Department of Immunology and Microbiology
1. Molecular Mechanisms of Inflammatory Injury
Studies are being conducted on the role of leukocytic proteolytic enzymes, oxidants and phospholipases released in the inflammatory reaction that induce damage to host tissues. Models of inflammatory injury in the lung allow for a comparative analysis of biochemical and morphologic changes in cells and supporting connective tissue matrix proteins and accompanying changes in physiologic parameters in the lung.
2. Development of a Synthetic Peptide Pulmonary Surfactant
for Use in Infant and Adult Human Beings
Modeled on Surfactant Protein B (SP-B) which was found and sequenced in this and other laboratories in the late 1980's, a synthetic peptide was established that, when recombined with synthesized surfactant phospholipids, provides full function in expanding lungs of laboratory animals and human beings that collapse because of a deficiency of surfactant activity. The peptide, KLLLLKLLLLKLLLLKLLLLK (KL4), as well as the SP-B peptide, act by imparting lateral stability to the monolayer of phospholipid molecules through electrostatic and hydrophobic interactions. Final trials in human beings were successful and with FDA approval, the synthetic peptide surfactant will receive world-wide distribution. Work continues on the biochemical means by which the surfactant replacement inhibits inflammatory injury.
Centennial "Live and Breathe Award", The American Lung Association, 2004
Jackson, J., Schraufstatter, I.U., Hyslop, P.A., Vosbeck, K., Sauerheber, R., Weitzman, S.A., and Cochrane, C.G. Role of oxidants in DNA damage: Hydroxyl radical mediates the synergistic DNA damaging effects of asbestos and cigarette smoke. J. Clin. Invest., 80:1090-1095, 1987.
Cochrane, C.G., and Revak, S.D., Pulmonary surfactant protein B
(SP-B): Structure-function relationships. Science 254:566-568, 1991.
Cochrane, C.G., Revak, S.D., Merritt, T.A., Heldt, G.P., Hallman, M., Cunningham, M.D., Easa, D., Pramanik, A., Edwards, D.K., and Alberts, M.S. The efficacy and safety of KL4-Surfactant in preterm infants with RDS. Am. J. Resp. & Crit. Care Med., 153:404-410, 1996.
Cochrane, C.G. A critical examination of the role of SP-B in alveolar expansion. Applied Cardiopulmonary Pathophysiology; the Interface Between Laboratory Research and Clinical Practice. 13:27-28 ,2004.