tbuckley/cabot-search huggingface dataset:
Prostate Cancer Susceptibility Locus on Chromosome 1q: a Confirmatory Study
Authors: K. A. Cooney, L. Huang, H. M. Sandler, E. Lange, K. Lange, S. Miesfeldt, J. D. McCarthy, J. E. Montie, J. E. Oesterling
Journal: JNCI Journal of the National Cancer Institute (1997)

Background: Recent recognition that a predisposition to prostate cancer can be inherited has led to a search for specific genes associated with the disease. Through a study of families with three or more affected first-degree relatives, a region on the long arm of chromosome 1 (i.e., 1q24-25) has been tentatively identified as containing a gene, HPC1, involved in the development of hereditary prostate cancer. Confirmation of this finding is needed, however, before attempts are made to isolate and characterize the putative HPC1 gene. Purpose: To confirm that chromosome 1q24-25 contains a gene relevant to hereditary prostate cancer, we analyzed an independent set of families, each with two or more affected individuals. Methods: Fifty-nine unrelated families were selected for analysis on the sole criterion that more than one living family member was affected by prostate cancer. DNA samples were subsequently isolated from 130 individuals with the disease. These samples were genotyped at six polymorphic marker sequences (D1S215, D1S2883, D1S466, D1S158, D1S518, and D1S2757) covering the chromosomal region proposed to contain HPC1. The resulting data were analyzed by nonparametric multipoint linkage (NPL) methods, yielding NPL Z scores and corresponding one-sided P values. Results: When the entire set of 59 families was considered, the occurrence of prostate cancer (and, presumably, the HPC1 gene) was most tightly linked to marker D1S466 (NPL Z score = 1.58; P = .0574). Analysis of the 20 families (51 affected individuals) fulfilling one or more of the proposed clinical criteria for hereditary prostate cancer (i.e., three or more affected individuals within one nuclear family; affected individuals in three successive generations [maternal or paternal lineage]; and/or clustering of two or more individuals affected before the age of 55 years) revealed more convincing evidence of disease linkage to chromosome 1q24-25 (maximum NPL Z score [at marker D1S466] = 1.72; P = .0451). The 39 families (79 affected individuals) that did not meet the clinical criteria for hereditary prostate cancer exhibited no significant evidence of disease linkage to DNA sequences at chromosome 1q24-25 (maximum NPL Z score [at marker D1S466] = 0.809; P = .208). The six African-American families in our study contributed disproportionately to the observation of linkage, with a maximum NPL Z score at marker D1S158 of 1.39 ( P = .0848) for these families. Conclusions and Implications: Our data confirm that chromosome 1q24-25 is likely to contain a prostate cancer susceptibility gene. Future efforts at positional cloning of the HPC1 gene should focus on families who meet the proposed clinical criteria for hereditary prostate cancer.
An fMRI Study of Episodic Encoding and Recognition of Words in Patients With Schizophrenia in Remission
Authors: Alex Hofer, Elisabeth M Weiss, Stefan M Golaszewski, Christian M Siedentopf, Claudia Brinkhoff, Christian Kremser, Stephan Felber, W Wolfgang Fleischhacker
Journal: American Journal of Psychiatry (2003)

Verbal memory deficits are among the most severe cognitive deficits observed in patients with schizophrenia. This study examined patterns of brain activity during episodic encoding and recognition of words in patients with schizophrenia.Functional magnetic resonance imaging (fMRI) was used to study regional brain activation in 10 healthy male comparison subjects and 10 male outpatients with schizophrenia during performance of a modified version of the words subtest of Warrington's Recognition Memory Test.Despite having intact performance in word recognition, the patients with schizophrenia had less activation of the right dorsolateral and anterior prefrontal cortex, right anterior cingulate, and left lateral temporal cortex during word encoding, compared with the healthy comparison subjects. During word recognition, the patients had impairments in activation of the bilateral dorsolateral prefrontal and lateral temporal cortices.Schizophrenia was associated with attenuated frontotemporal activation during episodic encoding and recognition of words. These results from an fMRI study replicate earlier findings derived from a positron emission tomography study.
EFFECT OF THE AMINO ACIDS AND DIALYZABLE CONSTITUENTS OF EMBRYONIC TISSUE JUICE ON THE GROWTH OF FIBROBLASTS
Authors: Lillian E. Baker, Alexis Carrel
Journal: The Journal of Experimental Medicine (1926)

The ultrafilterable constituents of embryonic tissue extract are unable to support cell life in vitro. They stimulate cell migration and possibly multiplication, without increasing the mass of the tissue. Embryonic tissue extract freed from amino acids by dialysis still retains a considerable part of its growth-promoting properties. The area of growth of tissues in embryonic tissue extract free from amino acids is appreciably less than that with the whole extract, probably owing to the denaturation of part of the protein, or perhaps to the inactivation or loss of an enzyme. The addition of either the ultrafilterable components or an artificial mixture of amino acids to this dialyzed extract increases the area of cell migration but does not restore all the activity lost on dialysis. The observed differences in growth of tissue, due to the addition or removal of dialyzable and ultrafilterable constituents of the extract, prove that the amino acids produce a more active cell migration and possibly multiplication, but no building up of new protoplasm.
Hemodynamic and electrophysiological actions of cocaine. Effects of sodium bicarbonate as an antidote in dogs.
Authors: K J Beckman, R B Parker, R J Hariman, J L Gallastegui, J I Javaid, J L Bauman
Journal: Circulation (1991)

Cocaine abuse has been implicated as a cause of death due to sudden cardiac arrest.We examined the hemodynamic and electrophysiological effects of cocaine administered as a series of 5-mg/kg i.v. boluses coupled with a continuous infusion in anesthetized dogs. Sodium bicarbonate (50 meq i.v.) was administered as a potential antidote in 11 of 15 dogs, and intravenous 5% dextrose was given in the remaining four. In a dose-dependent fashion, cocaine significantly decreased blood pressure, coronary blood flow, and cardiac output; increased PR, QRS, QT, and QTc intervals and sinus cycle length; and increased ventricular effective refractory period and dispersion of ventricular refractoriness. No afterdepolarizations were noted in the monophasic action potential recording. Nonsustained monomorphic ventricular tachycardia occurred spontaneously in two dogs, and sustained ventricular tachycardia could be induced by programmed stimulation at the end of the dosing protocol in five of 11 animals. Sodium bicarbonate promptly decreased cocaine-induced QRS prolongation to nearly that measured at baseline but had no effect on the other electrocardiographic or hemodynamic variables. In one dog, sodium bicarbonate administration was associated with reversion of ventricular tachycardia to sinus rhythm.We conclude that high-dose cocaine possesses negative inotropic and potent type I electrophysiological effects. Sodium bicarbonate selectively reversed cocaine-induced QRS prolongation and may be a useful treatment of ventricular arrhythmias associated with slowed ventricular conduction in the setting of cocaine overdose.
Identification of Putative Cytoskeletal Protein Homologues in the Protozoan Host <i>Hartmannella vermiformis</i> as Substrates for Induced Tyrosine Phosphatase Activity upon Attachment to the Legionnaires' Disease Bacterium, <i>Legionella pneumophila </i>
Authors: Chandrasekar Venkataraman, Lian-Yong Gao, Subbarao Bondada, Yousef Abu Kwaik
Journal: The Journal of Experimental Medicine (1998)

The Legionnaires' disease bacterium, Legionella pneumophila, is a facultative intracellular pathogen that invades and replicates within two evolutionarily distant hosts, free living protozoa and mammalian cells. Invasion and intracellular replication within protozoa are thought to be major factors in the transmission of Legionnaires' disease. We have recently reported the identification of a galactose/N-acetyl-d-galactosamine (Gal/GalNAc) lectin in the protozoan host Hartmannella vermiformis as a receptor for attachment and invasion by L. pneumophila (Venkataraman, C., B.J. Haack, S. Bondada, and Y.A. Kwaik. 1997. J. Exp. Med. 186:537–547). In this report, we extended our studies to the effects of bacterial attachment and invasion on the cytoskeletal proteins of H. vermiformis. We first identified the presence of many protozoan cytoskeletal proteins that were putative homologues to their mammalian counterparts, including actin, pp125FAK, paxillin, and vinculin, all of which were basally tyrosine phosphorylated in resting H. vermiformis. In addition to L. pneumophila–induced tyrosine dephosphorylation of the lectin, bacterial attachment and invasion was associated with tyrosine dephosphorylation of paxillin, pp125FAK, and vinculin, whereas actin was minimally affected. Inhibition of bacterial attachment to H. vermiformis by Gal or GalNAc monomers blocked bacteria-induced tyrosine dephosphorylation of detergent-insoluble proteins. In contrast, inhibition of bacterial invasion but not attachment failed to block bacteria-induced tyrosine dephosphorylation of H. vermiformis proteins. This was further supported by the observation that 10 mutants of L. pneumophila that were defective in invasion of H. vermiformis were capable of inducing tyrosine dephosphorylation of H. vermiformis proteins. Entry of L. pneumophila into H. vermiformis was predominantly mediated by noncoated receptor-mediated endocytosis (93%) but coiling phagocytosis was infrequently observed (7%). We conclude that attachment but not invasion by L. pneumophila into H. vermiformis was sufficient and essential to induce protein tyrosine dephosphorylation in H. vermiformis. These manipulations of host cell processes were associated with, or followed by, entry of the bacteria by a noncoated receptor-mediated endocytosis. A model for attachment and entry of L. pneumophila into H. vermiformis is proposed.
Phase II Results of Dovitinib (TKI258) in Patients with Metastatic Renal Cell Cancer
Authors: Bernard Escudier, Viktor Grünwald, Alain Ravaud, Yen-Chuan Ou, Daniel Castellano, Chia-Chi Lin, Jürgen E. Gschwend, Andrea Harzstark, Sarah Beall, Nicoletta Pirotta, Matthew Squires, Michael Shi, Eric Angevin
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Fibroblast growth factor (FGF) signaling regulates tumor growth and vascularization and partly mediates antiangiogenic escape from VEGF receptor (VEGFR) inhibitors. Dovitinib (TKI258) is a tyrosine kinase inhibitor (TKI) that inhibits FGF receptor (FGFR), VEGFR, and platelet-derived growth factor receptor, which are known drivers of antiangiogenic escape, angiogenesis, and tumor growth in renal cell carcinoma (RCC). Experimental Design: Patients with advanced or metastatic RCC were treated with oral dovitinib 500 mg/day (5-days-on/2-days-off schedule). The study population was enriched for patients previously treated with a VEGFR TKI and an mTOR inhibitor. Results: Of 67 patients enrolled, 55 patients (82.1%) were previously treated with ≥1 VEGFR TKI and ≥1 mTOR inhibitor (per-protocol efficacy set). The 8-week overall response rate and disease control rate in this population were 1.8% and 52.7%, respectively. Disease control rate during the entire study period was 56.4% (50.9% ≥4 months). Median progression-free survival and overall survival in the entire population were 3.7 and 11.8 months, respectively. Pharmacodynamic analyses demonstrated dovitinib-induced inhibition of VEGFR (as determined by increased levels of placental growth factor and decreased levels of soluble VEGFR2) and FGFR (as determined by increased FGF23 serum measures). The most frequently reported treatment-related adverse events of all grades included nausea (65.7%), diarrhea (62.7%), vomiting (61.2%), decreased appetite (47.8%), and fatigue (32.8%). Conclusion: Dovitinib was shown to be an effective and tolerable therapy for patients with metastatic RCC who had progressed following treatment with VEGFR TKIs and mTOR inhibitors. Clin Cancer Res; 20(11); 3012–22. ©2014 AACR.
An Association of Herpes Simplex Virus Type 1 Infection With Type 2 Diabetes
Authors: Yuhua Sun, Weidong Pei, Yongjian Wu, Yuejin Yang
Journal: Diabetes Care (2005)

Although the primary cause of type 2 diabetes is unknown, two breakthroughs have been made regarding its development (1). First, insulin resistance in muscle is the earliest detectable defect in people in whom type 2 diabetes will later develop. Second, β-cell function has to be abnormal before hyperglycemia develops. One of the risk factors for diabetes development might be virus infection (2). Preexisting hepatitis C virus infection may increase the risk for type 2 diabetes (3,4).

Herpes simplex virus type 1 (HSV-1) has been recognized as a potential pathogen of cardiovascular diseases. The presence of antibodies to HSV-1 is reported to be associated with an increase in the risk of incident myocardial infarction and coronary heart death (5,6). Type 2 diabetes is a major risk factor for cardiovascular morbidity and mortality (7) and is recorded as a coronary artery disease risk equivalent (8). In this study, we attempted to investigate the potential relationship between HSV-1 infection and type 2 diabetes.

All subjects were consecutive inpatients at Beijing Fu Wai Heart Hospital. Diabetes was diagnosed as follows (9): patients who had overnight fasting plasma glucose ≥7.0 mmol/l (126 mg/dl) …
Outcome of an outbreak of acute hepatitis C among healthy volunteers participating in pharmacokinetics studies
Authors: Alberto Larghi, Massimo Zuin, Andrea Crosignani, Maria Lisa Ribero, Cristina Pipia, Pier Maria Battezzati, Giorgio Binelli, Francesco Donato, Alessandro Remo Zanetti, Mauro Podda, Alessandro Tagger
Journal: Hepatology (2002)

We identified 15 patients with acute hepatitis C (AHC) among 29 healthy volunteers participating in 2 consecutive pharmacokinetics studies. Molecular techniques were used to determine the relatedness of viral strains, whereas clinical and virologic follow-up was started to establish the course and outcome of the acute infection. After presentation, serum liver enzymes and HCV RNA were monitored weekly for 4 months, then monthly for at least 12 months. Liver biopsy was performed 6 to 12 months after AHC diagnosis. Phylogenetic analysis of coding regions for the envelope glycoproteins E1 and E2 was performed. At presentation, all 15 patients tested HCV RNA-positive and had HCV genotype 2c. Phylogenetic analysis indicated a common source of infection. Fourteen patients agreed to be followed prospectively. Infection resolved spontaneously in 8 patients, HCV RNA becoming undetectable by 4 to 5 months after the presumed time of infection in 5 of them and by 8, 13, and 24 months in the remaining 3. Six patients developed chronic infection. Liver biopsies performed in 9 subjects who were HCV RNA-positive 6 months after AHC diagnosis revealed that the prevalent histologic finding was lobular inflammation. In conclusion, our homogeneous cohort showed a wide spectrum of clinical, virologic and histologic features, and, more importantly, short-term outcome differed noticeably despite the common source of infection.
The relationship between corticosteroids and symptoms in patients with primary brain tumors: utility of the Dexamethasone Symptom Questionnaire–Chronic
Authors: Terri S. Armstrong, Yuan Ying, Jimin Wu, Alvina A. Acquaye, Elizabeth Vera-Bolanos, Mark R. Gilbert, Paul D. Brown, Janette Vardy, Caroline Chung
Journal: Neuro-Oncology (2015)

Corticosteroids can have many side effects that impact the patient's quality of life and functional status. The Dexamethasone Symptom Questionnaire–Chronic (DSQ-C) was developed to report corticosteroid side effects. This study's objective was to evaluate the utility of the DSQ-C and report associated signs and symptoms in brain tumor patients. Data collection included demographic and disease characteristics and the DSQ-C. Descriptive statistics were used to report associations among variables. Linear regression models were applied to assess the effects of the cumulative daily dose (mg/d × total d) on DSQ-C scores. Psychometrics included factor analysis to assess construct validity and Cronbach's alpha for internal consistency. Ninety-six adult patients with primary (77%) or metastatic (23%) brain tumors participated, with 74% on corticosteroids. Participants were primarily white (83%) males (65%) between 20 and 75 years of age (median, 53). Median corticosteroid dose duration was 4 mg/day for 1 month (range, 0–26 mo). The DSQ-C scores ranged from 17 to 54 (mean of 27), with 35% reporting increased appetite and trouble sleeping. Factor analysis indicated 6 underlying constructs explaining 53% of variance. DSQ-C internal consistency (reliability) was 0.77. The DSQ-C discriminated between patients who were on steroids and those who were not (P < .01), and cumulative dose predicted DSQ-C scores (P < .001). This study demonstrated the potential use of the DSQ-C as a screening tool for side effects associated with corticosteroid use in brain tumor patients. Future analyses should include longitudinal evaluation of severity and biologic underpinnings of variability of timing and severity of symptoms.
PREVALENCE AND PREDICTORS OF PREMATURE DISCONTINUATION OF CLOPIDOGREL AFTER DRUG-ELUTING STENT IMPLANTATION IN A NORTH AMERICAN POPULATION
Authors: Ana Laynez Carnicero, Michael A. Gaglia, Kohei Wakabayashi, Rafael Romaguera, Gabriel Maluenda, Gabriel Sardi, Itsik Ben-Dor, Manuel A. Gonzalez, Michael Mahmoudi, Rebecca Torguson, Zhenyi Xue, William O. Suddath, Lowell F. Satler, Kenneth M. Kent, Joseph Lindsay, Augusto D. Pichard, Ron Waksman
Journal: Journal of the American College of Cardiology (2011)
Bronchiolitis obliterans in a patient with localized scleroderma treated with D-penicillamine
Authors: A Boehler, P Vogt, R Speich, W Weder, EW Russi
Journal: European Respiratory Journal (1996)

D-penicillamine-associated bronchiolitis obliterans (BO) is a rare but well-known pulmonary complication in patients with rheumatoid arthritis or progressive systemic sclerosis. It has been assumed that in most, if not all cases, BO is a complication of the underlying disease rather than a side-effect of treatment. We report the case of a 46 year old man with scleroderma localized to his lower legs (morphea), who received a daily dose of 750 mg D-penicillamine. During the treatment of 1 yr duration, he developed progressive shortness of breath due to a worsening obstructive ventilatory defect suggesting BO, which was confirmed by surgical lung biopsy (constrictive BO). Bronchial obstruction progressed over the next 5 yrs and did not respond to corticosteroids. The patient finally underwent a successful single left lung transplantation. The histological features of constrictive BO were confirmed in the explanted lung. This observation suggests that D-penicillamine may induce bronchiolitis obliterans in the absence of a systemic connective tissue disease.
Critical analysis of relaxation: conventional methods and contemporary practice
Authors: Jolly Roy
Journal: British Journal of Sports Medicine (2010)

Relaxation techniques for sport are reviewed in relation to ‘muscle to mind’ and ‘mind to muscle’ strategies. The presentation addresses the different types of strategies and an overview of the overlap that exists in the techniques of relaxation. Most techniques offer a way to enhance self awareness to regulate arousals and behaviour. Without the knowledge and mastery of the different techniques, any application becomes limited. An understanding of different techniques would facilitate the use of the appropriate primary technique that works well for individual athlete and reserve back up techniques.
Expanded HIV Screening in the United States: Effect on Clinical Outcomes, HIV Transmission, and Costs
Authors: A. David Paltiel, Rochelle P. Walensky, Bruce R. Schackman, George R. Seage, Lauren M. Mercincavage, Milton C. Weinstein, Kenneth A. Freedberg
Journal: Annals of Internal Medicine (2006)

Background: An extensive literature supports expanded HIV screening in the United States. However, the question of whom to test and how frequently remains controversial. Objective: To inform the design of HIV screening programs by identifying combinations of screening frequency and HIV prevalence and incidence at which screening is cost-effective. Design: Cost-effectiveness analysis linking simulation models of HIV screening to published reports of HIV transmission risk, with and without antiretroviral therapy. Data Sources: Published randomized trials, observational cohorts, national cost and service utilization surveys, the Red Book, and previous modeling results. Target Population: U.S. communities with low to moderate HIV prevalence (0.05% to 1.0%) and annual incidence (0.0084% to 0.12%). Time Horizon: Lifetime. Perspective: Societal. Interventions: One-time and increasingly frequent voluntary HIV screening of all adults using a same-day rapid test. Outcome Measures: HIV infections detected, secondary transmissions averted, quality-adjusted survival, lifetime medical costs, and societal cost-effectiveness, reported in discounted 2004 dollars per quality-adjusted life-year (QALY) gained. Results of Base-Case Analysis: Under moderately favorable assumptions regarding the effect of HIV patient care on secondary transmission, routine HIV screening in a population with HIV prevalence of 1.0% and annual incidence of 0.12% had incremental cost-effectiveness ratios of $30 800/QALY (one-time screening), $32 300/QALY (screening every 5 years), and $55 500/QALY (screening every 3 years). In settings with HIV prevalence of 0.10% and annual incidence of 0.014%, one-time screening produced cost-effectiveness ratios of $60 700/QALY. Results of Sensitivity Analysis: The cost-effectiveness of screening policies varied within a narrow range as assumptions about the effect of screening on secondary transmission varied from favorable to unfavorable. Assuming moderately favorable effects of antiretroviral therapy on transmission, cost-effectiveness ratios remained below $50 000/QALY in settings with HIV prevalence as low as 0.20% for routine HIV screening on a one-time basis and at prevalences as low as 0.45% and annual incidences as low as 0.0075% for screening every 5 years. Limitations: This analysis does not address the difficulty of determining the prevalence and incidence of undetected HIV infection in a given patient population. Conclusions: Routine, rapid HIV testing is recommended for all adults except in settings where there is evidence that the prevalence of undiagnosed HIV infection is below 0.2%.
PIPE-CLIP: a comprehensive online tool for CLIP-seq data analysis
Authors: Beibei Chen, Jonghyun Yun, Min Soo Kim, Joshua T Mendell, Yang Xie
Journal: Genome biology (2014)

Abstract CLIP-seq is widely used to study genome-wide interactions between RNA-binding proteins and RNAs. However, there are few tools available to analyze CLIP-seq data, thus creating a bottleneck to the implementation of this methodology. Here, we present PIPE-CLIP, a Galaxy framework-based comprehensive online pipeline for reliable analysis of data generated by three types of CLIP-seq protocol: HITS-CLIP, PAR-CLIP and iCLIP. PIPE-CLIP provides both data processing and statistical analysis to determine candidate cross-linking regions, which are comparable to those regions identified from the original studies or using existing computational tools. PIPE-CLIP is available at http://pipeclip.qbrc.org/ .