Tobacco Documents Online

, TAF Couxciiu FOR Tosncco RESEARCH-U.S.A., Irc. March 24, 19'5 '~Y"f44s'6is Grant Application No. 1010 M Il~IlrlIJ1VOY;0fY TD: The coamittee comprising Drs. Bing, Feldman and Liebow (W.U.G. and SbC.S.) FROM: Robert C. Hockett StIDJECT: Carl G. Becker, M.D. and Gregory Siskind, M.D., Ccaarnel7. University Medical CoIe "Investigation of the Role of Allergy to Tobacco Constituents in the Pathogenesis of Arteriosclerosis and Myocardial Infarction." (Denied in its original form in October 1974.) (See memorandum of Feb. 21, 1975. In October 1974 the SAB suggested that a new application be submitted for one yehr preliminary clinical studies 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 offtces on March 19th to describe the work that has been done during the interva]l since Oct. 1974. He and Dr. Siskind have apperehtly been actively at work. Tobacco leaf glyco nrotein (TLG.) New preparations have been made. The active materia]l has a molecular weight of about 26,000 as indicatec3• by RF values on elec- trophoresis. There is a second substance of about 75,000 mol.wt. with sone activity. They have devised a preparative column and have been able to collect sufficient amounts of the quite homogenwaus 26,000 mol.wt. fraction for use in iam<unizing rabbits, with the object of preparing a radio-imuno-assay reagent. The itmnunization of goats tias begun (or is about to begin). ' Tests for antibody to TLG. A counter-electrophoresis system 3n agarose ge.1 has been used for a preliminary test of human and animal sera for antibodies to TLG, with the following results: Human adults (young - ranclom) 12 positives out of 31 cases Current human smokers 4 " out of 16 cases Current non-smokers 3 " out of 9 cases Hiaman fetal cord blood 1 " out of 5 cases Rhesus monkeys 0 " 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 under nitrogen pre sure. This filter retains molecules over 10,000 in mol. wt. The filtered material was treated like the TGP obtained from tobacco leaf including passage through Sephadex columns from which a substance emerged with the void volume. On subjection to electrbphoresis, a band of material was optained where TGPwas to be eapected. This stained as a glyzoprotein. This unexpected result suggests that tobacco glycoprotein is carried in the smoke from burning tobacco. Two sensitive subjects gave faint positive skin reactions to this material. This finding led to d3.scussion of plans for fractionation to tobacco smoke condensates prepared under defined and cbntrolled methods.

i i Match 24, 1975 Ii K90(i6i059 RIA for human imonunog].obulin E. The tagged antibodies for human 10 available ca®ercislly fYom $erentierger are not satisfactory for the puorposes of this study. A human sqyelaaua patient at the New Xcch f[ospital is serMng as a source for IgE fram which antibodies are being prepared by the Cornell team. -Q. n rc =otein from eggplant. PrAl;mino+ry esperiments with egg plant ha" isolateda substance qiiite• similar to the tobacco leaf glycoprote3n, but not identical with it. '!b ccmpl.ete his files on the subject of tobacco allergy, especially C23's history in this area, we furnished Becker with copies of nineteen papers including the output from C7R projects with Sul2berger, Fontana and Redischi and several papers on antibodies to tobacco mosaic virus found in smokPrs. R. C. H. RCH/lp