Request for Funding

Medical Student Research Fellowship for Summer 2001

Mentor: Jureta W. Horton, Ph.D.

Department: Surgery

Room number: H7.130

Mail Code: 9160

Phone number: 8-3762

E-mail: jureta.horton@utsouthwestern.edu

Project title: Cardiac myocyte performance after burn injury

Human subjects IRB approved project number (where applicable):

Animal subjects IRB approved project number (where applicable):

0139-00-045-14 0139-01-04-11

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects)

Animal-based research

Brief Description of Project:

Our current studies are directed to define the signal transduction mechanisms which regulate lung and cardiac synthesis and secretion of inflammatory cytokines such as TNF-a after burn trauma and to define the mechanisms by which these cytokines alter peripheral organ function. We have hypothesized that phosphorylation and degradation of I-kB and nuclear translocation of NF-kB are critical modulators of postburn TNF transcriptional events. We have hypothesized further that burn mediated increases in cytokine synthesis induce a cascade of mediators which contribute to cellular cytoskeletal remodeling which could result in pulmonary capillary leak as well as loss of coronary endothelial integrity (and subsequent emmigration of activated leukocytes into the cardiac matrix). Studies are conducted in adult Sprague Dawley rats and adult mice to examine lung and cardiac function in vitro. Cellular studies include isolation of cardiomyocytes and alveolar macrophages to examine the proinflammatory versus anti-inflammatory mediators secreted by these specific cell populations. We also focus on identifying the inducer of signal transduction pathways which initiate TNF secretion by specific cell types. Our studies are ultimately directed to develop therapeutic strategies that would provide organ protection not only for victims of burn trauma but for all patient populations who are at risk of developing adult respiratory distress syndrome and cardiac contractile function.

Previous Research Activities or Publications with Medical Students:

1. Curtis BB, II, Horton JW, and Buja LM: Quantitative morphometry of myocardial lesions in shock. Circulatory Shock 16(1):36, 1985.

2. Gutierrez YM and Horton JW: Myocardial cell volume regulation in hemorrhagic shock (HS) and ethanolism. Federation Proceedings 46(4): 6488, 1987.

3. McAllister KP, Horton JW, Kaufman TM, White DJ. Acute ethanol intoxication shows no effect in Ca2+-Uptake or Ca2+-dependent ATPase activity in myocardial sarcoplasmic reticulum vesicles. The FASEB Journal 3(3):A429, 1989.

4. Nelms CD, Murray JD, Kaufman TM, Horton JW. Evidence of lipid peroxidation in plasma and heart tissue after ischemia-reperfusion injury. The FASEB Journal 6(5):A2040,1992.

5. Kuo W, Horton J, Walker P, Geldon D. O2 free radicals mediate postburn cardiac cell membrane dysfunction. FASEB Journal 7(3):A421, 1993.

6. Coln EC, Horton JW, Minei JP. Cardiac cell membrane function in thermal injury complicated by infection. Circ Shock 1993: (Supplement 2):A143.

7. Ozumba D, Maass D, White D, Horton J. Effects of L-arginine on bacterial translocation and cardiac function. FASEB J 10:A598, 1996.

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