University of Tennessee Health Science Center

About: University of Tennessee Health Science Center is a education organization based out in Memphis, Tennessee, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 15716 authors who have published 26884 publications receiving 1176697 citations.

History and Development of Evidence-based Medicine

Abstract: This article illustrates the timeline of the development of evidence-based medicine (EBM). The term "evidence-based medicine" is relatively new. In fact, as far as we can tell, investigators from McMaster's University began using the term during the 1990s. EBM was defined as "a systemic approach to analyze published research as the basis of clinical decision making." Then in 1996, the term was more formally defined by Sacket et al., who stated that EBM was "the conscientious and judicious use of current best evidence from clinical care research in the management of individual patients." Ancient era EBM consists of ancient historical or anecdotal accounts of what may be loosely termed EBM. This was followed by the development of the renaissance era of EBM, which began roughly during the seventeenth century. During this era personal journals were kept and textbooks began to become more prominent. This was followed by the 1900s, during an era we term the transitional era of EBM (1900-1970s). Knowledge during this era could be shared more easily in textbooks and eventually peer-reviewed journals. Finally, during the 1970s we enter the modern era of EBM. Technology has had a large role in the advancement of EBM. Computers and database software have allowed compilation of large amounts of data. The Index Medicus has become a medical dinosaur of the past that students of today likely do not recognize. The Internet has also allowed incredible access to masses of data and information. However, we must be careful with an overabundance of "unfiltered" data. As history, as clearly shown us, evidence and data do not immediately translate into evidence based practice.

Adult Acute Lymphoblastic Leukemia: Concepts and Strategies

Abstract: Acute lymphoblastic leukemia (ALL), a clonal expansion of hematopoietic blasts, is a highly heterogeneous disease comprising many entities for which distinct treatment strategies are pursued. Although ALL is a success story in pediatric oncology, results in adults lag behind those in children. An expansion of new drugs, more reliable immunologic and molecular techniques for the assessment of minimal residual disease, and efforts at more precise risk stratification are generating new aspects of adult ALL therapy. For this review, the authors summarized pertinent and recent literature on ALL biology and therapy, and they discuss current strategies and potential implications of novel approaches to the management of adult ALL. Cancer 2010. (c) 2010 American Cancer Society.

MAPK interacts with occludin and mediates EGF-induced prevention of tight junction disruption by hydrogen peroxide

Abstract: The MAPK (mitogen-activated protein kinase) pathway is a major intracellular signalling pathway involved in EGF (epithelial growth factor) receptor-mediated cell growth and differentiation. A novel function of MAPK activity in the mechanism of EGF-mediated protection of TJs (tight junctions) from H2O2 was examined in Caco-2 cell monolayers. EGF-mediated prevention of H2O2-induced increase in paracellular permeability was associated with the prevention of H2O2-induced Tyr-phosphorylation, Thr-dephosphorylation and cellular redistribution of occludin and ZO-1 (zonula occludin-1). EGF also prevented H2O2-induced disruption of the actin cytoskeleton and the dissociation of occludin and ZO-1 from the actin-rich detergent-insoluble fractions. MEK (MAPK/ERK kinase, where ERK stands for extracellular signal related kinase) inhibitors, PD98059 and U0126, completely blocked these protective effects of EGF on TJs. EGF rapidly increased the levels of phosphorylated MEK (p-MEK) in detergent-soluble fractions and phosphorylated ERK (p-ERK) in detergent-insoluble fractions. p-ERK was colocalized and co-immunoprecipitated with occludin. GST (glutathione S-transferase) pull-down assay showed that the C-terminal tail of occludin binds to p-ERK in Caco-2 cell extracts. Pair-wise binding studies using recombinant proteins demonstrated that ERK1 directly interacts with the C-terminal tail of occludin. Therefore the present study shows that ERK interacts with the C-terminal region of occludin and mediates the prevention of H2O2-induced disruption of TJs by EGF.

NEJ1 controls non-homologous end joining in Saccharomyces cerevisiae

Abstract: Broken DNA ends are rejoined by non-homologous end-joining (NHEJ) pathways requiring the Ku proteins (Ku70, Ku80), DNA ligase IV and its associated protein Lif1/Xrcc4 (ref. 1). In mammalian meiotic cells, Ku protein levels are much lower than in somatic cells, apparently reducing the capacity of meiotic cells to carry out NHEJ and thereby promoting homologous recombination. In Saccharomyces cerevisiae, NHEJ is also downregulated in meiosis-competent MATa/MAT alpha diploid cells in comparison with diploids or haploids expressing only MATa or MAT alpha. Diploids expressing both MATa and MAT alpha show enhanced mitotic homologous recombination. Here we report that mating-type-dependent regulation of NHEJ in budding yeast is caused in part by transcriptional repression of both LIF1 and the gene NEJ1 (YLR265C)--identified from microarray screening of messenger RNAs. Deleting NEJ1 reduces NHEJ 100-fold in MATa or MAT alpha haploids. Constitutive expression of NEJ1, but not expression of LIF1, restores NHEJ in MATa/MAT alpha cells. Nej1 regulates the subcellular distribution of Lif1. A green fluorescent protein (GFP)-Lif1 fusion protein accumulates in the nucleus in cells expressing NEJ1 but is largely cytoplasmic when NEJ1 is repressed.