tbuckley/cabot-search huggingface dataset:
MRC OX-22, a monoclonal antibody that labels a new subset of T lymphocytes and reacts with the high molecular weight form of the leukocyte-common antigen.
Authors: G P Spickett, M R Brandon, D W Mason, A F Williams, G R Woollett
Journal: The Journal of Experimental Medicine (1983)

A mouse monoclonal antibody (MRC OX-22) is described that labels rat T cells which mediate graft-versus-host reactions and those responsible for the suppression of antibody synthesis in hosts undergoing these reactions. In contrast, most of the T cells that provide help for B cells are MRC OX-22 negative. These results, taken together with those published previously, demonstrate that the rat contains at least three phenotypically and functionally distinct subsets of T cells. The MRC OX-22 antibody also labels all B cells, 50% of bone marrow cells, but only 2% of thymocytes. Of these latter cells about half are found at the edge of the medulla and the remainder are randomly distributed throughout the cortex and medulla. These findings lend support to the view that mature thymocytes leave the thymus at the cortico-medullary junction, and also suggest that both cortex and medulla may be sites where thymocytes mature. Biochemical studies showed that the MRC OX-22 antibody reacts with the high molecular weight form of the leukocyte-common antigen (L-CA). Comparison with data on human L-CA suggests that the molecular and antigenic heterogeneity of this set of glycoproteins has been conserved between rat and man.
Proline-Directed Protein Kinase F<sub>A</sub> Is a Powerful and Independent Prognostic Predictor for Progression and Patient Survival of Hepatocellular Carcinoma
Authors: Yu-Chen Hsu, Hsiao-Hui Fu, Yung-Ming Jeng, Po-Huang Lee, Shiaw-Der Yang
Journal: Journal of Clinical Oncology (2006)

Purpose Molecular, cellular, and animal studies have established that overexpressed proline-directed protein kinase F A (PDPK F A ) is essential for the development of tumorigenesis, invasion, and metastasis of human cancer cells. However, the prognostic role of PDPK F A in cancer patients remains largely unknown. In this study, association of PDPK F A expression with poor prognosis of hepatocellular carcinoma (HCC) patients was examined. Patients and Methods PDPK F A expression in the resected tumors of 134 HCC patients (112 men and 22 women) with ages ranging from 33 to 83 years (mean, 55 years) was analyzed by immunohistochemistry. Highly condensed cytoplasmic and nuclear PDPK F A associated with tumor cells was used as the major scoring parameter for positive PDPK F A expression. Results Approximately 68% of the patients (91 of 134) exhibited positive PDPK F A expression. Patients with positive PDPK F A showed poorer disease-free survival and overall survival (P &lt; .001). Cox multivariate regression analysis further established PDPK F A as the strongest independent prognosticator for progression and patient survival of HCC (hazard ratio [HR], 2.878; 95% CI, 1.634 to 5.067 for disease-free survival; and HR, 5.035; 95% CI, 2.137 to 11.866 for overall survival; P &lt; .001). Conclusion Consistent with PDPK F A ’s essential role in the development of highly malignant phenotypes, the present study establishes the potential prognostic role of PDPK F A in progression and patient survival of surgically resected primary HCC. Taken together, PDPK F A represents a new modifiable signal-transducing target for prognostic prediction and adjuvant treatment of patients with aggressive HCC after hepatic resection.
Regular tai chi chuan exercise enhances functional mobility and CD4CD25 regulatory T cells
Authors: S-H Yeh, H Chuang, L-W Lin, C-Y Hsiao, H L Eng
Journal: British Journal of Sports Medicine (2006)

The duration and vigour of physical exercise are widely considered to be critical elements that may positively or negatively affect physical health and immune response.To investigate the effect of a 12 week programme of regular tai chi chuan exercise (TCC) on functional mobility, beliefs about benefits of exercise on physical and psychological health, and immune regulation in middle aged volunteers.This quasi-experimental research design involving one group with testing before and after the programme was conducted to measure the effect of 12 weeks of TCC exercise in 14 men and 23 women from the normal community.Regular TCC exercise had a highly significant positive effect on functional mobility (p = 0.001) and beliefs about the health benefits of exercise (p = 0.013) in the 37 participants. Total white blood cell and red blood cell count did not change significantly, but a highly significant (p<0.001) decrease in monocyte count occurred. A significant (p = 0.05) increase in the ratio of T helper to suppressor cells (CD4:CD8) was found, along with a significant (p = 0.015) increase in CD4CD25 regulatory T cells. Production of the regulatory T cell mediators transforming growth factor beta and interleukin 10 under specific antigen stimulation (varicella zoster virus) was also significantly increased after this exercise programme.A 12 week programme of regular TCC exercise enhances functional mobility, personal health expectations, and regulatory T cell function.
Comparative genomics of mutualistic viruses of Glyptapanteles parasitic wasps
Authors: Christopher A Desjardins, Dawn E Gundersen-Rindal, Jessica B Hostetler, Luke J Tallon, Douglas W Fadrosh, Roger W Fuester, Monica J Pedroni, Brian J Haas, Michael C Schatz, Kristine M Jones, Jonathan Crabtree, Heather Forberger, Vishvanath Nene
Journal: Genome biology (2008)

Abstract Background Polydnaviruses, double-stranded DNA viruses with segmented genomes, have evolved as obligate endosymbionts of parasitoid wasps. Virus particles are replication deficient and produced by female wasps from proviral sequences integrated into the wasp genome. These particles are co-injected with eggs into caterpillar hosts, where viral gene expression facilitates parasitoid survival and, thereby, survival of proviral DNA. Here we characterize and compare the encapsidated viral genome sequences of bracoviruses in the family Polydnaviridae associated with Glyptapanteles gypsy moth parasitoids, along with near complete proviral sequences from which both viral genomes are derived. Results The encapsidated Glyptapanteles indiensis and Glyptapanteles flavicoxis bracoviral genomes, each composed of 29 different size segments, total approximately 517 and 594 kbp, respectively. They are generated from a minimum of seven distinct loci in the wasp genome. Annotation of these sequences revealed numerous novel features for polydnaviruses, including insect-like sugar transporter genes and transposable elements. Evolutionary analyses suggest that positive selection is widespread among bracoviral genes. Conclusions The structure and organization of G. indiensis and G. flavicoxis bracovirus proviral segments as multiple loci containing one to many viral segments, flanked and separated by wasp gene-encoding DNA, is confirmed. Rapid evolution of bracovirus genes supports the hypothesis of bracovirus genes in an 'arms race' between bracovirus and caterpillar. Phylogenetic analyses of the bracoviral genes encoding sugar transporters provides the first robust evidence of a wasp origin for some polydnavirus genes. We hypothesize transposable elements, such as those described here, could facilitate transfer of genes between proviral segments and host DNA.
Downregulation of Endothelial Nitric Oxide Synthase in Rat Aorta After Prolonged Hypoxia In Vivo
Authors: Mourad Toporsian, Karuthapillai Govindaraju, Mohammed Nagi, David Eidelman, Gaetan Thibault, Michael E. Ward
Journal: Circulation Research (2000)

Abstract —The goal of this study was to determine whether hypoxia alters expression of endothelial nitric oxide synthase (eNOS) in the systemic circulation. Rats breathed either air or 10% oxygen for 12 hours, 48 hours, or 7 days. Thoracic aortas were excised and either mounted in organ bath myographs or frozen in liquid nitrogen for later extraction of protein and RNA. eNOS protein (Western blotting) was decreased (20% of normoxic control) after 12 hours, 48 hours, and 7 days of hypoxia. eNOS mRNA (ribonuclease protection assay) was similarly reduced. Acetylcholine (10 −4 mol/L) reversed phenylephrine (10 −5 mol/L) preconstriction by 53.3±5.6% in aortic rings from normoxic rats and 26.1±4.8% in rings from rats exposed to hypoxia for 48 hours ( P &lt;0.05), with comparable impairment of relaxation by the calcium ionophore A23187 (10 −5 mol/L). Responses to diethylamine nitric oxide and 8-bromo-cGMP were unaffected. Aortic cGMP levels after incubation with acetylcholine (10 −6 mol/L) averaged 14.0±1.8 fmol/mg in rings from normoxic rats compared with 8.7±1.0 fmol/mg in rings from hypoxic rats ( P &lt;0.05). Similarly, nitrate concentration (by capillary electrophoresis) in the media in which the rings were incubated was reduced in the hypoxic group (5.6±0.23 μmol/L for hypoxic rats and 7.8±0.7 μmol/L for normoxic rats). Impaired endothelial NO release may handicap the vascular responses that defend vital organ function during hypoxia.
Mutation in the γ2-Subunit of AMP-Activated Protein Kinase Stimulates Cardiomyocyte Proliferation and Hypertrophy Independent of Glycogen Storage
Authors: Maengjo Kim, Roger W. Hunter, Lorena Garcia-Menendez, Guohua Gong, Yu-Ying Yang, Stephen C. Kolwicz, Jason Xu, Kei Sakamoto, Wang Wang, Rong Tian
Journal: Circulation Research (2014)

AMP-activated protein kinase is a master regulator of cell metabolism and an attractive drug target for cancer and metabolic and cardiovascular diseases. Point mutations in the regulatory γ2-subunit of AMP-activated protein kinase (encoded by Prkag2 gene) caused a unique form of human cardiomyopathy characterized by cardiac hypertrophy, ventricular preexcitation, and glycogen storage. Understanding the disease mechanisms of Prkag2 cardiomyopathy is not only beneficial for the patients but also critical to the use of AMP-activated protein kinase as a drug target.We sought to identify the pro-growth-signaling pathway(s) triggered by Prkag2 mutation and to distinguish it from the secondary response to glycogen storage.In a mouse model of N488I mutation of the Prkag2 gene (R2M), we rescued the glycogen storage phenotype by genetic inhibition of glucose-6-phosphate-stimulated glycogen synthase activity. Ablation of glycogen storage eliminated the ventricular preexcitation but did not affect the excessive cardiac growth in R2M mice. The progrowth effect in R2M hearts was mediated via increased insulin sensitivity and hyperactivity of Akt, resulting in activation of mammalian target of rapamycin and inactivation of forkhead box O transcription factor-signaling pathways. Consequently, cardiac myocyte proliferation during the postnatal period was enhanced in R2M hearts followed by hypertrophic growth in adult hearts. Inhibition of mammalian target of rapamycin activity by rapamycin or restoration of forkhead box O transcription factor activity by overexpressing forkhead box O transcription factor 1 rescued the abnormal cardiac growth.Our study reveals a novel mechanism for Prkag2 cardiomyopathy, independent of glycogen storage. The role of γ2-AMP-activated protein kinase in cell growth also has broad implications in cardiac development, growth, and regeneration.
2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults
Authors: Michael D. Jensen, Donna H. Ryan, Caroline M. Apovian, Jamy D. Ard, Anthony G. Comuzzie, Karen A. Donato, Frank B. Hu, Van S. Hubbard, John M. Jakicic, Robert F. Kushner, Catherine M. Loria, Barbara E. Millen, Cathy A. Nonas, F. Xavier Pi-Sunyer, June Stevens, Victor J. Stevens, Thomas A. Wadden, Bruce M. Wolfe, Susan Z. Yanovski
Journal: Journal of the American College of Cardiology (2013)
Liver collagen synthesis in murine schistosomiasis.
Authors: M A Dunn, M Rojkind, K S Warren, P K Hait, L Rifas, S Seifter
Journal: Journal of Clinical Investigation (1977)

Collagen synthesis was measured in liver slices obtained from mice with hepatosplenic schistosomiasis. Enlarged fibrotic livers from these mice contained 20 times more collagen than normal. This model of hepatic fibrosis results from an inflammatory granulomatous host response to Schistosoma mansoni ova in portal tracts, rather than from direct lover cell injury as with carbon tetrachloride-induced liver fibrosis. Collagen synthesis, as measured by the formation of labeled protein-bound hydroxyproline, occurred in granulomas isolated from fibrotic livers. Labeled collagen that cochromatographed with type I collagen was extracted with neutral salt solution from liver slices incubated with labeled proline. The free proline pool of the liver was doubled in infected mice; coordinately, liver slices from these animals showed maximal collagen production when the concentration of free proline in the medium was raised to 0.4 mM, the same level measured in the fibrotic livers. Under such conditions, collagen synthesis was at a rate equivalent to the formation of 5.4 nmol of protein-bound hydroxyproline per g liver in 6 h. In comparative incubations in medium containing 0.2 mM proline, fibrotic liver slices produced 16-fold more collagen than normal slices. The proline analogue, L-azetidine 2-carboxylic acid, effectively inhibited synthesis of labeled collagen by fibrotic liver slices. These studies show the synthesis of collagen in a reproducible animal model of the most prevalent form of human liver fibrosis. Difinitition of the controlling factors in this system is of interest for the general problem of fibrosis produced by immunological responses.
Differential responses to genotoxic agents between induced pluripotent stem cells and tumor cell lines
Authors: Yinghua Lu, Dazhong Xu, Jing Zhou, Yupo Ma, Yongping Jiang, Wenxian Zeng, Wei Dai
Journal: Journal of Hematology & Oncology (2013)

Abstract Given potential values of induced pluripotent stem (iPS) cells in basic biomedical research and regenerative medicine, it is important to understand how these cells regulate their genome stability in response to environmental toxins and carcinogens. The present study characterized the effect of Cr(VI), a well-known genotoxic agent and environmental carcinogen, on major molecular components of DNA damage response pathways in human iPS cells. We compared the effect of Cr(VI) on human iPS cells with two established cell lines, Tera-1 (teratoma origin) and BEAS-2B (lung epithelial origin). We also studied the effect of hydrogen peroxide and doxorubicin on modulating DNA damage responses in these cell types. We demonstrated that ATM and p53 phosphorylation is differentially regulated in human iPS cells compared with Tera-1 and BEAS-2B cells after exposure to various genotoxic agents. Moreover, we observed that inhibition of CK2, but not p38, promotes phosphorylation of p53 S392 in iPS cells. Combined, our data reveal some unique features of DNA damage responses in human iPS cells.
Anaemia in systemic lupus erythematosus: aetiological profile and the role of erythropoietin
Authors: Michalis Voulgarelis, Styliani I G Kokori, John P A Ioannidis, Athanasios G Tzioufas, Despina Kyriaki, Haralampos M Moutsopoulos
Journal: Annals of the Rheumatic Diseases (2000)

To study the prevalence of different causes of anaemia in patients with systemic lupus erythematosus (SLE) and their associations with immunological and clinical parameters and to evaluate the contribution of erythropoietin (Epo) and anti-erythropoietin (anti-Epo) autoantibodies to the development of SLE anaemia.132 SLE patients with anaemia (defined as haemoglobin of 12 g/dl or less for women and 13.5 g/dl or less for men) from among a total of 345 consecutive SLE patients were prospectively enrolled into the study. Standard haematological and immunological tests were performed and serum Epo and anti-Epo antibodies were assayed.The identified causes were anaemia of chronic disease (ACD) n=49 (37.1%), iron deficiency anaemia (IDA) n = 47 (35.6%), autoimmune haemolytic anaemia (AHA) n = 19 (14.4%) and other causes n = 17 (12.9%). There was significant heterogeneity in the severity of anaemia between the four groups (p<0.01) with AHA cases being on average more severe. The proportion of patients with anticardiolipin antibodies, low complement levels and anti-dsDNA differed significantly among the four groups; these markers were particularly common in patients with AHA, and uncommon in patients with IDA. Twenty one of 100 tested patients had anti-Epo antibodies. Such antibodies were seen practically only in patients with ACD (odds ratio 3.1, p = 0.041) and in patients with high lupus activity (ECLAM) scores (odds ratio 1.27 per point, p = 0.055). Epo response was inadequate in 42.4% and 41.2% of patients with ACD and AHA, respectively.Anaemia in SLE usually takes the form of ACD and IDA, however autoimmune haemolysis is not uncommon. SLE patients with different causes of anaemia differ in regard to several immunological parameters. Epo response is blunted in anaemic SLE patients, particularly those with ACD and AHA.
A Randomized, Double-Masked, Placebo-Controlled Study of Alicaforsen, an Antisense Inhibitor of Intercellular Adhesion Molecule 1, for the Treatment of Subjects With Active Crohn’s Disease
Authors: Bruce Yacyshyn, William Y. Chey, Mark K. Wedel, Rosie Z. Yu, David Paul, Emil Chuang
Journal: Clinical Gastroenterology and Hepatology (2007)
Bop encodes a muscle-restricted protein containing MYND and SET domains and is essential for cardiac differentiation and morphogenesis
Authors: Paul D. Gottlieb, Stephanie A. Pierce, Robert J. Sims, Hiroyuki Yamagishi, Elizabeth K. Weihe, June V. Harriss, Shanna D. Maika, William A. Kuziel, Heather L. King, Eric N. Olson, Osamu Nakagawa, Deepak Srivastava
Journal: Nature Genetics (2002)
Cardiovascular Evaluation and Management of Severely Obese Patients Undergoing Surgery
Authors: Paul Poirier, Martin A. Alpert, Lee A. Fleisher, Paul D. Thompson, Harvey J. Sugerman, Lora E. Burke, Picard Marceau, Barry A. Franklin
Journal: Circulation (2009)

Obesity is associated with comorbidities that may lead to disability and death. During the past 20 years, the number of individuals with a body mass index >30, 40, and 50 kg/m(2), respectively, has doubled, quadrupled, and quintupled in the United States. The risk of developing comorbid conditions rises with increasing body mass index. Possible cardiac symptoms such as exertional dyspnea and lower-extremity edema occur commonly and are nonspecific in obesity. The physical examination and electrocardiogram often underestimate cardiac dysfunction in obese patients. The risk of an adverse perioperative cardiac event in obese patients is related to the nature and severity of their underlying heart disease, associated comorbidities, and the type of surgery. Severe obesity has not been associated with increased mortality in patients undergoing cardiac surgery but has been associated with an increased length of hospital stay and with a greater likelihood of renal failure and prolonged assisted ventilation. Comorbidities that influence the preoperative cardiac risk assessment of severely obese patients include the presence of atherosclerotic cardiovascular disease, heart failure, systemic hypertension, pulmonary hypertension related to sleep apnea and hypoventilation, cardiac arrhythmias (primarily atrial fibrillation), and deep vein thrombosis. When preoperatively evaluating risk for surgery, the clinician should consider age, gender, cardiorespiratory fitness, electrolyte disorders, and heart failure as independent predictors for surgical morbidity and mortality. An obesity surgery mortality score for gastric bypass has also been proposed. Given the high prevalence of severely obese patients, this scientific advisory was developed to provide cardiologists, surgeons, anesthesiologists, and other healthcare professionals with recommendations for the preoperative cardiovascular evaluation, intraoperative and perioperative management, and postoperative cardiovascular care of this increasingly prevalent patient population.
Hematopoietic stem cells do not repair the infarcted mouse heart
Authors: A DETEN, H VOLZ, S CLAMORS, S LEIBLEIN, W BRIEST, G MARX, H ZIMMER
Journal: Cardiovascular Research (2004)

Objective: Recent reports suggest that hematopoietic stem cells (HSC) can transdifferentiate into cardiomyoctes and contribute to myocardial regeneration after injury. This concept has recently been challenged by studies in which bone-marrow (BM)-derived cells do not acquire a cardiac phenotype after direct injection into ischemic myocardium.
G3139, a Bcl-2 antisense oligodeoxynucleotide, induces clinical responses in VAD refractory myeloma
Authors: N W C J van de Donk, O de Weerdt, G Veth, M Eurelings, E van Stralen, S R Frankel, A Hagenbeek, A C Bloem, H M Lokhorst
Journal: Leukemia (2004)
Aquaporin-4–binding autoantibodies in patients with neuromyelitis optica impair glutamate transport by down-regulating EAAT2
Authors: Shannon R. Hinson, Shanu F. Roemer, Claudia F. Lucchinetti, James P. Fryer, Thomas J. Kryzer, Jayne L. Chamberlain, Charles L. Howe, Sean J. Pittock, Vanda A. Lennon
Journal: The Journal of Experimental Medicine (2008)

Neuromyelitis optica (NMO)-immunoglobulin G (IgG) is a clinically validated serum biomarker that distinguishes relapsing central nervous system (CNS) inflammatory demyelinating disorders related to NMO from multiple sclerosis. This autoantibody targets astrocytic aquaporin-4 (AQP4) water channels. Clinical, radiological, and immunopathological data suggest that NMO-IgG might be pathogenic. Characteristic CNS lesions exhibit selective depletion of AQP4, with and without associated myelin loss; focal vasculocentric deposits of IgG, IgM, and complement; prominent edema; and inflammation. The effect of NMO-IgG on astrocytes has not been studied. In this study, we demonstrate that exposure to NMO patient serum and active complement compromises the membrane integrity of CNS-derived astrocytes. Without complement, astrocytic membranes remain intact, but AQP4 is endocytosed with concomitant loss of Na+-dependent glutamate transport and loss of the excitatory amino acid transporter 2 (EAAT2) . Our data suggest that EAAT2 and AQP4 exist in astrocytic membranes as a macromolecular complex. Transport-competent EAAT2 protein is up-regulated in differentiating astrocyte progenitors and in nonneural cells expressing AQP4 transgenically. Marked reduction of EAAT2 in AQP4-deficient regions of NMO patient spinal cord lesions supports our immunocytochemical and immunoprecipitation data. Thus, binding of NMO-IgG to astrocytic AQP4 initiates several potentially neuropathogenic mechanisms: complement activation, AQP4 and EAAT2 down-regulation, and disruption of glutamate homeostasis.
453 SIGNATURE RESISTANCE MUTATIONS TO DIRECTLY ACTING ANTIVIRAL AGENTS OCCUR AT LOW PREVALENCE IN TREATMENT NAIVE SUBJECTS WITH RECENTLY ACQUIRED HEPATITIS C INFECTION
Authors: S. Gaudieri, T. Applegate, M. Tshochner, A. Plauzolles, K. Pfafferott, M. Lucas, H. Diepolder, A. Ulsenheimer, S. Mallal, J. Grebely, M. Hellard, A. Lloyd, J. Kaldor, G. Pore, G. Matthews
Journal: Journal of Hepatology (2011)