Tobacco Documents Online

THr CaU\CIL FOR'rC3BACC0 RCS[.AIdCSl-L'.S.A., YNC. HK0i'124050 February 4, 1976 MEMORANDUM i / TO: Dr.s. Ho^kett. Jacobson, Meier, Soimners and Stone FROM: W. U. Gardner S[7BJECT : Application 1084. Gerard M. Turino, M.D., College of Physicians & Surgeons, Columbia University, New York, N.Y. "Chemical Basis of Tissue Destruction in Obstructive Lung Disease." Four senior investigators will work on the problem: Turino, Professor of Medicine and on the Task Force COLD and Chairman of the Subcommittee "Chemical Structure and Function of the Lung." Fierer, Assistant Professor of Pathology and Director of Imaunopathology. FIe also has e.m. facility. Mandl, Associate Professor of Reproductive BioCheinistsy is trained in biochemistry. Parshley, Ph.D., ReSearch Associate ik: Pathology, has been well trained in tissue culture. Bu~t. Approximately 60% for 1 1/2 tech.nicians. The remainder for expendable supplies and aniimal care. The senior applicant has a grant from NIHL at about $260,000 per year which goes through April 1978, and 523,000 from the New York Lung Association terminating March 31, 1916. Proposal. Emphysonatous destruction of human lungs and elastase activity of ?MN and aiJeolat mactophages in animals will be studied. Differences will be sought in function of alveolar macrophages of emphysematou.s and normal subjects, smokers and nonsmokers. Human and animal alveolar macrophages will be grown and maintained in vitro and the effects of several substances on the level of elasta3e activity determined. There is evidencE that elastase modifying elastin produces a condition resembling emphyseYna; collagenase does not, it reduces tensile strength. They have recently found that the PMNs of MM phenotypes with COLD have a higher elastase a:aivity. Comparative elastAse activity of PMN and alveolar macrophages in hamsters, rats and dogs will be done. Cbntrol determinations will be done and then their activity will be followed after intratracheal exposure to pancreatic protease for up to 2 months. Thioglycolate, cytochalasin B and coichicine will be given to determine their effect on peritoneal macrophage elastase. Specific inhibitors of elastase will be tested. Morphological studies, light and e.m. will be done. They have already observed that subject; with COLD have PMNs with higher elastase activity. They plan a similar study using alveolar macrophages. Alveolar macrophages will be maintained in culture and elastase determined in 30 patients and 30 controls. The application is straightforward. The maximal emphasis is on the comparison of the PMN and alveolar macrophaaes and elastases, effects of inhibitors on them in laboratory animals and man. W.U.G. WUG:ek