Tobacco Documents Online

E COUNCIL FOR TOBACCO RESGARCH-U.S.A., INc. March 24, 1975 NKOu673Q15 Grant Application No. 1010 M IMKUNOIAC4X Ta: The eemtnittee comprising Drs. Bing, Feldman and Liebow (W.U.G. and S.C.3.) FROM: Robert C. Hockett StIDJDCT: Carl G. Beckei,c, M.D. and Gregory Siskind, M.D., Cornell Lfiiversity Medical CoBc "tnvestigation of the Role of Allergy to Tobacco Constituents in the Pathogenesis of Arteriosclerosis and Myocardial Infarction." (Denied ia its original form in October 1974.) (See memorandum of Feb. 21, 1975. In October 1974,the SAD suggested that a new application be submitted for one year prelimins.ryy clinical studies on human allergic responses to tobacco, at a budget not te exceed $30,000. (Hence the coatprehensive title above is deceiving.) Dr. Recker visited the CTR offices on March 19th to describe the work that has been done during the interval since Oct. 1974. He and Dr. Siskind have apparp.ntly been actively at work. Tobacco leaf g1yco protein (TLG.) New preparations have been made. The active material has a molecular wetght of about 26,000 as indicated by RF values on elec- trophoresis. There is a second substance o: about 75,000 mol.w*. with some activity. They have devised a preparative column and have been able to collect sufficient amounts of the quite homogendous 26,000 mol.wt. fraction for use in iramtanizing rabbits, with the ob3ect of preparing a radio-immuno-assay reagent. The imtsunization of goats has begun (or is about to begin). • tests for antibodv to TLG. A counter-electrophoresis system in agarose gel has been used for a preliminary test of human and animal sera for antibodies to ThG, with the following results: Human adults (young - random) Current human smokers Current non-smokers Human fetal cord blood Rhesus monkeys Rabbits 12 positives out of 31 cases 4 " out of 16 cases 3 " oat of 9 cases 1 " out of 5 cases 0 ° out of 4 cases 0 " out of 5 cases TGP in tobacco smoke. In a preliminary rough experiment, cigarette smoke was passed through saline which was then filtered through on Ar.ticon filter under nitrogen pre sure. This filter retains molecules over 10,000 in mol. wt. The filtered material was treated like the TGJ' obtained fran tobacco leaf including passage through Sephadex columns t)rom which a substance emerged with the void volume. On subjection to electrophoresis, a band of material was obtained where TGP was to be expected. This ? tsined as a otein. This unexpected result suggests that tobacco glycopro sin is carr ed in the smoke 71rom burning tobacco. TWo sensitive subjects gave faint positive kin reactions to this material. This finding led to discussion of plans for fractionotion to tobacco smoke condensates prepared under defined and controlled methods. f' ll-S t Ps~` ~iet~hieric c ~+ S.-h~ ff r I M, a rs For htlyeis - n.t deF.n,t e Qe. 3J_J (_,)lre}rin, Mar.lr eer.f-.f: et .".. , a.F.t1fLIR . - -

I -2- March 24, 1975 NKOab73o16 P.iA for human immunoglobulin E. The tagged antibodies for hunan IgE availe` .Le coroonercially fran Berenberget are not satisfactory for the ptaposes of tb9s study. A human m,yeloma patient at the New York Hospital is servi.ng as a source for IgE Prom which antibodies are being prepared by the CornF.7.71 team. 6lycoprotein txom eggplant. Preliminsry experiments with egg plant have isolateda substance quite• similer to the tobacco leaf glycoproteia, but not identical with it. To complete his files on the subject of tobacco allergy, especially CTFt's history in this area, we furnished Becker with copies of nineteen papers including the output from C1`lt projeets with Sulzberger, Fontana and ltedisch, and sevrt+xal papers on antibodies to tobacco mosaic virus found in smeokers. B. C. H. BCB/lp