tbuckley/cabot-search huggingface dataset:
Association of γ-Glutamyltransferase and Risk of Cancer Incidence in Men: A Prospective Study
Authors: Alexander M. Strasak, Kilian Rapp, Larry J. Brant, Wolfgang Hilbe, Martin Gregory, Willi Oberaigner, Elfriede Ruttmann, Hans Concin, Günter Diem, Karl P. Pfeiffer, Hanno Ulmer
Journal: Cancer Research (2008)

Abstract Although several epidemiologic studies have shown that γ-glutamyltransferase (GGT) is independently associated with cardiovascular disease and all-cause mortality, its relationship with cancer incidence remains widely unexplored. In several experimental models, the ability of cellular GGT to modulate crucial redox-sensitive functions has been established, and it thus may play a role in tumor progression, as has been repeatedly suggested. We prospectively investigated the association between GGT and risk of overall and site-specific cancer incidence in a large population-based cohort of 79,279 healthy Austrian men with serial GGT measurements. Median follow-up was 12.5 years. Adjusted Cox proportional hazards models were calculated to evaluate GGT as an independent predictor for cancer incidence, and nonparametric regression splines were fitted to flexibly capture the dose-response relationship. Elevated GGT significantly increased overall cancer risk, showing a clear dose-response relationship (P for GGT log-unit increase &amp;lt; 0.0001; P for trend &amp;lt; 0.0001). In comparison with the reference GGT concentration (25 units/L), we found adjusted relative risks (95% confidence intervals) equalling 1.19 (1.15-1.22) for GGT concentrations of 60 units/L, 1.32 (1.28-1.36) for 100 units/L, 1.67 (1.60-1.75) for 200 units/L, and 2.30 (2.14-2.47) for 400 units/L. In cancer site-specific models, GGT was significantly associated with malignant neoplasms of digestive organs, the respiratory system/intrathoracic organs, and urinary organs (all P &amp;lt; 0.0001). Age of participants significantly modified the association of GGT and cancer risk (P &amp;lt; 0.001), revealing markedly stronger associations in participants ages ≤65 years. Our findings, for the first time, show that elevated GGT is significantly associated with increased cancer risk in men. [Cancer Res 2008;68(10):3970–7]
Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor α inhibitors (GO-AFTER study): a multicentre, randomised, double-blind, placebo-controlled, phase III trial
Authors: Josef S Smolen, Jonathan Kay, Mittie K Doyle, Robert Landewé, Eric L Matteson, Jürgen Wollenhaupt, Norman Gaylis, Frederick T Murphy, Jeffrey S Neal, Yiying Zhou, Sudha Visvanathan, Elizabeth C Hsia, Mahboob U Rahman
Journal: The Lancet (2009)
Increased Atherosclerosis in Mice Lacking Apolipoprotein A-I Attributable to Both Impaired Reverse Cholesterol Transport and Increased Inflammation
Authors: Ryan E. Moore, Mohamad Navab, John S. Millar, Francesca Zimetti, Susan Hama, George H. Rothblat, Daniel J. Rader
Journal: Circulation Research (2005)

To test the hypothesis that apolipoprotein A-I (apoA-I) functions specifically to inhibit atherosclerosis independent of the level of high-density lipoprotein cholesterol (HDL-C) by promoting both reverse cholesterol transport and HDL antiinflammatory function in vivo, we established a murine atherosclerosis model of apoA-I deficiency in which the level of HDL-C is well maintained. ApoA-I −/− mice were crossed with atherosclerosis susceptible low-density lipoprotein receptor −/− /apobec −/− (LA) mice to generate LA mice with apoA-I +/+ , apoA-I +/− , and apoA-I −/− genotypes. There were no major differences in the amounts of non–HDL-C and HDL-C in the plasma between different apoA-I genotypes. A significant inverse relationship was observed, however, between apoA-I gene dose and atherosclerosis in both female and male mice. Compared with LA-apoA-I +/+ mice, serum from LA-apoA-I −/− mice had a significantly reduced capacity to function as an acceptor of ABCA1- and SR-BI-mediated cellular cholesterol efflux, and also had markedly reduced lecithin cholesterol acyltransferase activity. In addition, LA-apoA-I −/− mice had significantly reduced macrophage-derived cholesterol esterification and reverse cholesterol transport in vivo. There was significantly reduced plasma paraoxonase (PON-1) activity, impaired HDL vascular antiinflammatory function, and increased basal levels of monocyte chemotactic protein-1 in the plasma of LA-apoA-I −/− mice compared with LA-apoA-I +/+ mice. In LA-apoA-I −/− mice, there was also greater induction of some, but not all, inflammatory cytokines and chemokines in response to intraperitoneal injection of lipopolysaccharide than in LA-apoA-I +/+ mice. We conclude that apoA-I inhibits atherosclerosis by promoting both macrophage reverse cholesterol transport and HDL antiinflammatory function, and that these anti-atherogenic functions of apoA-I are largely independent of the plasma level of HDL-C in this mouse model.
Vav3-Rac1 Signaling Regulates Prostate Cancer Metastasis with Elevated Vav3 Expression Correlating with Prostate Cancer Progression and Posttreatment Recurrence
Authors: Kai-Ti Lin, Jianli Gong, Chien-Feng Li, Te-Hsuan Jang, Wen-Ling Chen, Huei-Jane Chen, Lu-Hai Wang
Journal: Cancer Research (2012)

Prostate cancer remains the second leading cause of cancer death in men in the Western world. Yet current therapies do not significantly improve the long-term survival of patients with distant metastasis. In this study, we investigated the role of the guanine nucleotide exchange factor Vav3 in prostate cancer progression and metastasis and found that Vav3 expression correlated positively with prostate cancer cell migration and invasion. Stimulation of the receptor tyrosine kinase EphA2 by ephrinA1 resulted in recruitment and tyrosine phosphorylation of Vav3, leading to Rac1 activation as well as increased migration and invasion in vitro. Reduction of Vav3 resulted in fewer para-aortic lymph nodes and bone metastasis in vivo. Clinically, expression of Vav3 and EphA2 was elevated in late-stage and metastatic prostate cancers. Among patients with stage IIB or earlier prostate cancer, higher Vav3 expression correlated with lower cumulative biochemical failure-free survival, suggesting that Vav3 may represent a prognostic marker for posttreatment recurrence of prostate cancer. Together, our findings provide evidence that the Vav3-mediated signaling pathway may serve as a therapeutic target for prostate cancer metastasis.
Tension pneumothorax complicating autologous "blood patch" pleurodesis
Authors: P Williams
Journal: Thorax (2005)

Autologous "blood patching" has been used successfully for the treatment of persistent air leak in patients with spontaneous secondary pneumothorax. The case history is presented of a 19 year old woman with cystic fibrosis who developed tension pneumothorax following this procedure, with rapid clinical deterioration until the obstruction was cleared. To avoid this potentially fatal complication we recommend that "blood patch" pleurodesis be performed only through large bore intercostal catheters, that blood is rapidly transferred into the catheter tubing, a sterile saline flush and full resuscitation equipment is available, and the operator is skilled in the management of tension pneumothorax.
Reversal of interstitial fibroblast hyperplasia via apoptosis in hypertensive rat heart with valsartan or enalapril
Authors: S Der Sarkissian
Journal: Cardiovascular Research (2003)

Renin-angiotensin system inhibitors transiently induce apoptosis at the onset of cardiac hypertrophy regression in spontaneously hypertensive rats (SHRs). The focus of this study is to evaluate the cell selectivity of this response.SHRs were treated with valsartan or enalapril (30 mg kg(-1) day(-1)) or placebo for 1 to 4 weeks. Stereological and morphological data were obtained from immunohistological analyses. Apoptosis was quantified by DEVDase (caspase-3-like) activity assay and immunoblot analysis of apoptosis-regulatory proteins (Bax and Bcl-2). Identification of the apoptotic cell type was conducted using in situ TUNEL labeling, in conjunction with alpha-sarcomeric actin or lectin immunoreactivity as markers for cardiomyocytes and endothelial cells, respectively.Stereological analysis of the left ventricle revealed significant non-cardiomyocyte hyperplasia in placebo-treated SHRs (239+/-29x10(6) nuclei) as compared to untreated age-matched normotensive Wistar-Kyoto (WKY) rats (107+/-12x10(6)). In contrast, the number of cardiomyocyte nuclei was comparable between untreated SHRs (48+/-4x10(6)) and WKY rats. After 4 weeks of valsartan or enalapril treatment, SHRs showed significant reductions in systolic blood pressure (>28%), left ventricular hypertrophy (>9%) and cardiomyocyte cross-sectional area (>17%). Moreover, these treatments abolished non-cardiomyocyte hyperplasia in SHR left ventricle without affecting cardiomyocyte number, capillary density or number of capillary per cardiomyocyte nucleus. As a mechanism of cell deletion consistent with apoptosis induction, ventricles showed increased caspase-3 activation (>4.5-fold) as well as Bax to Bcl-2 protein ratio (>3.2-fold) within 2 weeks of valsartan or enalapril treatment. Immunohistological analysis revealed a significant increase in TUNEL-positive, lectin-negative non-cardiomyocytes, suggesting a rise in apoptotic interstitial fibroblasts in the left ventricle within 2 weeks of treatment with valsartan or enalapril (>63%), with a return to baseline (0.033+/-0.003%) at 4 weeks. Treatments did not affect right ventricular mass, apoptosis or cellularity.Cardiac apoptosis induction during regression of left ventricular hypertrophy reverses interstitial fibroblast hyperplasia in SHRs treated with inhibitors of the renin-angiotensin system.
On the Administration of the Laws for the Prevention of Epidemic Small-Pox
Authors: G. Anderson
Journal: BMJ (1902)

SMALL-POX.LJVLY 5, I902, tion.iIn 1872 a law was passed in, the Netherlands making admission to a school dependent on a vaccination certificate, but this.does not affect the above comparison, because the chief force of the epidemic expended itself there in I87I and 1872 (rates 4,355 and 1,02I).The rate for Belgium in I871 was over 4,000.2. When we. examine the age classes of those who died, as far as they are available, we find, as we might expect, that where compulsory vaccination existed, the chief mortality was borne by the age class " above 20 years," but where there was no compulsory vaccination the chief mortality was amongkst children.3. One section of the various populations of Germany was only very slightly affected.That section was the German field army, numbering over a million men, though more exposed to the contagion than any other part of the population, for the epidemic raged with the greatest virulence in France.The total small-pox loss of the German field army was only 297.On the other hand, one small garrison town in France lost more than this, namely, 334.Now we know that the German field army was well vaccinated except as to some levies hastily raised, while it has been proved that the French army was very deficiently vaccinated.4. But perhaps Bavaria, a well-vaccinated country ever since I807, as far as regards vaccination in infancy, affords us the most valuable lesson of the epidemic, for England is now where Bavaria then was as regards vaccination.Thus the whole population of Bavaria had for the most part been vaccinated in infancy, and some had been revaccinated.Therefore nearly all the small-pox attacks occurred in the vaccinated.In Bavaria: 30,742 were attacked, of whom 29,429 were vaccinated persons.
Integrated genotype calling and association analysis of SNPs, common copy number polymorphisms and rare CNVs
Authors: Joshua M Korn, Finny G Kuruvilla, Steven A McCarroll, Alec Wysoker, James Nemesh, Simon Cawley, Earl Hubbell, Jim Veitch, Patrick J Collins, Katayoon Darvishi, Charles Lee, Marcia M Nizzari, Stacey B Gabriel, Shaun Purcell, Mark J Daly, David Altshuler
Journal: Nature Genetics (2008)
Chromosomal Breakpoints in Primary Colon Cancer Cluster at Sites of Structural Variants in the Genome
Authors: Jordi Camps, Marian Grade, Quang Tri Nguyen, Patrick Hörmann, Sandra Becker, Amanda B. Hummon, Virginia Rodriguez, Settara Chandrasekharappa, Yidong Chen, Michael J. Difilippantonio, Heinz Becker, B. Michael Ghadimi, Thomas Ried
Journal: Cancer Research (2008)

Abstract Genomic aberrations on chromosome 8 are common in colon cancer, and are associated with lymph node and distant metastases as well as with disease susceptibility. This prompted us to generate a high-resolution map of genomic imbalances of chromosome 8 in 51 primary colon carcinomas using a custom-designed genomic array consisting of a tiling path of BAC clones. This analysis confirmed the dominant role of this chromosome. Unexpectedly, the position of the breakpoints suggested colocalization with structural variants in the human genome. In order to map these sites with increased resolution and to extend the analysis to the entire genome, we analyzed a subset of these tumors (n = 32) by comparative genomic hybridization on a 185K oligonucleotide array platform. Our comprehensive map of the colon cancer genome confirmed recurrent and specific low-level copy number changes of chromosomes 7, 8, 13, 18, and 20, and unveiled additional, novel sites of genomic imbalances including amplification of a histone gene cluster on chromosome 6p21.1-21.33 and deletions on chromosome 4q34-35. The systematic comparison of segments of copy number change with gene expression profiles showed that genomic imbalances directly affect average expression levels. Strikingly, we observed a significant association of chromosomal breakpoints with structural variants in the human genome: 41% of all copy number changes occurred at sites of such copy number variants (P &amp;lt; 2.2e−16). Such an association has not been previously described and reveals a yet underappreciated plasticity of the colon cancer genome; it also points to potential mechanisms for the induction of chromosomal breakage in cancer cells. [Cancer Res 2008;68(5):1284–95]
Timely and spatially regulated maturation of B and T cell repertoire during human fetal development
Authors: Erez Rechavi, Atar Lev, Yu Nee Lee, Amos J. Simon, Yoav Yinon, Schlomo Lipitz, Ninette Amariglio, Boaz Weisz, Luigi D. Notarangelo, Raz Somech
Journal: Science Translational Medicine (2015)

Insights into the ontogeny of the human fetal adaptive immune system are of great value for understanding immunocompetence of the developing fetus. However, to date, this has remained largely uncharted territory, in large part because blood samples from healthy, early gestation fetuses have been hard to come by. In a comprehensive study, we analyzed levels of T cell receptor excision circles (TRECs), signal-joint κ receptor excision circles (sjKRECs), and intron recombination signal sequence-K-deleting element (iRSS-Kde) rearrangement, and T and B lymphocyte repertoire clonality in human fetuses from 12 to 26 weeks of gestational age. Using next-generation sequencing, we analyzed the diversity and complexity of T cell receptor β (TRB) and immunoglobulin heavy chain (IGH) repertoires in four fetuses at 12, 13, 22, and 26 weeks of gestation and in healthy full-term infants. We report the progressive increase of TREC, sjKREC, and iRSS-Kde levels over time and confirm that B cell development precedes T cell development in the human fetus. Temporally and spatially regulated maturation of B and T cell repertoire diversity and complexity during human fetal development was observed, including evidence that immunoglobulin somatic hypermutation and class switch recombination occur already during intrauterine life. Our results help define physiological levels of immunodeficiency in premature infants and may serve as a reference for future studies aimed at investigating the impact of intrauterine pathologies on fetal immune development and function.
Prevalence of active convulsive epilepsy in sub-Saharan Africa and associated risk factors: cross-sectional and case-control studies
Authors: Anthony K Ngugi, Christian Bottomley, Immo Kleinschmidt, Ryan G Wagner, Angelina Kakooza-Mwesige, Kenneth Ae-Ngibise, Seth Owusu-Agyei, Honorati Masanja, Gathoni Kamuyu, Rachael Odhiambo, Eddie Chengo, Josemir W Sander, Charles R Newton
Journal: The Lancet Neurology (2013)
Purification and characterization of a membrane protein (gp45-70) that is a cofactor for cleavage of C3b and C4b.
Authors: T Seya, J R Turner, J P Atkinson
Journal: The Journal of Experimental Medicine (1986)

Based on preliminary evidence indicating that a cell-associated protein of U937 (a human monocyte-like cell line) possessed cofactor activity and was not the C3b/C4b receptor, we sought to further characterize this protein. A sequential four-column purification procedure was devised that includes C3(H2O) affinity chromatography to isolate in reasonable yields and purity a cell-associated protein of U937 and several other human cell lines. Based on its pattern and Mr on SDS-PAGE, acidic pI, and ligand specificity, it is identical to a recently described C3(H2O) or C3b-binding membrane glycoprotein of human PBL and cell lines; having no presently identified function, it was termed gp45-70. After purifying this protein, we determined its functional capabilities and compared them to those of the other complement proteins with regulatory activity directed at components comprising the C3 convertases. This protein was the most efficient (50 times that of H) yet-described cofactor for the I-mediated first cleavage of C3b. It also was a cofactor for the first cleavage of C4b, but was not as efficient as C4bp. The second cleavage of C3b and C4b was not efficiently mediated. It had no ability to accelerate decay in the classical or alternative pathway C3 convertases. Based on this unique activity profile and ability to be surface labeled, we have renamed this molecule membrane cofactor protein (MCP). We suggest that this protein plays a major role in preventing autologous complement activation.
The Political Polarization of Physicians in the United States
Authors: Adam Bonica, Howard Rosenthal, David J. Rothman
Journal: JAMA Internal Medicine (2014)

<h3>Importance</h3> Few current data are available regarding the political behavior of American physicians as the number of female physicians has increased and the number of solo practitioners has decreased. <h3>Objective</h3> To analyze campaign contributions that physicians made from the 1991 to 1992 through the 2011 to 2012 election cycles to Republican and Democratic candidates in presidential and congressional races and to partisan organizations, including party committees and super political action committees (Super PACs). <h3>Design, Setting, and Participants</h3> We explored partisan differences in physician contributions by sex, for-profit vs nonprofit practice setting, and specialty using multiple regression analysis. We studied the relation between the variation in the mean annual income across specialties and the mean percentage of physicians within each specialty contributing to Republicans. <h3>Main Outcomes and Measures</h3> Differences in contributions to Republicans and Democrats, for all physicians and for subgroups. <h3>Results</h3> Between the 1991 to 1992 and the 2011 to 2012 election cycles, physician campaign contributions increased from $20 million to $189 million, and the percentage of active physicians contributing increased from 2.6% to 9.4%. Of physicians who contributed during the study period, the mean percentage contributing to Republicans was 57% for men and 31% for women. Since 1996, the percentage of physicians contributing to Republicans has decreased, to less than 50% in the 2007 to 2008 election cycle and again in the 2011 to 2012 election cycle. Contributions to Republicans in 2011 to 2012 were more prevalent among men vs women (52.3% vs 23.6%), physicians practicing in for-profit vs nonprofit organizations (53.2% vs 25.6%), and surgeons vs pediatricians (70.2% vs 22.1%). In 1991 to 1992, these contribution gaps were smaller: for sex, 54.5% vs 30.9%; for organizations, 54.2% vs 40.0%; and for specialty, 65.5% vs 32.7%. The percentage of physicians contributing to Republicans across specialties correlated 0.84 with the mean log earnings of each specialty; specialties with higher mean earnings had higher percentages of physicians contributing to Republicans. <h3>Conclusions and Relevance</h3> Between 1991 and 2012, the political alignment of US physicians shifted from predominantly Republican toward the Democrats. The variables driving this change, including the increasing percentage of female physicians and the decreasing percentage of physicians in solo and small practices, are likely to drive further changes.
Renal localization of the membrane attack complex in systemic lupus erythematosus nephritis.
Authors: G Biesecker, S Katz, D Koffler
Journal: The Journal of Experimental Medicine (1981)

The membrane attack complex (MAC) of the complement system was localized in both glomeruli and peritubular regions of 22 kidneys manifesting systemic lupus erythematosus (SLE) nephritis. A similar distribution was observed for immune complex markers (IgG, Clq, and C3) and MAC in glomeruli, although the deposits of MAC were more discrete and showed lesser immunofluorescence staining intensity compared with immunoglobulins and complement components. In contrast, peritubular immune complexes were present in only 7 out of 22 kidneys, involved comparatively small clusters of tubules, exhibited weaker immunofluorescence staining than MAC, and failed to correlate with interstitial foci of inflammation. Granular or irregular, linear aggregates of the MAC were observed at the periphery of larger groups of tubules contiguous to areas of interstitial inflammation. Comparable amounts of IgG, Clq, C3, and MAC were present in blood vessel walls in areas of fibrinoid necrosis. These data suggest that the MAC is a direct mediator of tissue injury occurring in renal glomeruli, tubules, and blood vessels. The discordance between immune complexes and MAC localized in the peritubular region, but not in glomeruli or blood vessels, raises the possibility that both immune complexes and nonimmune agents, such as bacterial antigens, may activate the classical or alternative complement pathways and thereby play a role in the pathogenesis of tubulointerstitial lesions of SLE nephritis.
Antibody-resistant mutants of Borrelia burgdorferi: in vitro selection and characterization.
Authors: A Sădziene, P A Rosa, P A Thompson, D M Hogan, A G Barbour
Journal: The Journal of Experimental Medicine (1992)

We used polyclonal antisera and monoclonal antibodies (mAbs) to inhibit the growth of clonal populations of two strains of Borrelia burgdorferi, the Lyme disease agent, and thereby select for antibody-resistant mutants. mAbs were directed at the outer membrane proteins, OspA or OspB. Mutants resistant to the growth-inhibiting properties of the antibodies were present in the populations at frequencies ranging from 10(-5) to 10(-2). The several escape variants that were examined were of four classes. Class I mutants were resistant to all mAbs; they lacked OspA and OspB and the linear plasmid that encodes them. Two other proteins were expressed in larger amounts in class I mutants; mAbs to these proteins inhibited the mutant but not the wild-type cells. Class II mutants were resistant to some but not all mAbs; they had truncated OspA and/or OspB proteins. Class III mutants were resistant only to the selecting mAb; they had full-length Osp proteins that were not bound by the selecting antibody in Western blots. In two class III mutants resistant to different anti-OspA mAbs, missense mutations were demonstrated in the ospA genes. Class IV mutants were likewise resistant only to selecting antibody, but in this case the selecting antibody still bound in Western blots.