Emory University

About: Emory University is a education organization based out in Atlanta, Georgia, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 51959 authors who have published 122469 publications receiving 6010698 citations.

Galaxy: A Web‐Based Genome Analysis Tool for Experimentalists

Abstract: High-throughput data production has revolutionized molecular biology. However, massive increases in data generation capacity require analysis approaches that are more sophisticated, and often very computationally intensive. Thus, making sense of high-throughput data requires informatics support. Galaxy (http://galaxyproject.org) is a software system that provides this support through a framework that gives experimentalists simple interfaces to powerful tools, while automatically managing the computational details. Galaxy is distributed both as a publicly available Web service, which provides tools for the analysis of genomic, comparative genomic, and functional genomic data, or a downloadable package that can be deployed in individual laboratories. Either way, it allows experimentalists without informatics or programming expertise to perform complex large-scale analysis with just a Web browser.

Role of the T cell in the genesis of angiotensin II–induced hypertension and vascular dysfunction

Abstract: Hypertension promotes atherosclerosis and is a major source of morbidity and mortality. We show that mice lacking T and B cells (RAG-1-/- mice) have blunted hypertension and do not develop abnormalities of vascular function during angiotensin II infusion or desoxycorticosterone acetate (DOCA)-salt. Adoptive transfer of T, but not B, cells restored these abnormalities. Angiotensin II is known to stimulate reactive oxygen species production via the nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase in several cells, including some immune cells. Accordingly, adoptive transfer of T cells lacking the angiotensin type I receptor or a functional NADPH oxidase resulted in blunted angiotensin II-dependent hypertension and decreased aortic superoxide production. Angiotensin II increased T cell markers of activation and tissue homing in wild-type, but not NADPH oxidase-deficient, mice. Angiotensin II markedly increased T cells in the perivascular adipose tissue (periadventitial fat) and, to a lesser extent the adventitia. These cells expressed high levels of CC chemokine receptor 5 and were commonly double negative (CD3+CD4-CD8-). This infiltration was associated with an increase in intercellular adhesion molecule-1 and RANTES in the aorta. Hypertension also increased T lymphocyte production of tumor necrosis factor (TNF) alpha, and treatment with the TNFalpha antagonist etanercept prevented the hypertension and increase in vascular superoxide caused by angiotensin II. These studies identify a previously undefined role for T cells in the genesis of hypertension and support a role of inflammation in the basis of this prevalent disease. T cells might represent a novel therapeutic target for the treatment of high blood pressure.

Viral Persistence Alters CD8 T-Cell Immunodominance and Tissue Distribution and Results in Distinct Stages of Functional Impairment

Abstract: Chronic viral infections often result in ineffective CD8 T-cell responses due to functional exhaustion or physical deletion of virus-specific T cells. However, how persisting virus impacts various CD8 T-cell effector functions and influences other aspects of CD8 T-cell dynamics, such as immunodominance and tissue distribution, remains largely unknown. Using different strains of lymphocytic choriomeningitis virus (LCMV), we compared responses to the same CD8 T-cell epitopes during acute or chronic infection. Persistent infection led to a disruption of the normal immunodominance hierarchy of CD8 T-cell responses seen following acute infection and dramatically altered the tissue distribution of LCMV-specific CD8 T cells in lymphoid and nonlymphoid tissues. Most importantly, CD8 T-cell functional impairment occurred in a hierarchical fashion in chronically infected mice. Production of interleukin 2 and the ability to lyse target cells in vitro were the first functions compromised, followed by the ability to make tumor necrosis factor alpha, while gamma interferon production was most resistant to functional exhaustion. Antigen appeared to be the driving force for this loss of function, since a strong correlation existed between the viral load and the level of exhaustion. Further, epitopes presented at higher levels in vivo resulted in physical deletion, while those presented at lower levels induced functional exhaustion. A model is proposed in which antigen levels drive the hierarchical loss of different CD8 T-cell effector functions during chronic infection, leading to distinct stages of functional impairment and eventually to physical deletion of virus-specific T cells. These results have implications for the study of human chronic infections, where similar T-cell deletion and functional dysregulation has been observed.

Long-term acceptance of skin and cardiac allografts after blocking CD40 and CD28 pathways.

Abstract: THE receptor–ligand pairs CD28–B7 and CD40–gp39 are essential for the initiation and amplification of T-cell-dependent immune responses1,2 CD28–B7 interactions provide 'second signals' necessary for optimal T-cell activation and IL-2 production3–5, whereas CD40–gp39 signals co-stimulate B-cell, macrophage, endothelial cell and T-cell activation6–12 Nonetheless, blockade of either of these pathways alone is not sufficient to permit engraftment of highly immunogenic allografts13–15 Here we report that simultaneous but not independent blockade of the CD28 and CD40 pathways effectively aborts T-cell clonal expansion in vitro and in vivo, promotes long-term survival of fully allogeneic skin grafts, and inhibits the development of chronic vascular rejection of primarily vascularized cardiac allografts The requirement for simultaneous blockade of these pathways for effective inhibition of alloimmunity indicates that, although they are interrelated, the CD28 and CD40 pathways are critical independent regulators of T-cell-dependent immune responses

American Association of Clinical Endocrinologists and American Diabetes Association Consensus Statement on Inpatient Glycemic Control

Abstract: People with diabetes are more likely to be hospitalized and to have longer durations of hospital stay than those without diabetes. A recent survey estimated that 22% of all hospital inpatient days were incurred by people with diabetes and that hospital inpatient care accounted for half of the 174 billion USD total U.S. medical expenditures for this disease (1). These findings are due, in part, to the continued expansion of the worldwide epidemic of type 2 diabetes. In the U.S. alone, there are ∼1.6 million new cases of diabetes each year, with an over all prevalence of 23.6 million people (7.8% of the population, with one-fourth of the cases remaining undiagnosed). An additional 57 million American adults are at high risk for type 2 diabetes (2). Although the costs of illness-related stress hyperglycemia are not known, they are likely to be considerable in light of the poor prognosis of such patients (3–6). There is substantial observational evidence linking hyperglycemia in hospitalized patients (with or without diabetes) to poor outcomes. Cohort studies as well as a few early randomized controlled trials (RCTs) have suggested that intensive treatment of hyperglycemia improved hospital outcomes (5–8). In 2004, this evidence led the American College of Endocrinology (ACE) and the American Association of Clinical Endocrinologists (AACE), in collaboration with the American Diabetes Association (ADA) and other medical organizations, to develop recommendations for treatment of inpatient hyperglycemia (9). In 2005, the ADA added recommendations for treatment of hyperglycemia in the hospitalto itsannual Standards of Medical Care (10). Recommendations from the ACE and the ADA generally endorsed tight glycemic control in critical care units. For patients in general medical and surgical units, where RCT evidence regarding treatment targets was lacking, glycemic goals similar to those advised for outpatients were advocated (9, …