tbuckley/cabot-search huggingface dataset:
Ventilatory lung function in young cigarette smokers: a study of susceptibility
Authors: Jaakkola, JJ Jaakkola, P Ernst, Becklake
Journal: European Respiratory Journal (1991)

The objective of this study was to estimate the effect of cigarette smoking on ventilatory lung function among young adults with special emphasis on the recognition of susceptible subgroups. In a cross-sectional study of 1,044 adults aged 15-40 yrs, a statistically significant linear relationship between quantity of smoking in cigarette-years and level of forced expiratory volume in one second (FEV1) was found. Among current cigarette smokers, FEV1 level was on average 35 ml lower for each 100 cigarette-years of exposure (corresponding to smoking of ten cigarettes per day for 10 yrs) compared to lifelong nonsmokers in a linear regression adjusted for confounding. Potentially susceptible subgroups were studied by introducing interaction terms between quantitative smoking and gender, wheezing, atopy, asthma, childhood respiratory illness and exposure to environmental tobacco smoke during the growth period, to the additive linear regression model explaining the FEV1 level. Wheezing was found to modify the effect of smoking significantly: the FEV1 level was on average 68 ml lower for each 100 cigarette-years due to interaction between smoking and wheezing. An introduction of the interaction term eliminated the independent effect of smoking. The results suggest that the detrimental effect of smoking on FEV1 in young adults may be limited to individuals with wheezing. Thus, the presence of wheezing among smokers indicates a higher risk for low level of ventilatory lung function compared to smokers who do not wheeze.
Upward shift of the lower range of coronary flow autoregulation in hypertensive patients with hypertrophy of the left ventricle.
Authors: A Polese, N De Cesare, P Montorsi, F Fabbiocchi, M Guazzi, A Loaldi, M D Guazzi
Journal: Circulation (1991)

BACKGROUND At any given perfusion pressure, coronary reserve is expressed by the difference between autoregulated and maximally vasodilated flow. In hypertension the raised coronary resistance reduces the steepness of the pressure-flow relationship at maximal vasodilatation. In the presence of cardiac hypertrophy the line of autoregulated flow becomes higher. For these reasons coronary reserve is reduced and the point at which baseline flow approaches the maximal achievable flow might be shifted to a higher perfusion pressure. Thus, any reduction below this elevated and critical value of pressure would lower the coronary flow. METHODS AND RESULTS The investigated patients were normotensive (controls, nine) and hypertensive with normal (group I, seven) or augmented LV mass index because of concentric LV hypertrophy (group II, eight). All had effort-induced angina and angiographically normal left epicardial branches. Flow in the great cardiac vein was measured by thermodilution in the baseline and during stepwise (5 mm Hg every 5 minutes) decrease of the coronary perfusion pressure with a titrated nitroprusside i.v. infusion; perfusion pressures of 60 mm Hg in the controls and 70 mm Hg in the hypertensives were taken as end points. Baseline flow averaged 102 ml/min in normotensives, 104 ml/min in hypertensive group I and 148 ml/min in hypertensive group II. At the end points flow was similar to baseline in the controls and group I. In group II coronary flow started to decline and myocardial O2 extraction started to slightly but significantly rise at perfusion pressures of 90-80 mm Hg; at the end point flow was reduced by 26% (p less than 0.01 from baseline). The perfusion patterns did not seem to be related to the changes in tension-time index and heart rate. CONCLUSIONS The association of high blood pressure (reduced ability of the coronary arterioles to dilate) and hypertrophy of the myocardium (augmented baseline coronary flow) may shift the point of exhaustion of coronary reserve to a higher perfusion pressure and make the myocardium vulnerable to treatment-induced relative hypertension.
When asthma diagnosis becomes a challenge
Authors: M. Contoli, A. Papi
Journal: European Respiratory Journal (2010)

Asthma is a worldwide disease affecting an estimated 300 million individuals 1, 2. Some authors refer to the increased prevalence of asthma reported during the past decades, in many parts of the world, as a wave of “asthma epidemic” 3. Given the recent increase in asthma-related healthcare costs 4, it has become important, in a time of economical restriction, to critically review the dimensions of this phenomenon and to investigate the underlying causes. First of all, is there a real epidemic threat? Indeed, besides several proposed explanations for increasing asthma prevalence ( e.g. exposure to tobacco smoke, air pollution and specific allergens, change in diet intake, obesity, exposure to infections and microbial substance in the environment) 3, there has also been an improved awareness of the disease over the past few years. Substantial effort has been made in the past decade for the development and the dissemination of international asthma guidelines. Such widespread publicity has certainly contributed to improve asthma management worldwide and to identify and treat new asthmatic patients. However, it might also have caused overdiagnosis of asthma and, more specifically, it may have contributed to the increased proportion of incorrectly diagnosed asthma cases. Inevitably, any misdiagnosed cases lead to over treatment or inappropriate treatments 5, and increased risk of side-effects in the absence of any pharmacological benefit.

Is it only a hypothetical situation? Unfortunately it does not appear to be a mere theory. International guidelines advise that asthma diagnosis be based on both the presence of symptoms and objective measurements of variable airflow …
Association of increased mycobacterium growth inhibitory factor with antituberculous immunity
Authors: S Chandrasekhar, VK Perumal
Journal: European Respiratory Journal (1991)

Cell-mediated immune mechanisms (CMI) were studied in 51 patients of pulmonary tuberculosis to evaluate the role of mycobacterium growth inhibitory factor in prognosis of the infection, before and after the administration of anti-tubercular drugs. Twenty five Mantoux negative individuals who were subsequently bacille Calmette-Guérin (BCG) vaccinated and 25 Mantoux positive, non-tuberculous controls were included in the study. Their clinical assessment was compared with skin sensitivity (Mantoux); lymphocyte transformation (LT) after stimulation with phytohaemagglutinin (PHA) and purified protein derivative (PPD); macrophage migration inhibitory factor (MIF), mycobacteria growth inhibitory factor (Myco IF) and listerial growth inhibitory factor (List IF). The tests were carried out at the beginning of the treatment and at intervals of three months, extending to one year. In the case of Mantoux positive controls, tests were carried out only once. It was found that Mantoux reaction had no correlation with LT, MIF, Myco IF and List IF. Both MIF and Myco IF, were significantly elevated in improving patients, whereas increase in List IF was not significant. An important finding was that Myco IF was at a higher level in improving patients whereas in those not responding to chemotherapy it was low.
PRDM5 Identified as a Target of Epigenetic Silencing in Colorectal and Gastric Cancer
Authors: Yoshiyuki Watanabe, Minoru Toyota, Yutaka Kondo, Hiromu Suzuki, Takashi Imai, Mutsumi Ohe-Toyota, Reo Maruyama, Masanori Nojima, Yasushi Sasaki, Yoshitaka Sekido, Hiroyoshi Hiratsuka, Yasuhisa Shinomura, Kohzoh Imai, Fumio Itoh, Takashi Tokino
Journal: Clinical Cancer Research (2007)

Abstract Purpose: PR (PRDI-BF1 and RIZ) domain proteins (PRDM) are a subfamily of the kruppel-like zinc finger gene products that play key roles during cell differentiation and malignant transformation. The aim of the present study was to begin to examine the involvement of epigenetic alteration of PRDM expression in gastric and colorectal cancer. Experimental Design: We used real-time PCR to assess expression of PRDM1-17. In addition, we used bisulfite PCR to assess DNA methylation and chromatin immunoprecipitation to assess histone modification in colorectal and gastric cancer cell lines lacking PRDM5 expression. Results: Among the 17 PRDM family genes tested, we found that PRDM5 is the most frequently silenced in colorectal and gastric cancer cell lines. Silencing of PRDM5 was mediated by either DNA methylation or trimethylation of Lys27 of histone H3. Introduction of PRDM5 into cancer cells suppressed cell growth, suggesting that it acts as a tumor suppressor in gastrointestinal cancers. Methylation of PRDM5 was detected in 6.6% (4 of 61) of primary colorectal and 50.0% (39 of 78) of primary gastric cancers but not in noncancerous tissue samples collected from areas adjacent to the tumors. Conclusions: Our data suggest that epigenetic alteration of PRDM5 (e.g., methylation of its 5′-CpG island or trimethylation of Lys27 of histone H3) likely plays a key role in the progression of gastrointestinal cancers and may be a useful molecular marker.
Why US Adults Use Dietary Supplements
Authors: Regan L Bailey, Jaime J Gahche, Paige E Miller, Paul R Thomas, Johanna T Dwyer
Journal: JAMA Internal Medicine (2013)

Background: Dietary supplements are used by more than half of adults, although to our knowledge, the reasons motivating use have not been previously examined in US adults using nationally representative data.The purpose of this analysis was to examine motivations for dietary supplement use, characterize the types of products used for the most commonly reported motivations, and to examine the role of physicians and health care practitioners in guiding choices about dietary supplements.Methods: Data from adults (Ն20 years; n=11 956) were examined in the 2007-2010 National Health and Nutrition Examination Survey, a nationally representative, cross-sectional, population-based survey.Results: The most commonly reported reasons for using supplements were to "improve" (45%) or "maintain" (33%) overall health.Women used calcium products for "bone health" (36%), whereas men were more likely to report supplement use for "heart health or to lower cholesterol" (18%).Older adults (Ն60 years) were more likely than younger individuals to report motivations related to site-specific reasons like heart, bone and joint, and eye health.Only 23% of products were used based on recommendations of a health care provider.Multivitaminmineral products were the most frequently reported type of supplement taken, followed by calcium and -3 or fish oil supplements.Supplement users are more likely to report very good or excellent health, have health insurance, use alcohol moderately, eschew cigarette smoking, and exercise more frequently than nonusers.Conclusions: Supplement users reported motivations related to overall health more commonly than for supplementing nutrients from food intakes.Use of supplements was related to more favorable health and lifestyle choices.Less than a quarter of supplements used by adults were recommended by a physician or health care provider.
Vascular remodelling of resistance vessels: can we define this?
Authors: M Mulvany
Journal: Cardiovascular Research (1999)

Time for primary review 31 days. 

As pointed out originally by Folkow [1], many of the haemodynamic features associated with essential hypertension can be accounted for by alterations in the structure of the resistance vessels. In vivo haemodynamic experiments (where forearm blood flow was measured with the vasculature fully relaxed under conditions of reactive hyperaemia) showed that the relaxed peripheral resistance in essential hypertensive patients was increased, that the pressor response to maximal concentrations of agonists was increased, but that the threshold concentration of agonists which caused vascular contraction was not altered. From simple physical reasoning, it was suggested that these findings could be accounted for by a slight change in the structure of the resistance vessels, such that there is a decrease in the lumen diameter and an increase in the wall (or media) thickness to lumen diameter ratio [2–5]. It is, however, only recently that it has become possible to quantify resistance vessel structure, and thus to describe the results of the remodelling process with any precision. This development has inevitably brought with it controversy about the terminology which is appropriate for characterizing the remodelling process. In this review, I will briefly summarize a recent scheme which has been proposed to define the forms of remodelling, and the current information concerning the remodelling of resistance vessel structure. I will then discuss the current debate concerning the terminology to be used. The review is restricted to the morphology of individual vessels, and not to possible changes in branching vascularity [6].

The resistance vessels exert their function through the resistance which they present to the blood flow. The resistance is determined by the lumen diameter (to the fourth power according to the Poiseuille relation), and the lumen diameter is a function of the passive and active mechanical … 

* Tel.: +45-8942-1726; fax: +45-8612-8804; e-mail: mm@farm.aau.dk
Anti-Fas/APO-1 antibody-mediated apoptosis of cultured human glioma cells. Induction and modulation of sensitivity by cytokines.
Authors: M Weller, K Frei, P Groscurth, P H Krammer, Y Yonekawa, A Fontana
Journal: Journal of Clinical Investigation (1994)

Fas/APO-1 is a transmembrane protein of the nerve growth factor/TNF alpha receptor family which signals apoptotic cell death in susceptible target cells. We have investigated the susceptibility of seven human malignant glioma cell lines to Fas/APO-1-dependent apoptosis. Sensitivity to Fas/APO-1 antibody-mediated cell killing correlated with cell surface expression of Fas/APO-1. Expression of Fas/APO-1 as well as Fas/APO-1-dependent cytotoxicity were augmented by preexposure of human malignant glioma cells to IFN gamma and TNF alpha. Further, pretreatment with TGF beta 2, IL1 and IL8 enhanced Fas/APO-1 antibody-induced glioma cell apoptosis whereas other cytokines including TNF beta, IL6, macrophage colony-stimulating factor, IL10 and IL13 had no such effect. None of the human malignant glioma cell lines was susceptible to TNF alpha-induced cytotoxicity. Fas/APO-1 antibody-sensitive glioma cell lines (n = 5), but not Fas/APO-1 antibody-resistant glioma cell lines (n = 2), became sensitive to TNF alpha when co-treated with inhibitors of RNA and protein synthesis. Resistance of human glioma cells to Fas/APO-1 antibody-mediated apoptosis was mainly related to low level expression of Fas/APO-1 and appeared not to be linked to overexpression of the anti-apoptotic protooncogene, bcl-2. Given the resistance of human malignant glioma to surgery, irradiation, chemotherapy and immunotherapy, we propose that Fas/APO-1 may be a promising target for a novel locoregionary approach to human malignant glioma. This strategy gains support from the demonstration of Fas/APO-1 expression in ex vivo human malignant glioma specimens and from the absence of Fas/APO-1 in normal human brain parenchyma.
Adipocyte Signaling and Lipid Homeostasis
Authors: Yi-Hao Yu, Henry N. Ginsberg
Journal: Circulation Research (2005)

For many years adipose tissue was viewed as the site where excess energy was stored, in the form of triglycerides (TGs), and where that energy, when needed elsewhere in the body, was released in the form of fatty acids (FAs). Recently, it has become clear that when the regulation of the storage and release of energy by adipose tissue is impaired, plasma FA levels become elevated and excessive metabolism of FA, including storage of TGs, occurs in nonadipose tissues. Most recently, work by several laboratories has made it clear that in addition to FA, adipose tissue communicates with the rest of the body by synthesizing and releasing a host of secreted molecules, collectively designated as adipokines. Several recent reviews have described how these molecules, along with FA, significantly effect total body glucose metabolism and insulin sensitivity. Relatively little attention has been paid to the effects of adipokines on lipid metabolism. In this review, we will describe, in detail, the effects of molecules secreted by adipose tissue, including FA, leptin, adiponectin, resistin, TNF-α, IL-6, and apolipoproteins, on lipid homeostasis in several nonadipose tissues, including liver, skeletal muscle, and pancreatic β cells.
Sodium influx via a non-selective pathway activated by the removal of extracellular divalent cations: possible role in the calcium paradox
Authors: S Bosteels
Journal: Cardiovascular Research (1999)

Cation non-selective conductances which are induced upon removal of extracellular divalent cations have been identified in cardiac and other cells. We have examined whether the conductance identified in cardiac myocytes mediates an increase in intracellular Na+ (Nai+) and have tested the ability of drugs to prevent this influx.Rat single ventricular myocytes at 22 degrees C were voltage-clamped in whole-cell mode to measure membrane currents or were loaded with SBFI to measure Nai+.Removal of extracellular Ca2+ (Cao2+) and Mg2+ (Mgo2+), which induced a current with reversal potential of -10 mV, also caused an increase in SBFI fluorescence ratio (340/380 nm). These changes were reversible on repletion of Cao2+ and/or Mgo2+. They could not be prevented by nifedipine, indicating that they were not mediated by L-type Ca2+ channels. Both increases in non-selective conductance and in Nai+ were prevented by trivalent cations (Dyo3+, Gdo3+ or Lao3+; 100 microM) or reduced by the aminoglycoside gentamicin.A cation non-selective conductance, different from L-type Ca2+ channels, contributes to the Nai+ accumulation obtained during perfusion with Ca2+/Mg(2+)-free media, hence also to the Cai2+ overload and cellular damage upon Cao2+ repletion (the Ca2+ paradox).
Large-Scale Analysis of Orthologs and Paralogs under Covarion-Like and Constant-but-Different Models of Amino Acid Evolution
Authors: R. A. Studer, M. Robinson-Rechavi
Journal: Molecular Biology and Evolution (2010)

Functional divergence between homologous proteins is expected to affect amino acid sequences in two main ways, which can be considered as proxies of biochemical divergence: a "covarion-like" pattern of correlated changes in evolutionary rates, and switches in conserved residues ("conserved but different"). Although these patterns have been used in case studies, a large-scale analysis is needed to estimate their frequency and distribution. We use a phylogenomic framework of animal genes to answer three questions: 1) What is the prevalence of such patterns? 2) Can we link such patterns at the amino acid level with selection inferred at the codon level? 3) Are patterns different between paralogs and orthologs? We find that covarion-like patterns are more frequently detected than "constant but different," but that only the latter are correlated with signal for positive selection. Finally, there is no obvious difference in patterns between orthologs and paralogs.
Signals through T cell receptor-zeta chain alone are insufficient to prime resting T lymphocytes.
Authors: T Brocker, K Karjalainen
Journal: The Journal of Experimental Medicine (1995)

Activation studies performed with transfected T cell hybridomas and tumors revealed that chimeric molecules containing the CD3 epsilon or zeta chain intracytoplasmic portions can induce the complete effector functions normally seen only when the complete T cell receptor (TCR)/CD3 complexes of T lymphocytes are triggered. Therefore, the zeta chain, with its three antigen recognition activation motives, is thought to connect the antigen-binding Ti chains with the intracellular signaling machinery of the T cell. Here we demonstrate that the cytoplasmic portion of the TCR-zeta chain is not sufficient to activate resting T lymphocytes when cells from transgenic mice expressing a chimeric zeta receptor are used. However, after (in vivo and in vitro) activation through their endogenous TCR/CD3 complexes, the preactivated T lymphocytes could be triggered through the zeta chimera to the same extent as when they were activated through their endogenous TCR/CD3 complexes. They were able to proliferate and elicit cytotoxic functions when triggered through their zeta chimeras. These results suggest that the triggering requirements for effector functions seem to be different in resting than in activated T cells.
Overexpression of Inducible Nitric Oxide Synthase by Neointimal Smooth Muscle Cells
Authors: Zhong-qun Yan, Göran K. Hansson
Journal: Circulation Research (1998)

The formation of a neointima represents an important repair mechanism in response to vascular injury. It is associated with the expression of a specific set of genes by the intimal smooth muscle cells. Recently, expression of the inducible isoform of NO synthase (iNOS) has been identified in injured arteries during neointimal formation, suggesting that intimal SMCs have a unique mechanism for regulating NO production. Therefore, we have analyzed the expression of iNOS in intimal SMCs. Although first expressed in the media within 1 day after injury, iNOS was confined to neointimal smooth muscle cells at 1 to 2 weeks after injury. Isolated intimal SMCs were found to consistently reexpress iNOS in reaction to proinflammatory mediators. This was associated with a 5- to 8-fold higher output of NO in comparison with SMCs derived from the media of uninjured arteries. Western blot and Northern blot analyses likewise revealed that the high production of NO by intimal SMCs was due to overexpression of iNOS. Moreover, the same stimuli induced a higher transcriptional activity in intimal than in medial SMCs, as detected by transfection of a reporter gene under the iNOS promoter. Induction of iNOS led to a reduced proliferation in both medial and intimal SMCs. This inhibitory effect was, however, less pronounced in intimal than in medial SMCs. Similarly, intimal cells were less sensitive to NO-induced inhibition of mitochondrial respiration. When SMC clones were analyzed, there was no correlation between iNOS expression and growth pattern, suggesting that iNOS expression is independent of the morphological phenotype of SMCs. Together, our data show that the intimal SMC is the main iNOS-expressing cell type in the injured artery, that it responds more vividly to iNOS-inducing cytokines because of a more efficient activation of the iNOS promoter, and that it is more resistant to the actions of NO compared with medial SMCs. Intimal production of NO via the inducible pathway may be important for the restoration of vascular homeostasis after injury.
Current and Future Considerations in the Use of Mechanical Circulatory Support Devices
Authors: Marc A. Simon, John Watson, J. Timothy Baldwin, William R. Wagner, Harvey S. Borovetz
Journal: Annual Review of Biomedical Engineering (2008)

Heart failure (HF) is a major public health problem in the United States, and its prevalence is likely to increase with the aging U.S. population. Mechanical circulatory support (MCS) utilizing bladder-based blood pumps generating pulsatile flow has been reserved for patients with severe HF failing medical therapy. As MCS technology has advanced to include rotary blood pumps, so has our understanding of the biological and clinical responses to MCS, which in turn has altered the risk/benefit profile of this therapy. This may lead to paradigm shifts in device usage from support of end-stage HF to temporary support for recovery of cardiac function and earlier usage, to, ultimately, prevention of disease progression. This review serves to explore the current state and future opportunities of MCS within our larger understanding of the epidemiology, pathophysiology, and treatment options for HF.