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Tim CciuNC». Tun Tol3Acc;o I2r.sra~trli-L'.5.~1., Irc. July 5, 1973 MEMORAIJDUM h K©08•1215~: TO: •Drs. Bing, Hockett, Loosli, Nordsiek, Semmers and Wyatt FROM: W. U. Gardner SUBJECT: Application 913. Anthony J. rbarra, Ph.D., St. Margaret's Hosvital, Boston. "The Interaction of Smoke, Alcoholism and Malnutrition on Phagocytic Function." This is a study of the effect of srroking, alcohol and malnutrition on alveolar macrophages and on blood leukocytes. It will include metabolic and microbiulogical experiments. These are outlined in brief on the first two pages. The basic assumption is that persons in the above categories are unusually susceptible to infections, an assumption that is not consistent in the literature. He reviews the work that has been done on phagocytosis and on oxidative enzymes of the pulmonary macrophaoes but criticizes it because much of it was not done during the reriod of active phagocytosis. The incidence of ir.fections is stated to be high in alcoholics who also may have nutritional difficulties, and under-nutrition predisposes to susceptibility to ir.fection. Patients from three different hospitals in t;,e Bhston aree will be used. They will be matched for combinations of the three variables to be studied. Approximately 8-10 patients are bronchioscoped each week and they will be the source of pulmonary leityocytes and peripheral blood leukocytes. Multiple tests will be done to determine nutritional status. Methods of separating the white cells, of getting the pulmonary macrophages and of their fractionation are given. It seems to me that it will be difficult to get enough mitochondria from lung macrophages to do all of the tests that he mentions. in vitro studies will be made by blowing smoke in using a 50 ml isyringe. Fresh smoke (?), gas phase and water-soluble material will be used to determine effects on enzymatic functions and phagocytosis. The applicant, a Ph.D., has a dual appointment in pathology at St. Margaret's Hospital, and in Obstetrics & Gynecology at Tufts. Most of the facilities will be at St. Marc,aret's. The laboratories seem well equipped. A Dr. Joseph Vitale at Boston City Hospital will obtain aiid prepared the patients' specimens. He has an AEC grant terminating August 6, 1973, and an NIH qrant pending. The )atter is cn metabolism of n,?oplasti • cells during pnago:ytcsis. The applicant has a long list of titles but it includes many abstracts of papers picsented at meetings. He has done a good hit on metabolism of macrophages. rhe biocl,erist on thc nrc-ject, from Indxa, received a Ph.D. frcr. McGill in 1962 and has b-en with the applicant since 1965.

HK@ 08 A 2 15 3 -a- Dr. Vitale is an Sc.D., Harvard School of Public Health, and an M.D. from the Universidad de Mtioquid (Columbia). He has done considerable work on nutritional problems and on alcohol. I'm inclined to doubt that much would come out of this project. It would be a good plan to have Dr. Lisanti look into the project if he is not already familiar with it. w.u.G. WUG:ek