tbuckley/cabot-search huggingface dataset:
Abstract 5256: Osteopontin-c and Osteopontin-b splicing isoforms activate important hallmarks of cancer contributing to prostate carcinoma progression
Authors: Tatiana M. Tilli, Aline Matos, Luis Ricardo Goulart, Georg F. Weber, Etel Rodrigues Pereira Gimba
Journal: Cancer Research (2011)

Abstract Introduction: Osteopontin (OPN) is a secreted glycophosphoprotein and is involved in tumorigenesis and metastasis in many solid tumors, including prostate cancer (PCa). Alternative splicing of OPN mRNA leads to the expression of 3 isoforms, named OPNa, OPNb and OPNc. However, the expression pattern and the roles of these isoforms have not been previously characterized in PCa. Objective and Methodology: Herein we evaluated the expression pattern of these OPN isofoms in PCa and BPH (benign prostate hyperplasia) tissue samples by using qRT-PCR. ROC curve analysis evaluated the performance of OPN isoforms tissue levels as compared to PSA serum levels for the diagnosis of PCa. Additionally, we investigated the roles of these isoforms on PCa progression using PC3 cells ectopically overexpressing each OPN isoform and in vitro and in vivo assays. Results: Our data demonstrate that these 3 isoforms are overexpressed in PCa in relation to BPH tissue samples and that OPNc presents the highest expression level. ROC curve analysis demonstrate that OPNa, OPNb and OPNc expression levels perform better (AUC 0,9; 0,81 and 0,88, respectively, p&amp;lt; 0,0001) than PSA serum levels (AUC 0,52; p&amp;lt; 0,0001) for the differential diagnosis of PCa and BPH patients. Furthermore, OPN isoforms expression levels are positively correlated to tumor Gleason Score (p &amp;lt; 0,001). Cells overexpressing OPNc and OPNb, but not OPNa, significantly activate cell features typically related to key hallmarks of cancer, such as cell proliferation, migration, anchorage-independent growth and tumor formation in vivo in nude mice, reflecting the potential of these isoforms to active PCa tumor progression. Besides, OPNc seems also to in involved in PCa tumorigenesis, once stimulate the proliferation of RWPE1 prostate non- tumoral cells. Trying to describe the signaling pathways involved on OPNc and OPNb roles on activating PCa progression steps, we demonstrated that the use LY-294002 inhibitor significantly inhibited the proliferation of cells overexpressing OPNc and OPNb, suggesting that these OPN splicing isoforms on activating cell proliferation occurs via PI3K/Akt signaling pathways. Conclusions: Taken together, these results suggest that the evaluation of OPN splicing isoforms expression levels could be used as molecular parameter to improve the differential diagnosis of PCa in relation to BPH. Besides, we provide evidence that OPNc and OPNb activate important steps in PCa progression and hence could be important targets for the development of therapeutic approaches. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5256. doi:10.1158/1538-7445.AM2011-5256
Effect of Growth Hormone on Carbohydrate and Lipid Metabolism
Authors: MAYER B. DAVIDSON
Journal: Endocrine Reviews (1987)

APPROXIMATELY 60 yr ago, Houssay and his colleagues (1) described hypersensitivity to insulin in hypophysectomized (hypox) animals. Further work documented a primary effect of GH in this phenomenon (1). Over the ensuing years, numerous investigators have sought to define the role of GH in carbohydrate and lipid metabolism. Unfortunately, no unified picture has emerged. Both insulin-like and antiinsulin-like effects have been documented, although the physiological significance of the former is uncertain. Major controversies surround the relationship between structure and function of the GH molecule. Indeed, some believe that most of the reported effects of GH are due to contaminants in the hormone preparation. With two exceptions (2, 3), reviews in this area (4–10) have focused mainly on the author's own work in a circumscribed field; e.g. in vivo effects after GH administration (6, 7, 9), tissue effects in vitro (5, 7), or effects on lipolysis (4, 8,10). Furthermore, these reviews were published more than 10 yr ago.
Reviews and Notes: Ethics: Priorities in Health Care: Ethics, Economy, Implementation
Authors: John W. Burnside
Journal: Annals of Internal Medicine (1996)

Literature of Medicine1 March 1996Reviews and Notes: Ethics: Priorities in Health Care: Ethics, Economy, ImplementationJohn W. Burnside, MDJohn W. Burnside, MDUniversity of Texas Southwestern Medical Center, Dallas, TX 75235-9005Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-124-5-199603010-00026 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The Swedish Parliamentary Priorities Commission. 180 pages. Stockholm: Ministry of Health and Social Affairs; 1995.The United States deliberates on biomedical ethical dilemmas in various ways and in a distinctly U.S. context. Individual persons, professional groups, health care institutions, universities, and government organizations have all participated in these deliberations. The Institute of Medicine has gathered together an impressive panel of scholars and has charged them to pause and examine what has been done, who has done it, and whether it has been successful and to suggest future directions. Their report, Society's Choices: Social and Ethical Decision Making in Biomedicine, is ... Author, Article, and Disclosure InformationAffiliations: University of Texas Southwestern Medical Center, Dallas, TX 75235-9005 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 March 1996Volume 124, Issue 5Page: 537-538KeywordsBioethicsDecision makingForecastingGraduate medical educationHealth careInstitutional review boardsMedical ethicsPalliative careProblem solving ePublished: 15 August 2000 Issue Published: 1 March 1996 Copyright & PermissionsCopyright © 1996 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Correlation between cytosolic free calcium, contracture, ATP, and irreversible ischemic injury in perfused rat heart.
Authors: C Steenbergen, E Murphy, J A Watts, R E London
Journal: Circulation Research (1990)

The relations between ATP depletion, increased cytosolic free calcium concentration [( Cai]), contracture development, and lethal myocardial ischemic injury, as evaluated by enzyme release, were examined using 19F nuclear magnetic resonance to measure [Cai] in 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N',N'-tetraacetic acid (5F-BAPTA)-loaded perfused rat hearts. Total ischemia at 37 degrees C was induced in beating hearts, potassium-arrested hearts, magnesium-arrested hearts, and hearts pretreated with 0.9 microM diltiazem to reduce but not abolish contractility. In the beating hearts, time-averaged [Cai], which is intermediate between the systolic and the basal [Cai], was 544 +/- 74 nM. In contrast, in the potassium- and magnesium-arrested hearts, the time-averaged values are lower than in beating hearts (352 +/- 88 nM for potassium arrest, 143 +/- 22 nM for magnesium arrest). During ischemia, ATP depletion, contracture, and a rise in [Cai] are delayed by cardiac arrest, but all occur more rapidly in the potassium-arrested hearts than in the magnesium-arrested hearts. The diltiazem-treated hearts were generally similar to the magnesium-arrested hearts in their response to ischemia. Under all conditions, contracture development was initiated after tissue ATP had fallen to less than 50% of control; invariably, there was a progressive rise in [Cai] during and following contracture development. Reperfusion with oxygenated perfusate shortly after peak contracture development resulted in a return of [Cai] to its preischemic level, resynthesis of creatine phosphate, no significant enzyme release, and no substantial loss of 5F-BAPTA from the heart. The data demonstrate that an increase in [Cai] precedes lethal myocardial ischemic injury. This rise in [Cai] may accelerate the depletion of cellular ATP and may directly contribute to the development of lethal ischemic cell injury.
Nonlinear Power Loss During Exercise in Single-Ventricle Patients After the Fontan
Authors: Kevin K. Whitehead, Kerem Pekkan, Hiroumi D. Kitajima, Stephen M. Paridon, Ajit P. Yoganathan, Mark A. Fogel
Journal: Circulation (2007)

Background— We previously demonstrated that power loss (PL) through the total cavopulmonary connection (TCPC) in single-ventricle patients undergoing Fontan can be calculated by computational fluid dynamic analysis using 3-dimensional MRI anatomic reconstructions. PL through the TCPC may play a role in single-ventricle physiology and is a function of cardiac output. We hypothesized that PL through the TCPC increases significantly under exercise flow conditions. Methods and Results— MRI data of 10 patients with a TCPC were analyzed to obtain 3-dimensional geometry and flow rates through the superior vena cava, inferior vena cava, left pulmonary artery, and right pulmonary artery. Steady computational fluid dynamic simulations were performed at baseline conditions using MRI-derived flows. Simulated exercise conditions of twice (2×) and three times (3×) baseline flow were performed by increasing inferior vena cava flow. PL, head loss, and effective resistance through the TCPC were calculated for each condition. Each condition was repeated at left pulmonary artery/right pulmonary artery ratios of 30/70 and 70/30 to determine the effects of pulmonary flow splits on exercise PL. For each patient, PL increases dramatically in a nonlinear fashion with increasing cardiac output, even when normalized to calculate head loss or resistance. Flow splits had a significant effect on PL at exercise, with most geometries favoring right pulmonary artery flow. Conclusions— The relationship between cardiac output and PL is nonlinear and highly dependent on TCPC geometry and pulmonary flow splits. This study demonstrates the importance of studying the TCPC under exercise conditions, because baseline conditions may not adequately characterize TCPC efficiency.
Abstract P6-05-18: A53, cell cycle phenotype and Cdc7 kinase: Identifying patients likely to benefit from targeted Cdc7 therapy
Authors: P Ian, E Leigh, M Fizza, S Kai, WH Gareth, S Richard
Journal: Cancer Research (2013)

Abstract We previously reported multiparameter analysis of cell cycle regulatory proteins in breast cancer and identified three prognostic ‘cell cycle phenotypes’. Phenotype iii represents cells traversing through the mitotic cell division cycle and is associated with poor prognosis and high Cdc7 levels1. Cdc7 kinase initiates DNA synthesis at chromosomal replication origins and is rate-limiting for S phase entry. In cell-based studies we discovered a new, p53-dependent cell cycle checkpoint which reversible arrests normal cells in G1 phase if DNA replication initiation is perturbed. In cancer cells treated with Cdc7 inhibitors this checkpoint function is lost, resulting in aberrant S phase entry and subsequent apoptotic cell death2,3. Cdc7 kinase is therefore emerging as a novel therapeutic target in cancers bearing mutant p53. In this study we investigated whether the inclusion of p53 mutation status adds further prognostic power to the cell cycle phenotype. We also questioned whether p53 mutant breast cancers express high Cdc7 levels and are thus more likely to be of cell cycle phenotype iii (susceptible to Cdc7-targeted therapy). Our results show that Cdc7 levels are inversely correlated with p53 mutation status (n = 173) and are highest in cell cycle phenotype iii and harder to treat Her-2 and triple negative breast cancer subgroups. Cell cycle phenotype is the strongest predictor of early relapse compared to p53, Ki67 and Cdc7 on univariate analysis and remains so on multivariate analysis after adjusting for p53 status (HR = 3.80, p = 0.002). These findings support the supposition that p53 negatively regulates Cdc7 expression. Combined testing for p53 status, cell cycle phenotype and Cdc7 expression identifies those patients with breast cancer most likely to benefit from targeted therapy with Cdc7 inhibitors. 1 Br J Cancer. 2009 Mar 24;100(6):959-70 2 EMBO J. 2010 Oct 6;29(19):3381-94 3 Am J Pathol. 2010 Oct;177(4):2034-45. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-05-18.
Macrophage- and astrocyte-derived transforming growth factor beta as a mediator of central nervous system dysfunction in acquired immune deficiency syndrome.
Authors: S M Wahl, J B Allen, N McCartney-Francis, M C Morganti-Kossmann, T Kossmann, L Ellingsworth, U E Mai, S E Mergenhagen, J M Orenstein
Journal: The Journal of Experimental Medicine (1991)

The multifunctional cytokine, transforming growth factor beta (TGF-beta), was identified by immunocytochemistry in the brain tissues of four patients with acquired immune deficiency syndrome (AIDS), but not in control brain tissue. The TGF-beta staining was localized to cells of monocytic lineage as well as astrocytes, especially in areas of brain pathology. In addition, the brain tissues from the AIDS patients contained transcripts for human immunodeficiency virus 1 (HIV-1) by in situ hybridization, suggesting a correlation between the presence of HIV-1 in the brain and the expression of TGF-beta. However, the expression of TGF-beta was not limited to HIV-1-positive cells, raising the possibility of alternative mechanisms for the induction of TGF-beta in these AIDS patients' brains. To investigate these mechanisms, purified human monocytes were infected in vitro with HIV-1 and were shown to secrete increased levels of TGF-beta. In addition, HIV-1-infected monocytes released a factor(s) capable of triggering cultured astrocytes that are not infected with HIV-1 to secrete TGF-beta. The release of TGF-beta, which is an extremely potent chemotactic factor, may contribute to the recruitment of HIV-1-infected monocytic cells, enabling viral spread to and within the central nervous system (CNS). Moreover, TGF-beta augments cytokine production, including cytokines known to be neurotoxic. The identification of TGF-beta within the CNS implicates this cytokine in the immunopathologic processes responsible for AIDS-related CNS dysfunction.
Evidence Suggests Complex Links Between Violence and Schizophrenia
Authors: Bridget M. Kuehn
Journal: JAMA (2012)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The Cytosolic Endopeptidase, Thimet Oligopeptidase, Destroys Antigenic Peptides and Limits the Extent of MHC Class I Antigen Presentation
Authors: Ian A. York, Annie X.Y. Mo, Kristen Lemerise, Wanyong Zeng, Yuelei Shen, Carmela R. Abraham, Tomo Saric, Alfred L. Goldberg, Kenneth L. Rock
Journal: Immunity (2003)
NHS competition rules are “not fit for purpose,” think tank chief says
Authors: Gareth Iacobucci
Journal: BMJ (2013)

The government’s new rules governing competition in the NHS are not fit for purpose and should be re-examined to ensure that necessary service changes can take place, says the head of an influential health think tank.

Chris Ham, chief executive of the King’s Fund, said that new laws introduced under the Health and Social Care Act 2012 were hampering efforts to integrate services and diverting resources from where they were most needed.

Ham’s remarks came after a debate at the King’s Fund last week, where the deputy chairman of the healthcare regulator Monitor argued that the new system, which requires potential mergers to be assessed firstly by Monitor before potentially being referred to the Office of Fair Trading …
Parainfluenza Pneumonia in Adults
Authors: Richard P. Wenzel
Journal: JAMA (1972)

Parainfluenza virus, frequently a cause of respiratory disease in children, is uncommonly associated with illness in adults. A study sample of 160 incoming Marine Corps recruits showed that 25% to 48% had no detectable complement-fixing antibody to one or more of the three parainfluenza viruses. The remaining trainees had low levels of preexisting antibody. Five men were hospitalized with parainfluenzarelated pneumonia, including one with a moderate pleural effusion.
Isolation and translation of hemoglobin messenger RNA from thalassemia, sickle cell anemia, and normal human reticulocytes
Authors: Arthur W. Nienhuis, W. French Anderson
Journal: Journal of Clinical Investigation (1971)

Human hemoglobin messenger RNA was isolated by sucrose gradient centrifugation from reticulocytes of patients having various hemolytic anemias. Using a messenger RNA-dependent cell-free system derived entirely from rabbit reticulocytes, the human hemoglobin messenger RNA has been translated and the products analyzed by carboxymethylcellulose column chromatography. Normal messenger RNA directs synthesis of normal human alpha- and beta-globin chains in nearly equal amounts. Sickle cell anemia messenger RNA directs the synthesis of normal alpha- and sickle beta-chains, beta-thalassemia messenger RNA directs the synthesis of normal alpha- and beta-chains, but the amount of beta-globin synthesized is markedly reduced. Thus the inability of the thalassemia reticulocyte to produce beta-globin is clearly attributable to the beta-globin messenger RNA.
Insulin Resistance: A Multifaceted Syndrome Responsible for NIDDM, Obesity, Hypertension, Dyslipidemia, and Atherosclerotic Cardiovascular Disease
Authors: Ralph A DeFronzo, Eleuterio Ferrannini
Journal: Diabetes Care (1991)

Diabetes mellitus is commonly associated with systolic/diastolic hypertension, and a wealth of epidemiological data suggest that this association is independent of age and obesity. Much evidence indicates that the link between diabetes and essential hypertension is hyperinsulinemia. Thus, when hypertensive patients, whether obese or of normal body weight, are compared with age- and weight-matched normotensive control subjects, a heightened plasma insulin response to a glucose challenge is consistently found. A state of cellular resistance to insulin action subtends the observed hyperinsulinism. With the insulin/glucose-clamp technique, in combination with tracer glucose infusion and indirect calorimetry, it has been demonstrated that the insulin resistance of essential hypertension is located in peripheral tissues (muscle), is limited to nonoxidative pathways of glucose disposal (glycogen synthesis), and correlates directly with the severity of hypertension. The reasons for the association of insulin resistance and essential hypertension can be sought in at least four general types of mechanisms: Na+ retention, sympathetic nervous system overactivity, disturbed membrane ion transport, and proliferation of vascular smooth muscle cells. Physiological maneuvers, such as calorie restriction (in the overweight patient) and regular physical exercise, can improve tissue sensitivity to insulin; evidence indicates that these maneuvers can also lower blood pressure in both normotensive and hypertensive individuals. Insulin resistance and hyperinsulinemia are also associated with an atherogenic plasma lipid profile. Elevated plasma insulin concentrations enhance very-low-density lipoprotein (VLDL) synthesis, leading to hypertriglyceridemia. Progressive elimination of lipid and apolipoproteins from the VLDL particle leads to an increased formation of intermediate-density and low-density lipoproteins, both of which are atherogenic. Last, insulin, independent of its effects on blood pressure and plasma lipids, is known to be atherogenic. The hormone enhances cholesterol transport into arteriolar smooth muscle cells and increases endogenous lipid synthesis by these cells. Insulin also stimulates the proliferation of arteriolar smooth muscle cells, augments collagen synthesis in the vascular wall, increases the formation of and decreases the regression of lipid plaques, and stimulates the production of various growth factors. In summary, insulin resistance appears to be a syndrome that is associated with a clustering of metabolic disorders, including non-insulin-dependent diabetes mellitus, obesity, hypertension, lipid abnormalities, and atherosclerotic cardiovascular disease.
Cell-surface antigens associated with dualtropic and thymotropic murine leukemia viruses inducing thymic and nonthymic lymphomas.
Authors: M Haas, V Patch
Journal: The Journal of Experimental Medicine (1980)

Unique type-specific antigens were detected on cells infected with dualtropic and thymotropic viruses isolated and x-ray-induced T cell- and B cell-malignant lymphomas of C57BL/6 mice. These antigens were defined by membrane fluorescence with antisera made in rabbits against rabbit cells chronically infected with cloned virus. The antisera were qualitatively absorbed with a group of cells chronically infected with related dualtropic, ecotropic, and xenotropic viruses. The absorbed antisera detected type-specific, virus-related cell-surface antigens that were unique for different dualtropic virus isolates. The unabsorbed sera also reacted with antigens found specifically on ecotropic and xenotropic virus-infected cells. These findings support the contention that T cell lymphoma (TCL)-inducing and B cell lymphoma (BCL)-inducing viruses isolated from x-irradiated C57BL/6 mice are env gene recombinants in which ecotropic gene sequences have been substituted by xenotropic sequences. We found that unique antigenicities are associated with each TCL-inducing and BCL-inducing dualtropic virus, and that the thymotropic TCL-inducing virus isolates (e.g., 136.5 adn 136.7 viruses) represent a separate serologic group, different from the dualtropic TCL-inducing viruses. By using a series of absorbed antisera in microimmunofluorescence tests we could perform serologic virus mapping of dualtropic clones isolated by us or by others and relate them serologically to previously isolated clones. These virus mapping experiments indicated that many serologically different recombinant viruses can be isolated from C57BL/6 mice. It is suggested that many distinct recombinant viruses may exist in lymphomagenic C57BL/6 mice, some of which are associated with specific lymphoma induction.