Tobacco Documents Online

h 1;Pi, fif;6N 0 i" Tar COUNCIL Foe Tosacco RrsLaRc1t-U.S.A., Ixc. March 24, 1975 Grant Application No. 1010 M IN![JNOIAGY Ta: The ccnmittee comprising Drs. Bing, Feldman and Liebow (W.U.G. and S.C.S.) FROM: Robert C. Hockett SU3JkCT: Carl G. Becker, M.D. and Gregory Siskind, M.D., Cornell University Medical Co11 "Investigation of the Role of Allergy to Tobacco Constituents in the Pathogenesis of Arteriosclerosis and Nlyocardial Infarction." (Denied in its original form in October 1974.) (See memorandwn of Feb. 21, 1975 In October 1974 the SAB suggested that a new appli.cation be submitted for one year preliminary clinical studies on hman allergic responses to tobacco, at a budget not to exceed $30,000. (Hence the comprehensive title above is deceiving.) T,r. Becker 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 apparently been actively at work. Tobacco leaf glyco protein (TLG.) New preparations have been made. The active material has a molecular weight of about 26,000 as indicated by IV values on elec- trophoresis. 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 homogencous 26,000 mol.wt. fraction for use in immunizing rabbits, with the object of preparing a radio-immuno-assay reagent. The immunization of goats has begun (or is about to begin). Tests for antibody to TLG. A counter-electrophotesis system in agarose gel has been used for a preliminary test of human and animal sera for antibodies to TLG, with the following results: Human adults (young - random) Current human smokers Current non-smokers H:oe.an feta7l cord blood Rhesus monkeys Rabbits 12 positives out of 31 cases 4 " out of 16 cases 3 " out of 9 case: ]. " 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 Amicon filter under nitrogen pra sure. This filter retains molecules over 10,000 in mol. wt. The filtered materia7l was treated like the TGP obtained from tobacco leaf including passage through Sephades columns from which a substance emerged with the void volume. On subjection to electruphoresis, a band of material was obtained where TGP 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 d.iscussion nf plans for fractionation to tobacco smoke condensates prepared under defined and controlled methods.

2- March 24, 1975 H KOAQW`i(;J50 RYA for hummh immunoalobalin E._ The tagged antibodies for humsan IgE available ccmmaerciaL'ty frae Bere,nberger are not satisfactory for the purposes of this study. A. humen myelc®a patient at the New York Hospital is serving as a sonwce :r: 7$E frm which antibodies are being prepared by the Cornell team. Glycaprotein from eEULnt. PrPi manaJ experiments with egg plant have isolateda subs ance quite• simil.ax to the tobacco leaf glycoprotein, but not identical with it. Tb cem~lete lais files on the subject of tobacco allergy, especially C7R's history in this a~ea, we furnished Becker with copies of nineteen papers including the output from C'1R pro3ects with Sulzberger, Fontana and Redisch, and severreal papers on entimod3.es to tobacco mosaic virus fouud in smokers. R. C. H. RC$/lp i