University of Tennessee Health Science Center

www.uthsc.edu/
Memphis, TN, United States

The University of Tennessee Health Science Center in Memphis includes the Colleges of Allied Health science, Dentistry, Graduate Health science, Medicine, Nursing and Pharmacy. Its pediatric residency program is affiliated with Le Bonheur Children's Medical Center and residents in pediatrics, radiology, and other fields spend time working at St. Jude Children's Research Hospital in Memphis. There are also graduate medical education programs in Knoxville, Chattanooga, and Nashville, family medicine centers in Knoxville, Jackson, and Memphis, and public and continuing education programs across the state. The Health Science Center is part of the statewide, multi-campus University of Tennessee system. As of 2010, US News and World Report ranked the College of Pharmacy 16th among American pharmacy schools. Wikipedia.


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Ferrannini E.,University of Pisa | Cushman W.C.,University of Tennessee Health Science Center
The Lancet | Year: 2012

High blood pressure is reported in over two-thirds of patients with type 2 diabetes, and its development coincides with the development of hyperglycaemia. Many pathophysiological mechanisms underlie this association. Of these mechanisms, insulin resistance in the nitric-oxide pathway; the stimulatory effect of hyperinsulinaemia on sympathetic drive, smooth muscle growth, and sodium-fluid retention; and the excitatory effect of hyperglycaemia on the renin-angiotensin-aldosterone system seem to be plausible. In patients with diabetes, hypertension confers an enhanced risk of cardiovascular disease. A blood pressure of lower than 140/85 mm Hg is a reasonable therapeutic goal in patients with type 2 diabetes according to clinical trial evidence. People with controlled diabetes have a similar cardiovascular risk to patients without diabetes but with hypertension. A renin-angiotensin system blocker combined with a thiazide-type diuretic might be the best initial antihypertensive regimen for most people with diabetes. In general, the positive effects of antihypertensive drugs on cardiovascular outcomes outweigh the negative effects of antihypertensive drugs on glucose metabolism.


Luce E.A.,University of Tennessee Health Science Center
Plastic and Reconstructive Surgery | Year: 2015

Summary: Relationships between physicians and industry, whether it be pharmaceutical companies, medical device manufacturers, or purveyors of medical technology, contain both an element of potential for good and a potential for harm. Certainly, the potential for good is realized when the collaboration results in improved plastic surgery patient care due to product and technology development. If the collaboration contains a financial component, the potential for harm exists in the form of a financial conflict of interest on the part of the physician. Recently, considerable discussion has been directed toward the pervasiveness of financial conflict of interest in all three arenas of the profession of medicine: education, research, and clinical practice, although an overlap exists among all three with respect to the issue of conflict of interest. This article will focus on conflict of interest in plastic surgery education, both continuing medical education for practitioners and graduate medical education for plastic surgery residents, as well as conflict of interest in research, such as conflicts related to publications in our literature. © 2015 by the American Society of Plastic Surgeons.


Quarles L.D.,University of Tennessee Health Science Center
Experimental Cell Research | Year: 2012

FGF23 is a bone-derived hormone that regulates systemic phosphate homeostasis, vitamin D metabolism and α-Klotho expression through a novel bone-kidney axis. FGF23 inhibits renal tubular reabsorption of phosphate through mechanisms independent of PTH as well as reduces circulating 1, 25(OH) 2D through its dual effects to suppress Cyp27b1 production and to stimulate Cyp24 catabolism of 1,25(OH) 2D. 1,25(OH) 2D and other factors regulating bone remodeling/mineralization are the major physiological regulators of FGF23 expression. FGF23 also suppresses the gene transcription of α-klotho by the kidney, which exists as a membrane and soluble protein. Membrane Klotho acts as a coreceptor for and dictates organ specificity of FGF23, whereas soluble Klotho act as an endocrine factor that regulates activity of cell surface glycoproteins and receptors in multiple tissues. Elevated FGF23 levels are responsible for several hereditary and acquired hypophosphatemic rickets disorders. FGF23 and Klotho deficiency have similar phenotypes characterized by hyperphosphatemia, elevated 1,25(OH) 2D and tumoral calcinosis. FGF23 levels progressively increase during chronic kidney disease (CKD). FGF23 has been proposed to be the initial adaptive response leading to reductions in 1,25(OH) 2D and secondary hyperparathyroidism (HPT) in CKD. The overall biological effect of this initial step may be to orchestrate a coordinated adaptation to protect the organism from the adverse effects of excess phosphate retention. The second step involves the effects of PTH on bone remodeling that further stimulates FGF23 production through both direct and indirect mechanisms related to alterations in extracellular matrix factors. PTH further amplifies FGF23 expression in later stages of CKD to compensate for the increased phosphate efflux from bone caused by excessive bone turnover. While many aspects of the regulation and functions of FGF23 remain to be established, the idea that FGF23 hormone is the initial adaptive hormonal response in CKD that suppresses 1,25(OH) 2D, reduces gastrointestinal calcium and phosphate absorption and leads to a secondary HPT represents a paradigm shift in the conceptualization of the pathogenesis of secondary hyperparathyroidism. In addition, the prevalent thought that CKD is a functional "vitamin D deficient state" requiring therapy with 1,25(OH) 2D analogs is challenged by effects of FGF23 to potentially lower both 25(OH)D and 1,25(OH)D by induction of Cyp24-mediated degradation. Finally, increments in FGF23 are associated with increased cardiovascular mortality in CKD. Whether these effects represent direct effects of FGF23 or represent a marker of other abnormalities in CKD remains to be determined. © 2012 Elsevier Inc.


Quarles L.D.,University of Tennessee Health Science Center
Nature Reviews Endocrinology | Year: 2012

The discovery of fibroblast growth factor 23 (FGF-23) has expanded our understanding of phosphate and vitamin D homeostasis and provided new insights into the pathogenesis of hereditary hypophosphatemic and hyperphosphatemic disorders, as well as acquired disorders of phosphate metabolism, such as chronic kidney disease. FGF-23 is secreted by osteoblasts and osteocytes in bone and principally targets the kidney to regulate the reabsorption of phosphate, the production and catabolism of 1,25-dihydroxyvitamin D and the expression of α-Klotho, an anti-ageing hormone. Secreted FGF-23 plays a central role in complex endocrine networks involving local bone-derived factors that regulate mineralization of extracellular matrix and systemic hormones involved in mineral metabolism. Inactivating mutations of PHEX, DMP1 and ENPP1, which cause hereditary hypophosphatemic disorders and primary defects in bone mineralization, stimulate FGF23 gene transcription in osteoblasts and osteocytes, at least in part, through canonical and intracrine FGF receptor pathways. These FGF-23 regulatory pathways may enable systemic phosphate and vitamin D homeostasis to be coordinated with bone mineralization. FGF-23 also functions as a counter-regulatory hormone for 1,25-dihydroxyvitamin D in a bone-kidney endocrine loop. FGF-23, through regulation of additional genes in the kidney and extrarenal tissues, probably has broader physiological functions beyond regulation of mineral metabolism that account for the association between FGF-23 and increased mortality and morbidity in chronic kidney disease. © 2012 Macmillan Publishers Limited. All rights reserved.


Inaba H.,University of Tennessee Health Science Center | Greaves M.,Institute of Cancer Research | Mullighan C.G.,University of Tennessee Health Science Center
The Lancet | Year: 2013

Acute lymphoblastic leukaemia occurs in both children and adults but its incidence peaks between 2 and 5 years of age. Causation is multifactorial and exogenous or endogenous exposures, genetic susceptibility, and chance have roles. Survival in paediatric acute lymphoblastic leukaemia has improved to roughly 90% in trials with risk stratification by biological features of leukaemic cells and response to treatment, treatment modification based on patients' pharmacodynamics and pharmacogenomics, and improved supportive care. However, innovative approaches are needed to further improve survival while reducing adverse effects. Prognosis remains poor in infants and adults. Genome-wide profiling of germline and leukaemic cell DNA has identified novel submicroscopic structural genetic changes and sequence mutations that contribute to leukaemogenesis, define new disease subtypes, affect responsiveness to treatment, and might provide novel prognostic markers and therapeutic targets for personalised medicine.


Nelson D.R.,University of Tennessee Health Science Center
Philosophical transactions of the Royal Society of London. Series B, Biological sciences | Year: 2013

The neighbourhoods of cytochrome P450 (CYP) genes in deuterostome genomes, as well as those of the cnidarians Nematostella vectensis and Acropora digitifera and the placozoan Trichoplax adhaerens were examined to find clues concerning the evolution of CYP genes in animals. CYP genes created by the 2R whole genome duplications in chordates have been identified. Both microsynteny and macrosynteny were used to identify genes that coexisted near CYP genes in the animal ancestor. We show that all 11 CYP clans began in a common gene environment. The evidence implies the existence of a single locus, which we term the 'cytochrome P450 genesis locus', where one progenitor CYP gene duplicated to create a tandem set of genes that were precursors of the 11 animal CYP clans: CYP Clans 2, 3, 4, 7, 19, 20, 26, 46, 51, 74 and mitochondrial. These early CYP genes existed side by side before the origin of cnidarians, possibly with a few additional genes interspersed. The Hox gene cluster, WNT genes, an NK gene cluster and at least one ARF gene were close neighbours to this original CYP locus. According to this evolutionary scenario, the CYP74 clan originated from animals and not from land plants nor from a common ancestor of plants and animals. The CYP7 and CYP19 families that are chordate-specific belong to CYP clans that seem to have originated in the CYP genesis locus as well, even though this requires many gene losses to explain their current distribution. The approach to uncovering the CYP genesis locus overcomes confounding effects because of gene conversion, sequence divergence, gene birth and death, and opens the way to understanding the biodiversity of CYP genes, families and subfamilies, which in animals has been obscured by more than 600 Myr of evolution.


Dwivedi N.,University of Tennessee Health Science Center
Arthritis and rheumatism | Year: 2012

To test the hypothesis that autoantigen modifications by peptidylarginine deiminase type 4 (PAD-4) increase immunoreactivity. We assembled sera from patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Felty's syndrome (FS), and antineutrophil cytoplasmic antibody-associated vasculitides (AAVs), as well as sera from control subjects without autoimmune diseases. The sera were tested for binding to activated neutrophils, deiminated histones, and neutrophil extracellular chromatin traps (NETs). IgG binding to lipopolysaccharide-activated neutrophils was assessed with confocal microscopy, and binding to in vitro-deiminated histones was measured using enzyme-linked immunosorbent assay (ELISA) and Western blotting. In addition, we quantitated histone deimination in freshly isolated neutrophils from the blood of patients and control subjects. Increased IgG reactivity with activated neutrophils, particularly binding to NETs, was paralleled by preferential binding to deiminated histones over nondeiminated histones by ELISA in a majority of sera from FS patients but only in a minority of sera from SLE and RA patients. Immunoblotting revealed autoantibody preference for deiminated histones H3, H4, and H2A in most FS patients and in a subset of SLE and RA patients. In patients with AAVs, serum IgG preferentially bound nondeiminated histones over deiminated histones. Increased levels of deiminated histones were detected in neutrophils from RA patients. Circulating autoantibodies in FS are preferentially directed against PAD-4-deiminated histones and bind to activated neutrophils and NETs. Thus, increased reactivity with modified autoantigens in FS implies a direct contribution of neutrophil activation and the production of NET-associated nuclear autoantigens in the initiation or progression of FS. Copyright © 2012 by the American College of Rheumatology.


Steketee J.D.,University of Tennessee Health Science Center | Kalivas P.W.,Medical University of South Carolina
Pharmacological Reviews | Year: 2011

Repeated exposure to drugs of abuse enhances the motor-stimulant response to these drugs, a phenomenon termed behavioral sensitization. Animals that are extinguished from self-administration training readily relapse to drug, conditioned cue, or stress priming. The involvement of sensitization in reinstated drug-seeking behavior remains controversial. This review describes sensitization and reinstated drug seeking as behavioral events, and the neural circuitry, neurochemistry, and neuropharmacology underlying both behavioral models will be described, compared, and contrasted. It seems that although sensitization and reinstatement involve overlapping circuitry and neurotransmitter and receptor systems, the role of sensitization in reinstatement remains ill-defined. Nevertheless, it is argued that sensitization remains a useful model for determining the neural basis of addiction, and an example is provided in which data from sensitization studies led to potential pharmacotherapies that have been tested in animal models of relapse and in human addicts. © 2011 by The American Society for Pharmacology and Experimental Therapeutics.


Kovesdy C.P.,University of Tennessee Health Science Center
Nature Reviews Nephrology | Year: 2014

Hyperkalaemia is common in patients with chronic kidney disease (CKD), in part because o. The effects of kidney dysfunction on potassium homeostasis and in part because o. The cluster of comorbidities (and their associated treatments) that occur in patients with CKD. Owing to its electrophysiological effects, severe hyperkalaemia represents a medical emergency that usually requires prompt intervention, wherea. The prevention of hazardous hyperkalaemic episodes in at-risk patients requires measures aimed a. The long-term normalization of potassium homeostasis. The options for effective and safe medical interventions to restore chronic potassium balance are few, and long-term management of hyperkalaemia is primarily limited t. The correction of modifiable exacerbating factors. This situation can result in a difficult trade-off in patients with CKD, because drugs that are beneficial to these patients (for example, renin-angiotensin-aldosterone-system antagonists) are ofte. The most prominent cause of their hyperkalaemia. Maintainin. The use of these beneficial medications while implementing various strategies to control potassium balance is desirable; however, discontinuation rates remain high. The emergence of new medications that specifically target hyperkalaemia could lead to a therapeutic paradigm shift, emphasizing preventive management over ad hoc treatment of incidentally discovered elevations in serum potassium levels. © 2014 Macmillan Publishers Limited. All rights reserved.


Nelson D.R.,University of Tennessee Health Science Center
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2013

The world we live in is a biosphere influenced by all organisms who inhabit it. It is also an ecology of genes, with some having rather startling effects. The premise put forth in this issue is cytochrome P450 is a significant player in the world around us. Life and the Earth itself would be visibly different and diminished without cytochrome P450s. The contributions to this issue range from evolution on the billion year scale to the colour of roses, from Darwin to Rachel Carson; all as seen through the lens of cytochrome P450. © 2013 The Author(s) Published by the Royal Society. All rights reserved.

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