tbuckley/cabot-search huggingface dataset:
Variations in the Promoter Region of the Glutaminase Gene and the Development of Hepatic Encephalopathy in Patients With Cirrhosis
Authors: Manuel Romero-Gómez
Journal: Annals of Internal Medicine (2010)

Hepatic encephalopathy is a major complication of cirrhosis and is associated with a poor prognosis.To identify mutations in the gene sequence for glutaminase in humans that could be responsible for the development of hepatic encephalopathy in patients with cirrhosis.Cohort study.Outpatient clinics in 6 Spanish hospitals.109 consecutive patients with cirrhosis in the estimation cohort, 177 patients in the validation cohort, and 107 healthy control participants.Patients were followed every 3 or 6 months until the development of hepatic encephalopathy or liver transplantation, death, or the end of the study.The genetic analyses showed that glutaminase TACC and CACC haplotypes were linked to the risk for overt hepatic encephalopathy. Mutation scanning of the glutaminase gene identified a section in the promoter region where base pairs were repeated (a microsatellite). Over a mean follow-up of 29.6 months, hepatic encephalopathy occurred in 28 patients (25.7%) in the estimation cohort. Multivariable Cox models were used to determine the following independent predictors: Child-Turcotte-Pugh stage (hazard ratio [HR], 1.6 [95% CI, 1.29 to 1.98]; P = 0.001), minimal hepatic encephalopathy (HR, 3.17 [CI, 1.42 to 7.09]; P = 0.006), and having 2 long alleles of the microsatellite (HR, 3.12 [CI, 1.39 to 7.02]; P = 0.006). The association between 2 long alleles of the microsatellite and overt hepatic encephalopathy was confirmed in a validation cohort (HR, 2.1 [CI, 1.17 to 3.79]; P = 0.012). Functional studies showed higher luciferase activity in cells transfected with the long form of the microsatellite, which suggests that the long microsatellite enhances glutaminase transcriptional activity.Other genes and allelic variants might be involved in the clinical expression of hepatic encephalopathy.This study identifies a genetic factor that is associated with development of hepatic encephalopathy in patients with cirrhosis.Instituto de Salud Carlos III, Spanish Ministry of Health.
Comparative systemic and renal effects of dopamine and angiotensin-converting enzyme inhibition with enalaprilat in patients with heart failure.
Authors: C S Maskin, S Ocken, B Chadwick, T H LeJemtel
Journal: Circulation (1985)

Renal and systemic hemodynamics were measured during titration of dopamine and serially after intravenous administration of enalaprilat in nine patients with chronic severe congestive heart failure. During titration of dopamine, renal blood flow increased by 99%, from 304 +/- 120 to 604 +/- 234 ml/min (p less than .01) at a dose of dopamine of 2.1 micrograms/kg/min, which produced only a 21% increase in cardiac index, from 1.96 +/- 0.36 to 2.38 +/- 0.35 liters/min/m2 (p less than .05). Cardiac index was increased maximally at a dose of 4.0 micrograms/kg/min dopamine; however, renal blood flow was not further augmented. In contrast, after intravenous administration of enalaprilat, peak improvement of renal blood flow and cardiac index occurred concomitantly. Renal blood flow increased by 35%, from 316 +/- 97 to 427 +/- 107 ml/min (p less than .05), and cardiac index increased by 18%, from 1.99 +/- 0.40 to 2.35 +/- 0.40 liters/min/m2 (p less than .05). At similar increases in cardiac index, dopamine produced a greater increase in renal blood flow than enalaprilat: 604 +/- 234 vs 427 +/- 107 ml/min (p less than .05). Mean systemic arterial pressure, however, was greater with dopamine than with enalaprilat (78.1 +/- 16.7 vs 70.2 +/- 17.2 mm Hg; p less than .05) at peak effect. Thus, although both drugs appear to be potent renal vasodilators in patients with severe congestive heart failure, dopamine may be more effective in augmenting renal blood flow.
Intermittent Hypoxia Causes Insulin Resistance in Lean Mice Independent of Autonomic Activity
Authors: Nao Iiyori, Laura C. Alonso, Jianguo Li, Mark H. Sanders, Adolfo Garcia-Ocana, Robert M. O'Doherty, Vsevolod Y. Polotsky, Christopher P. O'Donnell
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale and Objectives: Although many clinical physiology and epidemiology studies show an association between obstructive sleep apnea (OSA) and markers of insulin resistance, no causal pathway has been established. The purpose of the current study was to determine if the intermittent hypoxia (IH) stimulus that characterizes OSA causes insulin resistance in the absence of obesity. Furthermore, we assessed the impact of IH on specific metabolic function in liver and muscle. Finally, we examined the potential mechanistic role of the autonomic nervous system (ANS) in mediating insulin resistance in response to IH.Methods and Results: Hyperinsulinemic euglycemic clamps were conducted and whole-body insulin sensitivity, hepatic glucose output, and muscle-specific glucose utilization assessed in conscious, chronically instrumented adult male C57BL/6J mice exposed to (1) IH (achieving a nadir of FiO2 = 5–6% at 60 cycles/h for 9 h), (2) intermittent air as a control, (3) IH with ANS blockade (hexamethonium), or (4) IA with ANS blockade. IH decreased whole-body insulin sensitivity compared with intermittent air (38.8 ± 2.7 vs. 49.4 ± 1.5 mg/kg/min, p < 0.005) and reduced glucose utilization in oxidative muscle fibers, but did not cause a change in hepatic glucose output. Furthermore, the reduction in whole-body insulin sensitivity during IH was not restored by ANS blockade.Conclusion: We conclude that IH can cause acute insulin resistance in otherwise lean, healthy animals, and that the response is associated with decreased glucose utilization of oxidative muscle fibers, but that it occurs independently of activation of the ANS.
Activation of Protein Kinase A Modulates Trafficking of the Human Cardiac Sodium Channel in <i>Xenopus</i> Oocytes
Authors: Jingsong Zhou, Jianxun Yi, NingNing Hu, Alfred L. George, Katherine T. Murray
Journal: Circulation Research (2000)

Abstract —Voltage-gated Na + channels are critical determinants of electrophysiological properties in the heart. Stimulation of β-adrenergic receptors, which activate cAMP-dependent protein kinase (protein kinase A [PKA]), can alter impulse conduction in normal tissue and promote development of cardiac arrhythmias in pathological states. Recent studies demonstrate that PKA activation increases cardiac Na + currents, although the mechanism of this effect is unknown. To explore the molecular basis of Na + channel modulation by β-adrenergic receptors, we have examined the effects of PKA activation on the recombinant human cardiac Na + channel, hH1. Both in the absence and the presence of hβ 1 subunit coexpression, activation of PKA caused a slow increase in Na + current that did not saturate despite kinase stimulation for 1 hour. In addition, there was a small shift in the voltage dependence of channel activation and inactivation to more negative voltages. Chloroquine and monensin, compounds that disrupt plasma membrane recycling, reduced hH1 current, suggesting rapid turnover of channels at the cell surface. Preincubation with these agents also prevented the PKA-mediated rise in Na + current, indicating that this effect likely resulted from an increased number of Na + channels in the plasma membrane. Experiments using chimeric constructs of hH1 and the skeletal muscle Na + channel, hSKM1, identified the I-II interdomain loop of hH1 as the region responsible for the PKA effect. These results demonstrate that activation of PKA modulates both trafficking and function of the hH1 channel, with changes in Na + current that could either speed or slow conduction, depending on the physiological circumstances. ( Circ Res. 2000;87:33-38.)
High independent prognostic and predictive value of circulating tumor cells compared with serum tumor markers in a large prospective trial in first-line chemotherapy for metastatic breast cancer patients
Authors: J.-Y. Pierga, D. Hajage, T. Bachelot, S. Delaloge, E. Brain, M. Campone, V. Diéras, E. Rolland, L. Mignot, C. Mathiot, F.-C. Bidard
Journal: Annals of Oncology (2011)

Circulating tumor cells (CTCs) are a prognostic marker in metastatic breast cancer, but comparisons with serum tumor markers (CA 15-3, carcinoembryonic antigen and lactate dehydrogenase) variations are needed.
Tuberculosis with diabetes mellitus: Does delayed sputum conversion always needs MDR evaluation?
Authors: Shital Patil, Sanjay Mundkar, Anil Jadhav, Nitin Kalme
Journal: European Respiratory Journal (2014)

Background- In India, in 2011, there were 61.3 million people living with diabetes, and 1.98 million people developing TB.   Methods- Prospective study conducted at MIMSR Medical College Latur, India during Jan. 2011 to Nov. 2013 included 200 cases of Diabetes Mellitus (DM) with TB, compared with 200 cases of TB without DM. Objectives of study were to correlate impact of DM on sputum conversion rate and on clinic-radiological overlap of DM and PTB. Sputum smear AFB examinations were done at diagnosis and subsequently at completion of intensive phase. Liquid Culture DST (MGIT-960) were done in all the cases those doesn9t showing sputum conversion even after extension of one month therapy post-intensive phase.   Results  -  PTB was observed in 141 (70.5%) cases with DM as compared to 173 (86.5%) cases without DM (p   Conclusion- DM affects the clinical, bacteriological and radiological presentation of PTB. Failure of sputum conversion should be interpreted cautiously, as many cases were showing delayed sputum conversion after extension of one month of intensive phase; this may be because of generalized immunosupression due to underlying comorbidity of DM.
Maximal step-up height as a simple and relevant health indicator: a study of leg muscle strength and the associations to age, anthropometric variables, aerobic fitness and physical function
Authors: Lillemor A Nyberg, Mai-Lis Hellénius, Per Wändell, Jan Kowalski, Carl Johan Sundberg
Journal: British Journal of Sports Medicine (2013)

Background Low muscle strength is related to an increased risk for several chronic diseases. Increased muscle strength improves daily function and quality of life. Objective To measure maximal step-up height, an assessment of leg strength and function, and its association to age, anthropometric variables, maximal oxygen uptake (VO 2 -max) and self-reported physical function before and after a physical activity programme. Methods Female patients (n=178, 22–83 years) with musculoskeletal disorders, metabolic risk factors and other chronic diseases were recruited from primary care. Maximal step-up height (standardised step-up without a kick-off with the floor foot), anthropometric variables, VO 2 -max and self-reported physical function (Short Form 36 (SF-36)) were assessed before and after a 3-month group training intervention programme. Associations between maximal step-up height and other variables were examined using univariate and multivariate methods. Results At baseline and after intervention, maximal step-up height was negatively correlated to age, waist circumference and body weight and positively correlated to VO 2 -max, self-reported physical function and height. Furthermore, maximal step-up height correlated to training intensity at follow-up. Variations in changes in maximal step-up height were significantly explained by changes in waist circumference and physical function, regardless of age and changes in VO 2 -max. Maximal step-up height below 24 cm discriminated patients with self-reported severe limitation in physical function. Conclusions Maximal step-up height, assessed simply with a standardised step-up test, may function as a relevant indicator of health since it correlated negatively to the metabolic risk factors, waist circumference, body weight and age, and positively to VO 2 -max and physical function.
Pulmonary Function Tests in Preschool Children with Cystic Fibrosis
Authors: Nicole Beydon, Francis Amsallem, Mireille Bellet, Michèle Boulé, Michèle Chaussain, André Denjean, Régis Matran, Isabelle Pin, Corinne Alberti, Claude Gaultier
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Pulmonary function tests have rarely been assessed in preschool children with cystic fibrosis (CF). The objective of this multicenter study was to compare pulmonary function in 39 preschool children with CF (height, 90–130 cm; 16 homozygous ΔF508) and in 79 healthy control children. Functional residual capacity (helium dilution technique) and expiratory interrupter resistance (Rintexp) (interrupter technique) were measured. As compared with control children, children with CF had significantly higher Rintexp, expressed as absolute values and as Z-scores (1.05 ± 0.36 versus 0.80 ± 0.20 kPa·L−1 · second, p < 0.0001; and 1.31 ± 1.72 versus 0.19 ± 0.97, p < 0.0001), and significantly lower specific expiratory interrupter conductance (1.29 ± 0.34 versus 1.63 ± 0.43 kPa−1 · second, p < 0.0001). The effect of the bronchodilator salbutamol on Rintexp was not significantly different between children with CF and control children. Rintexp Z-scores were significantly higher in children with CF who were exposed to passive smoke (n = 8) (p < 0.03). Children with CF and with a history of respiratory symptoms (n = 31) had significantly higher functional residual capacity Z-scores (p < 0.02) and lower specific expiratory interrupter conductance Z-scores (p < 0.04). Genotype did not influence the data. We conclude that Rintexp and functional residual capacity measurements may help to follow young children with CF who are unable to perform reproducible forced expiratory maneuvers.
TOPK inhibitor induces complete tumor regression in xenograft models of human cancer through inhibition of cytokinesis
Authors: Yo Matsuo, Jae-Hyun Park, Takashi Miyamoto, Shinji Yamamoto, Shoji Hisada, Houda Alachkar, Yusuke Nakamura
Journal: Science Translational Medicine (2014)

TOPK inhibitor kills cancer cells by causing a cytokinesis defect and promotes tumor regression in mouse models.
Clinicopathologic Characteristics of Angioimmunoblastic T-Cell Lymphoma: Analysis of the International Peripheral T-Cell Lymphoma Project
Authors: Massimo Federico, Thomas Rudiger, Monica Bellei, Bharat N. Nathwani, Stefano Luminari, Bertrand Coiffier, Nancy L. Harris, Elaine S. Jaffe, Stefano A. Pileri, Kerry J. Savage, Dennis D. Weisenburger, James O. Armitage, Nicholas Mounier, Julie M. Vose
Journal: Journal of Clinical Oncology (2012)

The International Peripheral T-Cell Lymphoma Project was undertaken to better understand the subtypes of T-cell and natural killer (NK) -cell lymphomas.Angioimmunoblastic T-cell lymphoma (AITL) was diagnosed according to the 2001 WHO criteria by a central review process consisting of panels of expert hematopathologists. Clinical, pathologic, immunophenotyping, treatment, and survival data were correlated.Of 1,314 patients, 243 (18.5%) were diagnosed with AITL. At presentation, generalized lymphadenopathy was noted in 76% of patients, and 89% had stages III to IV disease. Skin rash was observed in 21% of patients. Hemolytic anemia and hypergammoglobulinemia occurred in 13% and 30% of patients, respectively. Five-year overall and failure-free survivals were 33% and 18%, respectively. At presentation, prognostic models were evaluated, including the standard International Prognostic Index, which comprised the following factors: age ≥ 60 years, stages III to IV disease, lactic dehydrogenase (LDH) > normal, extranodal sites (ENSs) > one, and performance status (PS) ≥ 2; the Prognostic Index for Peripheral T-Cell Lymphoma, comprising: age ≥ 60 years, PS ≥ 2, LDH > normal, and bone marrow involvement; and the alternative Prognostic Index for AITL (PIAI), comprising: age > 60 years, PS ≥ 2, ENSs > one, B symptoms, and platelet count < 150 × 10(9)/L. The simplified PIAI had a low-risk group (zero to one factors), with 5-year survival of 44%, and a high-risk group (two to five factors), with 5-year survival of 24% (P = .0065).AITL is a rare clinicopathologic entity characterized by an aggressive course and dismal outcome with current therapies.
Tumor Chemotherapy: Efficacy Dependent on Mode of Growth2
Authors: Ronald F. Hagemann, Larry L. Schenken, S. Lesher
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Tumor Chemotherapy: Efficacy Dependent on Mode of Growth Get access Ronald F. Hagemann, Ronald F. Hagemann Cell and Radiation Biology Laboratories, Department of Radiology, Allegheny General Hospital, Pittsburgh, Pennsylvania 15212 Search for other works by this author on: Oxford Academic PubMed Google Scholar Larry L. Schenken, Larry L. Schenken Cell and Radiation Biology Laboratories, Department of Radiology, Allegheny General Hospital, Pittsburgh, Pennsylvania 15212 Search for other works by this author on: Oxford Academic PubMed Google Scholar S. Lesher S. Lesher Cell and Radiation Biology Laboratories, Department of Radiology, Allegheny General Hospital, Pittsburgh, Pennsylvania 15212 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 50, Issue 2, February 1973, Pages 467–474, https://doi.org/10.1093/jnci/50.2.467 Published: 01 February 1973 Article history Received: 10 August 1972 Accepted: 04 October 1972 Published: 01 February 1973
Treatment of Wilson's disease with zinc. I. Oral zinc therapy regimens
Authors: Gretchen M. Hill, George J. Brewer, Ananda S. Prasad, Connie R. Hydrick, Deborah E. Hartmann
Journal: Hepatology (1987)

The standard therapy for preventing copper accumulation in Wilson's disease, D-penicillamine, has been a life-saving drug, but it has many side effects and some patients are completely intolerant. We have been using oral zinc as another approach to the therapy for Wilson's disease, with copper balance studies as the key initial assessment of the adequacy of a given dose or regimen of zinc therapy. We earlier reported that an intensive regimen of zinc (zinc taken every 4 hr) was effective in controlling copper balance. We have now shown with balance studies that a simplified zinc therapy regimen of 50 mg zinc taken 3 times per day is effective in controlling copper balance. Preliminary work presented here with other simplified regimens also indicate their effectiveness. These studies increase the data base, in terms of copper balance, for zinc therapy of Wilson's disease, and expand the dose range and regimens of zinc which have been shown to control copper balance.
Collagen Cross-Linking with Photoactivated Riboflavin (PACK-CXL) for the Treatment of Advanced Infectious Keratitis with Corneal Melting
Authors: Dalia G. Said, Mohamed S. Elalfy, Zisis Gatzioufas, Ehab S. El-Zakzouk, Mansour A. Hassan, Mohamed Y. Saif, Ahmed A. Zaki, Harminder S. Dua, Farhad Hafezi
Journal: Ophthalmology (2014)
Determination of human platelet antigen typing by molecular methods: Importance in diagnosis and early treatment of neonatal alloimmune thrombocytopenia
Authors: Suzanne A. Arinsburg, Beth H. Shaz, Connie Westhoff, Melissa M. Cushing
Journal: American Journal of Hematology (2011)

Neonatal alloimmune thrombocytopenia (NAIT) is the most common cause of severe thrombocytopenia and intracranial hemorrhage in the perinatal period. While the gold standard for making a diagnosis of NAIT is detection of a human platelet antigen (HPA)-specific antibody in maternal serum, together with identifying an incompatibility between the parents for the cognate HPA antigen, platelet genotyping is the gold standard method for HPA typing. Platelet genotyping is critical in screening at-risk fetuses for the presence ofthe HPA corresponding to the maternal antibody. In addition, platelet genotyping may play a role in population screening to identify women at risk for sensitization, and thus, fetuses at risk for NAIT. The most commonly used methods of platelet genotyping are sequence-specific primer-polymerase chain reaction (PCR-SSP), restriction fragment length polymorphism-PCR (PCR-RFLP), and TaqMan real-time PCR. PCR-SSP and PCR-RFLP are relatively inexpensive and technically simple methods, but they are not easily automated and require expertise for reliable interpretation of results. Newer methods that allow for multiplexing, automation, and easily interpretable results, such as bead arrays, are currently in development and available for research purposes.
Casq2 deletion causes sarcoplasmic reticulum volume increase, premature Ca2+ release, and catecholaminergic polymorphic ventricular tachycardia
Authors: Björn C. Knollmann, Nagesh Chopra, Thinn Hlaing, Brandy Akin, Tao Yang, Kristen Ettensohn, Barbara E.C. Knollmann, Kenneth D. Horton, Neil J. Weissman, Izabela Holinstat, Wei Zhang, Dan M. Roden, Larry R. Jones, Clara Franzini-Armstrong, Karl Pfeifer
Journal: Journal of Clinical Investigation (2006)

Cardiac calsequestrin (Casq2) is thought to be the key sarcoplasmic reticulum (SR) Ca2+ storage protein essential for SR Ca2+ release in mammalian heart. Human CASQ2 mutations are associated with catecholaminergic ventricular tachycardia. However, homozygous mutation carriers presumably lacking functional Casq2 display surprisingly normal cardiac contractility. Here we show that Casq2-null mice are viable and display normal SR Ca2+ release and contractile function under basal conditions. The mice exhibited striking increases in SR volume and near absence of the Casq2-binding proteins triadin-1 and junctin; upregulation of other Ca2+-binding proteins was not apparent. Exposure to catecholamines in Casq2-null myocytes caused increased diastolic SR Ca2+ leak, resulting in premature spontaneous SR Ca2+ releases and triggered beats. In vivo, Casq2-null mice phenocopied the human arrhythmias. Thus, while the unique molecular and anatomic adaptive response to Casq2 deletion maintains functional SR Ca2+ storage, lack of Casq2 also causes increased diastolic SR Ca2+ leak, rendering Casq2-null mice susceptible to catecholaminergic ventricular arrhythmias.
Mechanosensitive connective tissue: potential influence on heart rhythm
Authors: P. Kohl, D. Noble
Journal: Cardiovascular Research (1996)

Connective tissue is an essential component of cardiac histo-architecture. In particular the sinus node region of the healthy heart is rich in fibrous connective tissue [l]. The distinctive division of sino-atria1 node cells in multiple strands of different size reported in the original first description of the node by Keith and Flack [2] appears to be brought about by cardiac fibroblasts forming sheet-like extensions that enwrap groups of pacemaker cells [3]. According to different quantitative studies, connective tissue occupies between 45% [4] and 73% [5] of the volume of the sinus node in man. A number of pathological states is associated with excessive growth of fibrous tissue in other parts of the heart. These pathologies include focal scar development in regions of myocardial ischaemia and infarction, or more scattered fibrosis induced by inflammation during rheumatic heart disease and other processes. The predominant contribution of fibroblasts to post-traumatic atria1 or ventricular restoration is based on their sustained proliferative potential in the adult organism, while myocyte proliferation is confined mainly to fetal periods of development t6,71. Cardiac fibroblasts are known to be mechanosensitive. They respond to mechanical stimulation by changes in gene expression and collagen synthesis in vivo [8,9] and in vitro [lo]. This generative response to changes in the mechanical environment is assumed to find clinical expression in fibrosis induced by pressure overload [l l] and tissue dilatation [ 121. Recently, cardiac fibroblasts have been implicated as a possible alternative substrate for some forms of cardiac mechano-electric feedback [13] observed in the sino-atria1 node region and in cardiac scar tissue [14]. This short