PURPOSE: The Imaging Core will have 2 service functions. The first function is to provide technical support for state-of-the-art morphological methods. The second function is to collect and evaluate human tissue from autopsies, surgical resections and transplant procedures. 1. To provide technical expertise for state-of-the-art morphological methods. These methods include routine and specialized quantitative histology and electron microscopy, immunohistochemistry, and in situ hybridization. We have considerable expertise with in vivo experimental animal studies, in vivo experiments, and human tissue analyses. 2. To collect human tissues from autopsies, surgical resections and transplant procedures. The second function of the Imaging Core is to exploit the human tissue bank that Dr. Albertine established, with the invaluable assistance of Drs. Zimmerman. Michael and McIntyre. Such studies of the human lung in the ARDS are desperately needed to correlate with measurements of factors in bronchoalveolar lavage and plasma samples and to use as a """"""""gold standard"""""""" for immunohistochemical and other studies in animal models of acute lung injury, as recognized by others (Pittet et al., 1997). We are particularly excited by the future plan of extending the analysis beyond the immediate goals of the specific projects, once the inflammatory phenotype of in situ endothelial cells has been defined, to analysis of the display of signaling factors, surface adhesion molecules, and other key variable sin other cell types in the milieu of the inflamed lung in ARDS. One of the exciting future plans is to share our human tissue bank with other SCOR programs, such as we are planning with Dr. Hudson's SCOR group in Seattle. SIGNIFICANCE: The contributions of the Imaging Core will substantially improve our understanding of dysregulated cell-cell interactions and intercellular signaling at different stages of the ARDS (e.g., early versus late injury, and injury versus repair).

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center (P50)
Project #
2P50HL050153-06
Application #
6110237
Study Section
Project Start
1998-12-01
Project End
1999-11-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
6
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Utah
Department
Type
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Yost, Christian C; Weyrich, Andrew S; Zimmerman, Guy A (2010) The platelet activating factor (PAF) signaling cascade in systemic inflammatory responses. Biochimie 92:692-7
Gomes, Rachel N; Bozza, Fernando A; Amancio, Rodrigo T et al. (2006) Exogenous platelet-activating factor acetylhydrolase reduces mortality in mice with systemic inflammatory response syndrome and sepsis. Shock 26:41-9
Matthay, Michael A; Zimmerman, Guy A (2005) Acute lung injury and the acute respiratory distress syndrome: four decades of inquiry into pathogenesis and rational management. Am J Respir Cell Mol Biol 33:319-27
Lindemann, Stephan W; Weyrich, Andrew S; Zimmerman, Guy A (2005) Signaling to translational control pathways: diversity in gene regulation in inflammatory and vascular cells. Trends Cardiovasc Med 15:9-17
Ishizaka, Akitoshi; Matsuda, Tomoyuki; Albertine, Kurt H et al. (2004) Elevation of KL-6, a lung epithelial cell marker, in plasma and epithelial lining fluid in acute respiratory distress syndrome. Am J Physiol Lung Cell Mol Physiol 286:L1088-94
Zimmerman, Guy A; McIntyre, Thomas M (2004) PAF, ceramide and pulmonary edema: alveolar flooding and a flood of questions. Trends Mol Med 10:245-8
Wu, Xiaoqing; Zimmerman, Guy A; Prescott, Stephen M et al. (2004) The p38 MAPK pathway mediates transcriptional activation of the plasma platelet-activating factor acetylhydrolase gene in macrophages stimulated with lipopolysaccharide. J Biol Chem 279:36158-65
Lindemann, Stephan W; Yost, Christian C; Denis, Melvin M et al. (2004) Neutrophils alter the inflammatory milieu by signal-dependent translation of constitutive messenger RNAs. Proc Natl Acad Sci U S A 101:7076-81
Yost, Christian C; Denis, Melvin M; Lindemann, Stephan et al. (2004) Activated polymorphonuclear leukocytes rapidly synthesize retinoic acid receptor-alpha: a mechanism for translational control of transcriptional events. J Exp Med 200:671-80
Ghio, Andrew J; Carter, Jacqueline D; Richards, Judy H et al. (2003) Iron and iron-related proteins in the lower respiratory tract of patients with acute respiratory distress syndrome. Crit Care Med 31:395-400

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