Abstract

The long-term goal of the proposed research is to define relationships that may exist between specific genetic markers, the inflammatory response to injury, and post-injury organ dysfunction. To accomplish this goal we shall collect and store data from patients with acute thermal injury, the most quantitative inflammatory stimulus experienced by humans. In the initial studies we shall look for associations between (a) two allelic polymorphisms in or near the TNF-alpha locus on chromosome 6, (b) blood cytokine markers of pro- and anti-inflammatory responses, and (c) specific measures of organ dysfunction. This approach should make it possible to define, for the first time, clinically relevant interactions between specific genetic polymorphisms, the production of TNF-alpha and other mediators, and inflammation-induced organ dysfunction. The CNA and data to be stored will also make it possible to assess other inflammation-related polymorphisms that are identified in the future. In addition to providing novel insights into pathogenesis, the proposed research should uncover genetic and/or acute inflammatory response parameters that correlate with subsequent organ dysfunction-that identify patients at """"""""high risk""""""""- and could therefore significantly improve the management of patients with thermal injury.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center (P50)
Project #
3P50GM021681-36S1
Application #
6435857
Study Section
Special Emphasis Panel (ZGM1)
Project Start
2001-02-01
Project End
2002-01-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
36
Fiscal Year
2001
Total Cost
$197,196
Indirect Cost

  Institution

Name
University of Texas Sw Medical Center Dallas
Department
Type
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390

  Publications

Lin, Keng-Mean; Hu, Wei; Troutman, Ty Dale et al. (2014) IRAK-1 bypasses priming and directly links TLRs to rapid NLRP3 inflammasome activation. Proc Natl Acad Sci U S A 111:775-80
Lu, Dongmei; Sun, Hui-qiao; Wang, Hanzhi et al. (2012) Phosphatidylinositol 4-kinase II? is palmitoylated by Golgi-localized palmitoyltransferases in cholesterol-dependent manner. J Biol Chem 287:21856-65
Sun, Yi; Dandekar, Radhika D; Mao, Yuntao S et al. (2011) Phosphatidylinositol (4,5) bisphosphate controls T cell activation by regulating T cell rigidity and organization. PLoS One 6:e27227
Hassan, Monique; Pham, Tam N; Cuschieri, Joseph et al. (2011) The association between the transfusion of older blood and outcomes after trauma. Shock 35:3-8
Gatson, J W; Simpkins, J W; Yi, K D et al. (2011) Aromatase is increased in astrocytes in the presence of elevated pressure. Endocrinology 152:207-13
Huebinger, Ryan M; Gomez, Ruben; McGee, Daphne et al. (2010) Association of mitochondrial allele 4216C with increased risk for sepsis-related organ dysfunction and shock after burn injury. Shock 33:19-23
Wang, Lin; Quan, Jiexia; Johnston, William E et al. (2010) Age-dependent differences of interleukin-6 activity in cardiac function after burn complicated by sepsis. Burns 36:232-8
Huebinger, Ryan M; Rivera-Chavez, Fernando; Chang, Ling-Yu et al. (2010) IL-10 polymorphism associated with decreased risk for mortality after burn injury. J Surg Res 164:e141-5
Huebinger, Ryan M; Garner, Harold R; Barber, Robert C (2010) Pathway genetic load allows simultaneous evaluation of multiple genetic associations. Burns 36:787-92
Chen, Mark Z; Zhu, Xiaohui; Sun, Hui-Qiao et al. (2009) Oxidative stress decreases phosphatidylinositol 4,5-bisphosphate levels by deactivating phosphatidylinositol- 4-phosphate 5-kinase beta in a Syk-dependent manner. J Biol Chem 284:23743-53

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