA), genistein and 8-cyclopentyl-1,3-dipropylxanthine (CPX). The CF bronchial epithelial cell line CFBE41o-, which expresses the deltaF508 mutation, was treated with these agents and loss of Cl-, indicating Cl- efflux, measured by X-ray microanalysis. 8-bromo-cAMP alone did not induce Cl- efflux in CFBE41o- cells, but after incubation with 4PBA a significant efflux of Cl- occurred. Stimulation of cells with a combination of genistein and cAMP also induced Cl- efflux, whereas a combination of pretreatment with 4PBA and a combined stimulation with genistein and cAMP induced an even larger Cl- efflux. Cl- efflux could also be stimulated by CPX, but this effect was not enhanced by 4PBA pretreatment. The deltaF508 mutation leads to impaired processing of the cystic fibrosis transmembrane conductance regulator. The increased efflux of chloride after 4-phenylbutyrate treatment can be explained by the fact that 4-phenylbutyrate allows the deltaF508 cystic fibrosis transmembrane conductance regulator to escape degradation and to be transported to the cell surface. Genistein and 8-cyclopentyl-1,3-dipropylxanthine act by stimulating chloride ion efflux by increasing the probability of the cystic fibrosis transmembrane conductance regulator being open. The combination of 4-phenylbutyrate and genistein may be useful in a potential pharmacological therapy for cystic fibrosis patients with the deltaF508 mutation.
Adenovirus-Mediated Gene Transfer of the Human Tissue Inhibitor of Metalloproteinase-2 Blocks Vascular Smooth Muscle Cell Invasiveness In Vitro and Modulates Neointimal Development In Vivo
Authors: Linda Cheng, Giuditta Mantile, Rebecca Pauly, Cynthia Nater, Angelina Felici, Robert Monticone, Claudio Bilato, Yehezkiel A. Gluzband, Michael T. Crow, William Stetler-Stevenson, Maurizio C. Capogrossi
Journal: Circulation (1998)

Endovascular injury induced by balloon withdrawal leads to the increased activation of matrix metalloproteinases (MMPs) in the vascular wall, allowing smooth muscle cells (SMCs) to digest the surrounding extracellular matrix (ECM) and migrate from the media into the intima. The objective of this study was to examine the effects of a replication-deficient adenovirus carrying the cDNA for human tissue inhibitor of metalloproteinase-2 (AdCMV.hTIMP-2) on SMC function in vitro and neointimal development in the injured rat carotid artery.Infection of cultured rat aortic SMCs at a multiplicity of infection of 100 with AdCMV.hTIMP-2 resulted in high-level expression of hTIMP-2 mRNA and protein secretion into the medium. Conditioned media (CM) from AdCMV. hTIMP-2-infected but not control virus (AdCMV.null or AdCMV. betagal)-infected SMCs inhibited MMP-2 activity on gelatin zymograms as well as the chemoattractant-directed migration of SMCs across reconstituted basement membrane proteins in the Boyden chamber assay. In contrast, AdCMV.hTIMP-2 CM had no effect on chemoattractant-directed migration of SMCs occurring in the absence of an ECM barrier or on the proliferation of cultured neointimal SMCs. Delivery of AdCMV.hTIMP-2 (2.5x10(9) pfu) to the carotid artery wall at the time of balloon withdrawal injury inhibited SMC migration into the intima by 36% (P<0.05) at 4 days and neointimal area by 53% (P<0.01) at 8 days and by 12% (P=NS) at 21 days after injury. AdCMV.hTIMP-2 had no effect on medial area.Adenovirus-mediated hTIMP-2 gene transfer inhibits SMC invasiveness in vitro and in vivo and delays neointimal development after carotid injury.
Thalidomide reduces IL-18, IL-8 and TNF- release from alveolar macrophages in interstitial lung disease
Authors: Q. Ye, B. Chen, Z. Tong, S. Nakamura, R. Sarria, U. Costabel, J. Guzman
Journal: European Respiratory Journal (2006)

Thalidomide exhibits diverse actions of anti-inflammation, immunomodulation and anti-angiogenesis. The efficacy of thalidomide treatment in sarcoidosis with lupus pernio is thought to be due to inhibition of tumour necrosis factor (TNF)-α. The mechanisms that underlie the properties of thalidomide are still unclear in interstitial lung disease. The current authors investigated the potential inhibitory effects of thalidomide at concentrations of 0.1, 0.01 and 0.001 mM on the production of transforming growth factor-β, TNF-α, interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p70, IL-12p40 and IL-18 by alveolar macrophages from bronchoalveolar lavage in patients with sarcoidosis (n = 8), hypersensitivity pneumonitis (HP; n = 8) and idiopathic pulmonary fibrosis (IPF; n = 12). In sarcoidosis and HP patients, thalidomide induced a dose-dependent, partial suppression of lipopolysacchride (LPS)-stimulated TNF-α, IL-12p40 and IL-18 release. At the highest thalidomide concentration (0.1 mM), LPS-stimulated IL-8 production was also suppressed. In IPF patients, although spontaneous production of TNF-α, IL-12p40, IL-18 and IL-8 was lower than in sarcoidosis and HP patients, with LPS stimulation the cytokines were significantly elevated and also partially inhibited by thalidomide. In conclusion, thalidomide has the potential to improve the therapeutic regimens for sarcoidosis, hypersensitivity pneumonitis and idiopathic pulmonary fibrosis by reducing tumour necrosis factor-α, interleukin-12p40, interleukin-18 and interleukin-8 production.
Corrigendum to: “FibroTest is an independent predictor of virologic response in chronic hepatitis C patients retreated with pegylated interferon alfa-2b and ribavirin in the EPIC3 program” [J Hepatol 2011;54:227–235]
Authors: Thierry Poynard, Mona Munteanu, Massimo Colombo, Jordi Bruix, Eugene Schiff, Ruben Terg, Steven Flamm, Ricardo Moreno-Otero, Flair Carrilho, Warren Schmidt, Thomas Berg, Thomas Mcgarrity, E. Jenny Heathcote, Fernando Gonçales, Moises Diago, Antonio Craxi, Marcelo Silva, Navdeep Boparai, Louis Griffel, Margaret Burroughs, Clifford Brass, Janice Albrecht
Journal: Journal of Hepatology (2013)
Investigating liver stiffness and viscosity for fibrosis, steatosis and activity staging using shear wave elastography
Authors: Thomas Deffieux, Jean-Luc Gennisson, Laurence Bousquet, Marion Corouge, Simona Cosconea, Dalila Amroun, Simona Tripon, Benoit Terris, Vincent Mallet, Philippe Sogni, Mickael Tanter, Stanislas Pol
Journal: Journal of Hepatology (2014)
Downregulation of Peroxisome Proliferator–Activated Receptor-α Gene Expression in a Mouse Model of Ischemic Cardiomyopathy Is Dependent on Reactive Oxygen Species and Prevents Lipotoxicity
Authors: Oliver Dewald, Saumya Sharma, Julia Adrogue, Rebecca Salazar, Georg D. Duerr, James D. Crapo, Mark L. Entman, Heinrich Taegtmeyer
Journal: Circulation (2005)

Background— The peroxisome proliferators–activated receptor-α (PPARα), a transcription factor that modulates fatty acid metabolism, regulates substrate preference in the heart. Although in acute ischemia there is a switch in substrate preference from fatty acids to glucose, metabolic gene expression in repetitive ischemia is not well described. In a mouse model of ischemic cardiomyopathy induced by repetitive ischemia/reperfusion (I/R), we postulated that downregulation of PPARα is regulated by reactive oxygen species and is necessary for maintaining contractile function in the heart. Methods and Results— Repetitive closed-chest I/R (15 minutes) was performed daily in C57/BL6 mice, mice overexpressing extracellular superoxide dismutase, and mice treated with the PPARα agonist-WY-14,643. Echocardiography, histology, and candidate gene expression were measured at 3, 5, 7, and 28 days of repetitive I/R and 15 and 30 days after discontinuation of I/R. Repetitive I/R was associated with a downregulation of PPARα-regulated genes and both myosin heavy chain isoform transcript levels, which was reversible on discontinuation of I/R. Overexpression of EC-SOD prevented the downregulation of PPARα-regulated genes and myosin iso-genes by repetitive I/R. Furthermore, reactivation of PPARα in mice exposed to repetitive I/R worsened contractile function, induced microinfarctions, and increased intramyocardial triglyceride deposition, features suggestive of cardiac lipotoxicity. Conclusions— Metabolic and myosin isoform gene expression in repetitive I/R is mediated by reactive oxygen species. Furthermore, we suggest that downregulation of PPARα in repetitive I/R is an adaptive mechanism that is able to prevent lipotoxicity in the ischemic myocardium.