The University of Oklahoma Health Sciences Center
Lindsay, OK, United States

The University of Oklahoma Health science Center is the health science branch of the University of Oklahoma. Located in Oklahoma City, it serves as the primary place of instruction for many of Oklahoma's health professions. It is one of only four health centers in the United States with seven professional colleges.The nineteen buildings that make up the OUHSC campus occupies a fifteen block area in Oklahoma City near the Oklahoma State Capitol. Surrounding these buildings are an additional twenty health-related buildings some of which are owned by the University of Oklahoma. The Health science Center is the core of a wider complex known as the Oklahoma Health Center. The major clinical facilities on campus are part of OU Medicine and include the OU Medical Center hospital complex, The Children's Hospital, OU Physicians and OU Children's Physicians clinics, Harold Hamm Diabetes Center and the Peggy and Charles Stephenson Oklahoma Cancer Center. Also part of the major clinical facilities is the Oklahoma City VA Medical Center. Wikipedia.

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Biosense Webster Israel Ltd. and The University of Oklahoma Health Sciences Center | Date: 2017-01-18

A method, consisting of ablating tissue for a time period, measuring a contact force applied during the time period, and measuring a power used during the time period. The method further includes ceasing ablating the tissue when a desired size of a lesion produced in the tissue, as estimated using an integral over the time period of a product of the contact force raised to a first non-unity exponent and the power raised to a second non-unity exponent, is reached.

McEver R.P.,The University of Oklahoma Health Sciences Center | Zhu C.,Georgia Institute of Technology
Annual Review of Cell and Developmental Biology | Year: 2010

Rolling adhesion on vascular surfaces is the first step in recruiting circulating leukocytes, hematopoietic progenitors, or platelets to specific organs or to sites of infection or injury. Rolling requires the rapid yet balanced formation and dissociation of adhesive bonds in the challenging environment of blood flow. This review explores how structurally distinct adhesion receptors interact through mechanically regulated kinetics with their ligands to meet these challenges. Remarkably, increasing force applied to adhesive bonds first prolongs their lifetimes (catch bonds) and then shortens their lifetimes (slip bonds). Catch bonds mediate the counterintuitive phenomenon of flow-enhanced rolling adhesion. Force-regulated disruptions of receptor interdomain or intradomain interactions remote from the ligand-binding surface generate catch bonds. Adhesion receptor dimerization, clustering in membrane domains, and interactions with the cytoskeleton modulate the forces applied to bonds. Both inside-out and outside-in cell signals regulate these processes. Copyright © 2010 by Annual Reviews. All rights reserved.

Biosense Webster Israel Ltd. and The University of Oklahoma Health Sciences Center | Date: 2016-06-09

A method, consisting of ablating tissue for a time period, measuring a contact force applied during the time period, and measuring a power used during the time period. The method further includes ceasing ablating the tissue when a desired size of a lesion produced in the tissue, as estimated using an integral over the time period of a product of the contact force raised to a first non-unity exponent and the power raised to a second non-unity exponent, is reached.

Cunningham M.W.,The University of Oklahoma Health Sciences Center
Current Opinion in Rheumatology | Year: 2012

Purpose of review: To give an overview of the current hypotheses of the pathogenesis of rheumatic fever and group A streptococcal autoimmune sequelae of the heart valve and brain. Recent findings: Human monoclonal antibodies (mAbs) derived from rheumatic heart disease have provided evidence for crossreactive autoantibodies that target the dominant group A streptococcal epitope of the group A carbohydrate, N-acetyl-beta-D-glucosamine (GlcNAc), and heart valve endothelium, laminin and laminar basement membrane. T cells in peripheral blood and in rheumatic heart valves revealed the presence of T cells crossreactive with streptococcal M protein and cardiac myosin. For initiation of disease, evidence suggests a two-hit hypothesis for antibody attack on the valve endothelium with subsequent extravasation of T cells through activated endothelium into the valve to form granulomatous lesions and Aschoff bodies. Autoantibodies against the group A streptococcal carbohydrate epitope GlcNAc and cardiac myosin and its peptides appear during progression of rheumatic heart disease. However, autoantibodies against collagen that are not crossreactive may form because of the release of collagen from damaged valve or to responses to collagen bound in vitro by certain serotypes of streptococci. In Sydenham chorea, human mAbs derived from disease target the group A carbohydrate epitope GlcNAc and gangliosides and dopamine receptors found on the surface of neuronal cells in the brain. Human mAbs and autoantibodies in Sydenham chorea were found to signal neuronal cells and activate calcium calmodulin-dependent protein kinase II (CaMKII) in neuronal cells and recognize the intracellular protein biomarker tubulin. Summary: To summarize, pathogenic mechanisms of crossreactive autoantibodies which target the valve in rheumatic heart disease and the neuronal cell in Sydenham chorea share a common streptococcal epitope GlcNAc and target intracellular biomarkers of disease including cardiac myosin in the myocardium and tubulin, a protein abundant in the brain. However, intracellular antigens are not believed to be the basis for disease. The theme of molecular mimicry in streptococcal autoimmune sequelae is the recognition of targeted intracellular biomarker antigens such as cardiac myosin and brain tubulin, while targeting extracellular membrane antigens such as laminin on the valve surface endothelium or lysoganglioside and dopamine receptors in the brain. Antibody binding to these cell surface antigens may lead to valve damage in rheumatic heart disease or neuropsychiatric behaviors and involuntary movements in Sydenham chorea. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Esmon C.T.,The University of Oklahoma Health Sciences Center
Thrombosis and Haemostasis | Year: 2014

Great advances have been made in recent years in understanding the haemostatic system and the molecular and cellular basis of thrombus formation. Although directly targeting factor Xa or thrombin (factor IIa) for effective anticoagulation is now well established, evidence has emerged suggesting that factor Xa and thrombin are involved in other physiological and pathophysiological cellular processes, including inflammation. These non-haemostatic activities of factor Xa and thrombin are predominantly mediated via the activation of proteinaseactivated receptors. Studies have indicated a potential role of coagulation proteins (including factor Xa and thrombin) in the progression of disease conditions such as atherothrombosis. Preclinical studies have provided evidence for the effects of direct factor Xa or direct thrombin inhibition beyond anticoagulation, including anti-inflammatory activities and atherosclerotic plaque stabilisation. In this article, the non-haemostatic activities of factor Xa and thrombin and the effects of direct inhibition of these coagulation factors on these activities are summarised. In addition, the potential roles of factor Xa and thrombin in atherosclerosis and atherothrombosis are explored and the cardiovascular profiles of rivaroxaban, apixaban and dabigatran etexilate observed in phase III clinical studies are discussed. © Schattauer 2014.

Chernausek S.D.,The University of Oklahoma Health Sciences Center
Journal of Clinical Endocrinology and Metabolism | Year: 2012

Intrauterine growth restriction (IUGR) is prevalent worldwide and affects children and adults in multiple ways. These include predisposition to type 2 diabetes mellitus, the metabolic syndrome, cardiovascular disease, persistent reduction in stature, and possibly changes in the pattern of puberty. A review of recent literature confirms that the metabolic effects of being born small for gestational age are evident in the very young, persist with age, and are amplified by adiposity. Furthermore, the pattern of growth in the first few years of life has a significant bearing on a person's later health, with those that show increasing weight gain being at the greatest risk for future metabolic dysfunction. Treatment with exogenous human GH is used to improve height in children who remain short after being small for gestational age at birth, but the response of individuals remains variable and difficult to predict. The mechanisms involved in the metabolic programming of IUGR children are just beginning to be explored. It appears that IUGR leads to widespread changes in DNA methylation and that specific "epigenetic signatures" for IUGR are likely to be found in various fetal tissues. The challenge is to link such alterations with modifications in gene expression and ultimately the metabolic abnormalities of adulthood, and it represents one of the frontiers for research in the field. Copyright © 2012 by The Endocrine Society.

Cunningham M.W.,The University of Oklahoma Health Sciences Center
International Reviews of Immunology | Year: 2014

The group A streptococcus, Streptococcus pyogenes, and its link to autoimmune sequelae, has acquired a new level of understanding. Studies support the hypothesis that molecular mimicry between the group A streptococcus and heart or brain are important in directing immune responses in rheumatic fever. Rheumatic carditis, Sydenham chorea and a new group of behavioral disorders called pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections are reviewed with consideration of autoantibody and T cell responses and the role of molecular mimicry between the heart, brain and group A streptococcus as well as how immune responses contribute to pathogenic mechanisms in disease. In rheumatic carditis, studies have investigated human monoclonal autoantibodies and T cell clones for their crossreactivity and their mechanisms leading to valve damage in rheumatic heart disease. Although studies of human and animal sera from group A streptococcal diseases or immunization models have been crucial in providing clues to molecular mimicry and its role in the pathogenesis of rheumatic fever, study of human monoclonal autoantibodies have provided important insights into how antibodies against the valve may activate the valve endothelium and lead to T cell infiltration. Passive transfer of anti-streptococcal T cell lines in a rat model of rheumatic carditis illustrates effects of CD4+ T cells on the valve. Although Sydenham chorea has been known as the neurological manifestation of rheumatic fever for decades, the combination of autoimmunity and behavior is a relatively new concept linking brain, behavior and neuropsychiatric disorders with streptococcal infections. In Sydenham chorea, human mAbs and their expression in transgenic mice have linked autoimmunity to central dopamine pathways as well as dopamine receptors and dopaminergic neurons in basal ganglia. Taken together, the studies reviewed provide a basis for understanding streptococcal sequelae and how immune responses against group A streptococci influence autoimmunity and inflammatory responses in the heart and brain. Copyright © 2014 Informa Healthcare USA, Inc.

George J.N.,The University of Oklahoma Health Sciences Center
Blood | Year: 2010

Thrombotic thrombocytopenic purpura (TTP) is the common name for adults with microangiopathic hemolytic anemia, thrombocytopenia, with or without neurologic or renal abnormalities, and without another etiology; children without renal failure are also described as TTP. The diagnosis of TTP is an indication for plasma exchange treatment, but beginning treatment requires sufficient confidence in the diagnosis to justify the risk of plasma exchange complications. Documentation of a severe deficiency of plasma ADAMTS13 activity, defined as less than 10% of normal, is not essential for the diagnosis of TTP. Some patients without severe ADAMTS13 deficiency may benefit from plasma exchange treatment; in addition, some patients with severe ADAMTS13 deficiency may subsequently be diagnosed with another cause for their clinical features. However, severe acquired ADAMTS13 deficiency does define a subgroup of patients who appear to benefit from treatment with corticosteroids and other immunosuppressive agents in addition to plasma exchange but who have a high risk for relapse. Approximately 80% of patients survive their acute episode, a survival rate that has not changed since the introduction of plasma exchange treatment. Although recovery may appear to be complete, many patients have persistent minor cognitive abnormalities. More effective as well as safer treatment for TTP is needed. © 2010 by The American Society of Hematology.

McEver R.P.,The University of Oklahoma Health Sciences Center
Cardiovascular Research | Year: 2015

The selectins are transmembrane, Ca2+-dependent lectins that mediate leucocyte rolling on vascular surfaces, the first adhesive step during inflammation and immune surveillance. Leucocytes express L-selectin, activated platelets express P-selectin, and activated endothelial cells express E- And P-selectin. Rolling involves force-regulated, rapidly reversible interactions of selectins with a limited number of glycosylated cell surface ligands. Rolling permits leucocytes to interact with immobilized chemokines that convert β2 integrins to high-Affinity conformations, which mediate arrest, post-Arrest adhesion strengthening, and transendothelial migration. However, rolling leucocytes also transduce signals through selectin ligands, the focus of this review. These signals include serial activation of kinases and recruitment of adaptors that convert integrins to intermediate-Affinity conformations, which decrease rolling velocities. In vitro, selectin signalling enables myeloid cells to respond to suboptimal levels of chemokines and other agonists. This cooperative signalling triggers effector responses such as degranulation, superoxide production, chemokine synthesis, and release of procoagulant/ proinflammatory microparticles. In vivo, selectin-mediated adhesion and signalling likely contributes to atherosclerosis, arterial and deep vein thrombosis, ischaemia-reperfusion injury, and other cardiovascular diseases. © The Author 2015. All rights reserved.

Agency: NSF | Branch: Standard Grant | Program: | Phase: Genetic Mechanisms | Award Amount: 188.07K | Year: 2016

This project will study a unique mechanism of gene expression in ancient single-celled parasites called trypanosomes. Unlike most organisms that use the RNA copied from DNA as is for directing protein synthesis, in the energy-generating mitochondria of trypanosomes (and other organisms), the RNA is edited by addition or removal of specific information. Why editing occurs is not clear, but understanding how it happens may provide important clues about the function of this type of genetic alteration. The project will have broad educational impact by providing interdisciplinary training opportunities for postdoctoral, graduate, undergraduate, and high school students. In addition, specific efforts will target students from groups traditionally underrepresented in the STEM disciplines.

This project focuses on the process of RNA editing in the mitochondria of trypanosomes. Through the action of a central editing enzyme, called RECC, uridylates are inserted or deleted at thousands of specific sites in dozens of mRNAs. This extensive editing process is directed by hundreds of small non-coding guide RNAs and involves several auxiliary factors. However, the mechanistic basis of the regulation of editing remains a long-standing question in trypanosomal RNA biology. In previous work, a regulatory editing subcomplex, called REH2C, was identified and found to contain three protein subunits. Two of these, a helicase and a zinc-finger protein, appear to participate directly in editing. A combination of genetic, biochemical, bioinformatics, and proteomic approaches will be used to address how these proteins assemble with mRNAs and guide mRNAs into editosome complexes in vivo and how the complexes carry out editing functions. These studies may establish new paradigms in RNA editing regulation. In a broader sense, the studies will allow a better understanding of how this amazing process evolved. This system can be used to draw analogies with related RNA helicases and RNA processes that are directed by small guide RNAs and that evolved more recently in eukaryotic lineages.

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