Abstract

Aim 1 will determine the optimal combination of supplemental AOE required to protect cells from hyperoxia. This will be done using a pulmonary epithelial cell culture system exposed to hyperoxia.
Aim 2 is to improve the distribution and uptake of AOE in the lung. Stabilized suspensions will be tested in cell culture and in mice exposed to hyperoxia for their effects on cell viability, virus infectivity, multiple gene delivery and expression, and degree of injury.
Aim 3 will use viral constructs containing AOE genes under the control of the human SP-B promoter (to target Type II or Clara cells) or the CMV promoter.
Aim 4 is to compare the effects of PFC-protein or adenoviral-associated AOE suspensions on normal or injured, preterm or term lamb lungs, using assays for levels and duration of transgene expression.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL064158-03
Application #
6537738
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Berberich, Mary Anne
Project Start
2000-07-01
Project End
2005-06-30
Budget Start
2002-08-01
Budget End
2003-06-30
Support Year
3
Fiscal Year
2002
Total Cost
$455,129
Indirect Cost

  Institution

Name
Winthrop-University Hospital
Department
Type
DUNS #
065937856
City
Mineola
State
NY
Country
United States
Zip Code
11501

  Publications

Lee, Jennifer W; Davis, Jonathan M (2011) Future applications of antioxidants in premature infants. Curr Opin Pediatr 23:161-6
Arita, Yuko; Kazzaz, Jeffrey A; Joseph, Ansamma et al. (2007) Antioxidants improve antibacterial function in hyperoxia-exposed macrophages. Free Radic Biol Med 42:1517-23
Brunelli, Luca; Hamilton, Eric; Davis, Jonathan M et al. (2006) Perfluorochemical liquids enhance delivery of superoxide dismutase to the lungs of juvenile rabbits. Pediatr Res 60:65-70
Arita, Yuko; Harkness, S Hella; Kazzaz, Jeffrey A et al. (2006) Mitochondrial localization of catalase provides optimal protection from H2O2-induced cell death in lung epithelial cells. Am J Physiol Lung Cell Mol Physiol 290:L978-86
Koo, Hshi-Chi; Davis, Jonathan M; Li, Yuchi et al. (2005) Effects of transgene expression of superoxide dismutase and glutathione peroxidase on pulmonary epithelial cell growth in hyperoxia. Am J Physiol Lung Cell Mol Physiol 288:L718-26
Oliver, Rees E; Rozycki, Henry J; Greenspan, Jay S et al. (2005) Tracheal gas insufflation as a lung-protective strategy: physiologic, histologic, and biochemical markers. Pediatr Crit Care Med 6:64-9
Kinsella, John P; Parker, Thomas A; Davis, Jonathan M et al. (2005) Superoxide dismutase improves gas exchange and pulmonary hemodynamics in premature lambs. Am J Respir Crit Care Med 172:745-9
Arita, Yuko; Joseph, Ansamma; Koo, Hshi-Chi et al. (2004) Superoxide dismutase moderates basal and induced bacterial adherence and interleukin-8 expression in airway epithelial cells. Am J Physiol Lung Cell Mol Physiol 287:L1199-206
Li, Yuchi; Arita, Yuko; Koo, Hshi-Chi et al. (2003) Inhibition of c-Jun N-terminal kinase pathway improves cell viability in response to oxidant injury. Am J Respir Cell Mol Biol 29:779-83
Jeng, Mei-Jy; Yang, Shyh-Sheng; Wolfson, Marla R et al. (2003) Perfluorochemical (PFC) combinations for acute lung injury: an in vitro and in vivo study in juvenile rabbits. Pediatr Res 53:81-8

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