Acute respiratory distress syndrome (ARDS) is a serious disorder with a mortality rate between 50-70%. It is characterized by intense inflammatory response. This response consists of an influx and sequestration of neutrophils into the lung with the release of noxious mediators such as neutrophil elastase. EIastase may cleave and destroy elastin as well as macromolecules such as surfactant apoproteins. Surprisingly, almost nothing is known about the functional relationship between surfactant dysfiinction and changes in elastin in ARDS during lung injury and repair. Whether the status ofelastin synthesis at the time of the injury or the presence of abnormaI clastin affect the overall response to lung injury is unknown. Furthermore, while phospholipids possess anti-inflammatory properties, it is unknown what effect exogenous would have on reducing the inflammatory response and the effect on elastin damage after lung injury. The overall goal of this proposal therefore is to analyze the role of surfactants in modulating elastin synthesis in a transgenic mouse model of acute lung injury, created by the intratracheal administration of bacterial endotoxin into transgenic mice harboring and actively expressing a number of different elastin gene mutations. New information from these studies may contribute to a better understanding of factors related to ARDS survival and recovery, with and without pulmonary sequelae. They may also contribute to a better understanding of the use of exogenous surfactant therapy in ARDS.

Project Start
2000-09-01
Project End
2001-08-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
15
Fiscal Year
2000
Total Cost
$163,492
Indirect Cost
Name
University of Hawaii
Department
Type
DUNS #
121911077
City
Honolulu
State
HI
Country
United States
Zip Code
96822
Priemer, David S; Wang, Mingsheng; Zhang, Shaobo et al. (2018) Small-cell Carcinomas of the Urinary Bladder and Prostate: TERT Promoter Mutation Status Differentiates Sites of Malignancy and Provides Evidence of Common Clonality Between Small-cell Carcinoma of the Urinary Bladder and Urothelial Carcinoma. Eur Urol Focus 4:880-888
Marciel, Michael P; Rose, Aaron H; Martinez, Verena et al. (2018) Calpain-2 inhibitor treatment preferentially reduces tumor progression for human colon cancer cells expressing highest levels of this enzyme. Cancer Med 7:175-183
Marciel, Michael P; Khadka, Vedbar S; Deng, Youpeng et al. (2018) Selenoprotein K deficiency inhibits melanoma by reducing calcium flux required for tumor growth and metastasis. Oncotarget 9:13407-13422
Pomozi, Viola; Brampton, Christopher; Szeri, Flóra et al. (2017) Functional Rescue of ABCC6 Deficiency by 4-Phenylbutyrate Therapy Reduces Dystrophic Calcification in Abcc6-/- Mice. J Invest Dermatol 137:595-602
Norton, Robert L; Fredericks, Gregory J; Huang, Zhi et al. (2017) Selenoprotein K regulation of palmitoylation and calpain cleavage of ASAP2 is required for efficient Fc?R-mediated phagocytosis. J Leukoc Biol 101:439-448
Baumer, Yvonne; McCurdy, Sara; Weatherby, Tina M et al. (2017) Hyperlipidemia-induced cholesterol crystal production by endothelial cells promotes atherogenesis. Nat Commun 8:1129
Wilcox, Christie L; Headlam, Jasmine L; Doyle, Thomas K et al. (2017) Assessing the Efficacy of First-Aid Measures in Physalia sp. Envenomation, Using Solution- and Blood Agarose-Based Models. Toxins (Basel) 9:
Yanagihara, Angel Anne; Wilcox, Christie L (2017) Cubozoan Sting-Site Seawater Rinse, Scraping, and Ice Can Increase Venom Load: Upending Current First Aid Recommendations. Toxins (Basel) 9:
Chang, Linda; Løhaugen, Gro C; Andres, Tamara et al. (2017) Adaptive working memory training improved brain function in human immunodeficiency virus-seropositive patients. Ann Neurol 81:17-34
Doyle, Thomas K; Headlam, Jasmine L; Wilcox, Christie L et al. (2017) Evaluation of Cyanea capillata Sting Management Protocols Using Ex Vivo and In Vitro Envenomation Models. Toxins (Basel) 9:

Showing the most recent 10 out of 347 publications