tbuckley/cabot-search huggingface dataset:
Quantitative Aspects of Dog Cardiac Microsomal Calcium Binding and Calcium Uptake
Authors: ARNOLD M. KATZ, DORIS I. REPKE
Journal: Circulation Research (1967)

Crude microsomes prepared from dog ventricular myocardium by differential centrifugation bound 0.029 µmole of Ca/mg of microsomal protein in the absence of oxalate, and accumulated 1.92 µmole Ca/mg in the presence of oxalate. Purified cardiac microsomes, obtained by sucrose density-gradient ultracentrifugation of the crude microsomes, bound 0.026 µmole Ca/mg and accumulated 2.32 µmole Ca/mg. The total Ca-binding capacity of the myocardium, based on the yields and Ca-binding activities of the crude microsomes, was 0.050 µmole/g wet weight of the ventricle. This value is very nearly equal to the amount of Ca believed to be removed from the actomyosin during relaxation, suggesting that myocardial relaxation may be effected by Ca binding to the sarcoplasmic reticulum. The binding constant for Ca binding to cardiac microsomes is approximately 10 5 M -1 . Purified cardiac microsomes lowered free Ca from 10 -5 M to approximately 10 -7 M in the presence of oxalate, but Ca uptake proceeded much less rapidly than did Ca binding. Calcium uptake followed first order kinetics. A typical rate constant was 0.24 sec -1 mg microsomal protein -1 , giving a rate constant of 0.047 sec -1 , for the initial uptake from a solution of 10 -5 M CaCl 2 by 1 g of heart based on the yields of purified microsomes. This rate is significantly lower than that of relaxation in the intact ventricle, and remains so even if the higher yields of crude microsomes are used in the calculation.
Emergence of levofloxacin-non-susceptible Streptococcus pneumoniae and treatment for multidrug-resistant tuberculosis in children in South Africa: a cohort observational surveillance study
Authors: Anne von Gottberg, Keith P Klugman, Cheryl Cohen, Nicole Wolter, Linda de Gouveia, Mignon du Plessis, Ruth Mpembe, Vanessa Quan, Andrew Whitelaw, Rena Hoffmann, Nelesh Govender, Susan Meiring, Anthony M Smith, Stephanie Schrag
Journal: The Lancet (2008)
Engineering the control of mosquito-borne infectious diseases
Authors: Paolo Gabrieli, Andrea Smidler, Flaminia Catteruccia
Journal: Genome biology (2014)

Abstract Recent advances in genetic engineering are bringing new promise for controlling mosquito populations that transmit deadly pathogens. Here we discuss past and current efforts to engineer mosquito strains that are refractory to disease transmission or are suitable for suppressing wild disease-transmitting populations.
Hanging in the balance
Authors: Rebecca Coombes
Journal: BMJ (2006)

Could the UK's long awaited screening programme for bowel cancer become a victim of the NHS's financial crisis? Rebecca Coombes reports 

Until last Christmas everything seemed to be going well for those involved in the field of bowel cancer. Funding for a national screening programme for the condition, the second most common cause of death from cancer in the United Kingdom, had been agreed back in October 2004. The £34m ($60m; €50m) initiative, the first of its kind in Europe, is due to be rolled out in April to everyone in England aged between 60 and 69 years old.

But experts have become anxious that, at the 11th hour, the programme could be a victim of the current spending crisis in the NHS. Although the Department of Health says it is committed to the roll-out, no assurance has been given that the agreed funding will be protected.

Bowel cancer kills about 16 000 people a year in the UK. The high mortality is attributed to late detection of the disease. Only 8-10% of the cancers are currently caught at an early stage, at which point survival is as high as 90%. Studies show that the screening programme could push early detection up to 27% of all cases.

The National Screening Committee estimates that the programme could save the lives of around 1200 people a year in England alone, which represents a reduction of about 9% in the 13 000 annual …
Mechanically Unloading the Left Ventricle Before Coronary Reperfusion Reduces Left Ventricular Wall Stress and Myocardial Infarct Size
Authors: Navin K. Kapur, Vikram Paruchuri, Jose Angel Urbano-Morales, Emily E. Mackey, Gerard H. Daly, Xiaoying Qiao, Natesa Pandian, George Perides, Richard H. Karas
Journal: Circulation (2013)

Background— Ischemia/reperfusion injury worsens infarct size, a major determinant of morbidity and mortality after acute myocardial infarction (MI). We tested the hypothesis that reducing left ventricular wall stress with a percutaneous left atrial-to-femoral artery centrifugal bypass system while delaying coronary reperfusion limits myocardial injury in a model of acute MI. Methods and Results— MI was induced by balloon occlusion of the left anterior descending artery in adult male swine. In the MI group (n=4), 120 minutes of left anterior descending artery occlusion was followed by 120 minutes of reperfusion without mechanical support. In the mechanically supported group (MI+unload; n=4), percutaneous left atrial–to–femoral artery bypass was initiated after 120 minutes of ischemia, and left anterior descending artery occlusion was prolonged for an additional 30 minutes, followed by 120 minutes of reperfusion with device support. All animals were euthanized after reperfusion, and infarct size was quantified by triphenyltetrazolium chloride staining. Compared with baseline, mean left ventricular wall stress and stroke work were not changed at any point in the MI group but were decreased after reperfusion in the MI+unload group (mean left ventricular wall stress, 44 658 versus 22 963 dynes/cm 2 ; stroke work, 2823 versus 655 mm Hg·mL, MI versus MI+unload). Phosphorylation of reperfusion injury salvage kinase pathway proteins from noninfarcted left ventricular tissue was unchanged in the MI group but was increased in the MI+unload group. Compared with the MI group, total infarct size was reduced in the MI+unload group (49% versus 28%, MI versus MI+unload). Conclusions— These data support that first unloading the left ventricle despite delaying coronary reperfusion during an acute MI reduces myocardial injury.
Multipotential phenotypic expression of genes encoding peptide hormones in rat insulinoma cell lines.
Authors: J Philippe, W L Chick, J F Habener
Journal: Journal of Clinical Investigation (1987)

The developmental origin of the four phenotypically distinct hormone-producing islet cells (insulin, glucagon, somatostatin, pancreatic polypeptide) is unclear. To investigate the potential for phenotypic differentiation of islet cells, we prepared several clonal cell lines from a radiation-induced rat islet tumor and analyzed them for insulin, glucagon, and somatostatin gene expression by cDNA hybridization, immunocytochemistry, and radioimmunoassay. We found expression of all three genes in the tumor and in the parental cell line and mixed variable phenotypes in the clonal lines derived from the parental line. We also observed the ectopic expression of the angiotensinogen gene in the tumor and the cell lines. The relative levels of hormonal gene expression differed among the cell lines but remained fixed during continuous passage. The three islet hormone mRNAs were larger compared to the pancreas owing to longer poly(A) tracts. These observations indicate that neoplastic islet cells retain the potential to differentiate into hormone-specific cellular phenotypes and may mimic developmental pathways of the pancreatic islets.
Health related virtual communities and electronic support groups: systematic review of the effects of online peer to peer interactions
Authors: Gunther Eysenbach, John Powell, Marina Englesakis, Carlos Rizo, Anita Stern
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To compile and evaluate the evidence on the effects on health and social outcomes of computer based peer to peer communities and electronic self support groups, used by people to discuss health related issues remotely. <b>Design and data sources</b> Analysis of studies identified from Medline, Embase, CINAHL, PsycINFO, Evidence Based Medicine Reviews, Electronics and Communications Abstracts, Computer and Information Systems Abstracts, ERIC, LISA, ProQuest Digital Dissertations, Web of Science. <b>Selection of studies</b> We searched for before and after studies, interrupted time series, cohort studies, or studies with control groups; evaluating health or social outcomes of virtual peer to peer communities, either as stand alone interventions or in the context of more complex systems with peer to peer components. <b>Main outcome measures</b> Peer to peer interventions and co-interventions studied, general characteristics of studies, outcome measures used, and study results. <b>Results</b> 45 publications describing 38 distinct studies met our inclusion criteria: 20 randomised trials, three meta-analyses of n of 1 trials, three non-randomised controlled trials, one cohort study, and 11 before and after studies. Only six of these evaluated "pure" peer to peer communities, and one had a factorial design with a "peer to peer only" arm, whereas 31 studies evaluated complex interventions, which often included psychoeducational programmes or one to one communication with healthcare professionals, making it impossible to attribute intervention effects to the peer to peer community component. The outcomes measured most often were depression and social support measures; most studies did not show an effect. We found no evidence to support concerns over virtual communities harming people. <b>Conclusions</b> No robust evidence exists of consumer led peer to peer communities, partly because most peer to peer communities have been evaluated only in conjunction with more complex interventions or involvement with health professionals. Given the abundance of unmoderated peer to peer groups on the internet, research is required to evaluate under which conditions and for whom electronic support groups are effective and how effectiveness in delivering social support electronically can be maximised.
A hospital based study of sleep in metabolic syndrome between obese & non obese North Indians
Authors: Dhruva Chaudhry, Inder Sehgal, Chirag Tandon, Viral Sangwan
Journal: European Respiratory Journal (2011)

Metabolic syndrome's association with sleep apnoea is established. However, differences amongst obese and non-obese patients of metabolic syndrome are not clear.

Methods: 50 consecutive patients fulfilling the criteria of metabolic syndrome as per revised National Cholesterol Education Program (NCEP) Adult Treatment PANEL-3 guidelines were included. They were divided into two groups based on body mass index (BMI) as applicable in Asian Indians-Group I with BMI ≤25kg/m2 and Group II with BMI >25kg/m2.Patients on CPAP therapy & having any other systemic diseases were excluded. All eligible patients underwent overnight polysomnography.

Results: Demographically there was no difference between two groups. The mean BMI of group I & II were 23.20±1.68 kg/m2, & 31.69±4.93 kg/m2 respectively. Snoring, unrefreshing sleep & daytime sleepiness were the commonest presenting symptoms. Both groups had similar Epworth sleepiness scale. Diabetes & hypertension was significantly higher amongst group I & group II respectively. Both groups had similar sleep time & disribution of all stages of NREM sleep. Group I had insignificant less REM sleep (7.18±23.57 versus 14.12±24.96,pvalue>.05).Snoring time was significantly higher among group II (95.82±51.48 vs 44.76±29.96) and apneic episodes were common during NREM sleep in both groups. However the mean apnoea/hypoapnoea index (AHI) was similar in both groups (34.10±30.04 v/s 32.72±30.90; p value=0.607).

Conclusion: The prevalence of sleep disordered breathing in selective North Indian population with metabolic syndrome irrespective of BMI was high. Community based epidemiological study is the need of hour to define the extent of the problem.
867 ARE CURRENT TREATMENT RATES SUFFICIENT TO REDUCE HCV PREVALENCE AMONG PEOPLE WHO INJECT DRUGS? MODEL PROJECTIONS IN SEVEN UK SETTINGS
Authors: N.K. Martin, P. Vickerman, A. Clements, M. Cramp, D. De Angeles, J.F. Dillon, S. Fahey, G.R. Foster, D.J. Goldberg, F. Gordon, S.J. Hutchinson, W. Irving, H. Lewis, S. Ryder, A. Ustainowski, J. Vilar, M. Hickman
Journal: Journal of Hepatology (2013)
Reproducibility of the proctometrogram.
Authors: J S Varma, A N Smith
Journal: Gut (1986)

The reproducibility of a method of measuring rectal distensibility by continuous controlled fluid inflation with a balloon has been evaluated in 15 patients. The volume at sensation threshold, constant sensation and maximal tolerance, the pressures at these volumes and rectal compliance were measured. The mean coefficients of variation of the seven variables measured ranged from 4.7%-7.9%. The expected correlation between rectal compliance and maximal tolerable volume was confirmed (r = 0.85, p less than 0.001). The high reproducibility makes this investigation reliable for use in clinical practice and research.
Cytoskeletal Rearrangement and Signal Transduction in TGF-β1–Stimulated Mesangial Cell Collagen Accumulation
Authors: Susan C. Hubchak, Constance E. Runyan, Jeffrey I. Kreisberg, H. William Schnaper
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. TGF-β1 has been implicated in glomerular extracellular matrix accumulation, although the precise cellular mechanism(s) by which this occurs is not fully understood. The authors have previously shown that the Smad signaling pathway is present and functional in human glomerular mesangial cells and plays a role in activating type I collagen gene expression. It also was determined that TGF-β1 activates ERK mitogen-activated protein kinase in mesangial cells to enhance Smad activation and collagen expression. Here, it was shown that TGF-β1 rapidly induces cytoskeletal rearrangement in human mesangial cells, stimulating smooth muscle α-actin detection in stress fibers and promoting focal adhesion complex assembly and redistribution. Disrupting the actin cytoskeleton with cytochalasin D (Cyto D) selectively decreased basal and TGF-β1–induced cell-layer collagen I and IV accumulation. The balance of matrix metalloproteinases (MMP) and inhibitors was altered by Cyto D or TGF-β1 alone, increasing MMP activity, increasing MMP-1 expression, and decreasing tissue inhibitor of matrix metalloproteinase-2 expression. Cyto D also decreased basal and TGF-β1–stimulated α1(I) collagen mRNA but did not inhibit TGF-β–stimulated α1(IV) mRNA expression. A similar decrease in α1(I) mRNA expression caused by the actin polymerization inhibitor latrunculin B was partially blocked by the addition of jasplakinolide, which promotes actin assembly. The Rho-family GTPase inhibitor C. difficile toxin B or the Rho-associated kinase inhibitor Y-27632 also blocked TGF-β1–stimulated α1(I) mRNA expression. Cytoskeletal disruption reduced Smad2 phosphorylation but had little effect on mRNA stability, TGF-β receptor number, or receptor affinity. Thus, TGF-β1–mediated collagen I accumulation is associated with cytoskeletal rearrangement and Rho-GTPase signaling. E-mail: [email protected]
Effects of a 5-lipoxygenase inhibitor, ABT-761, on exercise-induced bronchoconstriction and urinary LTE4 in asthmatic patients
Authors: B Lehnigk, KF Rabe, G Dent, RS Herst, PJ Carpentier, H Magnussen
Journal: European Respiratory Journal (1998)

The novel 5-lipoxygenase (5-LO) inhibitor, ABT-761, was investigated for its effect on exercise-induced bronchoconstriction in asthmatic subjects. The relationship between 5-LO inhibition and effects on the response of the airways to exercise was examined. In a double-blind, randomized, crossover clinical trial, 10 patients with mild to moderate persistent asthma (who exhibited a fall in forced expiratory volume in one second (FEV1) > or = 20% following standardized exercise challenge) received 200 mg ABT-761 or matched placebo, orally, 5 h prior to exercise on two study days, 7-10 days apart. Lung function, urinary leukotriene E4 (LTE4) and ex vivo calcium ionophore-stimulated LTB4 release in whole blood were measured prior to dosing, prior to exercise and at various time points up to 4 h post-exercise. The mean (SD) maximal percentage fall in FEV1 after exercise was 27.1 (12)% on placebo and 19.9 (10)% on ABT-761 days, respectively (p<0.05). Post-exercise fall in FEV1 was significantly attenuated at 5, 10, 15 and 30 min after exercise and the mean area under curve, representing the overall effect of exercise from 0-45 min post-challenge, was also significantly attenuated by ABT-761 (p<0.001). Ex vivo LTB4 release was inhibited by more than 80% throughout the 4 h post-exercise period, indicating that 5-LO was extensively inhibited at all time points. Urinary LTE4 in the post-exercise period was significantly lower after ABT-761 day than after placebo (40.1 (17.6) versus 89.8 (58.2) pg x mg creatinine(-1); p<0.05). Inhibition of LTB4 release in ABT-761-treated patients correlated positively with the attenuation of post-exercise FEV1 decline (r=0.711; p<0.05). We conclude that ABT-761 is effective in suppressing exercise-induced bronchoconstriction and that this protection is related quantitatively to the degree of 5-lipoxygenase inhibition.
Astrocyte-derived VEGF-A drives blood-brain barrier disruption in CNS inflammatory disease
Authors: Azeb Tadesse Argaw, Linnea Asp, Jingya Zhang, Kristina Navrazhina, Trinh Pham, John N. Mariani, Sean Mahase, Dipankar J. Dutta, Jeremy Seto, Elisabeth G. Kramer, Napoleone Ferrara, Michael V. Sofroniew, Gareth R. John
Journal: Journal of Clinical Investigation (2012)

In inflammatory CNS conditions such as multiple sclerosis (MS), current options to treat clinical relapse are limited, and more selective agents are needed. Disruption of the blood-brain barrier (BBB) is an early feature of lesion formation that correlates with clinical exacerbation, leading to edema, excitotoxicity, and entry of serum proteins and inflammatory cells. Here, we identify astrocytic expression of VEGF-A as a key driver of BBB permeability in mice. Inactivation of astrocytic Vegfa expression reduced BBB breakdown, decreased lymphocyte infiltration and neuropathology in inflammatory and demyelinating lesions, and reduced paralysis in a mouse model of MS. Knockdown studies in CNS endothelium indicated activation of the downstream effector eNOS as the principal mechanism underlying the effects of VEGF-A on the BBB. Systemic administration of the selective eNOS inhibitor cavtratin in mice abrogated VEGF-A-induced BBB disruption and pathology and protected against neurologic deficit in the MS model system. Collectively, these data identify blockade of VEGF-A signaling as a protective strategy to treat inflammatory CNS disease.
Asthma due to aluminium soldering flux
Authors: G. M. Sterling
Journal: Thorax (1967)

Two patients have been studied who complained of dyspnoea after the inhalation of fumes from a new soldering flux recently developed for use in jointing aluminium which has been replacing copper as a material for electric cables. A previous survey of respiratory complaints after the use of this particular flux had failed to show any objective change in lung function, and the present cases are the first to be reported. Both subjects have been investigated by means of serial spirometry, peak flow rates, and body plethysmography following inhalation of small amounts of flux fumes; delayed and prolonged bronchoconstriction has been demonstrated. Similar results have been obtained after the inhalation of one of the main constituents of the flux, namely amino-ethyl ethanolamine, which is presumably the active allergic agent. The bronchial response is unusual in being delayed in onset but otherwise resembles pollen-sensitivity asthma rather than the infiltrative process seen in farmer9s lung. The type of immune mechanism involved is speculative, but it is possible that some alteration of the amino-ethyl ethanolamine is needed before it can react with reaginic antibody fixed in the bronchial tissues.
Thymic reconstitution of nude F1 mice with one or both parental thymus grafts
Authors: RM Zinkernagel, A Althage, G Callahan
Journal: The Journal of Experimental Medicine (1979)

Thymus-derived lymphocytes (T cells) have two outstanding characteristics that distinguish them from other lymphocytes: (a) they express two specificities, one for self-antigens, the major transplantation antigens (H) coded by the major histocompatibility gene complex (MHC), and a second specificity for foreign antigenic determinants. (b) T cells must undergo differentiation or maturation in the thymus (1, 2). Apparently, an important step in T-cell differentiation in the thymus is the selection of T-cells' restriction specificity for self-H. This interpretation stems from experiments with chimeras formed by lethally irradiating parental type mice and reconstituting them with F(1) stem cells: the maturing F(1) T cells expressed predominantly the restriction specificities for the recipient parental MHC type (3-8). Alternatively, adult F(1) mice that were thymectomized, lethally irradiated, reconstituted with bone marrow, and then engrafted with a parental thymus had T cells that were restricted predominantly to the thymus donors' H-2 (4-8). The present study first extends these observations to nude mice that are born without a thymus and therefore do not develop functional T cells and second, attempts to study the possibility that suppression may be responsible for the apparent influence of the radioresistant portion of the thymus on T- cell restriction specificities. We tested the immunocompetence and restriction specificities expressed by lymphocytes from F(1) nude mice reconstituted with both parental thymus grafts; our expectation was that suppression of the expression of T-cell restriction specificity should result either in complete immunoincompetence or emergence of only one of the two possible sets of restriction specificities. Nude F(1)mice that simultaneously received thymus gratis from both parents developed spleen cells restricted to both parental H-2 types. These results are compatible with the idea that the thymus' influence on T- cell restriction is via positive selection rather than by suppression.
Proportion of Solvent-Exposed Amino Acids in a Protein and Rate of Protein Evolution
Authors: Yeong-Shin Lin, Wei-Lun Hsu, Jenn-Kang Hwang, Wen-Hsiung Li
Journal: Molecular Biology and Evolution (2007)

Translational selection, including gene expression, protein abundance, and codon usage bias, has been suggested as the single dominant determinant of protein evolutionary rate in yeast. Here, we show that protein structure is also an important determinant. Buried residues, which are responsible for maintaining protein structure or are located on a stable interaction surface between 2 subunits, are usually under stronger evolutionary constraints than solvent-exposed residues. Our partial correlation analysis shows that, when whole proteins are included, the variance of evolutionary rate explained by the proportion of solvent-exposed residues (P(exposed)) can reach two-thirds of that explained by translational selection, indicating that P(exposed) is the most important determinant of protein evolutionary rate next only to translational selection. Our result suggests that proteins with many residues under selective constraint (e.g., maintaining structure or intermolecular interaction) tend to evolve slowly, supporting the "fitness (functional) density" hypothesis.