tbuckley/cabot-search huggingface dataset:
Sexual transmission of HCV among monogamous heterosexual couples: Be careful with reassuring counseling messages
Authors: Philippe Halfon
Journal: Hepatology (2013)

To the Editor: We read with interest the article by Terrault et al.1 in HEPATOLOGY entitled “Sexual Transmission of HCV Among Monogamous Heterosexual Couples: The HCV Partners Study.” The authors conducted a cross-sectional study of hepatitis C virus (HCV)-positive persons and their partners to estimate the risk for HCV infection among monogamous heterosexual couples. Their findings based on 8,377 person-years of follow-up demonstrated that the maximum incidence rate of HCV transmission by sex was 0.07% per year (95% confidence interval [CI]: 0.01, 0.13) or ∼1 per 190,000 sexual contacts and that no specific sexual practices were related to HCV-positivity among couples. Large longitudinal studies of HCV-serodiscordant heterosexual couples have not yielded significant evidence of sexual transmission, so condom use for the prevention of HCV transmission has not been recommended for vaginal intercourse between monogamous HCV-serodiscordant sexual partners.2, 3 We agree with part of their conclusions on counseling messages. Indeed, the estimated risk for HCV infection in sexual partners is extremely low. However, we and others demonstrated that anal sexual practice significantly increases the risk of HCV transmission.4 Relative to vaginal intercourse, anal intercourse is a major cause of abrasions of mucosa, leading to the possibility of anal transmission. The high incidence of acute HCV infection among men who have sex with men (MSM) with human immunodeficiency virus (HIV) infection is mainly due to unprotected anal intercourse and the transmission depends on disruption of a barrier and exposure to infected fluids, usually blood. Also, certain sexual practices involving trauma of the rectal mucosa have been discussed as relevant risk factors among MSM.6, 7 Coinfections with bacterial sexually transmitted infections (STIs), especially ulcerative STIs such as syphilis or lymphogranuloma venereum, have also been proposed as risk factors for HCV transmission among HIV-positive MSM. Fisting was highly correlated with use of sex toys, group sex, and bleeding in a cross-sectional study from Urbanus et al.8 Terrault et al. found no association with specific sexual practices. They reported that vaginal intercourse during menses and anal intercourse (≥1 occasion) were reported by 65.2% and 30.4% of couples, respectively. Condom use during vaginal intercourse was reported by 29.9% of couples and condom use decreased over time for vaginal and anal intercourse. However, the results on sexual practices were declarative and may have some bias. In conclusion, although HCV transmission by sexual activity remains low in long-term monogamous HCV heterosexual couples, strict recommendations should be made regarding sexual practices, that is, protected anal intercourse and protected vaginal intercourse during menstruations. PHILIPPE HALFON, PHARM, M.D., PH.D. Hôpital Ambroise Paré, Laboratoire Alphabio, Marseille, France
Acyl-coenzyme A: Cholesterol acyltransferase inhibitor, avasimibe, stimulates bile acid synthesis and cholesterol 7?-hydroxylase in cultured rat hepatocytes andin vivo in the rat
Authors: Sabine M. Post, Paul J. Zoeteweij, Mettine H. Bos, Elly C. de Wit, Rick Havinga, Folkert Kuipers, Hans M. G. Princen
Journal: Hepatology (1999)

Acyl-coenzyme A:cholesterol acyltransferase (ACAT) inhibitors are currently in clinical development as potential lipid-lowering and antiatherosclerotic agents. We investigated the effect of avasimibe (Cl- 1011), a novel ACAT inhibitor, on bile acid synthesis and cholesterol 7α-hydroxylase in cultured rat hepatocytes and rats fed different diets. Avasimibe dose-dependently decreased ACAT activity in rat hepatocytes in the presence and absence of β-migrating very low-density lipoproteins (βVLDL) (by 93% and 75% at 10 μmol/L) and reduced intracellular storage of cholesteryl esters. Avasimibe (3 μmol/L) increased bile acid synthesis (2.9-fold) after preincubation with βVLDL and cholesterol 7α-hydroxylase activity (1.7- and 2.6-fold, with or without βVLDL), the latter paralleled by a similar induction of its messenger RNA (mRNA). Hepatocytes treated with avasimibe showed a shift from storage and secretion of cholesteryl esters to conversion of cholesterol into bile acids. In rats fed diets containing different amounts of cholesterol and cholate, avasimibe reduced plasma cholesterol (by 52% to 71%) and triglyceride levels (by 28% to 62%). Avasimibe did not further increase cholesterol 7α-hydroxylase activity and mRNA in cholesterol-fed rats, but prevented down-regulation by cholate. Avasimibe did not affect sterol 27-hydroxylase and oxysterol 7α-hydroxylase, 2 enzymes in the alternative pathway in bile acid synthesis. No increase in the ratio of biliary excreted cholesterol to bile acids was found, indicating that ACAT inhibition does not result in a more lithogenic bile. Avasimibe increases bile acid synthesis in cultured hepatocytes by enhancing the supply of free cholesterol both as substrate and inducer of cholesterol 7α-hydroxylase. These effects may partially explain the potent cholesterol-lowering effects of avasimibe in the rat.
Sulphasalazine and mesalazine: serious adverse reactions re-evaluated on the basis of suspected adverse reaction reports to the Committee on Safety of Medicines * Author's reply
Authors: R F Logan
Journal: Gut (2003)

We were interested to read the report by Ransford and Langman of their analysis of yellow card reports of suspected adverse drugs reactions for sulphasalazine and mesalazine ( Gut2002;51:536–9 [OpenUrl][1][Abstract/FREE Full Text][2] ). These reports, submitted to the Committee on Safety of Medicines, may provide useful flags to signal unrecognised hazards of drugs. However, as adverse reactions are not always recognised or reported to the regulatory authorities by physicians, these reports usually underestimate the frequency of any adverse drug reaction. Of greater importance, underreporting is usually not random but selective, which may introduce serious bias when comparing different drugs.1 Various examples have been described previously of drugs that showed substantive differences in reporting rates, which were not substantiated after further research.1 For this reason, it is recommended that, once there is a signal for a suspected adverse drug reaction, other sources of data are investigated.2 We recently initiated a study to quantify the risk of renal toxicity in patients taking aminosalicylate (5-ASA) drugs in the UK. The General Practice Research Database (GPRD) was used for this study, … [1]: {openurl}?query=rft.jtitle%253DGut%26rft.stitle%253DGut%26rft.issn%253D0017-5749%26rft.aulast%253DRansford%26rft.auinit1%253DR%2BA%2BJ%26rft.volume%253D51%26rft.issue%253D4%26rft.spage%253D536%26rft.epage%253D539%26rft.atitle%253DSulphasalazine%2Band%2Bmesalazine%253A%2Bserious%2Badverse%2Breactions%2Bre-evaluated%2Bon%2Bthe%2Bbasis%2Bof%2Bsuspected%2Badverse%2Breaction%2Breports%2Bto%2Bthe%2BCommittee%2Bon%2BSafety%2Bof%2BMedicines%26rft_id%253Dinfo%253Adoi%252F10.1136%252Fgut.51.4.536%26rft_id%253Dinfo%253Apmid%252F12235076%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=gutjnl&resid=51/4/536&atom=%2Fgutjnl%2F52%2F10%2F1530.atom
Notes from the NHLBI Director
Authors: Elizabeth G. Nabel
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

With fiscal year 2007 well under way, we write to report on the status of our budget for the National Heart, Lung, and Blood Institute (NHLBI). As a result of a Congressional joint resolution, the NHLBI received an allocation of $2,918,808,000, which represents an increase of about one percent over the comparable figure for fiscal year 2006. The NHLBI has a longstanding and powerful commitment to preserve and enhance investigator-initiated research and to develop and support new investigators. In these difficult times, the Institute’s top priorities will be to stay true to these core values. To accomplish this objective, we have developed a number of strategies to assist investigators in launching successful research careers and riding out tough times. Several policies are designed to ease the path to independence for new investigators (http:// www.nhlbi.nih.gov/funding/policies/operguid.htm).
Xanthine oxidase inhibition reduces reactive nitrogen species production in COPD airways
Authors: M. Ichinose, H. Sugiura, S. Yamagata, A. Koarai, M. Tomaki, H. Ogawa, Y. Komaki, P.J. Barnes, K. Shirato, T. Hattori
Journal: European Respiratory Journal (2003)

Reactive nitrogen species (RNS) have been reported to be involved in the inflammatory process in chronic obstructive pulmonary disease (COPD). However, there are no studies on the modulation of RNS in COPD. It was hypothesised that inhibition of xanthine oxidase (XO) might decrease RNS production in COPD airways through the suppression of superoxide anion production. Ten COPD and six healthy subjects participated in the study. The XO inhibitor allopurinol (300 mg·day −1 p.o. for 4 weeks) was administered to COPD patients. RNS production in the airway was assessed by 3‐nitrotyrosine immunoreactivity and enzymic activity of XO in induced sputum as well as by exhaled nitric oxide (eNO) concentration. XO activity in the airway was significantly elevated in COPD compared with healthy subjects. Allopurinol administration to COPD subjects significantly decreased XO activity and nitrotyrosine formation. In contrast, eNO concentration was significantly increased by allopurinol administration. These results suggest that oral administration of the xanthine oxidase inhibitor allopurinol reduces airway reactive nitrogen species production in chronic obstructive pulmonary disease subjects. This intervention may be useful in the future management of chronic obstructive pulmonary disease.
Isokinetics: which value is better to report?
Authors: L D Mendonça, G M Amaral, H V R Marinho, A A Silva, S T Fonseca
Journal: British Journal of Sports Medicine (2011)

Background Isokinetic tests are golden pattern for muscular performance evaluation. Nevertheless, there isn't any uniformity when reporting and analysing results, many authors have taken the peak torque value as major variable to be discussed. Objective To verify correlations between values reported in ‘Comprehensive Evaluation’ generated by the Biodex System III pro and to determine the main values related to the total variance. Design Data base analysis. Setting Results from knee isokinetic evaluations in volleyball and football male players realised in LAPREV. Participants 117 ‘Comprehensive Evaluation’, only the reports for dominant limb at 60°/s were used. Results ‘Comprehensive Evaluation’ reports generated 19 different values. Factorial analysis with Varimax Rotation (KMO=0.687; Bartlett's Test of Sphericity p=0.000) grouped all values in four main factors, named respectively: ▶ Muscle Strengthening (eigenvalue=7391) ▶ Performance Rise (eigenvalue=3073) ▶ Muscle Length (eigenvalue=1858) ▶ Performance Decay (eigenvalue=1223) ‘Total Work’ value showed bigger loading (0.949), this result represents its major contribution to total variance. This value represents the Muscle Strengthening Factor better than any other value. Furthermore, the ‘Peak Torque’ value was only the fourth value to contribute to this factor variance (0.889). The factor grouped 9 of 19 values, all of them related to work, torque and power. The Second Factor comprehended ‘Time to peak torque’ (0.904), ‘ROM’ (0.872) and ‘Acceleration time’ (0.576) values. The Muscle Length factor included ‘Peak Torque Angle’ (−0.912) and ‘Torque @25deg’ (0.798) values and the Fourth Factor comprised ‘Work Fatigue’ (0.838) and ‘Maximum work repetition#’ (−0.540) values. Conclusion These preliminary results suggested that, during scientific investigation process, to report the appropriate variables is necessary to better define muscular performance. Peak torque should not be the better value to represent Muscle Strengthening and it's necessary to discuss which variable properly answers ours questions.
Antiangiogenic Properties of 17-(Dimethylaminoethylamino)-17-Demethoxygeldanamycin
Authors: Gurmeet Kaur, Dorina Belotti, Angelika M. Burger, Kirsten Fisher-Nielson, Patrizia Borsotti, Elena Riccardi, Jagada Thillainathan, Melinda Hollingshead, Edward A. Sausville, Raffaella Giavazzi
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The purpose of this study was to investigate the antiangiogenic properties of 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG; NSC707545), a water-soluble benzoquinone ansamycin. Experimental Design: The activity of 17-DMAG, in vivo, was evaluated for inhibition of fibroblast growth factor (FGF)-2-induced angiogenesis in s.c. implanted Matrigel in mice. In vitro, the activity of 17-DMAG on endothelial cells (human umbilical vein endothelial cells; HUVEC) was tested in FGF-2; and vascular endothelial growth factor (VEGF)-induced proliferation and apoptosis, motility, and extracellular matrix invasion; and on the alignment of capillary like structures in Matrigel. The protein level of heat shock protein (Hsp)90 and client proteins was examined by Western blot in FGF-2 and VEGF-stimulated HUVEC. Results: Daily oral administration of 17-DMAG affected the angiogenic response in Matrigel in a dose-dependent manner. The hemoglobin content in the Matrigel implants was significantly inhibited, and the histological analysis confirmed a decrease of CD31+ endothelial cells and of structures organized in cord and erythrocyte-containing vessels. In vitro, the compound inhibited dose-dependently the migration and the extracellular matrix-invasiveness of HUVEC and their capacity to form capillary like structures in Matrigel. 17-DMAG treatment also inhibited FGF-2 and VEGF-induced HUVEC proliferation and resulted in apoptosis. Accordingly, the expression of Hsp90 direct client proteins (pAkt and c-Raf-1) or their downstream substrates including pERK was also affected. 17-DMAG consistently increased the expression of Hsp70. Throughout the study similar results were obtained with 17-allylamino-17-demethoxygeldanamycin (17-AAG; NSC330507), the analog compound currently undergoing clinical trials. Conclusions: We show that the Hsp90 targeting agents 17-DMAG and 17-AAG inhibit angiogenesis. The strong effects on endothelial cell functions, in vitro, indicate that the antiangiogenic activity of 17-DMAG/17-AAG could also be due to a direct effect on endothelial cells. The oral bioavailability of 17-DMAG might be of advantage in investigating the potential of this compound in clinical trials with antiangiogenic as well as antiproliferative endpoints.
Clinical features of paediatric pulmonary hypertension: a registry study
Authors: Rolf MF Berger, Maurice Beghetti, Tilman Humpl, Gary E Raskob, D Dunbar Ivy, Zhi-Cheng Jing, Damien Bonnet, Ingram Schulze-Neick, Robyn J Barst
Journal: The Lancet (2012)
Double-blinded infliximab dose escalation in patients with rheumatoid arthritis
Authors: M. U Rahman, I. Strusberg, P. Geusens, A. Berman, D. Yocum, D. Baker, C. Wagner, J. Han, R. Westhovens
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Abstract</h3> Short-read variant calling for bacterial genomics is a mature field, and there are many widely-used software tools. Different underlying approaches (eg pileup, local or global assembly, paired-read use, haplotype use) lend each tool different strengths, especially when considering non-SNP (single nucleotide polymorphism) variation or potentially distant reference genomes. It would therefore be valuable to be able to integrate the results from multiple variant callers, using a robust statistical approach to "adjudicate" at loci where there is disagreement between callers. To this end, we present a tool, Minos, for variant adjudication by mapping reads to a genome graph of variant calls. Minos allows users to combine output from multiple variant callers without loss of precision. Minos also addresses a second problem of joint genotyping SNPs and indels in bacterial cohorts, which can also be framed as an adjudication problem. We benchmark on 62 samples from 3 species (<i>Mycobacterium tuberculosis, Staphylococcus aureus, Klebsiella pneumoniae</i>) and an outbreak of 385 <i>M. tuberculosis</i> samples. Finally, we joint genotype a large <i>M. tuberculosis</i> cohort (N<i>≈</i>15k) for which the rifampicin phenotype is known. We build a map of non-synonymous variants in the RRDR (rifampicin resistance determining region) of the <i>rpoB</i> gene and extend current knowledge relating RRDR SNPs to heterogeneity in rifampicin resistance levels. We replicate this finding in a second <i>M. tuberculosis</i> cohort (N<i>≈</i>13k). Minos is released under the MIT license, available at https://github.com/iqbal-lab-org/minos.
The Pharmacology of the Cytochrome P450 Epoxygenase/Soluble Epoxide Hydrolase Axis in the Vasculature and Cardiovascular Disease
Authors: Ingrid Fleming
Journal: Pharmacological Reviews (2014)

Over the last 20 years, it has become clear that cytochrome P450 (P450) enzymes generate a spectrum of bioactive lipid mediators from endogenous substrates. However, studies focused on the determining biologic activity of the P450 system have focused largely on the metabolites generated by one substrate (i.e., arachidonic acid). However, epoxides and diols derived from other endogenous substrates, such as linoleic acid, eicosapentaenoic acid, and docosahexaenoic acid, may be generated in higher concentrations and may potentially be of more physiologic relevance. Recent studies that used a combination of phenotyping and lipid array analyses revealed that rather than being inactive products, fatty acid diols play important roles in a number of biologic processes including inflammation, angiogenesis, and metabolic regulation. Moreover, inhibitors of the soluble epoxide hydrolase that increase epoxide but decrease diol levels have potential for the treatment of the metabolic syndrome.
No major role for glutathione S-transferase gene polymorphisms in sensitization to para-phenylenediamine and other xenobiotics: a study of association and a meta-analysis
Authors: L.M. Pot, B.Z. Alizadeh, D. Ahrenberg, P.-J. Coenraads, H. Snieder, B. Blömeke
Journal: British Journal of Dermatology (2010)

Journal Article No major role for glutathione S‐transferase gene polymorphisms in sensitization to para‐phenylenediamine and other xenobiotics: a study of association and a meta‐analysis Get access L.M. Pot, L.M. Pot Department of Dermatology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar B.Z. Alizadeh, B.Z. Alizadeh Unit of Genetic Epidemiology & Bioinformatics, Department of Epidemiology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar D. Ahrenberg, D. Ahrenberg Department of Environmental Toxicology, University Trier, Am Wissenschaftspark 25–27, 54296 Trier, Germany Search for other works by this author on: Oxford Academic Google Scholar P.‐J. Coenraads, P.‐J. Coenraads Department of Dermatology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar H. Snieder, H. Snieder Unit of Genetic Epidemiology & Bioinformatics, Department of Epidemiology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar B. Blömeke B. Blömeke Department of Environmental Toxicology, University Trier, Am Wissenschaftspark 25–27, 54296 Trier, Germany Brunhilde Blömeke. E‐mail: bloemeke@uni‐trier.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 164, Issue 4, 1 April 2011, Pages 890–892, https://doi.org/10.1111/j.1365-2133.2010.10197.x Published: 01 April 2011
Association of DNA Methylation of Phosphoserine Aminotransferase with Response to Endocrine Therapy in Patients with Recurrent Breast Cancer
Authors: John W.M. Martens, Inko Nimmrich, Thomas Koenig, Maxime P. Look, Nadia Harbeck, Fabian Model, Antje Kluth, Joan Bolt-de Vries, Anieta M. Sieuwerts, Henk Portengen, Marion E. Meijer-Van Gelder, Christian Piepenbrock, Alexander Olek, Heinz Höfler, Marion Kiechle, Jan G.M. Klijn, Manfred Schmitt, Sabine Maier, John A. Foekens
Journal: Cancer Research (2005)

Abstract To understand the biological basis of resistance to endocrine therapy is of utmost importance in patients with steroid hormone receptor–positive breast cancer. Not only will this allow us prediction of therapy success, it may also lead to novel therapies for patients resistant to current endocrine therapy. DNA methylation in the promoter regions of genes is a prominent epigenetic gene silencing mechanism that contributes to breast cancer biology. In the current study, we investigated whether promoter DNA methylation could be associated with resistance to endocrine therapy in patients with recurrent breast cancer. Using a microarray-based technology, the promoter DNA methylation status of 117 candidate genes was studied in a cohort of 200 steroid hormone receptor–positive tumors of patients who received the antiestrogen tamoxifen as first-line treatment for recurrent breast cancer. Of the genes analyzed, the promoter DNA methylation status of 10 genes was significantly associated with clinical outcome of tamoxifen therapy. The association of the promoter hypermethylation of the strongest marker, phosphoserine aminotransferase (PSAT1) with favorable clinical outcome was confirmed by an independent quantitative DNA methylation detection method. Furthermore, the extent of DNA methylation of PSAT1 was inversely associated with its expression at the mRNA level. Finally, also at the mRNA level, PSAT1 was a predictor of tamoxifen therapy response. Concluding, our work indicates that promoter hypermethylation and mRNA expression of PSAT1 are indicators of response to tamoxifen-based endocrine therapy in steroid hormone receptor–positive patients with recurrent breast cancer.