Tobacco Documents Online

T71I: COUNCIL FOR TOBACCO RbSI•:AItCH-U...S~.A., INC. March 24 1975 HY0 0 !if;'s Q=i ~; Grant Application No. 1010 M IIOIIJNOLOGY TD: The committee comprising Drs. Bing, Feldman and T,i.ebow (W.U.G. and S.C.S.) FROM: Robert C. Hockett SZIDJBCT: Carl G. Becker, M.D. and Gregory Siskind, M.D., Cornell University Medical Co] "Investigation of the Role of Allergy to Tobacco Constituents in the Pathogenesis of Arteriosclerosis and Myocgrdial Infarction." (Denied in its original form in October 1974.) (See memorandum of Feb. 21, 197° In October 1974 the SAB suggested that a new application be submitted for one year preliminary clinical stu,dies on human allergic responses to tobacco, at a budget not to exceed $30,000. (Hence the comprehensive title above is deceiving.) Dr. Becker visited the CTR offices on March 19th to describe the work that has been done during the interwal since Oct. 1974. He and Dr. Siskind have apparently been actively at work. Tobacco leaf glvco-vrntein (TLG.) New preparations have been made. The active material has a molecular weight of about 26,000 as indicated by RF values on elec- f,rophoresis. There is a second substance of about 75,000 mol.wt. with some activity. They have devised a preparative column and have been able to collect sufficient amounts of the quite homogeneaus 26,000 mol.wt. fraction for use in immunizing rabbits, with the object of preparing a radio-imnuno-assey reagent. The imunization of goats has begun (or is about to bWtn), • Tests for antibody to TLG. A counter-electrophoresis system in agarose gel has been used for a preliminary test of human and animal sera for antibodies to TI,G, with the following results: Human adults (young - random) 12 positives out of 31 cases Current human smokers 4 out of 16 cases Current non-smokers 3 out of 9 cases Human fetal cord blood 1 " out of 5 eases Rhesus monkeys o " out of 4 cases Rabbits 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 Amicon filter fu-der nitrogen pr< sure. This filter retains molecules over 10,000 in mol. wt. The filtexed material was treated like the TGP obtained from tobacco leaf including passage through Sephadeg columns from which a substance emerged with the void volume. On subjection to electrophoresis, a band of material was obtained where TOP was to be expected. This stained as a glycoprotein. This unexpected result suggests that tobacco glyeoprotein is carried in the smoke from burning tobacco. Two sensitive subjects gave faint positive skin reactions to this material. This finding led to discussion of plans for fractionation to tobacco smoke condensates prepared under defined and controlled methods.

-2- Merah 2h~~ l )~~DC~~J~, l)~~DC~~J~ RIA for him= immunogloinlin E. The tegged antibodies fox human TgE available commerciatly~ from Berenberger are not satisfactory for the purposes of this study. A human myeloma patient at the New York Flospital is serving as a sonrce for IgE from which antibodies are being prepared by the Cornell teeh. G]sncoprotein f,rom eggplant. Preliminary eaperiments with egg plant have isolateda substance quite • similar to the tobacco leaf glycoprotein, but not identical with it. To ccocplete his Mes on the subject of tobacco allergy, especially CTA's history in this area, ve furnishe8 Becker wlth copies of nineteen papers inclwding the output from CTR projects with S,ulzberger, Fontana and Redisch, and several papers on antibodies to tobacco mosaic virus fbund in smokers. R. C. H. RCH/Ip