tbuckley/cabot-search huggingface dataset:
Pharmacogenetics of Anti-HIV Drugs
Authors: A. Telenti, U. M. Zanger
Journal: The Annual Review of Pharmacology and Toxicology (2007)

Pharmacogenetics holds promise in HIV treatment because of the complexity and potential toxicity of multidrug therapies that are prescribed for long periods. Thus far, few candidate genes have been examined for a limited number of allelic variants, but a number of confirmed associations have already emerged. A change in paradigm emerges from the availability of the HapMap, the wealth of data on less-common genetic polymorphisms, and new genotyping technology. This review presents a comprehensive analysis of the existing literature on pharmacogenetic determinants of antiretroviral drug exposure, drug toxicity, as well as genetic markers associated with the rate of disease progression. It is expected that larger-scale comprehensive genome approaches will profoundly change the landscape of knowledge in the future.
Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial
Authors: Y.-K. Kang, W.-K. Kang, D.-B. Shin, J. Chen, J. Xiong, J. Wang, M. Lichinitser, Z. Guan, R. Khasanov, L. Zheng, M. Philco-Salas, T. Suarez, J. Santamaria, G. Forster, P.I. McCloud
Journal: Annals of Oncology (2009)
Factorial phase III randomised trial of rofecoxib and prolonged constant infusion of gemcitabine in advanced non-small-cell lung cancer: the GEmcitabine-COxib in NSCLC (GECO) study
Authors: Cesare Gridelli, Ciro Gallo, Anna Ceribelli, Vittorio Gebbia, Teresa Gamucci, Fortunato Ciardiello, Francesco Carozza, Adolfo Favaretto, Bruno Daniele, Domenico Galetta, Santi Barbera, Francesco Rosetti, Antonio Rossi, Paolo Maione, Francesco Cognetti, Antonio Testa, Massimo Di Maio, Alessandro Morabito, Francesco Perrone
Journal: The Lancet Oncology (2007)
Role of NADPH Oxidase in the Vascular Hypertrophic and Oxidative Stress Response to Angiotensin II in Mice
Authors: Hui Di Wang, Shanqin Xu, Douglas G. Johns, Yue Du, Mark T. Quinn, Antonio J. Cayatte, Richard A. Cohen
Journal: Circulation Research (2001)

Oxygen-derived free radicals are involved in the vascular response to angiotensin II (Ang II), but the role of NADPH oxidase, its subunit proteins, and their vascular localization remain controversial. Our purpose was to address the role of NADPH oxidase in the blood pressure (BP), aortic hypertrophic, and oxidant responses to Ang II by taking advantage of knockout (KO) mice that are genetically deficient in gp91(phox), an NADPH oxidase subunit protein. The baseline BP was significantly lower in KO mice than in wild-type (WT) (92+/-2 [KO] versus 101+/-1 [WT] mm Hg, P<0.01), but infusion of Ang II for 6 days caused similar increases in BP in the 2 strains (33+/-4 [KO] versus 38+/-2 [WT] mm Hg, P>0.4). Ang II increased aortic superoxide anion production 2-fold in the aorta of WT mice but did not do so in KO mice. Aortic medial area increased in WT (0.12+/-0.02 to 0.17+/-0.02 mm(2), P<0.05), but did not do so in KO mice (0.10+/-0.01 to 0.11+/-0.01 mm(2), P>0.05). Histochemistry and polymerase chain reaction demonstrated gp91(phox) localized in endothelium and adventitia of WT mice. Levels of reactive oxidant species as indicated by 3-nitrotyrosine immunoreactivity increased in these regions in WT but not in KO mouse aorta in response to Ang II. These results indicate an essential role in vivo of gp91(phox) and NADPH oxidase-derived superoxide anion in the regulation of basal BP and a pressure-independent vascular hypertrophic and oxidant stress response to Ang II.
Risk of Tuberculin Conversion According to Occupation among Health Care Workers at a New York City Hospital
Authors: JOYCE LOUTHER, PEDRO RIVERA, JOSEPH FELDMAN, NORIEDA VILLA, JACK DeHOVITZ, KENT A. SEPKOWITZ
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Concern about the risk to health care workers of occupationally acquired tuberculosis has resulted in extensive and frequently revised guidelines from the Centers for Disease Control and Prevention (CDC). Most recent studies, however, have determined that community, rather than occupational, exposure is the more significant risk for tuberculin conversion. To assess the relative contribution of community versus occupational risk, we reviewed the health records of 1,303 persons employed from 1991 to 1994 at St. Clare's Hospital in New York City, a hospital with a high tuberculosis case-rate. Demographic information included age, gender, postal zone of residence, country of birth, and BCG vaccination status, while occupations were placed into one of five groups. In multivariate analysis, occupation was significantly associated with risk of tuberculin conversion, while postal zone of residence was not. The group that included housekeeping, laundry, and security personnel and the physician-nurse group had the highest conversion rates. After implementation of CDC guidelines, there was a significant improvement in the employee tuberculin conversion rate. At our hospital, occupation was strongly associated with risk of tuberculin conversion.
Human tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 suppresses hepatocellular carcinoma metastasis through inhibiting Rac1
Authors: Xuelei Cao, Li Zhang, Yongyu Shi, Yue Sun, Shen Dai, Chun Guo, Faliang Zhu, Qun wang, Jianing Wang, Xiaoyan Wang, Youhai H Chen, Lining Zhang
Journal: Molecular Cancer (2013)

Abstract Background Tumor invasion and metastasis are the major reasons for leading death of patients with hepatocellular carcinoma (HCC). Therefore, to identify molecules that can suppress invasion and metastasis of tumor will provide novel targets for HCC therapies. Tumor necrosis factor (TNF)-alpha-induced protein 8-like 2, TIPE2, is a novel immune negative molecule and an inhibitor of the oncogenic Ras in mice but its function in human is unclear. Our previous research has shown that TIPE2 is downregulated in human primary HCC compared with the paired adjacent non-tumor tissues. Results In present study, we provide evidence that TIPE2 inhibits effectively human hepatocellular carcinoma metastasis. The forced expression of TIPE2 in HCC-derived cell lines markedly inhibits tumor cell growth, migration and invasion in vitro and suppresses growth and metastasis of HCC in vivo . Clinical information from a cohort of 112 patients reveals that loss or reduced expression of TIPE2 in primary HCC tissues is significantly associated with tumor metastasis. Mechanically, TIPE2 inhibits the migration and invasion through targeting Rac1 and then reduces F-actin polymerization and expression of matrix metallopeptidase 9 (MMP9) and urokinase plasminogen activator (uPA). Conclusion Our results indicate that human TIPE2 is endogenous inhibitor of Rac1 in HCC by which it attenuates invasion and metastasis of HCC. The data suggest that TIPE2 will be a new target for HCC therapy.
A Brugada syndrome mutation (p.S216L) and its modulation by p.H558R polymorphism: standard and dynamic characterization
Authors: Stefano Marangoni, Chiara Di Resta, Marcella Rocchetti, Lucio Barile, Riccardo Rizzetto, Aurora Summa, Stefano Severi, Elena Sommariva, Carlo Pappone, Maurizio Ferrari, Sara Benedetti, Antonio Zaza
Journal: Cardiovascular Research (2011)

The Na+ channel mutation (p.S216L), previously associated with type 3 long-QT syndrome (LQT3) phenotype, and a common polymorphism (p.H558R) were detected in a patient with an intermittent Brugada syndrome (BS) ECG pattern. The study was aimed to assess the p.S216L electrical phenotype, its modulation by p.H558R, and to identify abnormalities compatible with a mixed BS-LQT3 phenotype. The mutation was expressed alone (S216L channels), or in combination with the polymorphism (S216L–H558R channels), in a mammalian cell line (TSA201). Functional analysis included standard voltage clamp and dynamic clamp with endo- and epicardial action potential waveforms. Expression of S216L channels was associated with a 60% reduction in maximum Na+ current (INa) density, attributable to protein misfolding (rescued by mexiletine pretreatment) and moderate slowing of inactivation. INa density partially recovered in S216L–H558R channels, but INa inactivation and its recovery were further delayed. The persistent component of INa (INaL) was unchanged. Under dynamic clamp conditions, INa decreased in S216L channels and displayed a 'resurgent' component during late repolarization. In S216L–H558R channels, INa density partially recovered and did not display a resurgent component. INa changes during dynamic clamp were interpreted by numerical modelling. The BS pattern of p.S216L might result from a decrease in INa density, which masked gating abnormalities that might otherwise result in a LQT phenotype. The p.H558R polymorphism decreased p.S216L expressivity, partly by lessening p.S216L effects and partly through the induction of further gating abnormalities suitable to blunt p.S216L effects during repolarization.
Species differentiation within the Staphylococcus intermedius group using a refined MALDI-TOF MS database
Authors: J. Murugaiyan, B. Walther, I. Stamm, Y. Abou-Elnaga, S. Brueggemann-Schwarze, S. Vincze, L.H. Wieler, A. Lübke-Becker, T. Semmler, U. Roesler
Journal: Clinical Microbiology and Infection (2014)
Randomized study on hydroxyurea alone versus hydroxyurea combined with low-dose interferon-alpha 2b for chronic myeloid leukemia
Authors: André Delannoy, AC Louwagie, Jc. Kluinnelemans, JF vandenBurgh, Ma. Boogaerts, André Bosly, Jl. Michaux, P. Zachee, Anne Hagemeijer, Hans Vandenberghe
Journal: Blood (1997)
Enrichment of CD4+ CD25high T cell population in patients with systemic lupus erythematosus treated with glucocorticoids
Authors: A Suarez, P Lopez, J Gomez, C Gutierrez
Journal: Annals of the Rheumatic Diseases (2006)

<b>Objectives:</b> To characterise and quantify the CD4+ CD25+ T cell population in patients with systemic lupus erythematosus (SLE) and to detect the possible influence of treatments and clinical manifestations. <b>Methods:</b> Characterisation of CD25<sup>low</sup> and CD25<sup>high</sup> CD4+ T cells from healthy controls and from patients with SLE was carried out using flow cytometry, analysing the expression of activation and differentiation markers. The percentage of both circulating cell subsets was determined in 56 controls and 110 unselected patients with SLE. Data were related to treatment during the past 3 months and to various clinical manifestations. <b>Results:</b> CD4+ CD25<sup>high</sup> lymphocytes from controls expressed low levels of CD69, CD154 or CD30, but also expressed glucocorticoid-induced tumour necrosis factor receptor, high levels of intracellular cytotoxin T lymphocyte-associated antigen 4, CD45RO and diminished amounts of CD4, all of which are phenotypic characteristics of natural regulatory T cells. CD4+ CD25<sup>low</sup> cells, on the other hand, expressed the highest levels of activation markers, indicating that they represent recently activated effector cells. Similarly, analysis of cells from patients with SLE showed the same two phenotypically distinguishable CD4+ CD25<sup>low</sup> and CD4+ CD25<sup>high</sup> populations, although both expressed slightly increased levels of activation markers. Quantitative analysis showed a considerably raised percentage of CD25<sup>low</sup> and, especially, CD25<sup>high</sup> cells in patients with SLE compared with controls. This increment was unrelated to clinical manifestations, but correlated with glucocorticoid treatment. Patients treated with glucocorticoids presented raised levels of CD25<sup>high</sup> cells, whereas untreated patients and those with anti-malarial or immunosuppressive drugs had levels similar to those in controls. <b>Conclusions:</b> The percentage of CD4+ CD25<sup>high</sup> cells was not altered in non-steroid-treated patients, whereas glucocorticoid treatment increased their frequency in patients with SLE.
MicroRNA Profiling Identifies MicroRNA-155 as an Adverse Mediator of Cardiac Injury and Dysfunction During Acute Viral Myocarditis
Authors: Maarten F. Corsten, Anna Papageorgiou, Wouter Verhesen, Paolo Carai, Morten Lindow, Susanna Obad, Georg Summer, Susan L.M. Coort, Mark Hazebroek, Rick van Leeuwen, Marion J.J. Gijbels, Erwin Wijnands, Erik A.L. Biessen, Menno P.J. De Winther, Frank R.M. Stassen, Peter Carmeliet, Sakari Kauppinen, Blanche Schroen, Stephane Heymans
Journal: Circulation Research (2012)

Viral myocarditis results from an adverse immune response to cardiotropic viruses, which causes irreversible myocyte destruction and heart failure in previously healthy people. The involvement of microRNAs and their usefulness as therapeutic targets in this process are unknown.To identify microRNAs involved in viral myocarditis pathogenesis and susceptibility.Cardiac microRNAs were profiled in both human myocarditis and in Coxsackievirus B3-injected mice, comparing myocarditis-susceptible with nonsusceptible mouse strains longitudinally. MicroRNA responses diverged depending on the susceptibility to myocarditis after viral infection in mice. MicroRNA-155, -146b, and -21 were consistently and strongly upregulated during acute myocarditis in both humans and susceptible mice. We found that microRNA-155 expression during myocarditis was localized primarily in infiltrating macrophages and T lymphocytes. Inhibition of microRNA-155 by a systemically delivered LNA-anti-miR attenuated cardiac infiltration by monocyte-macrophages, decreased T lymphocyte activation, and reduced myocardial damage during acute myocarditis in mice. These changes were accompanied by the derepression of the direct microRNA-155 target PU.1 in cardiac inflammatory cells. Beyond the acute phase, microRNA-155 inhibition reduced mortality and improved cardiac function during 7 weeks of follow-up.Our data show that cardiac microRNA dysregulation is a characteristic of both human and mouse viral myocarditis. The inflammatory microRNA-155 is upregulated during acute myocarditis, contributes to the adverse inflammatory response to viral infection of the heart, and is a potential therapeutic target for viral myocarditis.
Obliteration of Intracranial Aneurysms by Pilojection
Authors: John P. Gallagher
Journal: JAMA (1963)

Pilojection is presented as a new concept in the surgical treatment of saccular aneurysm of the brain. It employs shafts of stiff mammalian hair which are shot into the lesion in order to produce thrombosis in it. This technique has been used on four patients so far. The first patient died from a complication not directly related to the procedure. The other patients are alive and well. The autopsy findings on the first patient demonstrated successful clotting within a large saccular aneurysm of the circle of Willis.
Evidence-based treatments for depression and anxiety versus treatment-as-usual: A meta-analysis of direct comparisons
Authors: Bruce E. Wampold, Stephanie L. Budge, Kevin M. Laska, A.C. Del Re, Timothy P. Baardseth, Christoph Flűckiger, Takuya Minami, D. Martin Kivlighan, Wade Gunn
Journal: Clinical Psychology Review (2011)
Phase II Study on the Effect of Disease Sites, Age, and Prior Therapy on Response to Iodine-131-Metaiodobenzylguanidine Therapy in Refractory Neuroblastoma
Authors: Katherine K. Matthay, Gregory Yanik, Julia Messina, Alekist Quach, John Huberty, Su-Chun Cheng, Janet Veatch, Robert Goldsby, Patricia Brophy, Leslie S. Kersun, Randall A. Hawkins, John M. Maris
Journal: Journal of Clinical Oncology (2007)

To evaluate the effect of disease sites and prior therapy on response and toxicity after iodine-131-metaiodobenzylguanidine (131I-MIBG) treatment of patients with resistant neuroblastoma.One hundred sixty-four patients with progressive, refractory or relapsed high-risk neuroblastoma, age 2 to 30 years, were treated in a limited institution phase II study. Patients with cryopreserved hematopoietic stem cells (n = 148) were treated with 18 mCi/kg of 131I-MIBG. Those without hematopoietic stem cells (n = 16) received 12 mCi/kg. Patients were stratified according to prior myeloablative therapy and whether they had measurable soft tissue involvement or only bone and/or bone marrow disease.Hematologic toxicity was common, with 33% of patients receiving autologous hematopoietic stem cell support. Nonhematologic grade 3 or 4 toxicity was rare, with 5% of patients experiencing hepatic, 3.6% pulmonary, 10.9% infectious toxicity, and 9.7% with febrile neutropenia. The overall complete plus partial response rate was 36%. The response rate was significantly higher for patients with disease limited either to bone and bone marrow, or to soft tissue (compared with patients with both) for patients with fewer than three prior treatment regimens and for patients older than 12 years. The event-free survival (EFS) and overall survival (OS) times were significantly longer for patients achieving response, for those older than 12 years and with fewer than three prior treatment regimens. The OS was 49% at 1 year and 29% at 2 years; EFS was 18% at 1 year.The high response rate and low nonhematologic toxicity with 131I-MIBG suggest incorporation of this agent into initial multimodal therapy of neuroblastoma.
Genome-wide prediction and identification of cis-natural antisense transcripts in Arabidopsis thaliana.
Authors: Xiu-Jie Wang, Terry Gaasterland, Nam-Hai Chua
Journal: Genome biology (2005)

Natural antisense transcripts (NAT) are a class of endogenous coding or non-protein-coding RNAs with sequence complementarity to other transcripts. Several lines of evidence have shown that cis- and trans-NATs may participate in a broad range of gene regulatory events. Genome-wide identification of cis-NATs in human, mouse and rice has revealed their widespread occurrence in eukaryotes. However, little is known about cis-NATs in the model plant Arabidopsis thaliana.We developed a new computational method to predict and identify cis-encoded NATs in Arabidopsis and found 1,340 potential NAT pairs. The expression of both sense and antisense transcripts of 957 NAT pairs was confirmed using Arabidopsis full-length cDNAs and public massively parallel signature sequencing (MPSS) data. Three known or putative Arabidopsis imprinted genes have cis-antisense transcripts. Sequences and the genomic arrangement of two Arabidopsis NAT pairs are conserved in rice.We combined information from full-length cDNAs and Arabidopsis genome annotation in our NAT prediction work and reported cis-NAT pairs that could not otherwise be identified by using one of the two datasets only. Analysis of MPSS data suggested that for most Arabidopsis cis-NAT pairs, there is predominant expression of one of the two transcripts in a tissue-specific manner.
Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial
Authors: Richard AC Hughes, Peter Donofrio, Vera Bril, Marinos C Dalakas, Chunqin Deng, Kim Hanna, Hans-Peter Hartung, Norman Latov, Ingemar SJ Merkies, Pieter A van Doorn
Journal: The Lancet Neurology (2008)
Agreement Between Clinical Practice and Trained Central Reading in Reading of Sacroiliac Joints on Plain Pelvic Radiographs: Results From the DESIR Cohort
Authors: Rosaline van den Berg, Grégory Lenczner, Antoine Feydy, Désirée van der Heijde, Monique Reijnierse, Alain Saraux, Alain Rahmouni, Maxime Dougados, Pascal Claudepierre
Journal: Arthritis & Rheumatology (2014)

To investigate the degree of agreement between local rheumatologists/radiologists and central trained readers (external standard) on the presence/absence of sacroiliitis on radiographs of the sacroiliac (SI) joints.Patients with inflammatory back pain (duration ≥3 months but <3 years) suggestive of axial spondyloarthritis (SpA) were included in the Devenir des Spondylarthropathies Indifferérenciées Récentes (DESIR) cohort. Baseline radiographs of the SI joints were interpreted by 2 central readers (modified New York criteria); cases of disagreement were adjudicated by a third reader, yielding a positive or a negative result (central reading). The same radiographs were also interpreted by local radiologists/rheumatologists and were rated as "normal," "doubtful sacroiliitis," "obvious sacroiliitis," or "SI joint fusion" (local reading); positive findings were defined as "at least unilateral obvious sacroiliitis," "bilateral obvious sacroiliitis," or "at least unilateral fusion." Agreement and misclassifications between central readers and between central reading versus local reading were calculated (kappa values).Interreader agreement between the central readers was moderate (κ = 0.54); 108 of 688 radiographs (15.7%) were adjudicated. According to local reading ("at least unilateral obvious sacroiliitis"), 183 of the 688 patients (26.6%) had sacroiliitis, whereas according to central reading, 145 of 688 patients (21.1%) had sacroiliitis. Agreement between local reading and central reading was also moderate (κ = 0.55); 76 of 183 patients (41.5%) with "at least unilateral obvious sacroiliitis" (positive by local reading) and 32 of 109 patients (29.4%) with "bilateral obvious sacroiliitis" or "at least unilateral fusion" (positive by local reading) were rated as "negative" by central reading, and 38 of 505 patients (7.5%) and 68 of 579 patients (11.7%), respectively, without sacroiliitis (negative by local reading) were interpreted as "positive" by central reading.In patients with recent-onset inflammatory back pain, both trained readers and local rheumatologists/radiologists agreed only moderately on the recognition of radiographic sacroiliitis. A significant proportion of locally recognized ankylosing spondylitis (AS) patients were not confirmed as having AS by central reading (false positive), while a small minority of patients were false negative, indicating the necessity of reevaluating the role of radiographic sacroiliitis as diagnostic criterion for axial SpA.
Post-exposure prophylaxis against Ebola virus disease with experimental antiviral agents: a case-series of health-care workers
Authors: Michael Jacobs, Emma Aarons, Sanjay Bhagani, Ruaridh Buchanan, Ian Cropley, Susan Hopkins, Rebecca Lester, Daniel Martin, Neal Marshall, Stephen Mepham, Simon Warren, Alison Rodger
Journal: The Lancet Infectious Diseases (2015)