Tobacco Documents Online

Abstracts of Reports Each recipient of a grant-in-aid from The Council for Tob:,ccn Re- search - U.S.A is responsible for the initial presentation or publicatiom of the results of his rescarch t scientific mectin8s or in appropriate scicntific journals. Following are abstracts, approved by the authors, of report; rin new experimental research acknowledging suppo rt from The Council t!iat have appeared in scientific journals since publication of the 1968-69 P eport of the Scientific Director. The name of the grantee is in italics. These abstracts have been arcwped under these headings: 1. Psycho- Physiolo6ical Studies. 11. Carcinogenesis Studies, 111. Cardiovasc alar Sys- tem, IV. Respiratory System. V. Neurophysiok>Ry, VI. Tissue and Organ Culture, VII. Pharmacolo6y, VIII. Metabolic Studies. IX. Chcmtstry and Biochemistry, X. Reviews. 1. P.ycko-Phy,ioloRtcal Studies FFFECTS OF SMOKING ON PERIPIfERAL VISUAL A('UITY A total of 40 male university students, 30 smokers and ten non- smokers was tested on a modihed Ferree-Rand Perimeter in prdcr to determine the size of the pcriphcral visual field as a function or various combinations of smokinR, amo~in6 dcprivation, and smoking dcnicotinizcd cigarettes. The experimental design encompassed two control and two experimental test groups of ten subjects each: one group (CS) smoked regular cigarettes throughout the test period; one (CNS) never smoked; one (ES) smoked standard cigarettes preceding the first two peripheral vision tests, were deprived from amokin6 for the next eight test sessions, aqd smoked again preceding the last two vision tests; the last grou z(EDS) smoked standard ciaareltes preceding the first two tests, smoked denico- tinized cigarettes prcctdina the next eight test sessions, and smoked stand- ard eiauettes asain PtocedinR the last two vision tests. Results indicated that there were no significant long-term effects of smokin8 on peripheral vision by a comparison of smokers and nonamokera on the initial two test sessions. However, the relative change in performance from the initial tests produced a significant difference between the esperirnental and control groups. Specifrctlly, abstinence from srnokiq increased the size of the visual field. After aper{od of abaGnersoe, smoking reduced the size of the visual field. The major chanaes In peripheral vision were on the temporal meridian. Further, performaex.~e ot the two experimental broups, i.e., those who were deprived from srrsoklng and thoae who smoked the denicotinized ci6arettes, was identical. Thb indieated that the effect of smoking on periph- eral visloo may be attr(buted b the nicotine component of tobacco smoke. Krippner, R. A. and flrirnslra, N. W. F.Bccts of SnfokinR on Peripheral Visuaf Acuiry, The University of South Dakota: VermilGon, 1969, pp 1-57. From the Department of Psycholo6Y. University of South Dakota, Ver- million. A NOTE ON RESPONSES TO ETHYL ALCOHOL BEFORE AND AFTER SMOKING Differential taste sensitivity to ethyl alcohol was measured before and af ter smoking a cigarette by ten smokers; ten nonsmokers served as controls. Usi: ,6 a paired comparison rnethod of differential sensitivity, subjects evalu- ated eight paired sample sc:a consisting of 8% EtOH vs. 4%. S%, 6%, 7%, 9%, l 1%, and 12% E10111. No si8nificant differences were observed between smokers and nonsmokers or before vs. after smokin8, although slightly higher overall correct responses and correspondingly smaller just noticeable differences were obtained tor the nonsmokers. No practice effects were noted among the control group between the first and second set of samples. The findings confirm previous results which had been questioned recently. Martin. S. and Pongh.+rn. R. M. Perception A Psychophysics 8(3):169-170, 1970. From the Department of Food Science and Technolo6Y. University of California, Davis. RELATIONS BETWEEN PERSONALITY AND SMOKING BEIIAVIOR IN PREADULT SUBJECTS This study of 562 high school and junior high school students has yielded results which are strikingly similar to those found earlier with adults. In both studies, smokins status was assigned on the basis of self- report information, and personality scores were derived from peer ratings. With the preadults, as with the adults, amoken scored significantly lower on measures of "ABreeableness," and "Strength of Character," and scored significantly higher on measures of "Extnvenion." In addilion, the smokers (in both studies) scored si8nifkantly higher than the nonsmokers on the variable "crude," "happy-8o-lucky," aqd "trant." Amonj preadults, mul- tiple discriminant analyses permitted stl~rrokint status to be assigned with accuracy ranRm6 from 65% to 79%. IthouBh most information eoncern- in the psychodynamica of smoking has been obtained from studies of .ults, the present study supports the use of such Information in work with prcadults. Smith, G.M. Journat of Conrultrnr and CUrrkof Psycholoty 33 ( 6): 710-71 S, 1969. Other 8rawtor.r American Cancer Sodety and U. S. Public Health Service. From the DeQartment of Aneatheala, Massachusetts General lfcnpital, and Harvard Medical School, Boston. 17 16

SUICIDE AMONG US: CAN WE LEARN TO PREVENT 11? Dcaths reported in the course of a long-term study of students at The Johns Hopkins University School of Medicine point out the need for suicide prcvcntion. In the Study of the Precursors of Hypcrtension and (~uromary i)isease, many characteristics of the students in 17 consecutive classes were measured and recorded; all subjects are being followed through annual questionnaires. Among the 1.337 students enrolled in the study, there have been 31 premature deaths. Of these 31 deaths, 14, or nearly half the fatali- ties, have been caused by suicide. The other 17 deaths were due va;iously to accident, coronary heart disease, neoplasm, chronic alcoholism, nephritis with hypertension, acute ukerative colttis, and subacute bacterial endo- carditis. It is widely reeogrtiz,ed that psycho{ogical and stress factors, as well as somatic characteristics, play prominent roles in the evolution of most of the disordcrs from which the 31 former Johns Hopkins students died. It seems likely that the suicides and sorne of the other premature dealhs have certain kth.litr factors in common. With this in mird, the degree of personal Involvement In the wbjoet's own death was rated for the 31 fataiities, and other studies of precunort of suicide and risk i actors in coronary heart disease were examined. These studies provided statis- tical evidence that certain preeunon of suicide, aecident, fatal heart attack, and fatal stroke are already present and can be identified in youth. When more of these characteristics ore identified, it is hoped that not only single risk facte+n, but meaningful psychobiological patterns will be found, which may lead to nxxe effective methods of prevention. Thomas, C. B. loluu HopAint Mrdlcallourraf 125(5):276-285, 1969. Other Sr.r.tor.: National Hcart Institute and the Hcart Association of Maryland. From The lohns 1{opkirr University School o[ Medicine, Baltimore. H. CarctnoRene.Ia Studies }IEPATOMAS IN CBA/Cb/Se MICE tutd LIVER LESIONS IN GOLDEN HAMSTERS INDUCED BY HYDRAZINE SULFATE Intact virgin CBA/Cb/Se (CBA) mice and golden hamsters of both sexes were used to test the action evoked by daily administration of scalar doses of hydrazine sulfate (LIS). The daily administration of 1.13 and 0.56 mg of FIS was urdnogenic for the liver of CBA mice of both sexes. Such carcinogenk activity was reduced with 0.28 mg and was nonexistent with 0.14 mg. llistologically, the tumors were hepatocarcinomas. No mor- phologic differences esisted between the neoplasms induced with 1.13, 0.56, and 0.28 mg of the dru~. Four mice that received 1.13 m6 IIS daily also had lung metastases. 11S administertd to intact virgin golden hamsters of both setes caused liver rtticuloendothelial cell proliferation and cirrhosis, bile duct proliferation, and degeneration of fibrous cells in the hyalinized sclerotic tissue. These results are of importance since the liver tumors and lesions were induced by a drug that is the principal metaholite of isoniazid and that is widely used in the prophylaxis and therapy of human tuber- culosis. Biancifiori. C. Journal oJ the Nauona! Canrrr fnsrirutr 44(4):943-953, 1970. Other Rrantor: Anna Fuller Fund. From the Division of Cancer Research, University of Perugia, Italy. PATHOLOGY AS RELATED TO TRYPTOPHAN METABOLITIi EXCRETION. OCCUPATIONAL HISTORY, AND SMOKING LIABITS IN PATIENTS WITH BLADDER CANCER A combination of tiutx .ection examination, tryp(ophan metabolite aasay, and interview analysis wes employed in this initial attempt to asccr- tain the relationship betwcea the histology of bladder tumors and 1) the presence or absence of abnormal patterns of tryptophan metabolites in the urine, 2) (he occupational history of the patient, and 3) the history of the patient with regard to cigarette tunokin6. Results showed that there were no significant differences be:ween the bladder cancers in 39 patients with normal urinary excretion of tryptophan metabolites and those in ten patients with abnormal metabolite excretion patterns. Neither were there statistically significant differences in hstdogy between "occupational" and spc~n- tane wi ' tumon, nor between tumors in patienta who had "ever artxrkcd" cigarettes and those who had "never smoked" eitarettes. Nowever, in both the "occupational" and the "ever smoked" 6roups, apparently greater num- bers of carcinomas were either wholly or partially composed of squamow ekments, and further study of this point in larger series of cases seems indicated. Frirdrll, G. H., Burney, S. W., Betl, 1. R. and Soto. E. Journal o/ the National Cancer Institute 43(1):303-306, 1969. Other Rrm.torr National Cantxr Imtitute. From the Cancer Research Institute, New England Deaconess Hospital, Boston, and the Department of Pathology, Boston University School of Medicine, Boston. I MULTIPLE MALIGNANCIES IN THE URINARY BLADDER FOLLOWING A BY-PASS PROCEDURE A case with two separate transitional cell earciqomas of the bladder in which neither tumor was evident six monthsprim to resection is reported. In April. 1965, a bilateral uretostomy through an ikal conduit had been C riormed on the described patient. Microscopic examination of the distal tt ureter showed chronic ureteritia with foci of atypical epithelial hyper- plasia. Six months later, eatcinoma was noted; an anterior exenteratiun waspe rfortrted. 'lhe my ty of recent studies of carcinoma in siru of the bladder either state or imply that, just as in carcinoma of the cervix, the 18 19 '

natural history of bladder cancer often includes a slow progression from cellular atypi through carcinoma in srru to frank invasive carcinoma over a protracted period of time. In this case, although the exact date of devel- opment of malignant changes cannot be determined, the progression seems to have bcen very rapid In addition to the two large tunwrs, alm„at all of the mucnsa showed proliferative changes, including hypcrplasia, dys- ptasia, carcinoma in tiru, and multiple small papillary tumors. Ikspite the extensive cystitis cystica, no areas of adenocarcinoma were found. The dcvclopment or progrewicxt of invasive cancer following a by-pass proce- dure is of particular interest because it is decidedly unusual. Burney, S. W., Graves. R. C. and Fritdell, C. H. Umlorio Inrrrnationotis 25:69-75, 1970. Other Rra.tora: U. S. Public Health Service and Atomic Energy Com- miuion. From the ('ancer Research Institute and the Department of Surgery, New Fngland lkaconeu Ilospital, Botton. UNUSUAL METASTASIS OF A NUMAN COLONIC TUMOUR XI:NO(;RAFT IN THE HAMSTER BRAIN (iW-77 is a human carcinoid tumor of the transverse colon that has been successfully propagated in unconditioned golden hamsters for almost three years. When transplanted in the hamster check pouch, subcutaneously or intramuscularly, no morphological evidence of inetastasis Mas seen. However, after intracerebral implantation of the GW-77 tumor, tumor cell emboli and uthentic metastatic nodules were found in over 50°f% of the 30 treated hamsten. Transplantation of a 20% homogenatc of lu.igs from ten of these hamsters having 20-day-old brain transplants to check pouches of other animals has resulted in viable GW-77 tumors in almost all cases. This extracerebral retention and proliferation of GW-77 human cokmic tumor cells transplanted to the hamster brain is the first example reported of inetastasis o/ a acnogeneie tumor still exhibiting properties of its species of origin. CoWrnbot. D. M. Nature 226( 5245 ) :550, 1970. Frosn the Dcpartment of Pa(ho(ogy, University of Pittsburgh S.:hool of Medicine, Pittsburgh. IDENTITY AND NATURE OF ISOLATED LYMPIIOID TUMORS (SO-CALLED NODAL IIYPERPLASIA. IIAMARTOMA. ANI) ANGIOMATOUS EiAMARTOMA) AS REVEALEI) BY FfISTOLOGIC, ELECTRON MICROSCOPIC. AND IIE:`TE:ROTRANSPLANTATION STIJDIFS Two cases of iaolated lymphold tumors, one in an 11 -year-old girt and one in a 42-year-(ld man, are presented. While both wes exhibited histo- pathologic features of both neoplastic and non-neoplastic lesions, both tumors als) cuntaincd giant cells rnorphobgically indistinguishable from Stcrnbcrg-Recd cells characteristic of Flodgkin's disease. Virus-like par- ticles resembling those depicted as occurring in some murinc as well as human Icukcnrias and malignant lymphomas were also noted in the second paticnt's lesion. Similar particles were also observed in cells comprising "primary" growths and mctastases noted following hetcrotransplantalion of aliquots uf this tumor to the check pouch of unconditioned hamsters. This information strongly suggests that some lymphoid tumors may possess  malignant biological potential, being in this regard analogous to the situa- tion experienced with the nodal ksion apparently induced by antiepileptic drugs. Fisher, E. R., Sieracki, J. C. and Coldenbrra, D. M. Cancer 25(6):12R6-1300,1970. Other Rrar.torr U. S. Public Health Service. Fn+m the 1)cpartments of Pathology. University of Pittsburgh SchrKil of Medicine and the Veterans Administration Ilospital, Pittsburgh. TRANSPLANTATION TECNNIpUE FOR ACCELERATION OE: CARCINOGENESIS BY BENZJa/ANTHRACENE OR 3,4,9,10-DIBENZPYRENE JBENZO(RST)PENTAPEIENE/ Transplantation of combined carcirwgen-injection sites from four C57BL/6 J male mice into one secondary host significantly accelerated tumor growth in the secondary recipient. In this study, acceleration ot chemical carcinogenesis was obsetved after transplantation of injection sites with a small dose ( 25rg) of the strong carcinogen benzo( rst )pcntaphcne (DBP) and with a large dose (500 pg) of the weak carcinogen benzoia)- anlhraccne ( BA ). When BA was kft in tltu. two tumors developed among 48 mice 52 weeks following the original injeetion, whereas significant tumor incidences occurred within 24 weeks after the original injection when site tra! 'sfers had been made g, 12. 16, or 24 weeks after the administration of carcinogen. Site transfers made eifht weeks after the original injection yicldcd 67% tumors 24 weeks after injection. Following site transfers made 12 weeks after the first injection, there were 80% tumors 12 weeks later. More delayed site transfen gave lower tumor yields. With UBP, the first tumor appeared 12 weeks after single injeetion, whereas, following trans- plantaticxt af injection site six weeks later, the first tumor appearcd nine weeks after the original injection. IlomburRer. F. and Treger, A. Journaf of the Nurional Cancer Insrlrurr 44:357-360. 1970. Otlhrr Rrn..tor.: U. S. Public Fieallh Service and Virginia an(I 1) K I ud- wig houndation. From the Bio-Rescarch Institute, Cambridge. Mass. 20 21

FATE OF SU[1CUTANf=OUS1.Y INJECTED F1f3NT_O(RST)- PI-•.NTAPHFNE IN C57E3L/6 MICE Bcnzo(rst)pentaphene is an aromatic polycyclic hydrocarbon with high carcinogenic potential. Early studies on this compound indicated that when injected subcutaneously it remains at the injcction site and is not metabolized. flowever, experiments repotted here, run with "('-labeled benzo(rst)pentapherx, demonstrate that 95% o( the carcinogen is removed from the injection site. This removal is accomplished in two stages: first, removal of significant quantities which can be detected at other body sites and which is associated with the trauma of the injection, and secn,xily, a chronic renxoval, nearly compkte in ten weeks. No relationship was found between the rate of tumor formation and the amount of carcinogen remain- ing at the injection site. Kelley, T. F. (llomhurttr, F.) ): ProcredinRs of rhr Society for Esprrimtnrol Biology and Mrdic inr 133 (4 1402-1414, 1970. Other Rror.tor: l). S Public Hcalth Service. From the Bio-Research Institute, Cambridge, Mass. INIIIBITORY E:FFE~(T OF L-ASCORBATE ON TUMOR FORMATION IN URINARY BL-ADDERS IMPLANI ED WITEI 3-HYDROXYANTI IRANILIC ACID A 2 X 2 factorial experiment designed to test the effect of elevated urinary kvels of ascorbate on the carcinogenicity of 3-hydroxyanthranilic acid (3-HOA) waa carried out in Swiss albino mice. Pellets of 3-11OA, a known producer of uroepithelial tumors in mice, were inserted into the bladders of 121 mice. Blank cholestero( pellets were placed in 91 controls. A total of SI exposed nd 33 control mice were then fed L-ascorbate (250 mg/100 ml) in their drinking water ad libiturn. The probability of survival was checked and found to be the same in sll four of the working groups of mice. However, when all surviving mice were killed at IheTand o/`orty weeks, t)robse~rveryd In the diRerc the R o~rpsrrc tumots (pre gnan~-~ ~n vealed that ascorbic acid inhibited the anticipated carcinogenic etfcct of 3-IEOA. Pipkin, 0. E, Sch/eprf, l. U., Nishimura, R. and Shultr., G. N. rroceedings of the Society for Etptrlmtntol Biology and Medicine 131(2): 522-524, 1969. Other 6re.torr National Cancer Institute. From the Department of Surgery, Tulane University School of Medicinc, New Orleans. THf•. ROLE OF ASCORBIC ACID IN THE PREVENTION OF BLADDER TLIMOR I-ORMATION Pellcts containing 3-hydroxyanthranilic acid (3-I1OA ), one of the tryp- tophan metabolites, were implanted into the bladders of Swiss albino mice. Mice implanted with 3-LIOA had a significantly higher incidence of bladder tumors. Oral administration of large amounts of ascorbic acid which resulted in high urinary levels of ascorbate prevented this carcinogenic efiect, pre- sumably because of the competitive affinity for oxygen which prevented the oxidation of 3-l1OA. Because of this observation, it would appear that 3-HOA, in itself, is not a carcinogen, but rather that the oxidation of this compound is of importance in carcinogenesis induced by this orthoamino- phenol. On the basis of these results, recommendation for oral administra- tirxr of ascorbic acid as a possible preventive measure of spontaneous bladder turmrr fr+rmation and recurrence in man appears to be warranted; this suRgcstion is further supported by the evidence of lack of toxicity af the dosage required to maintain an adequate urinary level. Schlegel, !. U., Pipkin, G. E., Nishimura, R. and Shultz, G. N. Tron.ractions o/ the .I rrKricon Atsociation oJ Genito-Urinory Surgeuni 61:85-89. 1969. Other grantor: U. S. Public Health Service. From the Department of Surgery, Tulane University School of Medicine. New Orleans. NONENZYMATIC FORMATION OF CINNABARINIC ACID IN URINE OF PATIENTS WITH TUMORS OF TIIE URINARY BLADDER This study explores the identity of compounds formed by oxidation of 3-hydroxyanthranilic acid (3-HOA) in urrne, and checka for the pres- ence of these oxidative compounds in the urine of tumor patients. To accomplish this, identical amounts of 3-HOn, which is a urinary metabolite of dietary tryptophan in man, were added to urine samples collected from 12 subjects with tumors of the urinary bladder and from a group of normal subjccts (five heavy smokers, three smokers, and 14 nonsmokers). Ekrth groups of such urine samples were incubated overnight at 37"C in air. By use of chromatography and ultraviolet tpectroaeop)r, an in vino oxidative product of urinary 3-11OA was isolated, aemiquanUtated, and identified as cinnaharinie acid. This acid formed oxidatively from 3-II()A in urine samples from both I roups; however, quantltatively, more was formed in urine samples from the group of lumor p.tienta. Furtht:rmore, oral admin- islration of l; ascorbie acid to both groups of sub)eets in quantities sufficient to cause spillage of ascorb.te, an antfoxidant, Inlo the urine prevented the in vitro oxidation of urinary 3-EIOA and the formation of cinnabarinic acid in all urine samplcs. This instability of urinary 3-HOA could thus result in formation in vivo (if oxidative products such as cinnabarinic acid which could play a role in the etiology of carcinoma of the urinary bladder. 23 22

Nishimura, R., Pipkin, G. E., Duke. G. A. and Schlegel, !. fl. Invtru'4arivr f/roloRy 7(3):206-214, 1969. Otlhrr Rra,.tor: National Cancer Institute. From the Department of Surgery, Tulane University School of Medicine, New Orleans. TIlE AETIOLOGY OF BLADDER TUMORS The chemiluminescence o( urine from a number of nonsmoken, smok- ers, nd bladder-tumor patients was evaluated in this experimental attempt to assess the role rr[ redox environment in the aeliology of bladder tumors. Previous studies have indicated that redox environrnent might be important in determining whcther potential carcinogens would be capable of c><erting their earcinogcnic potential. Using the Dupont Luminescence BicNncter for measurement, chemilumineseence In urine was determined by placing l/ a(1 ml of urine in a vial and injecting 0.02 ml of 30% hydrogen pcroxidc. Examinin~ 43 nonsmoken, 36 smnken, and six bfadder-tumor patients it was found that there was a significant difference between the chcmilumi- nescence elicited by urine from nonsmoken on the one hand and smokers and bladder-lumor patients on the other. This difference was significant with a p value of lcss lhan (1.05. Since most of the bfaddcr-tumor patients were smokers, it is difficult to evaluate whether what was determined was a sig- nificant difference between smokers and nonsmokers, or between bladder- tumor patients and eontrols. The administration of ascorbic acid leading to significant concentrations in the urine showed as in previous studies a sup- pression of chemiluminesccrxe, thus indicating that thc presence of an anti-oxidant in the urine will prevent chemiluminescence. Schlt`rf, !.fl., Pipkin, G. E. and Shultz, G. N. Brirish Journal of flroloty 41(6) : 718-723, 1969. Ot11er grantorf Nationd Cancer Institute. From the Department of Surgery, Tulane University School of Medicine, New Orleans. Slll FATTORI INTRINSECI DELLA CANCEROGENESI POLMONARE DEL TOPO: EFFETTI DEL "COMPLETE FREUND'S ADIUVANT" Two groups e-4 40-dar-old virgin male and female BAI.B/c mice were injected subcutaneously with urethane at a dose of I mg/g of body weight. One week txfore and one after the injection of the carcinngen, or.e group of mice was also treated intraperitcxreally with 0.1 nil Complete I-rrund's Adjuvant (CFA ). Mice treated with CFA and urethane dcvchtfxd 17.1 lung tumors per m<wse at an average age of 414 days. Control mice stKrwed ten lung tumors per mouse t an average age of 435 days. Sex dependent variatioxts of the number of lun6 tumors were observed only in the group of mice treated with CFA and urethane. Analysis of incidence and of average number ol lung tumMKs per mouse in rclation to the sizc of tumors showed that larger tumon were seen mainly in the CFA treated mice. This paper includes a discussion of the mechanism through which CFA enhances urethane lung tumorigenesis in BALB/c mice. Ribaeehi. R. (Stveri, L.) I-ov. Anor. Por. Perugia 29( 2): 81-91, 1969. From the Division of Cancer Research, University of Perugia, Italy. 111. Cardiooa.calnr System BRONCFIOPl1LMONARY AND CARDIAC EFFECTS OF I IYDR(X'ORTISONE In an attempt to gain an insight into the therapeutic actions of hydro- cortisone as regards several heart disordcrs, experiments were designed to ascertain (a) the direct cardiopulmonary effects of hydrocortisone and (b) the interaction between hydrocortisone and isoproterenol. Canine heart- lung preparations and canine preparations with right-heart bypass were used for these investigations. In both preparations hydroeortisone accelerated the heart rate and stimulated contractility. There was also relaxation of bronchial snxx.th muscles and vasodilatatron of the pulmonary blood ves- scls. The cardiac stimulat(xy effects of isoproterenol were not potentiated but appeared to be reduced by hydrocorlisone. Oskoui, M. and Aviado, D. M. Archives Inrernorianoler de Plrarmocodynamie et de Thfropie 179(2): 314-325, 1969. From the Ekpartment of Pharmacology. University of Pennsylvania Schrx,l of Medicine, Philadelphia. EFFECT OF NICOTINE ON CONTRACTILITY OF TIIE INTACT EIEART The effects of nicotine on the instantaneous force-velocity of the intact left ventricle in closed-chest dogs were studied before and after the induc- tion of /3-adrenerRic blockade with propranolol. Nicotine was administered by intravenous infusion. Velocity of shortening was measured in the 22 lest dogs by means (if n intracardial strain-gauge catheter assembly. Nicotine, ahme, aurmcnted myocardial contractile atate as indicated by an increase in both Ihe force and velocity of shortening. When P-adrenergic bhxkadc prccedcd nicotine. Ix)wevcr, the rise in left ventricular systolic pressure was proportiunatcly greater but velocity of ahortenin¢ showed a reciprocal decline. Lcft ventricular end-diastolic pressure rose srgnificanlly; the increase in pressure rise was less marked. These findings suggest that pnopranulr,l impaired the rarepinephrine-like effects nf nicotine on the myoKardium while its peripheral vasopressor action became enhanced. Puri, P. S., Alamy, I). and Ring, R. 1. Cardiology DiResr 5: I9-25, 1970. 24 25

Other Rranror.: U. S. Public Health Service. Michigan Ilcirt A~cnciation, American Medical Association Education and Research Found:rt (in, and Detroit General Ftc.spital Research Corporation. From the Department of Medicine, Wayne State University School of Medi- cinc, Detroit. DIRECT ANE) RFFLEX EFFECTS OF IEYPOTHERMIA, IIYPOTENSION AND HYPOXIA ON THE HEART This book chapter deals with the effects of three lows - low tempera- ture, low blood pressure, and low oxygen content - on the working of the heart. Hypothermia, which is widely used in cardiac sur8ery, has b:ncfscial effects on the arrested heart. The lowered temperature reduces coronary blood flow and mrocardial oxygen consumplion, and usually causcs a fall in heart rate, cardiac output, and arterial pressure. Of course, such lk rcduc- tion in oxygen consumption must have generalized metabolic cf(ccts upon the heart and body tissues; many studies have been carried out in this area. Discussion in the section on hypotension is restricted to hemorrhagic shock. The roEe of the heart in initiating and sustaining the hypotensive state has been investigated widely. Although most of the dala point to the neart as being primaril~ responsible for irreversibility in hemorrhagic shock, some studies have dcmonstraled that the onset of myocardial failure c><curs at such a late stage that other causes could be implicated. In any case, the development of mrocardial failure is an ominous sign and usually heralds death. In the section on hrpoxia, the effects of myocardial infarction on myocardial metabolism and function, as produced by ligation of branches of the coronary artery, are rcportcd specdically. In addition to considcra- tion of the immediate and delayed myocardial responses to coronary artery occlusion, the stimulation of reparative processes following experimental myocardial infarcation is discussed. Robin, E., Gudhjarnason, S. and Bina. R. l. In Oaks, W. W. and Moyer. l. H. (eds.): 19th llahnrmann Svmposium, New York: Grune! Stratton Inc., 1970, pp 251-267. Otber rs.ror.r U. S. Public Health Service, American Medical Asuxia- tion Education and Research Foundation, and Detroit General Hospital Research Corporation. From Wayne State llnivenity School of Medicine, Detroit. THF. EFFECr OF NICOTINE ON EFFECTIVE AND TCYI'AL CORONARY BLOOD FLOW IN THE ANES71iES1-LED CEASED-CHFST DOG The use of rubidium" as a diRusible Indicator, kogethcr with a double coincidence counting systuem. Provides a techniyue to study the effect of nicotine on the total nd effective coronary flow in the closcd chrst anirnal and in man. Intravenous administration of nicotine ( I(X) Ng/kg in one minutc) in 12 healthy, closed-chest, anesthesized dogs caused incrcases in Icft ventricular wurk, in myocardial oxygen consumption, and in both elfec- tivc ( nutritional ) and toaal coronary flow. The increase in effective capillary flow to the uiyocardium after nicotine administration was suflicicnt tu mcct mycxardial oxygen dcmands. Effective capillary flow appcared to be pri- marily regulated by myrxardial oxygen consumption. The proportional in- crease in myocardial oxygen consumption and effective capillary flow indi- catcs that the eRcctive capllary flow to the myocardiurn is cluscly relatcd tu myocardial oxygen supply. Leb, G., Derntl, F., Robin, E. and Bing, R. l. The Journal of Pharmacology and Experimental Therapeutics 173(1 ): 138-1'4, 1970. Otiierr Rrar.tor.: U. S. Public Health Service and Michigan Heart Asscs cia/ion. From the Department o( Medicine. University of Southern California, liuntinston Memorial Ifospital, Pasadena, Cal., and Department of Fxpcri- mental Medicine, Wayne State University School of Medicine, Detroit. A ROLE OF TIlE CENTRAL NERVOUS SYSTEM IN THE CARDIOVASCULAR ACTIONS OF NICOTINE In the present series of experiments, blood pressure responses to nico- tine were measured in 39 adult mongrel dogs following general anesthesia, spinal ancsthesia, spinal transection, or decerebration. Results showed that all of these procedures reduced both the depressor and pressor responscs to nicotinc, thereby reinforcing the concept that an intact central nervous system is necessary for the o imal cardiovascular effects of nicotine. In addition to nicotine, the 8anionic stimulant dimethylphenylpipcrazinium (DMPP), cpinephrirx, norepmephrine, and isoProterenol were given intra- venously for comparative purposes. The finding that the cardiovascular effects of DMPP are reduced by pentobarbital in the same manner as nico- tine would suggest that peripheral reflex (chemoreceptor) or ganglionic facilitation, due to an active central autonomic dischar8e, is more likely than a direct action of both of these substances on the brain itself. (DMPP would not be expected to penetrate the bEood-brain barrier as readily as nicotine. ) Although further research in this area is obviously indicated, the evidence now vailable clearly indicates that the central nervous system has an important role in the overall cardiovascular actions of small drnes of nicotine in doEs, and is prominently involved in the overall pharma- cology or Ihis most interesting drug. 1)omino. E. F. ArchiveJ Intrrnarionalrt de Pharmocodynamle rt de Thlropir 179(1 ): 167-179, 1969. From thc Department of PharmacoloRy, University or MichiRan, Ann Arbor. 26 27

TIIF F.FFECT OF NICOTINE ON DIETARY ATFfEROGFKESFS IN RABBITS In this series of dietary experiments, four groups of ten New 7ealand rabbits each were fed either a stock diet; a stock diet plus nicotine injcc- lions; a cholesterolcontaining diet, or a cholesterol diet plus niartinc injcc- tions. Those rabbits on a cholesterol diet plus nicotine injections denxm- strated wider areas of involvement of the internal surface in the aorta than rabbits on a cholesterol diet alone. In both stock-fcd ^nd cholesterol-fcd animals, nicotine produced an increase in aortic triglrcerides and a decrease in the free cholesterol content. An increase inphospholipids, particuiarly in lecithin and cephalin, was observed In the eholesterol-fed rabbits treated with nicotine. Aortic acid mucopolrsaech^ride composition did not exhibit any significant changes following nicotine treatment. Concomitantly, it was shown in in virrn dialysis ei<periments that heparin and nico(jne fcrm a relatively stable complex, in a molar ratio of aMwt 1:2(1; nicotint also inhibits the hydrolysis of "C-Iabekd triolein in a homogenale frorn abhit aortic tissue. l hese data, indicating an apparent complex formation bc'wcen heparin ^nd nicotine, suggest that the basis for some of the biological t ficcts of nicotine may be related to an in vivo interaction with heparin. Stcfanovich. V., Gcwe, /., Kajiyama, G. ^nd Iwanaga, Y. Experimental and Mofrcvlor PorholoRy 11( 1):71-81, 1969. Other Rranto-t U. S. Public Nealth Service. From the Department of Pathology, University Hospital, and Boston Uni- versity Medical School, Boston. TIIE ESTIMATION OF BLOOD PLATELET SURVIVAL: 1. GENERAL PRINCIPLES OF TNE STUDY OF CELL SURV'VAL Estimation of plstckt survival is a matter of some importance today since the economy of the platelet has become recognized as sonkthing largely separable from the behavior of the coagulation system. Moreover, since many of the probkms concerned in the measurement of platelet sur- vival are common to lhox of ineasurenxnt for any migrating ccll, basic ideas and principks tested here could be adapted to other cell populr.tions. Since migrating cells cannot be individually Identified, inferences about their pattern of survival must be based on the collective behavior of a defined group of such cells. A precise nonxnclature for the aspects of such cells and their behavior is necessary. Accurate estimates of mean survival of cells depend on the use of a model, which can only be constructed by considering pertinent factort in the Internal ^nd external economy of the cell. But dermxtstration that a factor is indeed pertinent depends in large part on observing change in rne^n survival. This circularity may be avoided by studying those properties of such survival curves which are uninfluenced by the form of the drstnbuticxt of cell survival. Since these properties ^re logical necessities, there Is no need to verify them experimcntally. Murphy, E. A. and Frands, M. E. Thromhosh tt Diorhttit Hoemorrhoglcn 22(2):281-295, 1969. 28 From the Departments of Medicine and BioslaliStics, The Johns llopkins University SchcH,l of Mcdicinc, Baltimore. SERUM-FREE-FATfY-ACIDS AND THEIR RELATION TO COMPLICATIONS AFTER ACUTE MYOCARDIAL INFARCTION In an attempt to learn whether the concentrations of serum-frcc-fatty- acids (F.F.A.) noted at the onset of acute myocardial infarction (M.1.) are predictive for the development of complications or death, admission F.F.A. levels were measured in 78 M.I. patients and plotted against the patients' clinical courses. Serum F.F.A. kvels were also determined when- ever possible on fasting specimens drawn one day after admission, on the fifth day, three weeks after admission, and at the time of any complication. Results showed that there was no relationship between the initial levels of serum F.F.A. and the devclopnsent of arrhythmias, cardiogenic shock, or late deaths. Congestive heart-failure, persistent chest pain, and embolic accidenls, likewise, could not be predicted by the initial serum F.F.A. Ifowever, the serum F.F.A. tended to be elevated at the time that compli- cations developed throughout tle hospital course. While this temporal ele- vation was noted for most conplicalrons, it was not necessarily seen in t(xne patients who exhibited poot peripheral perfusion ("shock syn- dronse"). Thus it would seem that the elevation of serum F.F.A. ^t the time of complications may he related to increased catecholamines in the most savereiv ill patients, but the data do not support any independent adverse eRects of the increased serum F.F.A. Rutcnberg, I1. L., Pamintuan,l. C. and Solo#, L. A. The Lcncer 2:559-564, 1969. Other Pr^ntorr U. S. Public Health Service. From the Division of Cardiology, Temple University Hcalth Sciences Ccn- ter, Philadelphia. INCIDENCE OF SIGNIFICANT CORONARY ARTERY DISEASE IN RHEUMATIC VALVULAR HEART DISEASE Between 1963 and 1968 Ihere were 77 necropsiea performed at Tem- ple University Ilealth. Sciences Center in individuals who died afler surgical treatment for rheumatic valvular heart disea^e. Of these 77 palients, ten (13% ) were found to have clinically significant (g^de 3) coronary artery disease. This disorder occurred at all ^ges but was more common after age 40. It was commoner in aortic v^lvutar disease either alone ( 17.7% ) or combined with milral valvular disea^e (21.1%) than in isol^ted mitral valvular disease (8.6% ). This difference might be due to the older ^ge of death of the patients who had aortie lesions. Beeause clinically significant coronary ^rtcry disease complicating v^Ivular heart disease is ditTicult to recognize on clinical grounds and because it might adversely affect prog- 29

nosis, coronary cinearteringraphy and Icft ventricular angiography are suR- gested in the overall evaluation of patients for valvular heart surgery. Such studics should he made particularly in those above age 40 and in those with x-ray evidence of aortic calcification and with atherosclerosis detected dur- ing retrograde cathetcrixalion of the femoral artery. Coleman. E. 11. and SoloO. L. A. American Journal of Careiofoay 25 ( 4):401-404, 1970. Other grantor: U. S. Public Health Service. From the 1>ivision of CGrdiofogy, Temple University Health Sciences Cen- ter, Philadclphia. ON TffE AS.S(X'LATION OF CK7ARETTE SMOKIN(; WITFI CORONARY ANf) AORTIC ATHEROSCLEROSIS The association of cigarette smoking and atherosclerotic lesions in the coronary arteries and in the abdominal aorta was investigated in 747 autop- sied men, 20-64 yean of age. This paper, an interim report, presents results from approximately half of a projected study of 1.500 cases. In this study, aortic and coronary lesions were evaluated visually in coded specimens and objectively by analysis of radiographs. Using schedules that had been tested for validity and reliability on pairs of living persons, interviewers obtained estimates of cigarette smoking habits of the deceased men from surviving relatives. The data were analyzed with reference to total sample .nd also to subsamplcs grouped according to the presence or absence of diseases thought to be associated with smoking (emphysema, lung cancer, etc.) or with coronary heart disease (myocardial infarction, hypertension, diatxtes, rtOroke, etc.). Atherosckrotie involvement of aorta and coronary arterics was greatest in heavy smoken and least in ransmoken. Occupational physical activity and educational level achieved did not account for cbserved differences in extent (t( lesions. These preliminary studies suggest that smok- ing or an associated factor affects the development of mural athcrerszIcrosis, and that the apparent relationship of smoking to CHD is not limitcJ to the events surrounding the terminal occlusive episode. These suggestive tindings, if confirmed with larger numbers of cases, indicate the need for experi- ments in animals to determine whether cigarette smoking accelerates arterial lesions. StronR, /. P., Richarda, M. L., McGitl, H. C., lr., Eggcn, 1). A. nd McMurray, M. T. Journal of Athtroacfrrosfs Rextrrch 10:303-317, 1969. OtCrer grar.tor.r Louisiana ffeart Association and the National fleart Institute. From the Departments of Patand Biometrr, Louisiana State l)ni- versity ScFKx,l e~f Mediei*ne, New Orlcans, and "f fic Uni%crsity of 'lcxas Medical School at San Antonio, San Antonio, T'ex. SINUS ARRIfYTIfMIA IN DOGS AFTER CARJIAC T RANSPLANTA"ITON ERcrent reinnervation of the heart has been reporteo to occur within three to five months of transplantation. If such reinnervation is sufticicnt to give rise to a normal physiological phenomenon such as sinus arrhythmia, thc dcmonstrati„n cif this arrhythmia in a transplanted heart could prove a useful and simplc indication of cardiac reinnervation. With this in mind, the recurrence of sinus arrhythmia after cardiac transplantation was studied in 17 dogs previously subjected to cardiac autotransplantation and in two dogs after homotransplantation. Sinus arrhythmia was demonstratcd in 13 animals between 2'/: and 20 months after cardiac autotransplantation and in one dog 140 days after cardiac homotranspfantalion. Sinus arrhythmia recurred in these animals after parasympathetic reinnervation of the heart. These results show that sinus arrhythmia occurs in most animals with car- diac autotransplantaticxt after parasympathetic rcinncrvation of the heart. The recurrence of sinus arrhythmia after cardiac transplantation signifies the occurrence of parasympathetic rcinnervation of the heart; absence of sinus arrhythmia, howevcr, does not exclude the presence of such reinncr- vation. Thamts, M. [)., Kontos, 11. A. and Lower, R. R. (Student Fotlowship , Reeipient ) American Journal o/ Cardiology 24:54-58. 1969. Other grs.torr National Institutes of Health. From the Departments of Medicine and Suraery, Medical College of Vir- ginia, Richmond. DEVELOPMENTAL PATTERNS IN HYPERTENSIVE CARDIOVASCULAR DISEASE: FACT OR FICTION? Of 1,130 whitc mak medical students registered between 1947 and 1960 in a tong-term study of the rson of hypertension and coronary disease, 16 subjects had deve clinkal hr~ertension by 1968, while 89 others had exhibited transitory ypertension. When the prevalence of hyper- tension in the older gradualin classes was compared with that in the younger classes, it was found t~at the proportion of subjecta with clinical hypertension had tripled while the proportion with transitory hypertension had not quite duubted, suggesting a movement of some of the transitory group into the clinical group over time. No clear-cut differences were found between the clinical and transitory groups in respect to age at discovery of elevated blood pressure levefs, or to rtatin6 blood pressures recorded while in medical school. A study of the subjeeta' histories showed that in 62.5% of the subjects with clinical hypertension both Qarents evidenced hyper- tension and/or coronary diaease, as compared with 21.9% of the parents of the control group. The prevalence of disorders among both parents of subjects with transitory hypertension was intermediate (36.0% ). Hyper- tension alone was more frequent among the parents of Ihe clinical hyper- tension group than among the parents of the transitory hrpertension Rroup, while parcntal hypertension was more frequent in butb of these groups 30 31

than it was in two control groups. No definite crrnclusirms rcR:rrdinF the existence of develnpmental patterns could be reached on thc basis c.f this preliminary expk+ration. Thomas, C. R. Buffrtin o/ the New 1'orA Arodrmy of Medirinr 45(9):R31-850. 1969. Orher grantor: Maryland Heart Association. From The Johns Hopkins Univenity School of Medicine, Baltimore. DECREASED THROMBUS FORMATION IN RATS AfTER CHRONIC NICOTINE ADMINISTRATION A total of 70 fcmak Sprague-Dawky rats was used in this study of the effects of chronically administered nicotine upon in vivo thrombus sus- ccptibility. The ratt were divided into five grrwrs of 14 rats{x r Rroup; four groups received nicotine alkafoid In the drinking water ((157, I 14, 2.28, or 4.56 mg/k6/day) for 18 weeks. The fifth group was untreated All rats were tested for thrombus formation. A mean concentration of 90 6:! 10.9 N1H units/ml thrombin productd platelct thrombi within the ten-minute exposurepc riod in untreated rats. Groups treated with nicotine in doses of 0.57, 1.14, 2.28, or 4 56 required: 97.4 ± 8.5, 129.7 :! 16.0, 130.4 -± 13 4, and 158.1 ± 21.0 NIH units/ml respectively. Animals treated with the largest dcne of nicotine required a significantly higher concentration of thrombin to produce thrombi than did untreated rats or rats treated with the lowest doses (p < 0 0 1 ). Instead of an increased tendency to Ihrom- bosis, as anticipated from studies of smoking in man and frc.ni in vitro studies, chrnnically-administered nicotine increased the amount of throm- bin required to prcxluce thrombi. Wentrf, D. G. and Richards, M. H. European lournal o/ Pharmacology 10( 1): 143-144, 1970. From the f)epartment of Pharmacology and Toxicology, Univcnity of Kansas School of Pharmacy, Lawrence. IV. Respiratory Syt+tem Nose and Mouth EXPERIMENTA[1.Y INDUCED CHANGES IN NASAL MUCOUS SECRETORY SYSTEMS AND TNEIR EFFE(_ON VIRUS INFECTION IN CHICKENS: 1. EFFECT ON MUCOSAI. MORPHOLOGY AND FUNCTION Physiokogical chanles were Induced in domestic chickens by eeposure to drugs, systemic dchydration, temperature manipulation, vitamin /t depri- vation, (~ermfree environment, and cold. These different stresses had dif- ferent dfects on the ciliary and mueous systems. Cilia were directlr affected when paralyzed by cocaine and, of oourse, when cksquamated b) hcxyl- caine. Mucus quantity and quality as judged morphologically by histo- chemical staining were alfected in a diffetent way by each uf the stress methods. There was no evidence that any of the area-specific (lacrimal, olfactory, etc. ) systems was selectively affected quantitatively by any test method: if there was hyper- or hyposccretion or reduction in acinar size, it obtained generally This was usually true also of mucus quality; the single exception being that gcrmfree rearing induced intensive staining of the flask-shaped mixed acini, yet drastic depletion of the paraolfactory periodic acid-Schrff complex. With a few exceptions, there was no clear evidence that the normal balance between the Akian blue and pcriodic acid-Schiff components in the mixed alcini was altered either. Howevcr, there was distinct loss of the normal zoning of these components after cxp<nurc to intense cold, after repeated cocaine injectiorts, and after both pdocarpine stimulation and rehydration of severely dehydrated chicks. These results show clearly that respective areas of the mucosal blanket serve local func- tions to some cxtcnt, and it is known that innervation, sccrctory Iyfxs, and lymphoid resprxrses are fairly kxalited. The spectrum of effects pnxluced by altered physiology emphasizes how little is known about factors which control synthesis of mucous or serous secretions in the nose. Ban6, B. G. and Bona, F. B. lournal of E[prrimenral Medicine 130(1) :103-120, 1969. Otlher grantor: National Science Foundation. From the Department of Pathobio{ogy. The Johns Hopkins University School of Hygiene and Public Health, Baltimore. EXPERIMENTALLY INDUCED CHANGES IN NASAL MUCOUS SECRETORY SYSTEMS AND THEIR EFFECT ON VIRUS INFECTION IN CHICKENS: 11. EFFECTS ON ADSORPTION OF NEWCASTLE DISEASE VIRUS In the studies reported here, the actions of several pharmacological agents which affect the adsorption of Newcastle disease virus to the intact nasal mucosa of chicks are examined and interpreted. When chickens three weeks old were inoculated intranatally with a meso6enic (mcxkratcly viru- lent) strain of Newcastle disease virus, they developed necrotic lesions of the mucous acini, predominantly of the middle turbinates. Paral~sis of ciliary action by cocaine increased the number of infccted cells in the tur- binates about 10-fold at one, three, and five hours after viral exposure. Pilocarpine injection before virus inoculation caused a large increase in the amount of infected cells one hour after virus administration, but was followed by a sharp drop in infected cells by three or Ave hours. Pihrcar- pine given after the virus decreased the number of infected cells and changed the relationship of infected cells to adherent virus. Exposure of chicks to sustained or severe cold caused a similar but kss marked effect. The drop in infected cells was restored to control values if chicks were returnei to brooder temperatures. The marked drup of Infected cells pro- dueed by pilocarpine and cold in living ehicks, and in cultures e,t chicken 32 33

trachea (previous study), is consonant with the idea that virus has been adsorbed on mucus granulcs in the mucous cells of the lurbinates and then has hfen reescrcted. as unincory+orated virus, into the moving mucous sheet. Bang, F. R. and Foard, M. A. lnurnal oJ E.rperimental Medicine 1)0(l ): 121-140, 1969. From the Department of Pathobiology. The Johns Hopkins University School of Ilygiene and Public Health. Baltimore. REPLACEMENT OF VIRUS-DESTROYED EPITFIELIUM BY KERATINIZED SQUAMOUS CELLS IN VITAMIN A-DE?RIVED CHICKENS Intranasal inoculation of chickens with Newcastle disease virus ( NDV ) produced lesions in mucous cells in the inner surface of the middle turbinatc where thc mucous membrane is shallowest. This same quite extcnsivc mucrnal area showed urliest signs of incipient keratinizing mctaplasi in vitamin A-deprived (VAD) chickens; in NDV-infectcd VAD chickens, mucociliated cells in this region were rapidly destroyed and replaced by kcratiniring squamous cells. In normally-fed birds, desquamated epit(xlial cells were replaced by mucocitiated cells. These experiments raised several questions in relation to upper resPiratcx~ tract infection in vitamin A-defi- cicnt populalions, questions dealing with diRerential absorptions of virus, relative susceptibilities to virvs, and cellular effects of repeated insult on mucosal sites of normal and VAD populations. A means of studying these combined factors seems to be offered in this whole-animal model. Bang. B. G. nd Bona, F. B. Proceedings of rhr Society for E.tprrimenral Biology and Medicine 132( 1): 50-54, 1969. OtAcr `rwtorr National Science Foundation. From the Department of Patltobiology, Tfic Johns Flopkins University School of Nygictx and Public Health, Bdt"imore. TOBACCO SMOKE TOXICITY: LOSS OF HUMAN ORAL LEUKOCYTE FUNCTION AND FLUID-CELL METABOLISM The human moutb, which serves as a natural "srnokin machine" and trap for tobacco smoke, has been used as an in vivo open ~ioassay system for tracing undesirabk tubstanccs present in tobacco smoke. Employing a standardized method of sampling the oral nvity, oral fluid-cell harvests before and after smoklnj were obtained from 45 male and 41 female smok- en and mxmnokers. Control readings showed that such oral fluid-ccll harveats usually contain significant numbers of peripheral kukocytes, d)ughed epithelial cells, granular masses or casts, numerous mic roorgan- isms, and other bits of protoplasm. Results of these tests denr3nstrated that exposure of the mouth to whole tobacco smoke and its retairxd re- siduum (or to the partkk-frce gas phase and its retained residuum), after the subject had srpoked one cigarette, provided encwgh toxic material to inhibit completely the function of the in tiru exposed oral Icukocytcs. Exposure to whole tobacco smoke and its rctained residuum also induced 507o inhibition, or more, of the aerobic oxidative metabolism and anaero- bic glucolysis of the in tilu exposed oral fluid-cell components. In in vitro experiments, it was found that two important compounds in the gas phase of tobacco smoke, acrolein and cyanide at concentrations lower than that contained in a single puff of smoke, inhibited the function of oral Icukocytes and the metabolism of the oral components. Another series of experiments demonstrated that the functiorr of oral leukocytes remained unimpaired under conditions that selectively excluded the toxic substances contained in the gas phase, but which permitted significant amrwnls of the particle phase to enter the mouth. These results would indicate that the volatile gaseous phase of tobacco smoke (not the "tars" or nicotine) contains most of the undesirable substances toxic to the human oral kukocyte. F.irhel. R and Shahrik, FI. A. Science 166: 1424-142A, 1969. From (he Science Resources Foundation, Watertown, Mass. Bronchi and Lungs FIORMONES ANL) PULMONARY EFFECTS OF TOBAC CO. 11. PROGESTERONE This report deals with the influence of progesterone on the broncho- spasm induced by cigarette smoke and nicotine. Administered subcutane- ously, daily for seven daysM progesterone altered the pulmonary response of the anesthetized rat. There was a reduction or blockade of broncho- ccxrstrictor responses to the following procedures: inhalation of cigarette smoke and intravenous injection of nicotine, acetykholine and histamine. On the other hand, bronchodilator responses to cigarette smoke and iso- proterenol hydrochloride were not influenced by progesterone. "ilre fact that progesterone blocked moat bronchoconstrictor responses to a number of procedures was totally unexpected. Accordingly, it would appear that the relation of these observations to an antiemphysematous action of Pro- gesterone and the relation of the presence of progesterone to the lower inct- dcnce of pulmonary disease in females require further investigation. Shore, S. R. and Aviodo, D. M. Archivts of Environmental fltollh 19:59-69, 1969. From the Department of Pharmacology. University of Pennsylvania School of Medicine, Philadelphia. CARDIOPULMONARY EFFECTS OF NOREPINEPIIRINE AND PROPRANOLOI. Identification of a local action of propranolol on the bronchial srmx)th 34 35