tbuckley/cabot-search huggingface dataset:
Antibacterial activity of human neutrophil peptide-1 against Mycobacterium tuberculosis H37Rv: in vitro and ex vivo study
Authors: S. Sharma, I. Verma, G.k Khuller
Journal: European Respiratory Journal (2000)

The aim of the study was to investigate the activity of human neutrophil peptide (HNP)-1 to kill Mycobacterium tuberculosis H37Rv in vitro and ex vivo in the murine macrophage cell line J744A.1 on the basis of colony forming units. Macromolecular biosynthesis was studied by monitoring the incorporation of radioactive precursors into different macromolecules. The binding and localization studies were carried out with radioiodinated HNP-1 whereas the cytotoxicity of HNP-1 to macrophages was determined by trypan blue exclusion assay. A concentration dependent inhibition in the growth of M. tuberculosis H37Rv was observed in the presence of HNP-1. The minimum inhibitory concentration and median inhibitory concentration of HNP-1 were found to be 2.5 microg x mL(-1) and 0.8 microg x mL(-1). Treatment of both in vitro grown and phagocytosed mycobacterial cells with HNP-1 resulted in generalized inhibition in the macromolecular biosynthesis with maximum inhibition in deoxyribonucleic acid and lipid biosynthesis. HNP-1 exhibited equilibrium binding with respect to time and two-thirds of bound radioactivity was shown to be present inside the macrophages. Approximately 50% and 98% killing of intracellular mycobacteria was observed after 3 days of treatment with 5 microg x mL(-1) and 40 microg x mL(-1) of HNP-1, respectively. HNP-1 exhibited low cytotoxicity towards the macrophage cell line at the bactericidal concentration to mycobacteria. From the results of this study, it is concluded that human neutrophil peptide-1 possesses potent bactericidal activity against virulent mycobacteria in vitro as well as mycobacteria replicating within macrophages.
Using Drugs to Discriminate — Adverse Selection in the Insurance Marketplace
Authors: Douglas B. Jacobs, Benjamin D. Sommers
Journal: New England Journal of Medicine (2015)

Eliminating discrimination on the basis of preexisting conditions is a key feature of the Affordable Care Act. But insurers may be resorting to other tactics to dissuade high-cost patients from enrolling, such as categorizing all HIV drugs in the highest-cost-sharing tier.
Methods for Investigating Gene-Environment Interactions in Candidate Pathway and Genome-Wide Association Studies
Authors: Duncan Thomas
Journal: Annual Review of Public Health (2010)

Despite the considerable enthusiasm about the yield of novel and replicated discoveries of genetic associations from the new generation of genome-wide association studies (GWAS), the proportion of the heritability of most complex diseases that have been studied to date remains small. Some of this “dark matter” could be due to gene-environment (G × E) interactions or more complex pathways involving multiple genes and exposures. We review the basic epidemiologic study design and statistical analysis approaches to studying G × E interactions individually and then consider more comprehensive approaches to studying entire pathways or GWAS data. In addition to the usual issues in genetic association studies, particular care is needed in exposure assessment, and very large sample sizes are required. Although hypothesis-driven, pathway-based and agnostic GWA study approaches are generally viewed as opposite poles, we suggest that the two can be usefully married using hierarchical modeling strategies that exploit external pathway knowledge in mining genome-wide data.
Up-Regulation of Peroxiredoxin 1 in Lung Cancer and Its Implication as a Prognostic and Therapeutic Target
Authors: Joo-Heon Kim, Paul N. Bogner, Sun-Hee Baek, Nithya Ramnath, Ping Liang, Hak-Ryul Kim, Chris Andrews, Young-Mee Park
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Peroxiredoxin 1 and 2 are highly homologous members of the Prx (or Prdx) protein family. Prx1 and Prx2 are elevated in several human cancers, and this seems to confer increased treatment resistance and aggressive phenotypes. This study was undertaken to examine the expression profiles of Prx1 and Prx2 in non–small cell lung cancer (NSCLC), and to test their prognostic value in predicting patient survival. Experimental Design: To gain insight into the regulatory mechanisms of Prx1 and Prx2 expression in NSCLC, their respective transcript profiles were examined in NSCLC cell lines from the NCI-60 panel Affymetrix database sets, and the promoter compositions of the two genes were investigated using computer-based multiple sequence alignment analyses. Immunohistochemical analyses of Prx1 and Prx2 were done on a total of 235 NSCLC specimens with stage I through IV disease. The expression profiles of Prx1 and Prx2 in tumor specimens, and their associations with survival, were investigated. Results and Conclusion: The levels of prx1 transcript were higher than those of prx2 in NSCLC cell lines, and the upstream regulatory sequences of the two genes display striking differences. The relative risk of death increased as Prx1 expression levels increased (P = 0.036) in a multivariate Cox model, independent of other clinicopathologic variables associated with survival. No statistically significant correlation was observed between Prx2 and survival. These results suggest that Prx1 may possess unique functions and regulatory mechanisms in NSCLC which are not shared with Prx2, and that Prx1 may serve as a new prognostic biomarker and therapeutic target in NSCLC.
Prevalence of asthma and allergy in Hong Kong schoolchildren: an ISAAC study
Authors: R Leung, G Wong, J Lau, A Ho, JK Chan, D Choy, C Douglass, CK Lai
Journal: European Respiratory Journal (1997)

Asthma and allergic disease in children is increasing in many Western countries but such trend has not been well-defined in Chinese populations. This paper aims to determine the prevalence of asthma and allergic disease in Hong Kong schoolchildren and compare it with previous data to identify a changing trend. We studied 4,665 schoolchildren aged 13-14 yrs using the International Study of Asthma and Allergy in Childhood (ISAAC) protocol to determine prevalence rates for asthma, wheeze, respiratory symptoms, rhinitis and eczema in 1994-1995. Additional questions on education levels of the parents and smoking status were also asked. Concordance between responses to the written and video questionnaires was good (76% for wheeze ever, 80% for current wheeze). Prevalence rates for asthma ever, wheeze ever, and current wheeze were 11, 20 and 12%, respectively, and were greater in boys (p &lt; 0.05). Rhinitis affected slightly over half of the subjects (52%), and eczema was reported by a sixth (15%), whilst current rhinitis and current eczema were present in 44% and 3.6% of children, respectively. In multiple logistic regression: odds ratio male sex (OR) 1.47; (95% confidence interval (95% CI) 1.15-1.86); current rhinitis (OR 3.00; 95% CI 2.36-3.81); current eczema (OR 2.34; 95% CI 1.40-3.93); and active smoking (OR 2.00; 95% CI 1.38-2.89) were associated with current wheeze; whilst severe wheezing attack was associated with: current rhinitis (OR 2.72; 95% CI 1.47-5.02); current eczema (OR 6.13; 95% CI 2.82-13.33); and active smoking (OR 4.62; 95% CI 2.43-8.76). Age, parental education and passive smoking were not important factors. When compared to previous epidemiological data obtained in 1992, the prevalence rates for asthma ever and wheeze ever had increased by 71 and 255%, respectively, in Hong Kong schoolchildren. The severity of asthma and respiratory symptoms showed a similar increasing trend. Further studies should aim to identify the role of the environment in the pathogenesis of asthma.
Cardiomyopathy in a murine model of AIDS: evidence of reactive nitrogen species and corroboration in human HIV/AIDS cardiac tissues
Authors: A Chaves
Journal: Cardiovascular Research (2003)

Cardiomyopathy and other vascular complications are now recognized as significant components of HIV/AIDS pathogenesis. Although the mechanisms involved in cardiomyopathy are poorly defined, a role for direct retroviral action and/or focal infiltration of activated immune cells have been postulated. Here we investigated mechanisms in retrovirus associated cardiomyopathy using a well-defined mouse model of acquired immunodeficiency.Mice were dosed with LPBM5 retrovirus; cardiac performance was assessed by echocardiography followed by tissue collection at 5 and 10 weeks post-infection.Contractile deficits were observed at 5 and 10 weeks post-retrovirus infection and preceded the development of overt immunodeficiency. Selective and widespread cardiac infiltration of CD68+ cells, but not neutrophils, mast cells, or eosinophils was also observed at both 5 and 10 weeks. LPBM5 retrovirus was readily detectable in cardiac samples by RT-PCR. Time dependent increases in cardiac protein nitration (biomarker of reactive nitrogen species) were observed and were correlated to the extent of cardiac dysfunction whereas no changes in NOSII occurred at 5 and 10 weeks. We corroborated the mouse findings using cardiac tissues and clinical findings from human HIV/AIDS autopsies.These studies demonstrated that cardiac myocyte protein nitration in AIDS related cardiomyopathies, rather than focal immune cell lesions characterize retrovirus associated cardiomyopathies and differentiate them from non-retroviral cardiomyopathies.
A randomized study to evaluate the efficacy and safety of adding topical therapy to etanercept in patients with moderate to severe plaque psoriasis
Authors: Mark G. Lebwohl, Leon Kircik, Kristina Callis Duffin, David Pariser, Michele Hooper, Deborah Wenkert, Elizabeth H.Z. Thompson, Jun Yang, Greg Kricorian, John Koo
Journal: Journal of the American Academy of Dermatology (2013)
Biomonitoring of chemical exposure among New York City firefighters responding to the World Trade Center fire and collapse.
Authors: Philip Edelman, John Osterloh, James Pirkle, Sam P Caudill, James Grainger, Robert Jones, Ben Blount, Antonia Calafat, Wayman Turner, Debra Feldman, Sherry Baron, Bruce Bernard, Boris D Lushniak, Kerry Kelly, David Prezant
Journal: Environmental Health Perspectives (2003)

The collapse of the World Trade Center (WTC) on 11 September 2001 exposed New York City firefighters to smoke and dust of unprecedented magnitude and duration. The chemicals and the concentrations produced from any fire are difficult to predict, but estimates of internal dose exposures can be assessed by the biological monitoring of blood and urine. We analyzed blood and urine specimens obtained from 321 firefighters responding to the WTC fires and collapse for 110 potentially fire-related chemicals. Controls consisted of 47 firefighters not present at the WTC. Sampling occurred 3 weeks after 11 September, while fires were still burning. When reference or background ranges were available, most chemical concentrations were found to be generally low and not outside these ranges. Compared with controls, the exposed firefighters showed significant differences in adjusted geometric means for six of the chemicals and significantly greater detection rates for an additional three. Arrival time was a significant predictor variable for four chemicals. Special Operations Command firefighters (n = 95), compared with other responding WTC firefighters (n = 226), had differences in concentrations or detection rate for 14 of the chemicals. Values for the Special Operations Command firefighters were also significantly different from the control group values for these same chemicals and for two additional chemicals. Generally, the chemical concentrations in the other firefighter group were not different from those of controls. Biomonitoring was used to characterize firefighter exposure at the WTC disaster. Although some of the chemicals analyzed showed statistically significant differences, these differences were generally small.
IV. General Data and Summary
Authors: EARL D. BOND
Journal: American Journal of Psychiatry (1954)

There has been built up a library of large cards giving much information about all patients admitted in 10 years before the advent of shock therapies, sulpha drugs, and antibiotics. A similar set of cards covers all patients admitted for 7 years after the new therapies were in operation. (It is planned later to study 3 more years.) Information includes follow-up for 5 years or more after admission. This is fairly satisfactory for the early cases—half satisfactory for the later ones. All in all, when shock methods are used in the great groups of patients who show no symptoms of acute or chronic brain disease there is an encouraging increase in recoveries. In psychoses due to infection (including syphilis) there is a lessening of the number brought to a psychiatric hospital. There is a surprising amount of relief given to patients with psychoneuroses who enter a private mental hospital organized for psychotic patients. With many exceptions, recoveries in the control group seem more stable than those in the shock-treated series.
Functions and Dysfunctions of Adult Hippocampal Neurogenesis
Authors: Kimberly M. Christian, Hongjun Song, Guo-li Ming
Journal: Annual Review of Neuroscience (2014)

Adult neurogenesis, a developmental process of generating functionally integrated neurons, occurs throughout life in the hippocampus of the mammalian brain and showcases the highly plastic nature of the mature central nervous system. Significant progress has been made in recent years to decipher how adult neurogenesis contributes to brain functions. Here we review recent findings that inform our understanding of adult hippocampal neurogenesis processes and special properties of adult-born neurons. We further discuss potential roles of adult-born neurons at the circuitry and behavioral levels in cognitive and affective functions and how their dysfunction may contribute to various brain disorders. We end by considering a general model proposing that adult neurogenesis is not a cell-replacement mechanism, but instead maintains a plastic hippocampal neuronal circuit via the continuous addition of immature, new neurons with unique properties and structural plasticity of mature neurons induced by new-neuron integration.
Impact of a Mixed Strength and Endurance Exercise Intervention on Insulin Levels in Breast Cancer Survivors
Authors: Jennifer A. Ligibel, Nancy Campbell, Ann Partridge, Wendy Y. Chen, Taylor Salinardi, Haiyan Chen, Kristie Adloff, Aparna Keshaviah, Eric P. Winer
Journal: Journal of Clinical Oncology (2008)

Accumulating data suggest that exercise may affect breast cancer risk and outcomes. Studies have demonstrated that high levels of insulin, often seen in sedentary individuals, are associated with increased risk of breast cancer recurrence and death. We sought to analyze whether exercise lowered insulin concentrations in breast cancer survivors.One hundred one sedentary, overweight breast cancer survivors were randomly assigned either to a 16-week cardiovascular and strength training exercise intervention or to a usual care control group. Fasting insulin and glucose levels, weight, body composition, and circumference at the waist and hip were collected at baseline and 16 weeks.Baseline and 16-week measurements were available for 82 patients. Fasting insulin concentrations decreased by an average of 2.86 microU/mL in the exercise group (P = .03), with no significant change in the control group (decrease of 0.27 microU/mL, P = .65). The change in insulin levels in the exercise group seemed greater than the change in controls, but the comparison did not reach statistical significance (P = .07). There was a trend toward improvement in insulin resistance in the exercise group (P = .09) but no change in fasting glucose levels. The exercise group also experienced a significant decrease in hip measurements, with no change in weight or body composition.Participation in an exercise intervention was associated with a significant decrease in insulin levels and hip circumference in breast cancer survivors. The relationship between physical activity and breast cancer prognosis may be mediated, in part, through changes in insulin levels and/or changes in body fat or fat deposition.
Investigation of type 1 diabetes and coeliac disease susceptibility loci for association with juvenile idiopathic arthritis
Authors: Anne Hinks, Paul Martin, Edward Flynn, Steve Eyre, Jon Packham, Anne Barton, Jane Worthington, Wendy Thomson
Journal: Annals of the Rheumatic Diseases (2010)

Background There is strong evidence suggesting that juvenile idiopathic arthritis (JIA) shares many susceptibility loci with other autoimmune diseases. Objective To investigate variants robustly associated with type 1 diabetes (T1D) or coeliac disease (CD) for association with JIA. Methods Sixteen single-nucleotide polymorphisms (SNPs) already identified as susceptibility loci for T1D/CD were selected for genotyping in patients with JIA (n=1054) and healthy controls (n=3129). Genotype and allele frequencies were compared using the Cochrane–Armitage trend test implemented in PLINK. Results One SNP in the LPP gene, rs1464510, showed significant association with JIA (p trend =0.002, OR=1.18, 95% CI 1.06 to 1.30). A second SNP, rs653178 in ATXN2 , also showed nominal evidence for association with JIA (p trend =0.02, OR=1.13, 95% CI 1.02 to 1.25). The SNP, rs17810546, in IL12A showed subtype-specific association with enthesitis-related arthritis (ERA) subtype (p trend =0.005, OR=1.88, 95% CI 1.2 to 2.94). Conclusions Evidence for a novel JIA susceptibility locus, LPP , is presented. Association at the SH2B3/ATXN2 locus, previously reported to be associated with JIA in a US series, also supports this region as contributing to JIA susceptibility. In addition, a subtype-specific association of IL12A with ERA is identified. All findings will require validation in independent JIA cohorts.
Incidence of Venous Thromboembolism and the Impact on Survival in Breast Cancer Patients
Authors: Helen K. Chew, Theodore Wun, Danielle J. Harvey, Hong Zhou, Richard H. White
Journal: Journal of Clinical Oncology (2006)

The incidence of venous thromboembolism (VTE) and the risk factors associated with development of VTE have not been reported in a large population-based study of breast cancer patients.The California Cancer Registry was merged with the Patient Discharge Data Set, and the number of VTE events determined among patients diagnosed between 1993 and 1999.Among 108,255 patients with breast cancer, the 2-year cumulative VTE incidence was 1.2%, with a rate of 1.2 and 0.6 events/100 patient-years during the first and second half-year, respectively. The 1-year incidence of VTE was significantly increased compared with the general population (standardized incidence ratio of VTE, 4.2; 95% CI, 3.9 to 4.4). In a multivariate model, significant predictors of developing VTE within 2 years were: age (hazard ratio [HR], 2.0 if > 75 years v < 45; 95% CI, 1.6 to 2.6), the number of chronic medical comorbidities (HR, 2.9 if 3 v 0; 95% CI, 2.4 to 3.5), and advancing cancer stage (HR, 6.3; 95% CI, 5.3 to 7.5 for metastatic v local disease). In multivariate models, VTE was a significant predictor of decreased 2-year survival (HR, 2.3; 95% CI, 2.1 to 2.6) and when stratified by initial cancer stage, the effect was highest in patients with localized (HR, 5.1; 95% CI, 3.6 to 7.1) or regional stage (HR, 3.5; 95% CI, 2.5 to 4.8) cancer compared with patients with metastatic disease (HR, 1.9; 95% CI, 1.5 to 2.4).Approximately 1% of breast cancer patients developed VTE within 2 years, with the highest incidence in the first 6 months after diagnosis. Metastatic disease and comorbidities were the strongest predictors. The diagnosis of VTE was associated with a higher risk of death within 2 years.
Lipid Raft Microdomains
Authors: Sina Bavari, Catharine M. Bosio, Elizabeth Wiegand, Gordon Ruthel, Amy B. Will, Thomas W. Geisbert, Michael Hevey, Connie Schmaljohn, Alan Schmaljohn, M. Javad Aman
Journal: The Journal of Experimental Medicine (2002)

Spatiotemporal aspects of filovirus entry and release are poorly understood. Lipid rafts act as functional platforms for multiple cellular signaling and trafficking processes. Here, we report the compartmentalization of Ebola and Marburg viral proteins within lipid rafts during viral assembly and budding. Filoviruses released from infected cells incorporated raft-associated molecules, suggesting that viral exit occurs at the rafts. Ectopic expression of Ebola matrix protein and glycoprotein supported raft-dependent release of filamentous, virus-like particles (VLPs), strikingly similar to live virus as revealed by electron microscopy. Our findings also revealed that the entry of filoviruses requires functional rafts, identifying rafts as the site of virus attack. The identification of rafts as the gateway for the entry and exit of filoviruses and raft-dependent generation of VLPs have important implications for development of therapeutics and vaccination strategies against infections with Ebola and Marburg viruses.
Urocortin-induced relaxation in the human internal mammary artery
Authors: Z CHEN, Y HUANG, Q YANG, X LI, W WEI, G HE
Journal: Cardiovascular Research (2004)

Urocortin, a potent vasodilator, plays physiological or pathophysiological roles in the cardiovascular system. However, little is known about its action in human vascular tissues. The present study was designed to investigate the vascular effect of urocortin on human internal mammary artery (IMA) in vitro and the possible underlying mechanisms.Human IMA was obtained from patients undergoing coronary artery bypass grafting. The isolated IMA rings were mounted in organ baths and changes in isometric tension were measured by using Grass force-displacement transducer. Corticortropin-releasing factor-receptors (CRF-R) were also analyzed in the IMA by using RT-PCR analysis.In 9,11-dideoxy-11alpha,9alpha-epoxy-methanoprostaglandin F(2alpha) (U46619)-precontracted endothelium-intact rings, urocortin induced concentration-dependent relaxations with pD(2) of 8.69+/-0.11 and this effect was markedly reduced in endothelium-denuded rings. Relaxations to urocortin in endothelium-intact rings were attenuated to the same extent after treatment with N(G)-nitro-l-arginine (l-NNA) and 1H-[1,2,4]oxadizolo[4,3-a]quinoxalin-1-one (ODQ). Urocortin-induced relaxations were also inhibited by treatment with putative K(+) channel blockers, such as tetraethylammonium (TEA(+)), charybdotoxin (CTX), and iberiotoxin (IBX). In endothelium-denuded rings, treatment with TEA(+), CTX, or IBX attenuated relaxation to urocortin as well as sodium nitroprusside (SNP). The bands for CRF-R1, CRF-R2alpha, and CRF-R2beta mRNAs were observed in both endothelium-intact and endothelium-denuded human IMA.Urocortin produced both endothelium-dependent and -independent relaxation in human IMA rings. The endothelium-dependent component primarily involves the release of endothelial nitric oxide (NO) that in turn stimulates Ca(2+)-activated K(+) channels in vascular smooth muscle via cyclic GMP-dependent mechanisms. CRF-R1, CRF-R2alpha, and CRF-R2beta mRNAs are present in the human IMA.