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CTR HN 011620

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S(:IF.NTIFI(: AI/VIS(1RY It(/ARI1 to lhe Council for iohacco Research - t/.S A. KFNNIiIH MI: RRI1.1. LYN('i1, M 1), Sr' I)., 1.I. t7, C'hoirman ('honcrUor ond PrnJrsso. Emrrinus of Porhe'l.+Rr Medical ('olleRe of South C.rolina, ('harleston, South Carolina tNOWARI) B AN(N?RVONT, Sc D. Srirnri/Sc F dirn., f he )cwrnal of the Nationat ('ancer Institute Ilethcsda, Maryland RICHARD ). BIN(), M.D. ProJr,ror one ('hoirmon, Department of Medicine Wayne State l)niversity College of Medicinc, Iktroil, Michigan McKF.FN CATTF?LL, PN D., M.D. Prn/rssnr Fmrritw of PhsmaofoRv ('omell l)niversity Medical College. New York, New York I.FON O. JAC()BSON, M.D. Dean of the Diri,ion of Rioloticof .tclrncrs RrRerurrin Pro(rssor of Rioloticol.Scirncrs ()niversity of ('hk.g+, Illinois CLAYTON O. LOOSL1, Ph D., M D. //asfinR, Prn/rsror of M.Aicine mnA PorholnR y l/niversity of Southern C'alifornia School of Medicine I.vs Angeles, C.liforni. ('LARFNC'E COOK 1.ITT1.P, Sc D., 1.1. 11., 1.tt t 1) Scirnti/k l)irrcar, The Council for Tobacca Rrsearch - I I S A. Dirrctnr F.nrrrirus, Roscoe Is Jackson Memixial LaMiratory har Harbcn, Maine •STANLEY P. RF.IMANN, M 1)., Sc D. Dirrcror Emrrlrks, The Institute for Cancer Rc+earch Philadelphia. Pennsylvnni. WILLIAM F. RIENHOFF. 1.., M.D. Pro/rsso. Fmrrirus of SurRrry Johns Hopkins llniversity School of Medicine, Ilaltimore, Maryland SF1FLDt7N C. SOMMERS, M.D. Pro/rs,or of f arhofoRy Columbia l Inivenity College of Physicians & SurReons New York, New York RnBERT C. H(K'KI?fT, Ph I1. A»ociarr Stlrnrr/Sc l)irrcr,N 1 MORRISON RRADY, M 1) 1(NIN II KRFISFII'R, Ph 1). Amwiorr S(Irnrifir 1)irrrkrr As,(Niarr.~~irnri/S(~ l)rrrrfnr I I Stanley P. Reimann. M.D.. Sc.D. 1891-1968 Dr. Stanley Philip Reimann, a patho4ist and widely-published cancer speci.list, died on Wednesday, February 21. 1965. Dr. Reimann h.d served ns member of the Scientific Advisory Board to The Council for Tobacco Research-U.S.A. friooe 1954. As- sociated throughout the Tetus with the Uni- versiry of Pennsylvania. Crodn.te School of Medicine; llahnemann Medical Co11ege, and Lankenau Hospital. Dr. Reim.ne h.s.erved as president of the Amerk.n Association for Cancer Research and the American Sockty of Clinical Pathology. In 1925. Dr. Reimann founded the Institute for Cancer Research in Foa Chase. Pennsylvania, served as its tci- entific director from 1945-1956 and emeri- lus director. Believing that malignancy was a probkm of growth and teaching that the most eRective way to find a cure for cancer was to achieve an understanding of the pro- ccsses of growth. Dr. Reimann, through his life and writinRs, eserled a widespread in- fluence on cancer research. . VINC I N1 1: 1 ICnNfI, I)M1tI) l,tInn/,.44vv rore

TARLF OF c(1NTF.n7•S Inhoduction. . . . . . The ProRress of Research Abstracts of Reports . . Psycho-PhysiotoRical Studies Cardiovascular Studies . Carcinogenesis Studies . Studies at the ('cIlular ltvel FpidemiriloRy . . Pulntionary PhysiokrRy . NeurophysioloRy . . . . Chcmistry and Biochemistry 5 6 15 16 IB 33 r 36 39 41 46 49 Pharmacology and Psycho-Pharmacolo6Y . . . . . . . 52 Pregnancy Studies . . . . . . . . . . . . . . 54 ()ther Studies . . . . . . . . . . . . . . . . SS Recipien,s of Gr.nts . . 57 I introcluctiori I he Council came into being fourteen years ago (originally as the Tobacco Industry Research Committee) to sponsor financially a wide vari. ety of original independent research studies related to smokin6 and health. Other aRencies, both private and government, undertook also to support research in 1he same general arta. Thus, thett began a widespread ellort to gain more scientific knowkdge of a subject about which little was known. 1 he ramifscations of 7 he Council's research program have been and still are, quite e><tensive. Many scientists who have received and are receiving support from The Council have turned up knowledge and information of value in the ongoing eRort to uofve the riddks of cancer, heart disease, and other major ilments afllictirt mankind. Another benefit to both the general public and the scientific community of The Council's research program is perhaps more obscure but no less im- portant. The fact that reputabk, independent scientists at leading research or6anizations and institutions ree the need for more study is a clear indica- tion that the smokint and health situation is not as simple as some people would have us believe. The incidence of the various and suhdry diseases attributed by some to cigarette smoking would be a major public health problem even if smoking were not a worldwide custom and had never esisted. Many people who have never smoked now die and will continue to die from the same diseases as do those who do smoke. Many people who smoke do not die from the statistically implicated diseases. Whether smoking, as such, is ot is not involved in disease or death of certain individuals is still not the solution to the major problem. This solu- tion depends ors research which, it (s hoped, will lead to the detection nf thcne individuals who, with or witM.ut smokinR, face in cmmmum  greater riak of rkveMPinR or cr>sthactin` any of the diaascs which have hecume thc ma1or survival drreats tu m.nklnd. '1 here is increasing and significant evidence that cumple.. Rrnrtically, innate individual diflcrences In susceptibility and non-fusceprithrlity, whith aRr^,t the rate of aging and the imbalance of various organ and tissue lunc tions underlie and profawndly affect the three major f•ublic health laot.lenrs - eaneer, cardiovascular disease, and mental heallh. t 5

'I'hc I'ro ~9ress of Rcscarch The Council for Tobacco Research is and has been engaged in support- ing studies of thcne diseases that are currently the greatest causes of illness nd of death Of course, all these diseau-s occurred, and mtnl wete well known, hefore the use of cigarettes became prevalent, and they continue to occur among nommokers flence, any hypothetical or even real eRect of smoking could, at mcnt, he no more than a ctxNrihutory or ggravatinR factor in these dis- eases rather than an "all or nothinR" clouse of any. Fpidcmiolo6ical studies have been and still are the subject of debate by statisticians with respect to their rrliahility on tcchnical Rrounds. Addi- ticsnal research aimed al rectifying anme of their rkficiencies and clarifying rome of the curinui cnntradictirms an•I rcculiarities are nccdcd. It is a fact of histnry, nevrrlhelrss, tlrit theae rlnJrmudhiRi,.rl rerirrrts prnvidcd the im- petus for ahundant rcaeartir rrLrrurR in onr way -a another Iit °rnhiccrr rnd health" Ihal his auhsequently Lrrn undrrt.krn hir m.rny .crcntiua Ihit re- scarch has been sl.rrnsored by pwrrnnrrnt drparlmenta and by a number of voluntary hcalth aaociatir+ns and foundatruns rntludinR Ihc ('rruncil for Tobacco Research and the American Medical Aaarrciation Educalional and Research Ftwndaticxr. 7his was a logical development since a reco6nired - indeed, the major - rok of epidemiol..Rical research is to identify areas in which more minute and ettended studies of other kinds may be needed in the laboratory or clinic. Within the Iasl half century, notable progress has been made in the control of the Infectious disc.sts with a consequent great rise in life e><pecla- tion. T/x average infanl born In this country trday can e.ptct to live almost half again u Nrng as one born in 19(N) 'Ihis nxdical triumph has prnMluced a pnpulalion containing a larger prolxxticxr of older penons Ihan any herc tofore encountered In history. With this Increase in the older pnputatinn, disahility and death due to chrnnic nr drRenerative ailments such s cancer, disnrders of the heart and r.rterics, and chrrnnic respiratnry diseases have shown a rrfarive increase. 1 urther prnRrras in improving lifr e./tectancy must therefore cr+mc largely I I I from new methods for preventing or deferrin6 the development of such dis- eaaes, which characteristically have a slow and insidious onset. f:+tperts in these fields point out the complexities that are to be expected in the causation of such diseases. Their origin and development involve various degrces of host susceptibility or of resistance which are deep-seated in the constitutional or genetic nature+of each human individual. This "built in" susceptibility or resistance may then be•modified Importantly during the life span hy such factors n aging, sea, relative activity of the sever.l glands of internal secretion, and the individual characteristics of food absorption, utilizaticsn, storage and excretion. Daily life practicea such as eaercise, hours of tkep, use of coffce, tca, tobacco, akohol, and the common household dnrRs, eaptsures to all kinds of materials and substances on the job, psycho- N,6ical characteristicY, and the stresses that assail the psychrs-physioh,gical system, may play a role. So may also the numerous bacterial and virus infeclions, mild or acute, which all persons still eaperience even though these are much less often crippling or falal than formerly. Great bodies of date concerning such factors of internal and e><ternal envirnnmental oriRin, have been and are being collected in studies of cancer, cardirnascular diseases, chronic pulmonary diseases and general mortality. In such studies serious fallacies in perspective can result from over- interpretation of one-to-one correlations even though these may be valid mathematically. Hecause of the lack of multivariate analysis, emphasis on the single factor of smoking In a number of epidemiolnRical situalirrns involv- ing numerous unanalyzed factors may well have masked other Isrnsibly im- pnrtant factors and misstated or overstated any possible significance nl smoking. The pressing problem is therefore to bring the methods of multivariate analysis lo hear for weighting these various (acrors relalivcly, in a mathe- matical scnse, as contributors to the final evaluation of causation and devel- opment of a disease. The IaMaious classical method of multiple regression annlysis is now being superseded by new computer methods capable af handlinR a large number of variahles simultaneously and rapidly for "clusterinR Icndrncics." Such mrlMMls nerJ to he applied comprehensively hr many large awwlics uf dat* that have .Ircady t.een and will Le collected in thc srarch fnr tlurs to the elirduRy of tkgeneralive disease by epidendoluRical nredudh. I he Council is aiding in the development of such csxnlwler techniques and their application experimentally to certain bodies of dals that have been cnllrclcJ in its sfrinsr.red projects. There is also a great need for studies that will show how the many other 6 1 7

hahils and practices of life tend to he astt.ciated with smoking or nnnsrnoking. Only as wc develop a picture of how smukcrs nnd monsmrtkcrs di(Ter in such ways, will il become possible to distinguish between f+ncsihlc cf(ccts of smnk- ing per tr and the c/lccts of nthcr ssuuiatcd hahils in the causation o aRgra• vation of the various constitutirxral diseases. In this kind (if rcaarch also, computer techniques fnt multivariate analysis should he very helpful and tirne-saving (:(rrtcer of the I,trrrg In a sense, lung cancer carrks a particular emphasis in tohsrro and health investigatinns because of the reputcd "ttrcngth" (if its astix•ialion with cigarctte smoking nn monofactorial eridrminlr.gical sludics. Another reatnn is the rate at which this ditease is reported to have increased in incidence within recent decatks ~ T/Inr1a in Incrrlrnc• It ii certain that the rate of incrcace rrpnrtrd for this disease during recent dreadrs haa hern e>taggeratrd cttnvderahty by the progressively in- creasing skill of clinicians in diaRnnsis A number of autnfsy studies have shnwn that wherea. IunR car(inttma wat mnacd clinically as often as nine limri out of ten early in this century, il is presently dtaRnrncd clinically in eighty to ninety percent of casct Indeed, there are indicatitrnt now that Rcn- eral nwarencss of the diseate is leading ttr rrverdiaRntrtit Fven su, in tpite (if the fact that diagntnis has approached a high level (if efficiency, the curves of reported incidence have begun to show aigns of approaching a plateau rathcr than a continuing steep inerease. (anaai/icatlon ol /,unR Tumors Ilnman lung cancer tissues, still living afler surgical removal, are now being nbserved with respect to their behavior in standardired culture media. Such wide behavioral differences are bring seen in a single medium as to suggest that there are many mrxe differrnt tyftes snd Innhahly more di/lrrent cau.rt rlurn prrvirw.ty suspected hum the classilication uf fi.rd anJ slained sucth+ns on the bntis of yqtearance. f:.11 nml Tiaau. Culture Conj.r.nr• A tr.nfrrrnrr that Idacrel .Irtial rmPhaaia uitim thr hist~q~nthtrhtgicsl t h~nr .tn,l,,, r,1 n . rllt .u ,1 1-.ur , ul~ nr~ hv t irt ~m Rrrut :md nlher 1Rrnta i in rinrr, was heid March 6. 1967. In addition 10 staff and nxmbcrs of the Scientific Advistrry Board, the following Investigators participated: T. TIMnTIIY CR(KKFR, M.D., Professor of Mcdicine. Department of Internal Medicine. University of California Medical C'cntcr, San Francisco, C'alifornia. LFII-A DIAMOND, Ph.D.. The Wislar Institule, Philadelphia, Penn- sylvania. BERLE 1. NIFISF:N, A.B., Associate Specialist ((hmningy), Csncer Research Institute, University of California Medical ('enter, San Franciscn, California. I)ONAl f) M. PA('E:, Ph.D., 1lireclor of Cellular Research, 1)eparl- ment of Physiology and Pharmacok.Ry, llnivcrsily of the Psci/ic, Strkktcm, California. Rl1SSIa.1. P. SIIF:RWIN, M.D., flaslings Associate Professor of Path- ology. (lniversily of Southern California Schtxd of Medicine, Lrn Angcles, ('alifornia. f1ARHARA K. WATSON. Ph.D., Assistant Bacteriolo6ist, Massachu- sells (ieneral Hospilal, Boston, Massachusetts. (-IIARf I Y WAYMOUTH, Ph.l)., Senior Staff Scientist. The Jackson 1.aboralory, Bar Ilarbor, Maine. Cell and tissue culture studies hope for the in virro production and anal- ysis of such histopathological changes as are observed in the lungs of animals subjected to controlled eaposures to varioua agents. Subsequent direct obser- vations of the proliferative capacities of such tissues when replanted into the host animal may help relate microscopic appearance to tissue behavior. Stndira with (:iRerette Smoke (:ondenaotes F.><periments involving the painting of mouse-skins with cigarette smnke eondensates (t+ften erroneously called "lars°) have becn the chief basis for the view of srrme investigators that cigarette lmoke is to be regarded as a contact cucimogen for the human lung 1lowever. the relevance of auch ob servatirxrs lo the problem of human lung M quatinnable. First of all, there are greai differences between rodents and primates (mnnkeys and man ) in sus- cef•uhiitty to knitwn cau'inngens Secondly, the skits Is a very diflerent ussuc fram Ihe lung and shrrws very dlfkrent reqwinmcs In vatirrus irril.iting agents Thirdly, atntknaates of smoke collected by passing snrrrke thtouRh cnld tr:qK at very low ternperalures, such as --R(1^ eentigrade, •re not eyuivalrnr in either physical nr chemical properties tn whole smoke ('hemicnt and ifiyaical changes occur in smrtke, sonic rapidly, fGdluwing its formatinn in Ihc NnnntR mne nd these cnntinuc in Ihe condemate nfter etdtccrion M.'rrttver, .uch V

condens:,tes lack aIl Ihe Rasenus cnrnfwincnts of smnkc and some <+f tlrc vapras that arr not cnndcnacd nr that evalrrrate :rftcr colltctir+n Ihe rhysi<,-%I st.rtrs of whole smoke and of cnndensate ,re ohvir,usly quite dinerent Fin:rlly, ccr tiin srnnke comtituents are disprnprrrtionalcly cnncrnrratrd in the condcncite ITholeSmoke Irrhnlntion The cnntrnlled inhalation of whole fresh cigarette smoke by esl+rrinrental animals sccros to come much cltner to thc idcal of bringing thc riRht material, in the right form and right c<x+centratirnt into contact with the right nrRan, even though the wrnnR animal must still be employed Numtrrrus inhalati<.n studici were undertaken hy many invrsliR.t.rrs in the early days following p<rhlicatkxr of the reports linking cigarette smoking tn lung cancer 7 hrse added up to an impressive failure insofar as the af pear- ance of lung cancers was concerned I.itde account of this eRurt has been descrihcd in rrint, so that the estent of the work is relatively unknown tnJay, 7he Council has continued to sf.msnr such studies with cffnrt toward improvement of tcchniques lhese are now aPPrnachinR the point where a more cnmprchensive program can Le developed Among Ihc many other factnn which nced estensive sludy are Predi,lwninR factnrs in lung cancer Animal mrKlels for lung carcinnRrnrsis I ung clearance phenomena T7tr' (:arrli(rtursc•ulrrr I)i's(vrsr's Ath.roacleroaia There is broad agreement that the pr<xess of alherosclernsis tends in general lo predispcxe to ischemic diseascs of the heart and blood vessels "fhis gradual thickeninR and deReneratirrn of the vessrl walls occurs in all persons but 1 widely different rates A numher of diffcrent kinds nf evidcnce have cnmhincd to suRRrst that nicntine or smnkinR dtr not c<rnlributt tuward any acceltratinn of this prrxcss: ( 1) the fact that these diseases auc nrrt aplnr ciahFy more frequent anronR pipe and cigar snxrkers than anN+nR nonsn>,rkrts, 12 ) the inconclusive results In animal studies where nicotine was added to an athcrnRcnic dirt, ( 1) the occurrencr u/ angina /xti hrris no nxrre rdtrn In smokers than in nnrnm<+kers, and (, ) lNrfr mortrnr studies showing no siR nificantly incrrasrd Fwtvakncc of infarct~rns of the hrart anrnnR srn4rkers ()nr resrmlr rrfwwteal Mrrr m.wrrm stuily ha+, on the crmuary, found I snme relation between thickening uf arterial walls and ciRarette smrrkinR history Nevertheless, since so many other hahits and practiccs uf life tend to cluster with smoking, it cannot he concluded that Ihe smukinR per rr was resfxrnsihlc Further study of these life pallerns, (ir new and hrtter animal sludics as well as suitably controlled twin studies, may help to bring a dehnitc solulion. SmokinR and Ilyprrfenaion 'llsere is little evidence that smoking causes chronic hylrcrtrnsion ( i c, high M<wnl pressure ). AlthnuRh smoking ordinarily causes a snrall na in bhKrd pressure of a few minutes duration, many stu<lies shqrw Ihc restinR hhxxl pressures of habitual smokers to be lower generally Ihan thou of nun smokers. Nicotinc anrl SmokinR in Re/ntion to Blood Flnw A number of studies have shown that nicotine or smoking tend to in- crrarr the flow of bhrnd in mcnt of the vascular heds including thrne of the hcart, brain and skektal muscle. An e.ceptiun is blood flow in Ihe skin of the cutremitics. !'harmarnloRy of Nicotine There is a vast literature on the pharmacology of nicotine and ('ouncil projects have added a great deal to it. TIKw6h many transient eRects have been more fully described and mcasured in our proRram, no cvi<knce has emerged of any significant rnntritwtion by nicotine, at the levels smoktrs receive, to causatinn, aggravation of precipitatisxs of any cardiovascular di,. ease that conlrihutes significantly to mortality. (:Irrortir. I'ulntorrnry Uist•"trses Chronic anrl pr<Mressive diseases of the IunR, such as bronchitis, a,thma and emphyscrna are allractinR increasinR attentifNr as t'auses of disahility and drath ( linicians rclw)tt thal tuch aitments are htinR seen mone Ireyurutly and drry are appcarrnt nKrre often on dkath certiflcalcs as causrs rrf drnrlr 'I he rise in chnmk and proRressive Iwlmonauy disease, has f.rrn at tributed in part to the now frequent cure of acule lung infections by ann hiotics so that more people with damaged nr susceptilrle lungs are ahvr t4rlay than formerly. Alur, as has bccn pointed out, the conrlKrnent ut oldcr pcrq4c in the total population is greater than ever before in history. In this age puulr, and especially in males, these diseases are most frequent II

In this area, thc atatiatict are even more cnnfuud and tlf mrxe cluhiuus accuracy than they arc in the case td cancer ot cirdtuvacul:u diaca~rs, by reaafn fd laflhlcros tif diaRmnis and mlmenclatutc I he tcrm "cmphysema" his analumical dcfrnilinns and the patholfrpst uses the term Io Jescrit.e con- ditir,ns thal can he rrcr+Rnired under thc micrcncnPc, classified as to type antl tstimated in extcnt I he general /+ractitioncr, however, haa cnnrc to usc the Icrrn as hractically synnnymtws with a clinical relxItt of Jifficuhy in hrcathinR I here is an ahundant testimony that Persnns JiaRntviced clinically as havin6 scvere "crnllhyscma" often show little or none analr+nlicatly, when esamincd rrrfr mnrrr.rr ('c.nvcrxly. Patients who have hatl little breathing truuhk in life may show ctlcnsive snalnmical emlfhyaema at aulntsy In view of such variances in dcfinitinn and driRmsia, statcmcnts crln cerninR the estent kl whith "emphyxma" has incrcaud uver anv given perirwl as a cause fd death have limited meaning (:on f.rince on AIIirRfor enrl In.n.unnlnRir•nl Asp.rta nf ,SrnnkinR A cr+nfcrence on alkrRic and immnmiIrrRicil aslrcts nf Irlhaccn smi/kinR was held (in Mrrt h 1, 1967 In aJJitirm tu atifl and meml.ers ut the Scien tifK Atlvialty Hrurd, the IfdhlwrnR invrthgatnra LvUCil+atcd IIARRY S HI RNl(1N, M I), AttendinR AIIcrRist, Providence Ilfls- pital, WashinRtnn, I) (' RI('IIARI) S I'ARR, M 1) , IIc.u1, I)iviaifrn ut AIIcr6y. ImmunrlluRy and Rhrunuadr.Ry, Sc-rilqps ( hnrc and Rcscarch I fwndaUfln, la lulla, ('ahfcNnia PAUI-6(11.1)t1AHFR, 1) O S, Assfrciate Prufesanr nf Perir.dfrnuoInRy, Ilarvard SchtK-1 uf Dental MeJic'ine, Hrntun, Massachusctts 11AVIl) W. I At MAGI:, M 11., Prfdessor of Microhinhrgy and Asan- ciatc Ikan, (lniversity (if ('rlhrrado Schrwrl of MeJicinc, I)envcr, Cnlnradn. Ni(•(rcirrfr (rrifl [lle (;entr'fll N(rrlurrfs tiysrer/r Ihere is a recurrinR queatifln ,s Irr whether frrtain kinda /rl IKnplc eal.rcially need ur want to amf/ke wldrr the cnndrUrfns fd numlern life Ixr ause rrf a y/rcial need lor rrlief of Ierniun Is there any evrdrrKr that .utIr relief ia ctually Provided by snxrkinR7 In the past, dependence has had tf+ he Idaced largely upon Ihe suhjec- tive statements nl amflkers as tu+ why they like or nerd tf/ srnflke AmfrnR the fec-urfinR rrl"lrts arr such as Ihese ( I ) "It Rivea mr Illeasnre," (2) "1t gives me e I, r( kull nn, l hrll,t me Rrt R„u,R," 0) ..It tlcll,. rne tcl.rIt whcn I am lrflsc t I Sut h st.Hrrncnts raise the questions whether evidrncc tf/ chec k their imlvf+rt ttndd f.e larwidcd by any capcrimental methtnl. Stune answcrs rnay I+erhaPs hc furnishcd by psychological investi6atitrns and any PrranisinR alqpftl,ches along such Imcs shrwdd he cncouraRed. Anuther al-Pn+ach ia through the methods of psychn pharmacnhlRy, a relitivclv new licld nl science. Ity the study rif clcctrcxncephaln6rams it has been shown Ihat. Mrdr in animals and man, nict+tine has a hrief stimulatory or "arousal" effect r,n thc hrain, especially when this was nriRinally in a state of what might hc called telwrsc. When the hrain is in the kind trf stale aasnciatcd with aRitatitrn, nicre tine hat an effect ffn brain waves resembling Ilut uf wnx of the trYnquilinrs llrut paythupharmacohogy is PrnvidinR sume scientific auhatantiatirm If.r the seennnRly crrnlradainry suhjcctive testimony o( snmukcrs Nicutinc may M,th aruusc the lethargic and calm the agitated. Since direct electrical stimulalicxt of certain parts of the brain latKluces an effect that is pleasurabk, animal studies are being made tu determine whether nicotine alus stimulates the pkawre centers. Cechniyucs that Permit monkeys to inject themaelves with nicotinc at will, nrN only show that they find this a6reeahlc, but are shedJrnR light on the effects of envircrnmcnlal conditams on the anwwnls the animals will take sPr.ntanerwsly. In no case has any of the animals done damaRc tfl itsclf by srKh unreslriclcd self - adminislrati.n. Scvcral studies have also tapkxed thc eflects of nicotinc on the learning prtlcess in rals, usinR various rewards to stimulate the animals to learn their way through a mazc, press kvcra in snme pattern or avoid an electric shock by jumllinR (u a wooden Pok on signal. Several such caPcrimentt show Ihat nicu inc stimulates the karnin6 Process, mtxe particularly amflnR thc animalt that arc originally relatively slow learners. I Or(tl (,(ri!fily l irs(r(rr(•Ir lhe nral crvity is subjected Io direct contact with snulkc drrived fnrm Irilrs, tigira and ciy.aurttea mure quickly and in greater crfncen,ratif/ns Ihan Ithr IunRa I/ralnte thi., I1K irM irlrnt'e UI t"arlCrr Irf Ihe f•ra) t'hVlty 11.1% ahrrwrl nu vgnnc, ant intfrau iu ramfNrrrl, nr inciJrnce at n rarlirr rFr, flurruR Ihr dcc'arka in whk h/w cal+ila r.l>,aure tu t iRarctte sruoke haa ri.rn Rrr.rtly Ir is iml-Iul:mt to find Ihe esplanaliaxr for tfns /nti As rrpwlcd clsewhere, ('ouneil studies have shnwn that the nral riaurs rrf mice are far rnurc resistant tn certain carcinnRena than are Ihru akm. In nllce, liver dvnnRe ctlnsidetahly increasea the auacefaihitrty nf nce oral lisaues tn crrt.lin recrlRniled catcinrrRrnic suhN:rntes, 1,111 I'.I1ntinR nf Il I'

ciRarctle srnuke condensates inside the mouths of Iiver d.rnaReJ mice has not been f4dhrwed by appearance of any lumors. Much more study of the oral cavity is recommended by the fact thal il resemblcs the lung mcxe than does the tkin, yet is relatively arcetaihle. Since the saliva, oral structures and especially the oral Icucocytes al%o serve as a first line of defcnse against exlernal a`ents entering the lxK1y, they merit .Itenlion in their own riRht. The eRects of In vivn and in virr,r cwfa+ture of oral leucocyles to whole smoke and to smoke conatitucnts are LrinR sluJicd in recently inaugurated ('nuncil projects. Abstracts of Ilcports Pach recipient of agrant-in-aid from The Council for Tobacco Re- search - l/ S A. is responsible for the initial presentation or publication of the results of his rcsearch at scientific meelings or in appropriale scientific journals. Following are abstracts, .pprored by the authors, of reports on new eeperimcntd research acknowkdRing wpport from 7 he Council that have appeared in scien/ific journals since publication of the 19tS5-66 RryKUI uf the Scientific 1)ireclor. llrese atnlracts have been `rouped under the following beadinRs: 1. Psycho-PhysioloRical Studies. 11. ('ardinriscul.r Studies, 111. ('arcino genesis Sludies, IV. SluEiet at the Cellular E.evel, V. F.pidemioloRy, VI Pul- mon.ry Physiolo6y, VII. NeurophysioloRy, VIII. Chemistry and ifiuchem istr~ IX. PharmacokrRy and Psycho-Pharmacolo6y, X. Pregnancy Studies, and X1. Other Studies. A number of grantees of The Council for Tobacco Research - ll S A, participaled in The Third PeruRia Oradrennial International (bnfererwe on Cancer held at the l)nirersity of Peru6ia, June 21-29, 1965 "I.unR 1'umours In Animals; " the proceedings of this conferenoe, was published in lune, 1966, by the 1)ivision of Cancer Retearch, Peru6ia, Italy (iranlee cunlrihutions to the conference are as follows: "FPIDFMIOI.O(71C STUI)IES OF LUNO ('ANChR IN I)(x;S," by D. Cohen, J. S. Rcif and W. FI. Rhoiks. 'TEIP ROLE OF INFLUENZA VIRUS IN TIIE hFVFLOPMI?NI- 01: MALIONANT TRANSFORMATION IN V1TRO ANI) IN 1/11? RF.S- PIRATORY TRACT OF MICE. WITH AND WIT11Ol1I /iXPUSI/RF TO CIOARE3TTE SMOKP," by C. Ltr.chrcnDtrRn and R. I,cuchlenberRcr "TIIP RFLATIVF E?FFECTS OF SOME AIR POLL117 AN I SON 1111: HIIMAN RfSPIRAIORY EPIIIIELIl1M," by W. 1L (-ornrr and 1. F Muses. "1?III?('IS OF 1NIRAVI'.NOlIS ('AR(-IN(/(&N AND 1OIIA(ll) ('ONI)I-'NSAII! IN1F('IIONS 111'/IN 1111? IN('IINUN( I; 111. I IIN(i I I/Mr)RS IN A/lie MICE," by F. I/omDurRn anJ A. I reRcr "7l/MORS PRO1)l/('FI) IlY MEIFIYL(71(/1 AN I IIRIN1: . IN 1111: RIiSPIRAIORY 7RA('f Of IIIE W1111E 1'I-KIN 1)lt('K" hy R II Rirdon. I5 14

I. I',ycho-I'hy.it)(nRiral tifudir. "BIOL(Xill:'A1. ASPF("IS OF (1lJSTATIUN" fly Arnold R Kaplan, Phl), Laboratory of Medical Genetics, C'levcland Psychiatric Institute, Ohio. "Mutation in Population: Proceedings of a Sym(+rxium held in PraRue in August 9-1I, 1965;" pp 146-153, Cnechoslovak Academy of Sciences. Prague. 1966. Tris paper presents • sum2 and summation of early and recent studies of taste sensitivity. Differences in taste threshoklt have been found to be telaled to tnany facton. Including medkation, phases of the menstrual cTcle, preRnurc7, smoking habits, occurrence of duodenal (vs. gastric) ulcer, and dietary preferences. Tests In monoryRotk and dii,yRolx twins and In sibling pairs Iodkate that genetic factors ate invnlved in laste thresholds. ()tR.r Crantarr Natlooal Institwes o/ Ileakh "STVDIFS IN TASTT? ACl1rT'Y." By Arnold R. Kaplan. Phl), Iahoratory of Medkd (:cnetia, Ckvel.nd Psychiatric Institule, Uhio. Trchnicol Quartrrly 4/2:I3R-I44, April.lunc 1967. Intrapair thrcshold diflerences fnr hydrochloric acid, L-quinine sulfate, and PROP (6 n-ProPylthiouracil) were InvestiRated in pairs of one-egg twins, Iwocgg Iwlnt, and nnn twin siblinRa 'Ihere were no siRnificant differ- ersces in inttapair variations Irtween the two egg twin pairs and the non twin siblings. There werc, also, nr+ 1 rRnrhrant drllrrrnces hctwecn the nnc egg and two-egg twin ~airs for hydrrKhtruic uid and quinine, hut there was a very siRnifxant dilTcrcncx for PRUP Ihrrrfore, the innd.emrnt of genetic factors In etinkiRy of laste Ihre%hnlrl was rnH drmnnctrareJ for .nur ustrnR hydrochkxk acid or for bitter tavinR yurninc, hut was emphatically dcrnnn slrated for bitter tastinR PROP Sensitive tasten of quinine and PROP indicated relatively large numben of food dislikes and preference for relatively mild lastinR fcxids, compared to inscnsitive tasten, who indicated relatively few dislikes and preference for more strongly-IsstinR preparations. The sensitive tasters included a rela- tively high pro(+rxtiots of nonsrnokers, compared to the insensitive taslers, who inclurkd a relatively high proportion of hcav~ smokers l aste threshold was not found to be rclated to aRc or In uc when the dda were crrntrnikd lor difTerences In srsxokinR habits. The hcavr smokcrs, hnwever, shnwed rk- cre.ud lasle sensitivity asuxiated wilh lncrt.ud age Other factrxs InfluencinR taste sensitivity IrxlrHk (rh.us rd thr mrn stru.l cyck an.1 uker palhokrRy f)thrr Rrar.torr N.tion.l Institutes of Flcalth "ORAL.ITY, IMPUISIVITY AND ('1(IARF:1-T7? SMOKING IN MFN FIIRlIII'R FINI)tN(;S IN SUPPORI' OF A 11-1FORY." fly Martin A. lacnhi, Phl). I ukrn S Andcrsnn, Phl), T'mily (TrampaRne, MI), hath.niel I Karush, MI), Stephen 1. Richman, MD, and Peter H. KnapP, MI), T)ivision f Psychiatry, llostrm University School of Medicine, Massachuselts Thr Iournaf tr1 Nrrvnur and Mrnta! Distott 113/3:207-219, 1966 (()ranlee: Knapp) 76 college students and SR industrial workers, average age 26 years, served as subjects in this third of three studies designed to test shc hypothcsis that heavr cigarette smoking in men reflects part of a pattern r>< underlying oral craving defended against by active, impulsive behavior. T1u paid wd- unleer subjccts in this study look part in personal interviews after which they filled out a Parenl-(?rikl Ouestionnaire (P('V), • personalily inven- torr ( B11P1), and a form specially designed to directly test response set and social desirability. VoOunleen in the previous Investigations were unpaid and impersonally sent the completed forms by mail. The fint two studies revealed siRnificant differenocs between smokers and nonsmokers in the parental concepts of maternal conlrol, coldness and harshness, and in self-descriptions of defiance, impeluousness, thrill and dan6er-seekinR, neurotic emotional lability, and oral preoccupations In the last study, statistical comparison of mean scores for 54 cigarette smnkers and RO current nonsmokers supported the previous findings with the e.ceptiun of the maternal malevolence concept. On an individual prediction basis, overall 62.7 percent of the sample was correctly designated as either smokers or nonsmokers usinR this psy- chnloRic measure alone (chi square = 9.45, 1 df, P < 01 ) Presumably other factnn, such as sncin4ic and physiok>Rk, enter into the drlcrmina- lion of who will become a cigarette smoker and conlinue with the hahit, hut this theory seems significantly related to this outcome and accounts for an important portion of the variance. "AN ATLAS OF FIGURF? DRAWINGS: STUDIES ON '1 HT? PSY('llO- L(X;ICAI. CIIARA(TFRISIICS OF MEDICAI. Sftll)f;Nl'S -- I11." By Caroline Bedell Thomas, MI), lohns Hopkins University Schcw)1 of Medkine, Baltimore, Maryland. Published bythe Johns Hopkins Press, 1966 This third volume in the serks, Srudirs on rhr Psyr-lurloxical ('ha.a.vrr- lirict of Mrdiraf Srudrntt, presents the only compendium of fiRure drawinRs by healthy subjects to be hwnd in the psycholoRical lilcralure. The fiRmcs in this volume were an drawn by R)l) lohns 1lnpkins n.ed kal slurknts whrr were parlicipants In the krng term study of rhr 1'recurarrs of Ilylrerlcnslun .nd ('ourn.ry INscac, UrawinRs In thrs atla. .re Rr.rkd hy rkRrre of soqdristica/inn, and within sueh a RrnupinR .rc .rranRed .ccurd (nR In different parenlal hiiIrNies in regard to cc>.unary diseau and hylrrr tension, strnke, diabetes and obesity. Smoking habits and various nncer factors are also /,iven, •rkf a Strong Vocational Inlerrst "lcat is inclnrkd fur each suhjecl. Ihus, this Atlas provides a deflnilive drnuminsloa lur fiRure drawing studies involving healthy young adults of supcrinr inleiliRcnce OtArr Rrantnr.r Velerans Administration and the National lirart Institute Ih 17

11. Cnrt>tiorrtarrtfnr Slrttlir. "1NFI UFNCE OF ANTIARRIIYTHMIC AGFNIS ON MY(K'ANI)Inl. ('ON I RACT 11.1 TY." Ily F. T AnRelakos, Mh, Phl), Ikparlnxnt nf Physi- olnRy, Ho-tton I/niversity School of Medicine, Massachusetts. "MecMnisms and lherapy of ('ardiac Arrhylhmias," 141h Flahnemann SymMosium, Phila- detphia, April 26 29, 1965. Published by (3rune & Stratton, 1966 , lhe ultimate therapeutic aim In the suppression of arrhythmias with an antiarrhythmic agent is to improve cardiac dynamics. I( this aim is to he rerved, It is essential to know any direct effects that anliarrhythmic agents may have on myocardial contractkrn. Tests with the classical antiarrhythmks r,uinidinc and prrrcaineamitk, and with the newer ant.rnlinc, .II showed a distinct drlnession of myocardial tcnsion I his depression of contractility seems to be a direct eRrct of the drugs on the myocardium. Various mechanisms are proposed which could account for Ihis dc- prcssant ertrcl Ilnwever, the lundamcntal mechanisms which are actually respcrosibk fnr the eflect have txN been identified Practically all antiar- rhylhmres (when given in suRicicnl dnus and studied with appropriate Icchnics). have heen shown tn have a myr.cardial depr"sanl efiect Aa present it is nnt ckar whether this priri.rrly is inherent in anliarrhythmic activity or is a"sitk eflect" relatrd in simrlnilies in thc chemical nxrictics resfxmsthie for cach action In cithcr ca~c, stncc high hharmacnlnRic spcci- ficity is rnost desirahlc frnm a Ihrral.curic rwttnt td vrcw, tlte scarch must cnntinue for the development of mrrrc active, mnre sf.ccihc and kss rk- pressanl antianhylhmic agents OtArr Rr.nter.r National Science Fnundation and the 11 S Public Ikatth Service. "A[)RFNFRGIC FFFFCTS OF NICOTINF. ON CORONARY IIL.(x)h F•I.OW ANI) B1.(X)1) LIPII)S ` By Samucl fkllct, MI), 1)ivisinn of Cardiolt.Ry, Philadelphia (ieneral Ilrnpital, Pennsylvania. ('hapter IX (pp 74-8, ) in "Prevention of Ischcmic Ikart Uiscase." W. Raab, editor, ('harlcs C. Thomas, Springfield. Illinais, 1966. 7 he effects of nicotine and Inhaccn srrnrkc on certain rhysinlnr.ic raranxtcrs, n.nxly coronary hhxxl flow and hlrwxl lipids, tc Arscutiscd in lhis haper Fttlxriments with dogs showed that the nicotinc indtK'ed .uRmcnlation of coronary hirnrd flow was considerably Icss markrd in aninuls with artih- cially produced cnronary insufficicncy Ihan in cnrresfxrndins cnnutrls Fkctr<a-ardinRraphic changes were nnted, and the reslxrnsc of nther param eNers, such as cardiac oulfrut, nxyRcn cnnsumldiun and crrrnnnry a v th/lcr- cncc was >tlin alterrd 7hese findings wnuld npl+car tn have a hcarinR nn the ~linii al I r„hlrm rrl.lr.r t.. Ilrr rrTrr t~ 1 nu ntinc an0 of nrrr linr iitx'ratcd 1inn. an ror.•nary alirrv rh%r.ltr A rapid and consistent rise in serum free-fatly acids was prrxluced by nicotine in dogs and snx,kinA in humans. Patients with'myraardial infarclurn developed an elevation morc than twice that of normal subjects and non- coronary patients l)ther Arantor.r National Lnslitutes of Heallh and the Foundation for ('ar dioiascular Research. "[)IFFF.REN('FS IN FFFFCTS OF CIOAR AND CICiARF ITF. SM( )K- 1N(i ON FRF?E FAl-I Y ACID MOBILIZAI ION ANI) ('A 11 ('!1OI.A. MINE F:X('RF.7ION." By Alfred Kcrihhaum, MI), Samuel Ifellct, MU, lose liminer. MI), ark) I,erroard 1. Feinber`, Phl), 1)ivision of ('ardioluRy, Philadelphia (iencrd Ilcnpilal, Pennsylvania. luurnof of the Arnnrrun AlrJicol AtsrNiannn 193/1):1(/9S-I(We, March 28. 1966 ((irantrc: Belkl) lo eaperiments conducted among 43 normal mak subjccts who werc habitual moderate or heavy smokers of either cigars or ciRaretlcs, the com- parative effect of cigar anG cigarette smoking on free fatty acid (I;I;A) mnbilitalion and catecholar.ane eacrelion was observcd nd the influence of inhaling and diflerenccs in absorption of smoke contents was dctcrntined. Results showed that there was agrealer increase in FFA concentration in the serum with cigarette than with cigar smoking. Inhaling during sn>,rkinR caused a greater FFA response than nc( inhalinR, with InNh ciRars and ciRar- cltes. With tobacco containing glucose randomly labeled with radivactive carbon ("C), there was a greater absorption of '•(' with cigarette snNrkinR. Eacrelion of catccholamines followed the same pattern. The differences observed with the two forms of smoking prul.ably result from Ihe tendency to inhak with cigarette and not with cigar srnokinR and from the effcct of this on nicotine absorption. Otflrr Rrantor.r American Medical Association Fducalion and Rcscarch Foundation and the National Institutes of I leallh. "MODIFICATION OF NICOTINE-INDUCED FIYPFRI.IPII)FMfA l1Y ANTIAI)RFiNFR(iIC A(iFNTS." By Alfred Kcrshhaum, MD, losr limenez, MI), Samuel Belkt, MI), and 1). Tanullini, I)ivisiun af ('ardial)Ry. Philadelphia Grrn•ral llospilal, Pennsylvania lrrurnal of ,lrhrrnt, fnour Rirrmc)r 6i24-5 10, Nnv.-1)cc. 1966. ((iranlce: Ilkllcl ) In .n atlcmpl to elucidate the rolc uf sympathetic and carrt hulanune activity in the alteration of plasma fire fallr acid levcls. Ihe rllcrt uf a (I-adrenerRic rccelNUr hkrckin6 agent (ncthal~ak), an . rerclrtra hhxkinR agent (phenoxyhcnraminc), and a central suplnessur of adrencrRic activity (chlorrromarinc) nn the lipid response to nicutine was sludred in ancsthc lired dogs. Nicotine alnrx, in control c.heriments in 211 doRs, gave a rna.im:J rrvr in FFA ennccnlrntinn of 14 - 4'!~, Whrn the druRs wrtr given wtthoul m(t) 19 M

line to determine their intrinsic cffect on serum I'I A concrntritirrn., nr,hi lide and phennxyhenraminc pnxtuccd a vRnilicanl rise in I I A Icvcl. whtrcas chlnrPrnmatinc had no tiFnificant elfccl After ncthalide, there was a signlli cant suppressinn nf the I I A resryrnse tn nicrllinc Illc nther crrmlwrunds did not affect the nicnlinc induced ITA resfw,nsc. Nicotine caused a rise in serum IriRlyceridc levels in eight d•1Rs which was diminished by pre-Ircalment with nethalitk. The results nf tlxse eaperiments eml+hasi?e Ihe role of the tymnathn- adrenal systcnt in the hyrerlrpklemk effects of nicotine and suRgetl they arc mcdiated by /i adrencrRlc receptors. Other Rranrorar National Inslilules of Ilealth and the 11 S 1'uhhc llrallh Service. "SMOKINO AS A FA("TOR IN AIIIFROSCI.FROSIS: A RF.VII:W OF FP1UFM1O1(X;l('Al., PAlllOL.(X:I('AL, ANI) 1'XPFRIMI?NIA1. SI l1I)IUS " fly Alfred Kershhaum, MI). and Samuel Ilellel, MI), I) visitln of ('ardinlnRy, Philadcll+hia General Ifnspital, Pcnnsylvania. (:rrinr.ir t 21/12 15S 17l), Ikcemhcr 1966 ((Jrantee: Ilellel) The rnk of tobacco smoking in the Rerxsis and development nf athcrr/ aekrosis is e.amined by revicwinR epirkmalh,yical, rathulrrRical and ctlrcri mental sludies OulstandinR anxonR the firxhnRs in thls invectiRatum atc the fnlhlwinR 1 FpidcmirdnRical studirt have shrrwn, wilh little crmtridictr+ry evi- dence, a siRmficant assrx'iaUon hrtwr cn rlParctlc smnkrnR arld the nunlnJily nd mortality rll coronary hearl dl.cat 2. Pathological studies of the curnnary arterics in cnnsrcutivr rnutine autof+sics showed an association t.ctwcrn cigarette smnkinR antl Ihe stvcrlly of coronary alherosclcrosis. 3. lhe relatively fcw sludies of the cficcl of nicotine on cRf+rrltucrltal atherosclerosis have shown inconsistcnt resulls. lhcre is need frlr more investigation of lhis probkm, using newer techniques and other slrct'ics. Recently, much has bcen karrxd concrrninR the effect of smokinR :rnd nicotine on various melaholic, hemalologic, hormonal, and circulatory prnc- esses involved in alheroRenesis Some of these biological effects ctwld cnn- tribute to the initiation and progression uf atherosclcrnsis. (/rArr wrantnr.r Amerkan Medical Assrrcialitrn Fduc-alinn anrl Rc.rartlt Foundatinn and the National Institulcs uf Ilcahh "A NFW 111A(iNOSi IC 11~S1' FOR ('ORONARY AR 11'R1' I/1`VACI " fly Alherta ('ohen, MI), F.ide l)ilmar I.uFs, MI), I Jward 1 7alc%ki, MI), and Richard I fling, MI), Wayne Slate University Schrwd rrl Mcdicinc, Ikttoit, Mich A(rnnrtrNO tilrAirinr 19/1 17_2I, )anuary 1966 ((iranlcr RinR) Ihc thaRnrnuc prrardure here rl fluenliatcs rahully Irtwrrn the esl.1h lishcd thmlrnRs that niur.RlVtrrm rrKrra.rt twrlnarv hlN"l flow in nnrrnal individualt hut nnt in palienls with cornnary artery diseasc, hy the usc lrf a IMnitnm emitter and a coincidence counlinR system I he tcsl it Iechnit:Jly simple and ah)etlive, and is made without calhelodi7atiun, invrrlvinR only intravcnuus infu.nln nf ruhidium'• and an arterial f/unclore lu draw hI/MK1 through the cnunlcr I he dala are then processed by ulmpulcr, whic h caltu lales hhwHl flnw in nd/min, together with the slandard devialirlns and Ihc siRnificance of the change in flow prior to and following the suhlinRual aJ ministration n/ nitrnRlyccrin. It permits differentiation of patients with and without coronary artery disease with a reasonable degree of accuracy f)tAer Rrontnr.r ll. S. Public Ileallh Strvice, lhe John A Ilartfnrd Founda tion, and the Arnerican Mcdical Assxxialinn - 1 ducalion and I(esrarth Fnundaliun "A('ltll! ITIT('fS O/: AL('OHUI. ON THI? Ffl/MAN MYOt'AR- Ily V. 1?. Wendt, R. Aljuni,'f. A. hruce, A. S. Prasad and Richnrd 1. fling. Amrricon lournol of C'mdirdoRy 17/6:e01-It 12, June I96(h lhe effect of acute akohol ingeslion.(6 oz of RI proof V<afka/ was stut:icd ir I I patients with a known history of chronic alcohulisnl None had any evidence of vitamin rkficicncy nor of heart or liver discase No significant changes appeared in pulse rale, blood pressure, cardiac output, slrnke volume, arlcrial venous o>tyRen estraclinn or respiratury yuolicnt Iksllne the lack of Ihcse hemodynamic altcrations, flattened and invertcd 1' wavcs occurred in the clcclrocardioRrams of Iwo paticnls 10 minutes after Ihc ingestion of alcohul. 'I he significant metabolic findings included  rise in hhwal lactate, a decline in arterial hyruvate, a marked lall in blood Rlucose, a decGrre in frre rally acids and a rise in triRlycctides one half hour allcr Ihe inRcstion u/ alcohnl. 7inc was lihcratcd by the heart in Ihe majority of palicnls, and serum alcoholic dchydroRcnase activity cloaly followed that of hhtiKl rinc 1'hns phnlipid blood Icvcls rcmained unchanged It is tuPRcsted that rcpealyd esf+osurc to acute akoholism could result in permanent allcratirrns in myo cardial mclahnlisrn which could kad to the devchrrrncnl uf irrcversihle alcoholic cardiumyupathy. Other Rrnntora: l).S Puhlic Nealth Service, American Ilearl Assrxialinn, MichiRan Ilcarl Associatinn, Life Insurance Medical Rrsearch I'unJ, Ilur ruuPhs WellcrrnK• 1 und, Ihc ltlhn A Ilallfntd Puundaurrn and the Ilcuhlcln ('nmhany I "SI IM111 A1ION (1F R1TARAIIVI'. PR(X'I:SSI:% I(11 1OWINI: I X 1'ItItIMI NIA1 MY(I('ARI)1AI. INFAI(('IION" Ily S(:urlbl.unaarn lrrhn (' I•crdon, I'.lul I Wolf and Rithard l FlinR Arrlrncrr ./ Mrrrn,d lfr•duinr I I8/ 1: 11-16, July 1966 the reparative processes in cardiac muscle falluwinR eat•crimcnlal myrxordiil infarctir/n prrxlured in dr1Rs hy IiRalinn of Ihe crurm.lry artcrrrs wcre stimulatcd with anaht/lic hormrncs I rcalmcnl wilh insulin incrcaurl Ihe irxnrlMUatinn ltt Rlycinc 2"(' intu prulrrn ur inlarctcd u~suc hy )4':., 21 ?I/

/tralmrnl with Lnvine growth hrnmone raiut) Ihc incorfa.ratir n hy 16R^~, and trcatmcnl with Mah insuhn and Rrrtwlh Mnmrnrc rarticrl the intnrrurri- tion by 2S 1^, all witlrn 24 hnurs rd trcalmcnl Treatment with an inuavennus infusion of Rlucose, inarlin, K(1, cnervymcs and vitamins incrcasrd I+rrrtcin syntheais in infarc'tcJ musclc 7 hnurs after infarction by 171^L.; repeated infucinn led tn a further rice within 24 hnurs after infarction Ascorbic acid rncreaad protein synthesis in the center cd infarclcd area by 122% and Ihe anaMdic slernid methandro- slcnolonc auRrrxnted irxorporation into the center of infarct by 249%. 1 onR term treatment with Insulin or the anaholic sternid prevented development of aneurysm, whereas animals fed a protein free dicl had a siRnificanlly thinner scar and frequent development of aneurysm It should he rcemphasited that the biochemical tlemnnslratinn of protein synthesi; in Ihe infarctcd myncardium does not Imply synlhesis of prulein by necrotic heart muscle, hul is due to fibroblastic proliferatinn in thc injured area Othrr Rr.ntorar 11 S. Puhlk Hcalth Service (2). Ihc John A. Ilartfnrd Foundation, MichiRan Ncart l4.sociation, and the American Medical Acso- ciation Uducation and Research Fnundatinn. (hher (+arers published by Dr fling and asascialcs since Ihr 1965-66 Report of the Scientific hireclor, with credit for support by 1 he Council for Tobacco Rcscarch - II S A, follow Other Rraninrs are noted between parenlhcses "TI11' MV rAh(11.ISM O!' THf: IIFAR I' IN FAII IIRI: " Ry S Gudhjarn- ason and R. 1 HinR Ar ra (-mdurhoRir a 2/) 'S. 111 1Rt), 1965 ( PI IS, M(IIA, 1-IMRI', 11WI, AMA fRl' and 1A11F) "METABOI.I(' FACTORS IN ll)!' CUNIROL OF ('ARI)IA(' O11f- PITT." fly V. f Wendt, C. Wu. R Flalcon and R 1 IlinR ('h:rpter in "ShocA and 11YPrrrrnrirrn," puhl 1965. (irune b Stratton IPIIS, AIIA, M('IIA, I.IMR1;, I1WF, )Atll;) "CIR('ULAIORY CHANGhS FO1.1.OWIN(7 MY(X'ARI)IAL. INFARC'- TIUN." Hy V. 1? Wendt, R 1lalum, 1. Rihcilima and R. J. fling ('haptcr in "Shock and ll vpr,rrminn " puhl 19hS, (irunc & Stratton 11'l IS, AI IA, M(11A, I.IMR1:, I1WF, lAllF) "MP.IAIIOLISM OF TfIF lIFAR U IN hA11 I IRF " fly John (' Urnton, Symundur (iudhiarnason and Richarrl /. Ilin/ Amrrigon llrrnf Arv'ruirrn 11fnnoRrnph Nn /, Second Vditirrn, April 1966 12 411 (1'1I%, r•1( IIA, I.IMRF-, HWF, AMA-FiRh, /Alll-'/ "HYPOXIA IN /l(R GFNFSIS OF C'ARI)IA(' ARRIIY I IIMIAS " Hy luhn (' Fentnn, S(iudhjarnason and Richard I HinR Iroun "Mrrhanirmr and 7 hrnrpy n/ ( ardia' A rrh yfhmrat," 14th Ilahncmann Sym/nium, puhl 19h6. Grunc & Stnalton SR 61 IF'IIS, M('11A, IIWI:, A( S. AMA FRI', 1nI11 ) I "('APlI.I.ARWS IN IIFART ANr)SKFI.FTAI. M(1S('1.1: ()1: IXXi ANI) RAIlN1I-." Dy K. Rakusan and W. du Mesnil de Rochemont ((irantce: R. 1 F1inR ). 1'rrx rrdrnRa of fhr.fr>r irt y/rn F i prrfnvntal /1rn)n4 v and A1rJr rinr 124/3:R1R 940, March 1967. (PIIS, )AIIF, M('IIA, AMA fRf, Ixi1IR(') "FFFFCTS OF AI.PFIA-METfiYI-DOPA ON TTIF MY(X'ARUTAI. HLOOU Fl.OW, IITILIZIN(3 111E COIN('IUENCI? ('O(/N I ING MF-TFU)D" fly Alberto ('ohen, 1. S. Maxmcn, M. RaRheb, I1 1laleiron, E. 1. 7.kski and R. 1. HinR. lournd of l l.nical PharmaufuRy and lournof of New l)rurs 7/2:77-R3. March-April 1967. (MSI)RI., 1'IIS, IKiIIR(') "MI?AS(1RF?Mf?NT' OF Tl1E SHORTENING OF ('ARI)IA(' I-IIII:RS IN MAN." fly Richard 0. Madcira, Wolfgang du Mcsnil de RrxficnMmt, ('harks W. Oadd,1 homas B. Stock and Richard 1. Hin6 . Amr.i, nn luurrwl of C'ar4ioloRy 19/S:6R(~691, May 1967. (MCHA, IXi11R(') "PFRSISTC•NCE OF REFLEX SYMPATHETIC NFRVO(IS SYSfFiM ACTIVITY IN MAN ON GUANETHIUINE OR RI;SF.RPINF " Ity Jay 1). Coflman, MI), Department of Medicirx, Noslon Oniversily Medical C'enter, Massachusells. Ctrcularlon 35/2:319-346, February 1967. The eRect of oral Ruanelhidine or reserpine on the refkn vasoconstric- Iion in Ihe calf and foot resulting from a prolonRed. Reneralved sympathetic stimulus (body cooling) was studied In 12 normal suhjects. I.arRe daily clinical-doses of guanethidine or reserpine were given for 2 and 3 weeks, respectively. Fcxrt and calf blood flows were measured by venous ncclusion water pklhysmt>Rraphy. Two control studies were performed on each sub ject, one before and another long a/ler administration of the JruR. Flody cooling produced significant decreases in cal/ end foot bh>iK1 f ow and increases in vascular resistance in both conlrol stuJics. Suhjrcts evidenced drug eflects by a significant decrease in pulse rale, postural hyht tension, hypotcnsion following e.crcise, and bhx:kade or altcntuatUnn of the Valsalva maneuvcr "ovcrshoo/." 'ihe altenuatiun ol the syntpathetic nervnus-system vasoconslrklor rtflea to general FxKly cooling was nut stalis tically significant. Since large clinical doses of Ruanelhidine or reserpirx admini.trrcd orally for 2 or I weeks, respeclively, did nM inhihil Ihe rc0et va.rKirnutittrrr effccl of total IwKly coilinR, functional sympathetic neurulransrnittrr .ub starx•e cannot tre said tr) he absent (ItArr Rr.ntor r National Institutes of I/ralth. "REAPPRAISAI. OF PFIYSIOL(xil(' PRIN('IPI FS IN I lIr r Rf A 1 M!?NT (/F IS( IIIiMICHI?ART 1)ISFASF" Hy (?ril f: ('tn+t and 1'rtrr F. Sahsbnry, MI), Ihpartments of Medical Re%cernh anJ Mcrhtmc, St Joseph Ilospital, nnthank, C.lihnnia lnrernol Alr.trd rnc I)rReu 1 1') 14, February 1966 ((irantee: ('toss) ~' 21 ~~ 2 2 cT~

...3. .f.. 0 ~ m (-n .- 4e~t:f m .S.J~ m (T A course of treatment of ischemic heart discase hased ularn the main- tenance of hl(xxl pressure at the Irlwcat kvel compatible with normal funclum of the palicnt's vital nrRans is hreantcd in this paper I he recrrnuncndcd treatment is fnrmnlated upon a review of the current atalua nf kmrwtcdRe of the coronary circulatinn, consideralinn of recenl discovcrics and a reap- praisat of the rhysinlnRicat principles involved in acute, severe coronary disease. In order to understand the Impc»tant physirdr.Ric mechanisms involved, studies were undertaken of the interaction of cornnary pressures and flows with the function of the heart. When coronary htrxxl flow was measured in anesthclired doR., the resistance of the coronary vessels remained cnnstanl within the "normal" ranRe or cardiac outputs and of hkxxl pressures 1 he coronary vessels did not dilate when the work of Ihe heart incrrasrd nnr did they constrict when the work or the heart decrcascd Active curnnary vessel conslriction or dilalinn was obxrved only when highly abnormal slatrs of the circulation (for esampk, Intentionally produced high pressure in the aorla) were present The physiologic ohunatinns and clinical nxssures noted here suRRect the Ixnsihifity rd a future increace in Ihe survival rale in i%chcmic heart disease . /)rA.r Rr.nrnr.r National Ileart Institute, (/ S Public Ilcalth Service and the I ife Irnurar.ce Medical Rcscarch I und "('(/MP1 r('I11I(1NSl>F: ATFIFROMA1O(IS PI.AQl1FS" Hy Ira Gore, M[), lkpartment n/ PathnluRy, Ftnstun Univercity Medical Ccntcr, Massa- chusells At la ( a.dinlnRrr a X I R9 I IIR, 1966 In this revkw paf.rr, the complications of atheromatous playucs, namcly, thromhrnes, hcrnonhaRe, ancurysms, ulceratiun, cmlxdizatron and calcrfi- cation, are considcred in light of their relationship to the athcrnwlerolic process. Studics of coagulation and platelet utilization cited in this review favor the concept that alherosenesis and occlusive thromlxnis complicating intimat disease re both related to  common coagulative dislurf.ance. A frxal hns of the normal acid mucopolysacchatide determined anlicoaRulant finq,crties of the intima, which it produced by the atherosckrotic process, complements the action of systemic influences in facilitating IhromMNic comfdi( atinns. larcalization of plp ues, at Ieast Ihose formed by IhromMNic (klx/srt., is dependent u/xtn the hydraulks of hhxxl flow. IlcnwrrhaRe from ttrm wnikd inlimal eapiilarics aphean to be an early event in aherr.RrrKSis, lusl as lheromalous uiceration, entbrlism, aneurysm and cakilicatir,n alqx ar. Inr various remons, to be dependent ulxxt the growth and earnt ut athr r(r..le- rotic ptaques Ihfirr 1fr.nrorz N.Nnnal Ikart Inslihrtc "1-IItRINOl1'II(' A("IIVIIY //1 IIIt: . UNIH111II:I IItM" Ry Inkar) I ujinami, MI), anJ Ira (:orc M11, tlrlr;rrtmcnl yd ('ath(rLrRy. Iln vcr%rty ?.1 Flocpital, Boston University Medical Center, Massachusetts Japanese ('i.- culannnlournol )1/2:267-27), February 1967. ((;rantee: (:rae) Chemical and histological rnethods were used to study the fibrinolylic activity of the endothelium of blood vessels in guinea piRs, rals and rabbits Fihrinolytic activity was demonstrated in rats and guinea pigs but not in the rabhit, which is the most susceptibk animal to eaperimental atherosclennis. The observed lytic activity might have been due to plasmin aclivator (rum the vessels, since the endotheliurrt did not show anr aclivity wilh heated fibrin. Activity was weak in the I+roaimal .rxta (which is the prevalent area frx atherosclerosis in roaknts), and became proltressively Stronger down the length of the arxta 'Ihe strongest activity was observed in the inferiur vena cava 'ihese 6ndinRs suggest that fibrinolylic activity of the enduthehum may be one of the Important intrinsic faclcxa in alherrrytenesis. /)tlker gr.nterr National Fleart Institute. "INFIIfi1TION OF DIETARY AT1i'P-ROSCLFROSIS IN RAIIOITS BY NORETNYNOI)RFL." By Ita Gore, Y. Iwanaga and Harcl Gore, Bostnn University Medical C'enter. loun.al of ArAerotclrrozif Rerrarrh 7: J61-J66, 1967. Norethynodrel administered to rabbits reduces the athcrnRenicity of a cholesterol diet in part through its eRect on serum cholesterol I here is n increase of the aortic acid mucopolysaccharides of the treated animals, an observation which contradicts the thcory that such accumulations predis- pose to the occurrence and kxalizalion of lipid deposits. Other Rr.ntort National Fleart Institute. "AN UNUSUAL VFNOCONSTRICTION INDU('FI) IiY ACI:hYI,- CHOLINE." By A. 1. Rice and 1. P. Lon6, PhD. lkpartment of F'harma- colo6y. College of Medicine, ltniversit~ of lowa, Iowa ('ity. 7 hr Inurnal of 1'harmaolr.gy and F-~rptrinKnrol Thtraprurict I51/):42)-42Y, March 1966. ( Grantee : I .on` ) "LOCALIZATION OF VFNO('ONSTRICTOR RFSPONSFS " hy A. 1. Rice, C. R. F.eeson and 1. P. Long, Phl), Ihpartments of PharmacoluRy'n'1 Anatomy, ('o1kRe of Medicine, University of lowa, Iowa ('ity 7hr lournal of Phannocnlngy and Erprrimrnral Thrrapewicr I54/1:S19-S45, Ikccm- ber 1966. ((kantee: lAinR) Fsperinxntal ubservalkro of n unusual drug induced ven(.coostrie litxt, made whik studying the nteehanism of vencx:onstriclion InrwhKrd by aeetykholine (A('h), stimulated an invesliRatirrn of the site of thcsr vcnrr eons.rklor resfatnses lklails of these studies uf the mcctunisrn of vrnrcon striction are given in the present papers In esperinxms designed to study the In vivo eflect of /5( Tr (,n thc acccs urry, cerhalic vein of the d(rR, it was noted thst injccti(tns rrf MRh drnrs (,/ A(?r dtreclly inlu Ihr rerfu.ed vein prtxluceJ  nurked risc rn /-rrfumon pressure. The site of this A( h induced vcn(rconsuicti(m was I(Kalircd at 25 J

C) f5r1 :z .~ the reRion of venous bifurcatir.ns Several eitl+erimcnls suRRcatrd Ihal the vennconstriction did not result front a compcnsalnry rc11cit 1 hr prccan resfonse to A('h was blocked by auopine and hhcnlnlaminc and if was antaRnnired by rcurpinc (iuanelhiclirx, hcsamcthr+nium or chrrrnre syml.a- thectomy did not aflecl the resronse I he potenhaurrn of the Pressor reshrrnce by coc'aine and dircct assay of the venous hlrxxl on the chick cccum help support the conclusion that the fxessor resPrrnu is mediated by ^ relcase of catccholamines from eslraneural atores. Further investigation of this original observatirrn was carried out by correlative tests of the responses of four veins in the dog to several vaso constrictor stimuli lhe aRents used includcd nicotine, acetylchrrlinc, nnre- pinephrine and srmpalhetic nerve stimulation Nicutine did not pioduce venodmslriclion in any of the pre srations. I.crcaliycd reslxmses were in- duced by scetylcM,line, ncwepinesrine and vasrxonstriclor nerve stimu- lalion In the accesuxy ctf+halic and latcral saphemrus veins IlistolnRic eaaminatinn of these regions showed an area that contained valves and was richly invested with smcxrh muscle. Valves were present also in the creternal iliac and the spknic - the non-resclivc veins; however, these veins lacked ^ny appreciahk amount of snxxilh muscle fibers in the tunica media It would aMxar. Ihen, that vcnncnnstriction in Ihcse veins involved Incalired areas ccx+taininR valves and rich in smooth muscle OtArr Rranlnr: American Medical AS«sciatinn -- Fducatirrn and Reuarch Foundation "Slllhlf:S ON Illfi AltRl( 111 nR SIIM111 AI1N(; A('1I(1N OF NI('OI INF " Ily ) I' I unR. I'hls. end IG ( irr-%%, I>, h.utunrnt if I'h.uma- eoloRy, College of Medicine. lhuvcrcrty if tnwa, 1r,wa ( rty .4n hr.•n rnrrr- nofionofrr de phurnvandvnomrr rr di rhrrarrr Ihl 1 111 17, Mry IVhh ((irantee: I.onR) lhis erperinxnt was undertaken to study The mechaniam by which nicotine produces an increase in aurrcular rate and force of contraction In one phase of the eRperiment, ixrlated cat auricks were susf,enrkd in Locke-RinRer's solution, allowed to stahilite for at kast 15 minutes, and then wbjccled either to variation of the pll o( the medium or to vagal nerve rlimulalion. In another phase of the eRperirnenl, hemicholinium was admin- istered intravenously to 1) cats, and auricular activity was compared in cats suhjeeted to a) the action of hemicholinium, b) vaRid nerve stimulatiun, or c) the combined sction of hemichnlinium and vagal nerve stimulation Data prestnted In this paper supfxxts the fulhrwinR ohscrvaturns 1. the stimulating actirrn of nicotine is present at plf's of R I arid 7 4 1 he stimulatinR aclinn appears to he more marked in a more alkaline nrcdrum but this was accompanied by an ahered restinR auricular rate. 2. VaRsl nerve stimulation with the electrodes placed distally on the nerve in the iarleted cat auricle prrparatinn rrrxluced significant increase in the suricular ratr hnt not a sir.mhcant intrease in the force of eontraction 26 3 When hemicholinium was administered to cats in vivn and accom f+anied with right vagal nerve slimulation. the auricular slimulalinR actiuns of nicotine in the isolated auricular preparation was siRnificantly antaRonired 1 he evidence presented suggests nicotine acts on the Parasyrnrathetic nerves within the auricks and directly or indirectly produces release of norepinc phrine from the sympathetic nerve terminals. (RRrr Rrentnr: American Medical Association - I'ducation and Research houndation. "(Y)MPARATIVF Sllll)IFS OF ATRIAI- RF?SPONSIS FO1.1.(-W- IN(i NI('UfINF AND TRANSAlR1AL SIlMl/1.All(1N." fly F(; ('rruss, T S. Whitacre and J. P. InnR, Phl), (kparlmcnt of PharmacrrluRy. University of Iowa ('ollc6e of Medicinc, lowa ('ity. Archivrs Inrrrna-irrnnln de I'hornrocadVnamir rt de Thlrapir 166l2:273-21110, April 1967 ((:ranlec l.onR ) Atrial reactivity to nicotine and Iransatrial stimulation was evaluated in eight species (cals, dcW, (roRs. Ruirxa prRs, lurtks, chickens, rats and rabbits). Wide species variatinns were olnerved following ealxtswe to either nicotine or Iransatrial stimulation. Only the cat and rabbit rknx,n slrated both positive and negative chronolr( {+rc and inotropic reslxrnscs to nicotine. lhe cat, alone, demonstrated hiphasic resfxrnses to transatnal stimulation. 1-itllc, if any, correlation was noted in reslxmsivcncss whcn comparinR nicotine and transatrial stimulation. lbe great spccies variation recorded here sugifest that care musl be observed in evaluating the activity of compounds on isolalcd atria Other Rrr.ntorr Amcrican Medical Asurciation - Fducaliun and Rcscarch Foundalion. I "7IiF IIF.MOf)YNAMIC CONSFOl1(iN('FS OF ARRIIY f1IM1AS " Hy Flenry 1). Mcinlosh and James J. Morris, Jr., ('ardiovascular I aMaatmy, 1)uke University Medical (enler, Durham, N('. PruRrrrr in ('ardirrvar, ular f)irrasr R/4:)10-)67. January 1966. ((irantce: McIntosh) The rate of an arrhylhmia regardless of the type can he rrf siRnificance at either erttrrrne of the rate scale 1 he relation of atrial systole to vcnrricutar systole tktcrmines if the normal alrial transport function will tx• Ivcacnt as wcll as determininR the efficiency of atrioventricular valvr chnurr I he virr of migin and tylvc of cundur lion of The pacing stinwlus ate imlwrrt.rnr rlctrr minants of the eflecliverxss of venlricular systok ^nd atru,vcnlnruLv valvr cnrwlretency. '1 he patholoRic state of the heart as a pump ckterminrs how cflrctivrly and how long the ^dverse eRecls of ^rrhythmias may be trderatcd I tre intcRrily uf the vasonxNor cnnlrol mechanism serves as,hc final aiu- If aJfuvt mcnt to maintain adrquate perfusion of the vital center of the tural ouRaimm Associated tliaeases delermine how well a eomprnmiard circulation rn:ry be tnkralcd Ulhcr farturs inllucncc each of the alxwc mcntnrncd paramctrrs 27

1 hr final hemtxlynamic e/iect of the arrhythmia, Iherehnc. ArlrcnJk tin the summatiun of the eRecls n/ numcrnm chinycs of vatymr rnywut.rntc (lth.r Rrenrnr.: Natinnal FBcart Institutc ( I). John A. 1lartlrrrd I rrunrli lion, and the I ife Insurance Medical Rccearch I und "r:VFT .(-rS OF IIYPfRDARI(' nXYGI:NA 11ON ON CORONARY ARtURY (K'('LI/SION IN PI(iS." By Robert 11 Peler, MI), Ronald W Rau, (1S1?R, Rohert F. Whakn, M[), Mark 1. I ntman, MI) anJ Ilcnry 1) Mclntosh, MI), hurham, NC. C-rrru/o(irrn Rrvor,h IR,'I R9 96, lanuary 1966 ((iranlee M(intnsh) Tn evaluate mo(e precisely the possibk prntective effect of hypcrhatic osyRenalion in eaperitnental myncatdial Inf.rction, Rradual cn•cluuun of a coronary artery was produced in the piR Ameroid constrictors tksiRncd tn produce compkte occlusicm within 4R hours were placed on the left anlerinr dexendinR coronary artery of 24 young farm piRs Of these, 12 wcre placed In a hypcrbaric chamber at 1 25 atmospheres absolule and al'owed to breathe I(M)'76 oxyRen for  ma>;imum of )2 hcwrs For control studres 12 other rigs were handkd in a similar manner outside the chamber while breathing air at normal atmnspheric pressure Pigs treated with hyperharic nxyRenalinn outlived the untrealed piRs. Palhnlrrsical and hishuhemical studres of the hearls revealed that piRs treated with hypcrharic u.yRenathnn had a hiRh incidence of tnytrcatdral infarction, whereas only Iwn prRs in thc untrealcJ prnrp aht.wed iny evrdcnce of myncardial damage ihesc hndrnRc .uy'cst that nwxkrate hut )rrrrlunRed hyperbaric nryRenatian may IrnRthtn h/e rlurrnR and after trunnity trcclu sinn lhis prnlrrnRatu.n rd life may Lermrt Ihc dc.clr,l+rncnt rrf p:,th(JtrRrc'ally detectable myocardial infuctinns Other Rr.ntor.: U S. Puhlic Health Servicc, Nnrth ('aralin:t Ilcart Aaarci dinn, American Ifeart ASHK/aUnn, and l.ifc IrKurancc Mcnccil Rctcarch Fund. "POSIPERICARI)IOTOMY SYNDRUMF AS A ('OMPLICAIION 01: PFRCll1ANEOUS LE:Ff VIiNIRI('111.AR PI/N('1l1Rli." Dy Robert !1. Peter. MI), Robert F. Whakn, M(), Fdward S. Orgain, MI), and Iknry 1). Mclntosh, MI), Cardiovascular L ahnralnry, 1)cparlmcnl nf Medicine, 1)uke University Medical Center. Uurham, N(' Anvriron lnrumd t,/ ( nrdr- oGrRy 17/) R(i-9(), January 1966. (Grantee' Mclntosh) 1 wo caus of pt»Iperkardittlnmy syndrome fulluwinR pcr(ulancuus k/l venlricular puncture have been reported 11uth had symlrlnms irkntit a with the nther "c'atditNnmy" syndrrnucs and reafwrnJed prnmlNly trr adrennl slernld therapy. Ihe fact that one nf Ihe patiems had a acct,ncl clriatMk of pericarditis four weeks following open heart stnRery may nrcan that thc devehrprrsenl (rf Ihis syndrnme following k/t ventri(ular Irunclutc may lre assnciated with the develtrpnxnt of the (.rttllrcricardirrlrrmy ayndrrrmc (nllrrw- inR c11rthar 1rnRrry llthir /rwnf.v ~J.rurul IIr.r1 In~lrlulr 1! 1 "111F; IIFiMO1)YNAMIC FFEFCfS OF THE W IN1P('II(1N OF ('ON- 'IRASf M11)II1M (IS(1PAQllF:)." Dy Henry Mclnt.osh, MU, Victor . Hurst, MI), Iloward I(. lhompson, lr , MU,Ulamcs 1 Morris, lr , MU, and Robert F:. Whalen, MI), Cardiovascular l.ahcsralnry, Ikparlment of Mcdicine. Duke lJniversity Medical ('enter, hurham, Nurth ('aruhna ^nRrrrlrrRy IR/5:)1)6-)15, May 1967, (Grantee: McIntosh) h.ninR studies evaluating the hemodynamic changes (ulluwinR the intravascular injection of a new contrast aRent, sodium and N-mclhylRluca mine me/ri?nate ( Isnpaque ), it was found that within seconds after inlectiun of the contrast medium into the heart and great vessels there was a prnmhl decrease of hcmatocrit, due to Ihe loss of red cell water and a(educrinn of red cell volume Observalions br light microscopy of the eflnl of cuntrasl medium on ted cells indicated Ihat these changes occurred rapidly enough to he compkted dutinR the initial transit of the cont.ast-medium hlocKl misture. lhese agents alter the permeability of the cell membrane to patas- sium. Such changes in pcrmeability were not produced by 5'9o sodium chloride, despite a similar rapid reduction of cell volume. It is suggeated that similar changes may occur in endolhelial cells It is possible that the eftlu>t of ions from these cells may have an effect on the downstream "receptor" cells and be responsible for certain of the herrNr dynamic changes observed following the injection of contrast medium. (hh.r Rranrnr.: National Fleart Institute (2), the John A Hartfurd Foundation, and the Winthrop Lahoralotics. Other paPcrs published by [h. McIntosh and aasnciatea since the 1965-66 RryKxl of the Scientific Directnr, with credit for sulyytrl by Ihe ('ouncil for Tohacco Research - U S A., follow Other Rranluts are rwled between parenlheses. "INFIINI)IH(ILAR P111.MONICSTENOSIS hIII? 10 A 1TRI('ARUTAI DANI)." American Jaurnal of Cor4irrlaRy 16/2:21r2-266, AuRust 1965 (NIII) "TIIF. ASS(X'IATION OF N(X'TURNAI. ANGINA PE(-1ORIS W1111 I1RF.AMIN(i." Annoh of Internal Afrdicinr 61/ 6: 1114t/ 11/46, 1)ecernher 1961 (NIII(2), AIIA) "FI F('I RI(' SI I(X'K IIA7ARDS IN RADIOI (x iY 1)1 1'AR I MI N I S" Amrrir on Irnnnrrl rr/ RrrrnlRrrtrrMRy 95/4 976 9110. 1)ct cmlw r 1')A1 ( NI11, N('lIA ) I "1111 AIFRAI I IIN('II(/NAI.SIIIIAOR11('S11 Nt/SISIN 1111 Al 1 I ( aAIOR " l rnn tur Irnnt n/ rlhr Anvrrr rtn ( Irnn .rl nn.l ( Irrrr.rl.rL rRrr .d ,1 r r.r rionnn7R 119 1)R, 1966 (N111, )AtIF) "111F. MANA(7f'Mf_N1' OF SIIPRAVFNIRI('UT AR nRO(II\ 111 MIAS° Mrdrnnl .Innnlt trf Ilrr 1)rvrirl rr/ (nlumM1r,r 1% S2% S2), 5Jh 1966 (NIII, JAlll , I IMRF ) 29

III~M()1)1'NAMI(' RI'Sf'(1NCI C I()I 111 WI I I111m I11 (N/11 " 1 II,nJ Inlcrn:ninnal ( nnlrrrncc rm Ilyla•th:n,c M,Jn rnr. I)mlram N(, I'rf.C ) Nohnndl Rr,rnr, Ir (.rnnr rl I'uhhr rur..n 01404 1'1f.1. ( NI IA( )), A 1IA, N( IIA, I IMR1 ) "('INI ANG I(K'ARI)I(1(;RAI'IIY " 7irr /l,v,rr I'rn,rrrr nl Afr.brinr V 11, I')(r(r "IIIIi PROIf('IIVF FFFFCT OF ilYPFRIIARI(' OK1'(:1 NnII()N IN ('FRFHRAI. ANO)(IA" Arrhivrt of Nru.oh-Rv 14 I 15 2f). 1:mu:vy 1966 ( PItS( 1), N( l(A, AFIA / °FFFF'(-TS Or' 1(YPFRIIARI(' OXYGFNAIION ON VK( I S; I A( IA1V I'ROU(/('llON IN I XI R( ISIN(; I)(K;S" Arnrrirrrn Jnurnnl rrf I'hy+rnlnRy 21(1/1 471 477, March 1966 (NHI(1). N( IIA, AIIA) "RI I.ATIONSIIIP OF FIRRII (.AIURY WAVVS ANI) P WA'JI-S IN 11(1. FI F:(-IR(X'ARI)IO<iRAM "l r.rnlonnn 11'4 S99 MMr, Arrrl IV(,(. (NFII, N('IIA, I.IMRF) "TI(F PRF('(1R1)IAL IIONK ".Inrrarurr /rrurnol rrf ( mdud,rRv 17 . 4 5//9-515, April 1)(,6 (PIIS121. AIIA. N( I(A) "ATRAIIMAI I(' RIGII I VI-Nf 41( 1/1 AR ANf(IRYSM RI P(1R1 OF A('AS1: "( irculaliun 14 7 121 126. )nly IV(,h INIII( 1). 1A111 , N( IIA/ "F.LFC1 RI('AI. ('ONVI:RSI()N ()1 A I RIAL I IIIRII I A I IUN IMMF- 7) I)IATI: ANl) L.ON(i-11-RM RI S(II.IS ANI1 SI L/ ( II(/N (1F 1'A- '1 IVN I S" rl nnolt of Inrrrnn/ Mrdr, rnr hS 2 216 211, Aufu.t I'/A(, (NIII(2), NCIIA) "'i f+~ ..+1. "VI?NiRI('UI.AR VUL(IMF SIIIhIFS IN A PA1lFNi WI I11 IfYP1:R- 7 ROPIII(' S( /IlA( )R 11(' S I FN( )SIS "( irr ulannn 14 i 4: 5 79 SN4, ( klr+lrcr 1966 (NIFI, AITA, NCIIA) "A ('LINICAL AND iIFMOhYNAMIC EVAI.(IATION O1- A NFW (Y)NiRASf MFI)IIIM: ISOPAU(1F. 440 (SO1)IIIM ANI) N MF.I IIYI - .}~... GI.II('AMINii MF T R17OA 1 I/." An+rrir on lr,rr.nnf rrf RnrnrRrn,dr'Ry 0 1(X//2:4(tR 471., lunc 1967 (NIII, lAllV) "A(;F. AN(1 I)ISI?ASFi-RFI.AII:1) AI.IFRAIIONS IN 1•11fRINtH;1-N ftt(7LO11111 IN (FIIIRINUI.Y I I(') III IIAVIOR " Ify Krnncth M m ~ M,xcr, MI), and (;rurRe ('. Ilajjar, M1), 1)c(~artmrnt of Mccficinc, (;rurRc- luwn l/nivrrsity Mcdical Schrwd and Ihc I~nyyrnc Rctcarch I atH,raHny, 1) (' (;rncral IlnsPhal, WashinRton, 1) (' Ihr .Omrriran lrrurnnl rf rhr ~ t9 Afn/rru/ "irrrn,rr 251/S S16 544, May 1906 ((irantce: MnscrI ~ Studirs,d IA.r,rw.Ren crrnccntr.tum .nd fihrinnlyuc activiiy (ruRlnhulin w +. ~ ,r. lytic r,n,r ) wrrr r arrr,l r-ul tn J,Ilrrrnl I'aurnt Rr,n,l'c If waa caahl,thcd ~ til J © C III that thcrc it n,r cnrrelatiun hetwcen lihrinosen cnnccnU:duwn anJ hhrma,lync activity Attempts to dcfinc the day-to-day reproducihility of (ihrinulytic activily and fihrinuRcn mcasurcrrxnts indicated that fihrinuRcn (evrls rcmain y,nte stahle and that cnrresl>,rndinR meaturct of lihrinolyiic activity arc a,lryuatrly rehrnducihlc, althnuRh hhrinolylic aclivity, in gcncral, increascs dunaR thr I+crirKllxtween V INI a m and 2.(M) p m. Comparisrtn of lihrirndylic Ir•havuu in Rrnups of young, nld and intermediate age rnrrmajs, cinholics and dia hctics ditchncd thal tuch activity was tiRni/rcanlJy greater in Ihc cirrh,rtict, nNtst labile in the young normals FibrinoRen levels in Ihc dialretics wrre consislenlly higher than lhose in the (Nher Rroups, while old nrnmals had hiRher levels than young rw,rmals. 'Ihe fihrirNVRen and frhrinolytic behavior observrd in Ihetc .tudics may have inq+(icationt with respect lu thromlxrathcro6cnetis and the physiuluRy of /ihrinolysit which mcrit further investiRation. (/tA.r Rrnntor.: -1 he Natiopal Institule; of ileallh and 'ihe Office of Naval Research. "TFIF?RAPY OF ATRIOVFNTRICULAR NODA1. fA('IIY('ARI)IA " Ry l.ouis A. Srs1oR, MI), and William S. Frankel, MI), ('ardiovascular Uivi sion, 1)cpartmenl of Medicine, Temple Universily Medical SifirKd 1'hda- rklphis, Pennsylvania. From "Mechanisms and lhcrapy of ('ardiac Anhy- thmias," 14th Ifahnemann Symposium, Philadclphia, April 2(r 29, 19hS Puhlithed by Crune & Stratton, 1966. ((Iranlee: Sololl) Atrinventricular nodal lachycsrdits are usually separated into parn.ys- mal and nnn-paro>tysmal types. uistinction of these two types is worthwhile txcause the first is usually benign and easily reca.Rnired, while the seconJ is usually serious and hard to diagnose on clinical Rrounds Ihcrapy nl the parotysmal type is best accomplithed by mechanical measures whic h increne vaRal tone, sedalion or diRilaliratinn. bisital4aticm is also indicated for non paroxysmal arrhylhmias e><cepl when they occur in the diRitalvrd patient In lhis case, Ihc specific treatmcnt is discontinuance of drFilalie trlus the rotsihle use of anli-arrhythmia dnrRs such as pryx-aincamiJc ru .IurniJinc sulfate. (hlirr Rrnntnr.: I/.S Public Nealth Service and the Arlrne Ihcklrr (;rass Foundation, Ilrart Asa+ciation of Snutheaslcrn Pemnylvania "RI?I.AIH1NS1111' III?IWI'FN (:111('OSI? ANI) FAI IY A( II) IN MY(K'ARI)IAt. INVAR('11ON." Ily Lrruis A tir,lull, K11), rnd /lrrnr Schwar'r, MI), 1'h/), I)ivisiun of ('ardiohrRy, lcmhk Ilmver.ny Mrd,ral ('enler, Philadrll+hia, ('rnnsylvania l.onrre 1'44V 452, 1 cbruary lh, Ivnh ((Jrantce: Srrlull ) l he Rlueox and fatty acid resfainses to Rluco.c hradinR were Jrrrr mined in 15 Patients who were eonvrlrscinR frnm myrKardial infarcLi,rn, in 15 trealment-rk(~cn,knt dialxtics, nd in I S patienrt rrn healthy v,duntrrrs who had no evirkncc of hcart disca%e or of Jiatx•tcs 11

All ischemic ratitnls satisfitd the criteria rd chemical dialKles Fivc had :r falty acid res(x,nsc to Rlucnac similar In, hut actually Frcatcr than, the ntxmal and Itl had a fally acid respnnce simdar to the dialx•tics lhtsc 1(/ Palients were also charac'ICr'vtd by a diminishcd inhibition of slcaric acid rekasc provuked by Rlucnse Furthermtirc, all coronary palicnls. the second mup more than tlu first, had a diminishcd capacity tu liberate linn leic acit~on demand. Ortirr Rrenror r l I S. Public Ilcalth Service. "ON MFASl1RIN(i I.FFT VENTRICl1LAR VOI.UMIi" Hy Itruis A. SnhoR, MI/ 1)crarlmcnt of Mrdicine, t)ivision of ('ardiohrRy. Irmple lIni versily Mediral Schcxil, Philatklphia, Pennsylvania llrr Amr.n an h,urnal rr/ ('rndirrfnRy I R/ I 2 S, July 1966 lhe institution of a satislactory technic of tklcrmininR left ventricular volume in man is t.trenxly imfusrtant, for without it orx cannot tktcrmine thc over all (Krwer snd performance of the heart muxlc. Such a definitive technic, howcver, has rxA been rkvehq.rd as yet In Ihis review of the past M) years' eflnrts to measure the volume of the heart as  whole and of llx left vcnlrick, many technics are Ji.cusad. Methods cc.nsidtrcd include rrantRernrhrRy; anRi.carJioRra(+hy, direct vnlumciric mcaiuremenl by indicalws. Ihe cnmhinatit.n tit radirrpryuc dilu- litm curves snd anRinRraphy, snd the use af chanRc in a diameter nr circum- ferencc as an indcR nf change in volume I his la.t mclhtrl apl,•ars Lrnmis- inR but it rrmarni fnr the fulure tit drtrrmint if such fnrmulia are rlyplicahlc to the mormal human hcart and alan to clinical cardiac dnnrtkrs Othrr Rrenter: ll S Public Ilcalth Service. "CAROIAC Ol/IP1/T-, FIL.(N)O PRhSSIIRF ANI) FRFf. FA1-IY ACII) RFSPONSES TO SMOKIN(i IN l 111: NONIIASAL S 1 A 1 F" fly William S. (=rankl, MO, MS. Ronald hriedman, MI), and l.ouis A Schrfl, MI), tkrartrrxnl of ('ardioloRy and the ('ardiovascular Research ('rntcr, I cmlrle Unrversity Medical ('enter, Philacklphia, Pennsylvania. Amr.uun lrrurnnl of rhr Mrdn al St irrxrr 2 S2 / I:)9-44, July 1966. ((7rantoc : Stdu/l ) Other studica have shown cardiac output, cardiac inder, sunle volume and (ree fatty acids to rise after smukinR in the reslinR, hasal sfalr, hul Ihc /xcsent studies were matk in individuals in a nnn hasal state to dctcrmine the validity tit amtikcrs' claims that temions arc rascd hy InwrlinR SiR healthy younR hshitual SnNflcrs, all famthar wilh the inrravascular procedures used, were cmphryed in these tests After riRhl hcart cathrtcrira lion and hrachisl arterial purclure, each suhject smt+kcd 2 standarJ s'veA filter liP ciRarcttrs within 10 minutcs ('ardiac anJ circulatnry paramelrrs were mtasured l.efort snxikinR, durinR smtikinR, anJ I S, lU, /.l/, and 91) min utrs thereafter l'srtlinc ntnpul antl frrr fatty acirls were elrvatt'rl laim tti smokinR In nr,nr id Ihr ~ul,lrrts wat thrrr a ~iPnihtant huthrr ri+c in cardiac rnrtl.ut or I free fatty acids after smoking (except for a hnrdcrline sipnilicant rise in carJiac indc immcdiatcly aflcr complelinn of smoking ) 1 Irc cr hndmRs cast uimc Jrwht on whcthcr tohacco actually escrls any siRnitrc:rnt cflccl on cardiac nutput, stroke volume or hlaxl(rcc fatty aciJs in (hc non basal statt Orhrr Rrenrar: ll. S. Public Flcalth Service. "('IR('IILA'TY)RY VALIIES ANI) NI?MOI.YSIS 1)l1RING PVNIO RARIIIIAI. 1)IA1.-URIi1HANIi ANESIIIf.SIA IN INK7S 1'R1 M11)I ('AII U WIIFI MORI'111N1:." liy C. A. Papacostas, 1. Wciss anrl 1. A Solofl, I)epartmtnts of PharmaculnRy and ('ardioluRy, Icmple Ilniversily Medical ('enter, 1'hilarklphia, Pennsylvania. l.ifr .Scurnr rr 6111 1 1195 - 1199, June 1967 ((7ranlce: Scdufl) l hirty four adult rrxtngrel dogs were given morphine sul/ate su1K utanr- oucly anJ 1(1 minutes later were anesthct'vcd with a miraturc tit /Kntub:uhital and dial urethane From these doRs, control valucs were ubt:rinrd hir nxan arterial Pressurc, heart ratc, cardiac output, stroke vnlumc anJ Iwal IK•ri. pheral resistance. All vcnous blood samples taken in this scrirs showed evidence of nxxlcrate to marked htmolysis. Mechanical fathrrs did ntrt ap pear to he resPtinsihle and hcrrxrlysis apparently resulted frum the usc uf this often employed special anesthetic mi><ture. Orh.r Rrantor.: 11.S. Public Ilcalth Service anJ thc National Ilcart Institute. 111. CnrcinoRentlossiu Stl.diPa "('AR('IN(xiFNIC A(TIVITY OF ISONIATIt)t?, IIYI)RA7.IN1? ANI) IIYURA7.INF. 11(:RIVAIIVt=S." tly ('csare Iliancifitni, MI), Urvisinn of ('ancer Research, l)niversity of Pcrugia, Italy. Annari drrla ra,oha rli M.Jr cina rChirurRia drlla Univrr+ita drRli ,Srudr di l'rruRra 57/ 1 152-159, March 1966. "'iltf RI?LATION OF ISONIAT.11) (INII) ANI) A1 1.11:1) ( UM POIINUS IO ('ARCIN(X:TiNUSIS IN SUMI? SI'U('II?S OF SMA11. I.AIIORAIURY ANIMAIS: A RI-.VIIiW." fly Cesare Iliancdwri, M11. antl I ut'in Srvrri. MI), 1)ivisinn n/ ('ancer Rrsrarch, (lrrivrrsrty r I Pnu~i.t, Italy. Ihrnth lnu.nal of ('anrrr 211/):52R 51111. Srplcrnher 1966 "ISt)NIA711) AN11 AI I.IFI) ('OMPOI/Nl)S AS RF1 A 11 1) 10 1 l/N(i 111M(/RS IN ANIMAI.S" fly I ucro Stvcri. MI), snd ('csarr Ri.tn rh"rr MI). Uiviiirrn of ('anccr Researth, llniversity of I'cnrRra. I/.ily (:.-rh 10/ 4: 167 1R2, I)ccemher 1966. lhcsc,hrct Palars summarin the present stn,r tit scirntih, Arn,v.IrdRc conccrninR thr ihrssihlc carcinrrRcnic aclivily rrl i.r ni;riiJ I INI11, a rhuR used widcly in thc trt•atment trf tulrcrculusis 11 12

r o, I~nniarid and it1 allies, hydrarinc and other hydrarinc Jrrivitives, havc induced lung and liver tumcas in various cancer caaceptihlc and rraiclint strains nf nvice and rats, thus provinR thcmulves to be very cflcclrve carcinn Rens in ccrtain small laboratnry animals Initial labnratnry demonstrations were mark of the carcinogenic action 44 iaoniarid ( IN1I ), after which studies were instituted to identify the mcla- Milic drrivalivcs f•f INII nd to determine whether INII is carcin<+Rcnic in ilwlf or via its metabolites. INII, itself, hrts been shown to Induce lung tumnrs in "alhino," R111, IfAl.11/c, ('57H1 and CBA mice, and to enhance the development of Htown Pearce tumors and Itachcobronchial papillomas in rabbils. Since mer.bolic breakdown of INII resulls in the production of iami- cotinic acid and hyr)rarine (which in turn is converted to ammonia ), ctperi- mental investirations of hydraiine were underlaken These studies demon- straled the ertectivcness of hydrarinc in the production of tumors of the IunR in RALH/c/(b/Se, RAI 11/c/An/Se, ('HAi( b/Sc mice and ('b 1-on- don rats and tumors of the liver in Cf1A/('b/Sc mice. With the implication of hydrarine as a polential carcinogen in man, efforts were made to determinc the biological characteristics of hydrarine- induced lumors In various etperiments, induction time was determined, dose response was demnnstrated, influence of roule of administration was shown to hc neRliRibk and metaslasis and malignant invasion of vessels by these tumors was ethibiled The effrct of hydrarine sulfate on resistanl %pecies was tested in an eriperinKnt conducted with (Z+/Sc slrain rals, a suain noted for its low incidence of pulmonary tumors Of 32 treated rats, 25% had pulmonary tumors and 21% had adenomalous changes by the end of the etpenmenlal period. Other hydrarine derivatives have been shown to induce tumors of the lung and leukemia in HALH/c/Ct+/Se mice, lumors of the lung and ,eukemia In ('f),Fl mice and tumon of the mammary gland in (hlx.rne Mcndel rats. The summation of these es(+c rinxntal facts plus some disturtinR clin- ka1 nburvations suggest that INI1 and irs allied compounds may he related to the deveMprrrcnt of lung tumors in man. In this connection, other e.peri- menlal observations have introduced the possibility that the hrrrrnones of the adrenal cortes are involved in the origin of lung lumnrs. Other Rranrorr Anna Fulkr Fund, New Ifaven, ('nnnecticut. "(;I'Nl:.fl(' S111DIFS ON TNE f?l 101 (1(iY AN11 MORPIIOI.(XiY OF MAMMARY I IIMORS IN MI('F. " fly Wrlliam S Murray, 'nce 1ack.rrn I aMrratnry, Her N.rlKx, Maine. lournal of rhr National ('on4 .r Irnrrrul• 3M1/2:249 257. Fchruary 1966. Ptpcrimrntal use of hyhridiratinn, one of the more effrctive methods for the aturly (if the mammary lumorigenic cnmplct, is harnltcreJ bv sevcral c0rnlrl,c.rinR fa(ror. 1 hc hrrcrnl slurly dcils wilh two of ,hrsc fa(lrrrs: I) I the control of viral uansmission, and 2) the relationship of etiology to lumor morphology. llsinR mice of the strains C3H/Hel (a slrain highly susccprihlc to mouse mammary tumor virus (M1 V) and known to carry the viral prin- ciple in active form), C3NeH/Fe (a strain highly susceptiblc to M I V but one that has a low mammary tunwsr incidence), and MA/My (a strain highly susceptible to MTV but one which has been observed to have no mammary tumrrrs), four reciprocd crosses were carried out lhc first filial generation femaks of these crosses were then bred and observed until they developed mammary tumor or died. F.aaminalion of the dislribulion and morphokgy of the observed tumori led to the following conclusions: 1) The milk-transported M 1 V slimulates the development of A and B type mammary adcnrxarcinomas in early age and early middle age. 2) The other mammary tumors found - lype C, fibrosarcoma, heman- RirxndrNhelioma, and adenoacaothoma, which characteristically develop in Lte middk age and old age aod are independent of the direction in which reciprocal crosses are made - have a aeparate eliolosy. 3) The parallel between the lirne of occurrence of the late mammary tumors and the time spread of appearance of rumors in other organs suP,gesti a common ctioloRy for all late-appearins lumors. Otflrr Rranrorr National Cancer Institute. "GENETIC STUDIPS OF CARCINOGENESIS IN MI('E." fly William S. Murray, ScD, and Clarenoe C. Lillk, ScD, The lackscxt I atwrratory, liar f larbor, Maine. lournal o/ the Notional Cancer Institute 3R/5:619 656, May 1967. (Grantee: Murray) T1re reactions of physiolo6ks produced by various Rcnomet to the presence or absence of the mamm.ry lumor virus ( M I V) were studied throughout the lifespan of 3,630 F, femak mice. Particular atlenliun was paid to the relationship of age and of reproductive eaperience to the rxcur- rerxe of various types of mammary lumon. l)sins mice of the three aforementioned strains ((',11/11e), (',11rH/I-r, and MA/My) plus ('57H1/6 (a strain highly resistant to, and IKlievcd free of. M 1 V), anJ A/I le (a strain highly susceptible to M I V and one which carries Ihe virus in aclive form), seven reeiprrKal ctosses were carrierl rw 'Ihe first filial generation females of the 14 erosus were hrcd aoJ rhrn obxrvrd until they developed manmury lunMrr or dicd Results showed that there was a great increaae in tumru proJorwrn when M 1 V was inurrduced by the lrmale 7 he re%ulrs al.rt ohrrwrJ , I.rr ly that genetically di0crenl physrnloRies, when suhjecred to M I V.uirnul.uun, developed their tumors over eharacteristic age spreads that cnrrnnh:n.rd rhr 41h through 19th month; those phyainlrrRies which received no M I V ttimu lation devehrped thc great bulk of Ihrir Iumrna at aOcs rrf 211 nurnrhe rrr mruc lherefore, ap,e dittrihulirm of earty turnurs alqrars to dclrcnd un f41I V ,j (D 14 15 r j

i ~r I s ~ .+., ~..r ~ ,., rn .- ~ m Q, ird J e t.~ ttimulatinn and (m mcthrK) of tranamistinn I atc alqpc:rtinp turnnrs :ur indc- rcndcnt n/ these factors. Ccrtain s/*cculatinns and hylMithrtcs arc Incu'ntcd Jcalirnr, with malc trantmissinn (•f the mammary tunxrr virus and rtt rcl:rtinn trr thc nudulrr'cnic virus. ()tt1er Rranrnr: National ('ancer Institute. "INTRINSIC FACTORS OF PULMONARY ('AR('IN(NiI NFSIS U1= Tllli MUUSF: 1?FFECTS OF NliONAfAI- IIIYMF-("IOMY." Hy Rtxlolfn Rihacchi, 1)M, AV, and (iaetann (:iraltb, 1)M, 1)ivition o( ('anccr Rcsearch, llnivcrsity of PeruRia, Italy I avuri d.lflv,rur.r dr nna- Inrnra r itfnLrRia (.arnln><rca drlto (InivrrfTrd drRlr Srudr dr I'nuitro 2lr/ I 1: 127-1)6, 1966. ((iuntee: L. Severl ) In Ihii study of the eRctis of thyrnectomy upon lung tumor development. 204 male and femak BA1.8/c/Cb/Sc mice were divided into three groups. One group was Ihymrctomited at birlh, one "sham nrcratcd" and one kept as a cnntrol All mice, treated anJ untrcated, rcccived a sinRle intral.cri- toneal injcctimon td 9 mg urrthanc at 10 14 days (if aRc Arprrrzimatrty 17 mice from each pnur were then tacrifsccd at St), 70. 91/ or I I11 rliyt after treatment Among the mice sacrificrd at SO d.ys, I11O^;, (if the Ihymccl4rnrin-d mice had multiple IunR tum,rrs, whrIr only r,r, h"- rf thc "shim nlti r.rt,.1" and 64 7'"n of thc cnnUol< <hrr.. iI tutnl.ir I,n,hnp. I hrt rn,u.rl Aill, rcncc rlia- arrcared tatrr, snne atl msrc krllcrl ,r It,, vn I tU ,L,yc h.u1 mnll,l-lr lung tumors Ilnwcver, thr avrrarr nruntrr „/ luny tnrn„rv IMr m,.ucc wet always higher in the thymct tomvcJ rrmnlr thin rn rrthcr Ihc ',h.nn rqK•r:urd" animals or thc crrntrolt The results of this e>t(•crinxnt shaw that nennatal thymcctnmy favors the antet and development of urethane-induced lung lumrrrs Since thyrnec- tomy acls to reduce or inhibit the imrnuno(rrietic capacity (if the mrruse, it is eonsitkred that immumx/erentknce constitutes a new in,rinsic f.rctrrr which. k+nR with Rerxtic, environmental and pnssihle hurmtrnal facttns, infhrcnccs pulmonary tumor development. IV. Srttrl«, at thP Cr'llrtlrrr 1,err'l "PFIOSPIIOI.IPlI) SYNIIIFSIS IN 1111' I.AR(lli P(1I MONARY A1.- V1:OL.AR 11-S RI?I.A 1'1ON lO L.l /N(1 Sl /RFA('1 AN I S" Ily Sue 1luckinRham, MI), 11 (1. llcincmann, MI), Sheldon (- Srrmmcrt, MI), and William F. McNary, Phi). I)rpartmcnls n/ I'rdintrics. Mcdreinr and PathnHoRy, Columhia Oniversity ('olleRe (if l'hysiciant arrd SurRcnnt, and Francis I)elafic/d ifntrilal, New York. N Y., and the 1)chartnrent of Anatnmy, flr+atnn Univertity Sch4wrl of Medicine, Matt. Amerrr an lnurnal rrl I'nrhrb,rv 4R 6 11127 11/4I, lunr 1966 ((;rantcc' S 1luckinpham) lr, . 1 In an attempt to confirm the preferential incorlroralitrn trf acrtatc and pilmitalc into lung kcithin and to ckmtmslrate Ihc hrcah.-aturm (if Ihcse reactions in the large pulmonary alvcolar cellt, the uptakc and dnuihuthrm of lahclcd acetatc and ralrniule into lipid fractions of IunR wcre studied in rahhits, and the cellular kocali»tinn of the synthetic reactirrns was csamincd by means of scrial autoradiographs. Similar studies were carried uut on corresl.nndinR liver tissue for comparison. 7 hrcc groups of three White New Zealand rabbits each were treated respcclively with Iritiatcd sodium acetate (specific activity, 145 nK per mM ), tritrum lahekd palmilate (256 mc per mM) and (rilium Iahekd palmitate ( 21)0 mc per mM ). 1 he animals were sacrificed 15 to 90 minutes after intravenous injrclion and lung and liver specimens were subjrctcd to micra scnpic r.amination, auttxadia6raphy and lipid analysis. Onc half as much palmilate was taken up by lung as by liver (Rrarn (tx Rram ). In lunR, howevcr, palmitate was rapidly and preferentially incorrtr rated into phrnpholipids (>1S% ), mtnt of it (60% ) into lecithin In the liver, the label was equally distributed between the neutral and Irhosphulipid fractions. t.unR tissue per unit weight was twice as active as liver in incur(arrating 'If acetate into lipids Acetate was also metahulired rapidly into phntrhr, lipids in the lung (90%), cspccially into kcilhin (h(1`)'~ ): the liver uulrnd acetate to form varinus lipid components. Within the phnsphatitks of lung, the C,. (palmitalc) fraction accunro- latcd nearly all the label following either acetate or ralmrt:rtc, in the liver phns(rhatirks. both precursors were distributed ur cunvcrtcd into varirrus ratty acids. Autoradingraphic sludics of lung tissue Irom trcaled rahhitt shuwrJ silver Rranulet, indicating radioactivity, in the cytoplasm of the large alver,lar crlls by )t) minutes after injeetion. No other lissuc ekments, eaccht (ur an oecasional alveolar macrorhaRe, preuntetl evirknce of rarlinictive lahrl ing I hete silvcr grains were found bctwcen, hut nul intidc ol. Ihc tharai ter istic eylorlasmic inclusions of these cells. 'Ihesr findings are discussed with reference tr, the frrrmitirrn and turn over of lung surfacunt phospholipids. I)rhrr Rrantor: United States Public Health Service. "/'lll M(1NAR1' AL.VI'OIAR LFSIONS IN VA(i()1'()MI/1 I) RAIS" Ny Victor 1: (lnhknhrrR, MI), Suc lluckinrharn, M11, and ShrlJnn (' S.rro mcrs, MI), 1)r(rartrncnts of 1'alhuloRy anrl 1'cdiari, t, ('nlumhre IInrvcrarty ('ollrRe of rhyticians anJ Surgcont, and francis (h•L.JocId Ilrnhnal, New York, New Ynrk /oh.rrarury lnrrttrRorirrn 16/ti 691 IUt, M.ry /9hl .(Grantce: DuckinRham) I.unRt of rats wcrr studicd hy IiPht and elcctrrrn micrrracrqry at I tr) h hnurs alter vaRutr,my I he sahent hndinRt in thc rutrnunary alvrr,h ul Ihrsr 17

rats were an early ( I hnur ) and proRressive rlrcrcisc in the rKnuuphiha of the s/.ccial cyloPlasmic incluai,rns and duninishcd numtrn of nwluvcsicular Iwwlics in the large alveolar (c1ls Incrcascd caall.try cndtrthclr.,l i•rnra-yhras was also found I hour PodvaRolomy At later intervals the o%mrnphrGc inclu. sions were replaced by vacuoks, with increased intraccllular Ilui,l accumn• latinn and hluntcd microvilli I ale tkvclopmcnt (if massivc atelcctasis in thc IunRs corncidcd with the finding of abnormal uuface tcnsinn chalactcrislics in -kome lung e.tracts. The relationship of Ihe ullraslruclural changes to the frnmalion of surfactants is considered. Other grantor: ll.S. Public Heahh Service (2). "Ul1AN1IfAlIVE EIISTO('l1EMISTRY OF RAT Mll(-USA: I.AC- TAIF ANI) MALATE: 1)F11Y1)R(X;FNASI:.S" Ry Stanley !. (krson, I)1)S, 1'hl), lulia Mcyer. Ph11, and Ikrmann Matlcnheimcr, MI), l1e- partnscnt of Oral Patlsr+k.6y, l)niversity of Illinois ('a1kRe of 1>cntistry; 1)rparrment of Biochcmistry, l/niver.ity of Illinois ('o1kRe of Medicine, and Ikp artrsxnls of Pica•hemistry and Mcdicirx, Preshyterian•SI. Luke's Ilnspital,(lucaRrs Thrlournolo/Invrrrigarivrf)nntornlrrRy17i6 526-5J2, Ikcember 1966 ((;rantee: Meyer) Ultramicrcxhemical metMnls were used to assay lactate rkhydrnRenase (1.i)FI) and malate dchydroRenav (MI)1I) activities in thc histnlnRically dcrmsnsttahk laycrs of kcraunirinR oral rpnhcl/um SPecinxns of palatine and huccal mtKrr•a from young adult mate Simonsen alhino rats were frurcn in hqurd nltuoRcn, dried and dissected (usually into sis layers) ('omparison of cn>•ymc activitics in the sic successive cpilhelial layers showed that LI)II and MUII activity in both Ihe palatine arrd the huccal epithelium decreased between the basal and horny layers. AlthouRh MhFI activity was consistently higher than LI)F1 activity in honxdoRous layers and in the whole cellular layers. MDII activity tkcreased more rapidly with outward progression than LUFI activity, thus rcducinR the discrepancy between them. ('omParisons of palate and check c(+ithclium showed similar kvcls of enryme activity in homologous layers and in the whole cellular laycrs, hut diflertnces were noted in the rates nf peripheral decrease in the activity uf both cn?ymes 1)iRrtencrs in entlymc activity couhl I.e ctlrrclalcd with dltlrrcnccs in the diNrihuur.n of dividing cclls and of Urnrdihril. Ihhrr Rrantorr lI S Public Ileatth Scrvicc "NIl('LFO1 AR'('APS' INI)ll('1:1) IIY FI.YIN(; SPOf l/l I RAVIO1 liI Nll('I FAR IRRAI)IAIIt1N " Ily P(1'11 Mr.ntrumcry, MI1, R(' Rrynud lc MII inJ I 1 l".4 IICI I,(1k•I,artnicnt r-t P.Hhwdr-Ry, llnivcr.ily n1 Irrrs V11-01-r1lrrrl A1l 'I-- r1 %. h-I .rml Ihr 1 alwnilorirs frrr (-t•II 0 r r Rcsc-1rch, Wrwwtlawn Ilospilal, Oallas, Ter<as 7/v .1r.vrrrnn /.,urn,J nf I'aulr..LrRy 49; 1 55S-S67, September 1966 ((irantce: MunlRomery ) A shal+cd mictohcam of low intensity helerochrumatic ultravinlel light was slqnced Itr the nuclcolm of living (Tran6 liver cells and ttr the nuclrus with Ihc e.clusinn of the nuckolus. At varying time intcrvals these irratli ated cclls were appropriately rued, emhetkicd and serially Recliunrd fnr eRamination by ckcuon microscopy. When eaamincd, the nucleoli of these irradiated cells showed cadlapse of the nuclcoh/nema, an arparen( decreasc in nuckolar sire, and a rcurRam yation of the nuckolus resulting from the se6reRaticsn of the variuus tyiKs of granular armponenls of Ihe nuckolus. Nuckolar plaques and light nucle olar "cr,ps" wcre formed in Mwh groups of oells. In the cells in which the mrclcoplasm alone was irradiated, segregation of the nsKkular Rranuks resultcd in the formation of dark nuckolar "caps" similar tu thau prrKhkcd hy the actidine derivatives and milrKOycin C. T hree chcmicals, proftavine, acridine orange and mitomycin (', all compounds which form a compka with DNA and inhibit 1)NA and RNA synlhesis, produce an effect on nuckolar ultrastructure which is identical to that produced by the ultraviolet irradiation of Ihe nuckul+lasm exclusive uf the nuclcolus. 1 he effects of these agents which prtxluce nuticolar "calrs" support the hypothesis that the nucleolar ksian is Ihc result of an injury at the 1)NA kvcl of cellular metabolism., IhAer Rrenforrr Atomic FnerRy ('omnsission, I)amon Runyon Mcmrrual Fund, anti the National Institutes of Ilcallh. V. Epidemiology "NF.(;RO WllllE? I)IFFEiRFN('FS IN PI1I.MUNARY I IIN(-IIUN (VITAL ('APA('11Y, TIMFU VIT-AL ('APA('11Y, ANI) FXPIRA- TORY FLOW RATE.)." By Albert Damxm, MI), 1'hl), Ihhartmcnt of AnthroprdnRy. Ilarvard l/niversity, ('ambridRe, Massachusrtts Ilurnnn Rirrh,Ry 1R/1:)Rl/-)9J, 1)ecember 1966. Marked and significant differences in three pulmnnary functirrns were noted in tests ocmrductcd amonR )92 white and 61 NcRtu suldrrr s, aRrd I R 2'), durinR thc t'rrursc of an anthropornctric survey of U S Army drivcrs a 1.4,11 1)rvcns, Massarhuxus, Ihc NcRro scddicrs haJ I t'X, smallcr I.rrrmd aud lotal vital capacitres as wcll as a Ill"6 slower mid cltiruatury flr.w r.rlr Mcan aRc, hrrRht, wright, and chest tircumfcrencc wrrc .unrler ui rlK twei Rroups 1 he di0rrrnce in lung function can he re6arduJ as tnrly tuni wmi.J rrr Physirdt.Rical sirwe it cannot be accounted Inr by dr/lcrt•nres ut tm-uv:ru"n, in smrrkinR hahrls, or nwxe than minimally - Itr Jr/lrrrmt•% rn phy%nlur I hc whrlc solJrcrs anarkcd nNnc Ihon tltc NcRrrKs MrHrvation v.a% aplrarcnrly cquivak•nt, ia shown hy thc sLrtmRcr Rrilx ul the NcRrtw•%, Nhm vwcrc atsrr l a 19

I r muth more nxtomrrrrhic and "makculine" in physirlnt• I hr ~hortcr trunk and retluccd thcsl ettPansinn r+f the NrRrtxxs could nrN accourrt frn much rd the d//lcrrnce 1)iffererxes rd th/s m.Rnltut)c havc f.ccn rcfwutcJ frn ahrnrtu 100 ) yrars, and priru huln>,mary diseasc is unhkrly trr attrlunf hrr thcm Implitatirlns fru dncasc and for athletic Lcl/orncrncc arr slrlllLltlvc at flrescnf UTArr Rrantorr: American F(eart Asstxiatitrn, ('ommiaairrn rrn AcciJcntal lrauma of the Arrrnd Forces F.PidcmiuhrRlcal Iluard anJ the Natunl.J Sciencc I ounJatirm "PRfiVtOl/S Pl/l MONARY hISFASI: ANI) I.l1N(; ('Af\('FR A ('ASF (*ONIRU1. SIl1UY." Hy Alhcrt 1)amon, MI), I'lhl), and )cart P, Mc('IunR, 1)eparlmrnl of AnthrtqMrh+Ry, Harvald Ilniversity, ( am1.nJrc, Massachuse(ts Journal o/ ( hrrrnr( ]hlratrn 21)1 2 Sy bd, 1'chruary I'1h7. ( ( irantee : I )anion ) In a study of the relationship between previous pulmonary drscase and lung cancer it was shown that subayucnt lung cancer was not :tsstxialcd with either ItNal number of pulmonary diseascs or with any slvcillc Lul monary disease Among more than 17,0(k) mcn eramincd medically antl anff•rnlx+mct- rically at Ilirvard llniversily hclween IRM/) and 1920. 110 ha,l d/t•tl of lung canccr by lanuary I, IVhh F/+r conurd IrurJxnes, each IunR canccr tkcclknt was matthctl with thc ncst man of the sime age a+ he cnamincd. Of the cunurds, R 7 had dKd and d 1 were slill alive un lanu.rry I, 1966 1he IunR cantrr dcccdcnts and the crintrrrls dnl nrN drllcr in flrr numt.cr rrr nature of pritx f+ulrr>,+nary dlsracrs rr)Mntcd tlurrnR Iht'in rncJrr al caamina. tion at Harvard Among the cuntrols, siRnifitantly mruc Id thrr~c withrrul carly pulmonary discasc were still alive than td those with carly pulmrunary disease. OtA.r Rrantor: American Heart Asst+cia/ion. "FPII)FM1OI ((',Y OF (-IIRONIC I)RUN(11111S." Ity Ikrnald Massaro, MI), and I.inda Ilutlums, RN, Pulnxtnary 1)iscasc Research I.aMuatury, V A. Ilospital, Washinrton, I) C. and the I)epartmcnt td Mrdicine, (;corRctrlwn l lniversity Sc'htxll of Medicine. WashinRlon, I) (' /NrAa at 1 rnvr 9Si 2: 121- 12R,Ichruary 1967. ((7rantee: Massaro) lhe factors which predisl.nse to chronic hronchitis and avrnurs whith might he followed to prevem or am:liorale the drscasc are ctamrnrd irt Ihrt review paper. SnwlkinR, age, air f.rdlutirro and hlnt vari:Nirln arr the factrrls mosl «tinusly cttnsitkred in recent VIIII/cs tlf hr//rll Illfls fllt'v;llcrlln ccrr a1HI atrrnatl Ihc im(+ratance of snw+kiny and air Ltdlutrnn in the cpiJr'mirrlnyy rr( hrunchitis is sUcsud Amclioralive (ir /rtcvcntaflvc rnrasu/cs rc.rlmrnrntlyd intlurk the curtarlrncnl Irt furarnal air (wrllutrrrn in the hunl 44 clRatrate smukrnR and itx cnhucenxnl uf an cfleclivc an:u k rrn frncralircd air Iwrllntirln 40 ( ! 1 V I. Pulmonary PhyaioloRy "('ARI)IOPl1LMONARY I:FFFCfS OF T(111A('('O ANI) RITAIFI) SIIlISIAN( 1•S: I 7111: RF.I.F.ASF OF IIISIAMINF. 1)IIRIN(; INIIAI. A I ION OI' ( I(;ARlill F SMUKf ANl) ANOXI?MIA IN I fI1: . FIVAR 1 I t1N(; ANU INIA('1 INX; PRFPARAIION." Ily IAlrninRu h1 Aviadu, MI), Milan Samanek, M1), and I.uis E. Fol/e, MI), Ikparlmcnl trf Pharrna ctrloRy, Schrwrl u/ Medicine, llnivcrsily of PennsJ' (vania, Philadclphia AIth/vrt u/ I'nvrran.nrntaf llrahh 12/6:7(/5-711, June 1966. ((;ranlrr. Aviadtl ) "('ARI)IUI'l11 MONARY F.FFI:("IS (F •IY)HA('('O ANI) RFI A 11 1) 51/11SIAN(Y•S I11. P111 MONARY VAS('l1l.AR 1-.Pl-li(-IS1/1' ('IIiAR- li 1 1 li SM( )KIi ANI) NI('OI INF." Ify Luis F.. Fulk, MI), Milan Samanck, MI), and IkrminRo M. Aviatlo, MI), Ikparlnxn/ of PharmacoloRy. Schrwd of Mcdicine, l/niversity of Pennsylvania, Philadelphia. Art hivr, u( l.nvrr onmrnta/l/rahh 12/6: 712-716,lune 1966. (Grantee: Aviado) "CARDIUPI)1-MONARY FFFF('iS OF TOHA('C'O ANI) RFLA-Ifr) S1111S fAN('U5: 111. P111.MUNARY VASCULAR I:FFf?('1 S UF('1(iAR- lil I E SMOKF. ANI) NICOI INF." fly Milan Samanek, MI), and 1)rrmmr;u M. Aviado, MI), ll<pulment of PharmacoloRy. Schtnd of Medicine, llni versify of Pennsylvania, Philadelphia. Archivrr oJ l:nvnunmrnrol ]lealrh 12/6:717-72d, June 1966. ((;rantee: Aviado) II has been shown formerly that there are three imlKrrtanl participating mechanisms involved in the e0ects of lobacco on the tracheuhrnnchial /r- ways: I. direct action of tobacco smoke on the smtwfh muscle (of the air wa) s; 2. stimulation of the nervous stuuclures in Ihc lun6, and 3. release tuf hunKrral agents. I he present series of e.periments was designed to lest whether these three mechanisms also influence the cardiopulmonary system, slxcihcally the pulmonary circulation, coronary circulation and heart musclc. In Part I of this series, the rok of the humural nRent, histaminc, in mediating any chanRe in function of the heart ntusclc was cRl+lorcd l-rln'/i mcnas were cunducted both on dogs with intact cartliuvo.cul:u systcros :u1J on hcart-IunR /+rcparations. Results showed slrikin6 ditfcrcnccs f.rfwccn the cRecl of cigarette smoke upon the isolated hcaut tunR prcpar:uirrns :urd its eflcct upon the anesthclittd dog with an intact carthuvascular systrm 'Ihcre was a sfrikinR stimulation of force of mytxard/al cuntrattir/n m the inlact dog but no stimulalktn or dc/+ression of /urcc anJ vcutlrcul.u Lrr /rnrnarxe in thc 1K'att IunR Prtparatiun. Ihcsc cflccts with c/R.ucttc smrrAe tlld mH conhnnt witlt Previnusly uywrrlcd cflects rd nitrrtinc rrn nce hc.ut I lre rclrasc rrf histarninc (rurn tlre IunRs was tkmonsuarcJ in .rrmt' Iuuy. Irn 1r.Nh cigarcuc smrrkc anJ annsemia. lrr a sfurly of the efTccts of inhalation of cigarette smukc on the crlrrrn.u y circulation of the aneslhctircd dtrR, the It•rfused cruunary :utrry drd nnt shuw hKal vaaKVrnw/tiitrn in reslwlnsc Ilr etlrrsurt• nf the hlrKHl IrrfuNvc to eiRarctte srnoke. Ihc sank Ilcrfuscd currrnary artcry .huwrJ va.rKtm 41

strictinn in respnnsc to injcctcd nicolinc and to sytlcmlc cllccl of ciRaretle sn„rke I fx third of this scries of e.pcriments dcah with the cflccts nf ciRarctte smrrke and nicnlinr on the rulnx+nary circulatinn Rcsults shnwcd that Ihc inhalatinn of ciRarene snxtke of the injcctirrn of nicrHinr causcd cunstrictirm of thc pulmonaty bkxx) vessels Ikcause of Iht incnnsrctcnt restdls nbtaineJ with cy,arettr snxikc, nkoline was used Inrmarily as thr trst substance. I hc vasnconstriction clrciled by nkotinc in the fx•rluscd IunR of the anrslhctiprd dnR was inrkf+cmknt of the hronchoconatrictur reslxunr II was scen that the vasocvrnslriction prtsisted after acule vagotomy and administratinn of Mrcy+ine hut was cornpklely bincked by the adminntratir.n of a local ancs- thetrc agent 'the pcnsihility that the vnrxonstrictirrn was hrauylrl aMrul by the rekasc af histamine is discussed. "OXYGf=N ('ONSUMPI ION AND ALVf=OI.AR VF.NI11-AIIUN D(IR- IN(i INII RMIIlu.Nr POSIIIVF. PRI?SSIIRF IIRI:.AIIIIN(;." fly Stephen M Ayres, MI), and Sunlcy (iiannclli, Jr., MI), 1('('1 , 1)c- partmcnts of Medicine and Surgery, St Vinccnt's lloslrilal and Medical ('enter, New York ('ily, and New York Oniversily Schrw( of Medicine. l)israrri of the ('hr+r St)/4:41W 4 14, ()ctohcr 1966. ((;rantce: Ayres) '1 he siRnifxance of the rok of intermittent posilive pressure breathing devices ( IPt'II ) in the trcatnxnt of emlrhysema is dcpendcnt ulx,n the ahihty of II'I'll to siRniftcantly rkcrcase the work of breathing in aJdrlion to incrcas- inR minute ventilatiun Ihc larscnt paper rrlx)rts studics of the mcchanical work and r+ryRen cnnsunil.tum nf the reslriratury muscles tx•lore and durinR atsistcd ventilation wilh  vnlume cycled IPPlt apparatus In this sludy, otyRcn consumplion, alvcolar ventilation and arlcrial gas tensions were mcasured in riRht patients with ahnerrmil rcypiratnry Ras ewchanRe following recovery from an episrxk of respiratouy aci(bsis. I he patients - sit wilh severe ohslrurlive emphy'scma and Iwo whh neurological disease involving the chest wall - were studied t rest anJ durinR II'1'11. Results showed that the o><yRen eost per unit of ventilation rkcrrased nn average of )4(~cr cent durinR IPPU. (kad space ventilation was unchani;cd, hul the Ivcolar-arteria( o>ayRen diRerence was increased in all paticnts, indicating Ihat the distribution of ventilation with IPI II is diRerent from that with spontaneous rrspiralion. These studies indicate the prnlx•rly admin- istered IPPII increases the efficiency of the respiratory mucclcs and rkcreaus their entropy. ()t/lrr Rr.nrnr.r Atsxrkan Thoraek Srx-iely and the New Jersey McJicnl Research and TeachinR Fund "RfSI•(rNS1~SOFtIPf'UR RPSPIRAIOI(Y Mtl(Y)SA IUI)Rl/GSANI) VIRA1. INfI (."TIONS" fly I rederik 11. II:rnR, MI). 1lctsy G IIanR, AH, and Maric A Frrarrl, AR, Ikp:utnunl nf f'alhrrhirr6rRy. Sr hrwrl r+f Ilypicnc anrl I'irhlir IIralth, Ihe Ir+hn. Itopkins Ilnivcrsity, Il.rll mrue. Al:nylanrl ,Invrr,nn Rrvrrw n/ Rryrrenrr~ l)rcrarrr 91, 1 I1 142 1-IV, Marrh IVhh 1("ranirr I It IIanR) I I he present paper summau'vcs and analyses rrsulls obtained in a scrics of c.lx•nmcnls dcalinR with Ihe eflects of certain drugs and rrltrcr aFcn;- nn uppcr rc~laralory mucosal function. ~ Since a virus must have access to a susccpliblc cell in urJet to prodrkr infcctiuns, ap,cnls were tested to rklerntine whether they might al/er suscrpn hduy In a vrrulcnl strain of Newcastle 1)iseasc virus. 1 a obvratc thc qucstnrn ahlc asfrrcls of rn vrtrn sludies, experiments were conducted mc+stly on Ihe nasal mucusa of nurmal, unanesthctitcd chicks In the study of the differential enects of agents cm the cumlxmcnts of Ihe mucrcrbary syslem, it was shown that dchydration, pihx•arpinc and vitamin A rklrciency primarily aflectcd mucus sccreliun; crx:aine, .ylrkawc and lowered tcml.crature affected cihary rurxtion, and cyctainc, severe vitamin A rk/iciency and viruscs (influenra in ferrets. IarynRouacheitis in chicks) affected cellular integrity. Viruses, which seem to act by destroying the cells of the nmucosa. leave behind an epithelium which, during regcneration, has at fusl fcw or nu cilia I his destruclion, which involves both ciliated and mucuus cclls, e.lxrus Ibe clcnudcd mucosa to absorption of other loaic subslances ReReneratxm of the two component parts of 1he cpilhclial fyslcm dcrcs not always prucced of the same rate. As the motion of Ihe murnciliary blanket depends on the con certed activity of mucous cells and eilia, lack of nsovemetH of the hlanket r/,Ks not necessarily mean that ciliary •aelion itxlf has been inhihitcd Acrual eiliary paralysis induced by cocaine did inerease the numl.cr of infccted cells by It/ tn 51) times over the control values. tlth.r Rr.ntorr National Science Foundation. "I,ARYNGOfRAC11E:frIS VIRUS IN ('HI('KIiNS" fly Hctsy G HanR, AD, and I'rerkrik H. DanR, MI), Ikpartmenl of I'athohrolrrRy. Scfirxrl ul /ly6iene and Public Ileahh, 1 he lohns Ilupkins I/nivcrsily, llalnnuue, Maryland. /.rurndn/ l:xperimenrof Medicine I25/1:4(W 427, March 190) ((irantce: F. 11. Nang) Infectiuus IarynRdracheitis can he pnxluced in chickens as an e+IKri menlal mrxkl of severe nonfatal rhinilis and sinusilis. lfris study prrscnts a mnrpholnRical appraisal of the eRccts of (arynRrNrachcitis un the tiuuc systems of the nasal fossa. (InacslhNircd while I.eRhorn baby chicks received intranasal inocula tinns of a susprn.inn of Ihis virus and palholuRical chanRcs od thr ru.al thssues were followed sequentially fhum the esrliesl demonsunblr )rsiuns Ih(auRh the 4th rrNrNh of cnnvalescence. '1 he rrsultsnl viral rn/cr thuns, whrle remaining hmitcd ta the nssal frsss, pnx)rKCd acute Jrsrluanraur.n of nll nasal epithelia, resulled in functional recovery of the rrslaralury cpnhehum, hut left imprrrtanl residual abrnrrnulrties. Initial Irsiuns wcrr first idtntifiablc in the rnucrxiliarrd cctls of thc shalluwest Ixutiun of the eprthebum aMrul 21 hours alter inrwulatrnn nltrr a thrce ter seven day Len«1 nf acute sluuRhrnR, rclrau I nMr.ucd hy t11e ,., 43 42

I r,yTid spread uf a sheet of epithclial cclls ovcr tlre inhllr;rlcrl %ubmucuaa ) 1K•rnn and latlcd for cight tu 21 days After crrnv:dc%tcncc, hrrwcvcr, rqfit tlxrrnx•ns all shnwc(1 cr+mfdcte mctaPlasia rlf tlu olla(truy urP.rn Ir+ mutrr- crh.ucd ePilhchum, all showcd ahnrnmal fnrnrata-n and ahgnmcnt 0 mutuus acrnr, anti alwwt S(I^,:• had scvcre 1rrsistcnl cinuaitis. (hh.r Rranror: National Science Foursdation "A(l/lF VI NIILATORY FAILURE IN ( IIR(INI(' OIISIf(lI(•IIVF. I.IIN(i I)ISI'ASIi " Ily franklin 11 Sakscna, A11), anti Itcnl:rm(n Ilunuws, MI), Ik•Irarlnx•nt of Mcdieirx, llnivertily o/ ( IucaRu, Illinrnc 11rirnrrs of rhr ( hru Sl)/2 176-179, August 196,6. I(:r,rn,cc Ilurrrrws/ icn eris(.ks of scute venlilatory failure rn eiRht thrnnir:Jly IrylK•r cal'ncic patrcnts are rel+r+rte(1 Acute vrntilatnry failure. Rerxrally defrned as an :rhruhl incrt•ate in cartwrn (IrotlO(• (eTHllwl, is a eommon eompl:<;rlron u/ thrnmc r6s,ruclrve lung drscate, particularly in chronically hylrrcarencic haticnta untk-r Ihc slrcas of acnte resprtatrny infeetion r,r with etacerhaurTn (d conpcurvc tscart failure Wnh mihkt cpruKks of acutc vrntr/,rt(ny larlurc, fl:rtrrn,s u.uilly rctIwmJ tau~/.rclorrly tu manaRement of the unJerlyrng car(Jnqpulnunr.uy dr.rrrrkr, rcquurnR ncithcr anatcptic (1ruRt nru mcthanKal vcntilatnry aticratantc "1fIORnCI(' ('(1MPI IAN( I IN ( IIRONI(' O11SIRII( 1{VF I (IN(: IHSI ASI " Ily I ranlhn It S.rAtrna, h11), anJ Iknl:nnin 11urrowc, MI), Ik parrntcrU (if Mcdhcrnc. I/ruvcrvly rd ( tut:~rr, Ilhnmt lonnnaJof I~rhnr,nurv und ( hnn u7 AfrJ r mr h!t 1 427 4 12, S( I Irrntr r 1'!6A (( ir,rntcc Ilurtnw.) A weirhrcd sf+irnmctcr rcthni,luc wat uu (1 in Ihis.luJy I(l mca.urc /utal Ihuracic conrplrince in 17 (+iucnts with Ihc ernhhy.cm:r hn.n(hrric syn drnme. In R piticnts. lung and thc.l wall cnml.'I,1rKCt wcrc :rltU A-tcrmincJ With this mctMul, total Ihuracre antl chest wall compliance ,I,IK arrd cs.cn lially normal I his contrasted with thc low total rhtuacic and t hc.t wall com plianees found in similar patients when mcasurcmc•nts were rnarlc with the negative Pressure txxly box technique It is suRgcsrcJ that Ih(• htw chcst wall compliance obtained by the latter procedure and noted by rnhcrs with the relaxation pressure method may have been due to incnmpkle rclatatinn of the thoracic muscles of Paticnls with this t)rc of respiratory ir-tu0icicncy. It is doubtful that chest wall compliance can t.c nuasurcd wilh accuracy in such patients with any of the methods mcntiuncd (hArr Rrnnrorr U. S Puhlic f tcalth Scrvice. "('/1RF1(1N t)IOX11)1: II NSION ANh VI•N111 nl()RY N11 ( IInNI('S IN ( 11R(INI('<)lISI R11('1 IV/• I.I IN(i 1)1SI nS1 "lty Hrnpm n Ilunrrws, MI), I ranllin 11 SaAscna, MI), and (-arl I Ihcncr, A11), Ih•v:nrrucnt uf Mcrticirx. I/nrvertity uf ('hitaRrr, Illinr,is Arrn(rh o/ Inrrrrru7 A1rdrsrnr 0 4 fAS 71M1,(klnbt•r 1966 1(iranlcc Iturrrrwc) ('.vt.(rn (liotidc rrl(•ntwn tr•n(la Ir, vary prcaUy in p:Tticnl. wilh irrc 4 .1 I vcrsihk airways obstruction of unccrtain ctioloRy. I hic rcPr.rl, whi(h it based nn stutlics of vcntilalory mcchanics in 34 malc I)aticnls, attcmpts lu explain this variability. S(u(h(•s of Ihe relatitmsltip bctween earlx,n rhoaitle tcntiun :rnJ vcnhLr tory characleristics indicate that frank carMtn tlirraitk retention is c.IK• cially likely lu occur in patients who, in addition to having alvct,lir under. vcntil.rtirm and a Iunilcd ventilatory eapacity, show a rapid, sh:rlluw hrc.rth ing ITaUCrn Ihis type of breathing requires that u grcatcr IKUlirm n/ the nnnute volunse tx wasted in ventilating the anatomical dead alrace anti :rE~r:rv:dcs the c.istinR tendency lo hylrrcapnia It is prulnr.cd that pul rnunary comlrlianc•c is a factor in dclerminin6 breathing Irattcrn anJ, hcnce, in regulating the tendency to earhon dioxide retention 1'.rticnt. wirh relatively Mrw lung eunrplianccs, shallow r(•tlrrratiuns, high inslnratruy resistanccs, and hypercapnia shuw, chnical and IThysioloRic.l /c;rlures whit'h suRRcsl that Monchilbs and parcnchyrnal ooll:unmatury chanRcs are important in the pathogenesis of their tliseasc Su( h Paucnls ( whu Iravc been Inund to have relatively slight emphysematous Jc.vuclirrn of thc lung parcnchyma at postmortem examination) have tx•en desiRnatrd rt having tyla• Ft or "hrtrnt•hial typc" discase. In c(rnlrast, lyl.c A 1"cmplhy scmatous tyf~c" ) palicnts, who have features that in(licalc scvcre analunucal cmphyscnu, generally show normal ur high lung curnpli:rnt'c+, havc a dccp, slow breathing paltcrn, and show a Icsser tendency to hylx•rcal.nia I1tA.r Rranrorr 11.S. Public /lealth Service. "111F ' INhI.IIFiN('E OF c1(iARli7-f I: SMOKF ON 1 IIN(i ('1 FAR. AN(T " Hy ( harks W. I.alklk, Phl), Ikxolhca M Ikvd,rcyua, MA, anti Ilcinrith IlricRcr, MI), Ikparlmenl of Preventive M(•dn-inc, lellcrson Mrrt ical l'nllcRe, Philadclphia, Pennsylvania. Archivrs (r/ /,nvi.( nmrnrol llrahh 12:SRR-596. May 1966. (Grantee: (.alklle)' Unaneslhclizcd rabbits were exposed intermittently (n concentrations or cisarcttc smoke in such a way as lo approaimalc the )Taltcrn of smukinR hy hrunan Ix inRs. f he effect of the snwtke of filter and montiltcr ciR;uettrs was ca:rmincd on an aculc antl a suhchronit: exlwnure schcdulc 7 wo (h/lcrcnl radioactive Iesl parliculates were used in order to assay rapid anti dclayeJ pulmonary clearance following the imposition of insuluhle Iurticles In none of Ihe experiments did interference with pulmonary clenr:rncc rKcur Fluid retention and phaRoeyto+is were studied in additional c.fx•rimcnl% on rats. Ihe IunR-wciRht to hotlr weight ratios were Ihc samc in thc c1le•n mcntal anti in the cnnlrol ammats Ihc earlwrn inJuccd oUrnul.Hamn n/ 1ohorrK•ybnit was not miliRaled by the inhalaUnn (d t irerrrrc .nu~f c, n w.r. ctu:dly incrt i%t•J hy e.lwnure tu the sn>trke u/ nrrnhlter t iRarrnct "Rnl)Il)1(X;I(' ('ON7RIIIl1I1ONS -1() 111F NOSOI( 1(i1' tlI tlll SI Rll('l IVI I lIN(i 1)ISFASI? UN I11IFS "Hy Mauri(i» J I1ulfano, MI), •I)eeeased 4i

r t I I and John f(cwcluin, MI), 7 he I.unR Station ( lbfts ) and I)cl•artment nf RadiuhKy, Rnslnn ('ity Ituspital, (lnstnn, Massachusells Ihrrrtvt uf the ('hrst, tll/3 270 2Rt), September 1966 (Grantce: Scyat) Critcria for clinical classification of patienrs with the "ohstructive lung disease syndrnme" .re dcscribcd. Ihese crilcria, hased upon the consirkra• tion of simlrk clinical, physioloEic and radinlr,Ric dala, are usually sufficient for making a diflerential diasnosis of the patient's condirinn as ( I) asthma, (2) chronic brnnchitis, (3) chronic pulmonary emphysema or (4) com- hinalion thereof. Four case rcpo.ts are ~iven in iltuaratirrn Fmphasis is (+laccd on more decisive Interpretation of the plain chest X ray film, particu- larly In reccignirinR chronic bronchitis. OtA.r Rr.nrerr National Fleart Insdlute of thc (/ S Public Ilcalth Service. V11. NeurophyaoloRy "POSi(3ANG1.1(INIC NATURE OF PARASYMPAIFIFiT1C INNFR- VATION OF PIG IRIS SPI-IIN('If?R" fly O. Schacppi, Laboratory of Neurn(-hysioloRy nd NeunrharmacoA.Ry, Worcester Foundation for (iit- perimentd Biok>!(y, Shrewsbury, Mass. Amrrican Journal o/ !'hydnfogy 21U/ 1 : 9I-91, January 1966. The widrly-accepteal notion that the parasympathetic nerve supply of the iris is rrnlRanRlionic has nnr etcludcd rhr IMnsrhilily that Ihis inncrvation is in part prrRanRlirtnic lo clarify the naturr rd the parasyrntoathctic inncr- vation of the nis, rn vrtrn studres wrrc ntark r-f rsulatcd iris s/+hrncrccs (if piRs, a species with a strong para%)mhathruc inncr.itirm I wrr wccks after cilr.rry RanRtioncctnmy, isolated iris slfirncters showed enhanced musck lone, in• creased sfwintancous aulunurn-ws ar uvily, sulrrtrnsitivrly to acetylchuline, and marked decrease in electrical ercitahdhy, 211 of them symploms of post- ganglionic denervation. The feeble ekctrically-induced contraction which occurred in these sphincters was in part resistant to treatment with phentulaminc and arlupine. A similar electrically-induced contraclion occurred in sphincters from normal eyes which had been treated with these two blocking agents. I he fecble prntracted clcctricdly-induced contraction appears then to result from direct action of the electrical current upon the iris tissue. These observtations kad to the conclusion that the parasympathetic innervation of the Iris sphincter is entirely postRanRlionic. The observation that nicotine produced contraction of normal iris sphirxten but faikd to produce contraction of denervated sphincters su6- Rests that nimtine acts by rlimulation of poslRanRlionk pararympathelic nerve cndinRs which Induces 1he.utnequenl release of cholincrRic Iransminer. "NON GAN(7t.1ONIC PARASYMPAfII(1MIMIiT1(- A( TtON OF: NI(-OI INF UPON TIIF IS(11.A11:1) CA1 IRIS." Ity ll. Sch:rcp(+i, Fl. 1.. ()rrrnisrm nnd M IkK1d, Shrrwshury, Mess Irnnnol n/ I'hormn.n/nay and 46 I FtPrrimrrnal Theraprurict 154/2: 216-223, November 1966. ((iranlee. SchacpPi) Pupillary changes of isolated Intact cat irides were investiRated In vin.r Normal iridcs reacted to nicotine with micnis followed by mydriasis. 1 he threshold dose of nicotine for mio(ic effects varied (rum I to 1(/ mg (adrkd to the bath fluid). The response of the irides decreased or disap- rcared completely when the injection of nicotine was repeated, even afler intervals s long as two hours. Nicotine in doses as high as 10 mR had no effect on the response of the cat iris to ckctrical stimulation. ('hrnnically pa,asympathetkally denervated irides reacted to nicotine with mrdriasis, whik chronically sympathetically dcnervated iridks reacted with mKnis. Ihese findings together with the effects of atrupine, physostiR- mine and her<amelhonium upon ekclricdly irwluccd responses of normal irides furthcr support the earlier conclusion that nKo(ine-induced sphincter contraction resulted from pustRanRlionic slimulatiun of parasympathetic nerve fibers. "DF.MnNSTRATION OF AVERAGED OPERANI- POIFNIIAIS IN TIIE FIUMAN E[:G." By Alfrcdo 1. Vazquez, MU, and James E P. Tnman, Phl), 1)ivision of Behavioral Sciences, Chicago Medical Schrwd, Illinois. Elecrrorncrpholo=raphy ard Clinical NcuruphynufuRy 2I :381-3b1, 1966. (Gtantee: Toman) The averaged HEU activity preceding a voluntary moair act in m.n was studied for the purposes of: 1) searching for txrth rcr nKlucihk and modifiable features of the f:EG in the pie-decision pcritKl anrl 2) devcNrpinR useful methodology for such research. Ikmrxlulaled laped EEGs frontsubjects operating a key.press on thc basis of an initial general instruction were fed to a Mnemotrun 4lM/ 11 ('um puter of Average Transients which summed pre-action I?I;G traccs ( A(1/': averaged operant potentials). The intrinsic difficulties uf such an analysis are duly noted. A significant cluster of small amplilurk waves was fuund commonly present in bipolar recordings from the conlralalcral I+arrcral area, in the f+eritxl from 330 to 140 mscc pre•tri"er, in •particular a 3(M) msec positive peak. Uthrr gr.ntorr National Insti(utcs of ffealth. "PHARMACOL(x.;ICAL ANALYSIS OF EVOKED POI FNI IAI S IN RAIIBIT CORTEX." By A. 1. Varquez, MI), I1. ('. Sahelli, MI), R I t.udmer, MI), and 1. F. P. Toman, Phl), [)epartrnenl of 1'harmacrdrr6y rnrl Therapeutics, Chicago Medical School, Illinois ( lraptcr S( pp 51 71 ) in "Recent Advances in Biological Psychiatry," Volume VII1, 1'Icnum f'rrss, 1966. ((:rantee: 'luman) 1 his reptnt deals primarily with drug-induced chanRes of the cntirc evoked response of the rahbit sensorimutor cortea from I mscc to I scc aftcr brief stimulation of subconvulsive intensily. I?.pcrimenls were conJuc'ted on unancslhelired, lightly restrained rabbits ( I to 2 kR), chrrrnically im planted with a trianRular electrode atrayy lest dru6s includcd clNthncrRirs, 47

0 antimuscarinics, convrdsants, anliclTnvulsanta, psychlHlmumcflcc, and a/lrcn crRic prccursors, minxtics, rcleascrs, and hhKkcrs. I he "muscarinic" (N4 ) potential was Ihe only one tlt rh.pLly a clear pancrn of pharmacolosicat srnsitrvrty; all othcr climfwmcnls wcrc allcctcd by most druRs, hut wcre nnt aholrshed by any rd the synaptic inactwatnrs tested lhus, it appears that the correspondfnR end/1Rcnous cticmicals the not play an essential rok in cortical synaptic transmissirTn, hul a--ccondary nxxlulatinR furxlron. Uverall results su(rgeu that chlrluTcrRic cstcrs and picrnlo.in sensitive modulators may play a ruk• rrl the mrKlulatuon of cnrrical ekctrical ac/ivity, but suE,acst that other cntbll', nous chtnucaa, probably unknown as yH, have still more essential lunclwn in cortca. (lthrr grant.r.r 11 S. Public Ilulth Scrvice ( 2), AhtxNt I alNTra/nrics, and ('onseNs Naciona( de InvcstrRacicxxs Cicnlihcas y 1 ccrncas I ArRcntina ). "1)RtlO INI)UCFU RAGC IN CATS." By Alfredo 1. Vavqucr, MI), and flector C Sa(xlli, Mb, Phl), Ikparrmcnt of PharmacoluRy, the ChicaRo Mcdical Schtx>J, Illirsois. I hr ( hiroRv AfrAkof Sr hrnr! (jumrnly fTp 1 J7-144, F.II 1966 ((ir antee : l oman ) In this study of the role of acctykholine as a chemical nxdialor respltns- ihk (or the triggering of ra6e, cats rcccivmR intrapcritontal in/cctKTns of cer- tain druRs (cMdincrRics, ch1111ncrRrc musc:rnnics, atruhlnics and pcycho tomimttres ) were ohserved (or ovrrt signs of t.cltatron, s/crcoryred hustility, directed hostility and stereotyped aclivrty irenNTSin, o.otremorine. arrcohne, prhKarpine and muscarine pro- ductd a htntrk rcachon whKh nxlu/kd hrssrnR, scratchrnR anJ brlinR Prior to the devel'rpmcnt of aflcctlve chanRes, a)TCnl.d /1t intenu ITarasympathclic stimulation was rscNed I SI) 21 produced signs of dnecleJ and undirected hostilily, as well as dirterent typcs of stereotyped movements I he signs of htntility were milder than those ohserved wilh muscarinic druRs. In conlrast, hissing nd jumping were more frequcnt than with the chrllincrRic drugs. Atropink aRents produced stereotyped movements. 'the following drugs given prior lo the administralirTn of any of the rage-producing agents prc- vcntcd the rage response: atropinc, scopolaminc, diclharinc hydrochAxick and 1B-329. Although the specific site of action is not known, it is demonstrahle that the response is triggered at central cholinerRic receptors. On thc batis of these /ests, it is assumed that the fundamental neuronal pathway involved in druR-indrxed rage in cats is of a cholinrRic nature, but normally is held in abeyance by a strychnine sensitive presyna(Nic inhibitory mtchanism. (1tA.r Rr.nrnrr (1.S. Public Ilealth Service (2), V111. ChPntisfry rrnri ltirsr-hemi.(r-y "1W11 RMINA11ON Of' 111(x)I) VnRRON MONt)XII)1: . ('ONII:N1 11) f;A%f I(Itt rA(At f l! :II AI'I I\' " IIy Cfrph,n l\1 Aylc., t•111 Arnalintlft alan.llnrY. / rr r rlrr II. . .rr,.l \r rnL , 1., rr,r.r lir Ir /.111 ( .u~Inrlrulm. rnnlV I I 1 St. Vincent's Ilospital and Medical (?nter, and the f)cpartmcnts cif Mcdicine and SurRery, New York University, New York ('ily. /rrrrrnal of Applied l'hvSrrrLrRy 21 /4: 1369 1370, July 1966. (Grantee: Ayres) 7 his paper descri3es a simple 6as chromatographic techniqne fur measuring small concentrations of CO which cqu•Is the accuracy of the most satisfactory methods available up to now and has the additional advan taRe of allowing mcsdificaticm for the analysis of nitrogen, neon and othcr inert gases. Small anrounls of blood ('O were measured by this melhrwl following vacuum eatraction in a Van Slyke manometric pparatus. '1 he clxfl'icient of variation for 23 consecutive duplicate determinations on blood samples containing 0.(l11)-2.)IS3(1 ml/I(K) ml averaRed 1,95%. In • IarRer scrics of samples obtained from 22 nonsmokers and J l srssokers, bhKxl ( Y) conlenl was 0096 t 0,056 (mean .!: S!)) in the nonsmokers nd 0.549 ' 0.446 ml/ 1()() mt in the Imoken. OtA.r Rr.ntorr The Flealth Research Council of the City of New York. "CFI.LUL(>SF. COLUMN CFIROMATOQRAPHY FOR TH!'. FRA('- TlONAlION AND ISrJLAIION OF ACID Ml1COPOI.YSA('(:FIAR- IhFS." By Yukio Tanaka, MD, and Ira ('.ore, MD, lkpartnsent of Path- olc>sy, University Elospital, Boston University Medical ('enler, Massachu- sclts, lnurnol nJ ('hrornarography 23/2:254-260, 1966. ((:rantee: Gore) This palrcr describes in dctail a laboralor procedurc for the sharp separation of the acid mtscopolysaccaride (AMP~) mi.ture found in human arteries based upon the use of a single cellulose column A human arterial AMPS mixture may be separated into its individual constituents by eluting the cetyl pyrKlinium compknes from • cellutose column with II.3S M nNl 0 6 M NaCI, disruptinR the complexes with 90% ethyl alcohol nd elulinR further with 30 and 10% concentrations of ethanol. Acetate papcr electro- phoresis, infrared spectra, chemical andysis, hydrolysis with hyaluronidase rsd paper chromatography of products of acid hydrolysis u( AMPS are used to identify the separated components and to ascertain the adcqfucy of separation. Ilthrr gr.ntorr National Ile.rt Institute. "(IRINARY FXCR!?TION OF CON)llOA1N FORMS (1F I (3 PYRIhYL)ElIIANOL AFTER Al)MINISTRATION OF I-A(Ull'1, PYRII)INf?." Ify Flerbcrt McKennis lr., l.ennoa B'Iurnhull, ILlward R flowman, and ('. Norman t.ukhard, Ikpartment of PharmaculuRy, Medical ('o1kRe of VirRinia, Richmond. /ourna/ of RiofoRicaf ('/vrnive y 24 1/R 1879 tRtll, April 25, 1966. ((lrantee: McKennis) Oral administration of 7-acetytpyridinc to the It..R led 111 Ifhr r.crrrinn of I-( 1 ('yrNlyl)rthanol in two acidic conjuRate furnrs wfhiclh were fral liun ated whh the aid of ion exchange resins. 7 he more acidic of the conjugate forrrms had the pnqartirs Id a sultalc eUer in comlTaris/m with synthelic material Acidic hydrrllys/s /rf Ihr +ul/.ur eslcr fracliun kd to the release of ( I( 1 pyndyl/rthannl nl ydlc hyJlrrl 49

ysis of the other conjuRate form, which had prnrcrties of a Rlucunrnidr. Icd to the rekase of I-( l.pyridyl)ethanr,l which aftcr chromitrrRraph c Purilt- catirrn was apprnamalcly VS 7~ pure on the hasis of eottincuon ciK•ihcicnl and which was appro.imalely (d1 % in the kvorntalory furnt (in the havs of optical rolatbn I he pyridylcthanol separated allcr the hydrrrtysis (if the Rlucuronidr eontained, in aJJition. two other Krx'niR fxxilivc mmrrials Ity the chrr.matnRraphic hehavior of some of the Iatlrr anJ hy analuKy to the rnNaMrlism of phenyl• 1,2-ethanediol, the form:mon of a Rlucur,rniJr of () pyridyl)- 1,2-elhanediol is suggested. Other Rr.nrnrar National Instilules of 1lcalth, Anrcrican Medicat Asuui• alion IiJucation and Research Fund, and American 1 ubacco ('urnpany. "Illti FA71? ANI) DISf RIB(JTION OF t( 1 PYRII)YI.)[: I/IANO1. M[.f11tUUll)F. IN RFI.AI'ION 10 Tllli It)XI('1IY UI• 1-O PY- RIUY1.)F.I IIANO1. ANl) 3•ACETYLPYRIhINN." IRy John 1'. Ifcdcrka Jr. , F.skil Flamson, F.dward R. Bowman, and Hcrhert McKennis Jr. Brrr- chenucot rharmaofory 16/I:1-10. January 1967. (Grantee: M(Kennis) lhere was a rapid elimination of the radioactivity of ( I,-)-N-mcthyl- "('-l•( I-hydroraymrthyl)pyridinium iodick followinR intravenous adminis- tralion to mice In common with the estahlishcJ behavior (i/ many other quaternary amnw.nium axn(+rrunds, this eompounJ ShoweJ no great lend• erscy to pass the hkxxd brain barrier 1 he radioactivity of the conrpuund was eliminated IarRrly ( 7e-9q°lo ) by way of the urine within 24 hours, as was the case ufam inLrsperitoneal dministralion of the same comiK.unJ to rats 7his excreted radutactivity was prcJominantly in the form uf thc aJmin- istered catirrn. (hA.r gr.ntor.r National Institulcs of Ilealth, Anxrican McJit al Associa- tion Fdueation snJ Research I oundation, American I uha.co ('ompany, aod Swedish 7 obacco Company. "ST(JDIFS ON TIIE SFPARATION OF ACII)1(' MlifAlt(11.1IFS OF NICOT INF. BY GAS CfIROMATO(iRAPf1Y." fly Ilencerl McKcnnis Jr , E. R. 1lowman, and Mohammad Sared Dar. f'irRinia lrrurnul ul Sr irnce IS NS/1:1)-18, January 1967. (Grantee: McKennis) As part o( an investiRation of procedures for the gas chrontak>Rraphic determination of mammalian metafxilites o( nicutine, a synthetic mi.ture of the methyl esten of nieotinic aciJ, l•pyridylacetic aciJ, r-( YpyriJyl ) t'utyric acid, y-(J-pyridyl)-r-onobutyric acid, and 5-(3-pyridyl) trtrahydrofura- none-2 was investigated and found to give adequate separation on aCartxi- wax 20M column (5.6% on Anakrom A[1S). Aqueous solutinns of srnthelie ( ' )-y-(3-pyridyl)-y-mrthylamino- Mrtyric acid, (~repued by an improved procedure, were convrrtrJ by the a(q, aratua anr1 codumn eondilirxrs In t'ulinine as Ih'tc/rnincd hy (rnnp:unrrn with the reyamse of equinxrlar amounts of cutinrnc in a flamc iunvatirrn detector ('utinirx. in contrast to tnethyl r(1 pyridyt) y-onohutyralc and 5- (I f rr'tlyt / trtnhydrr4urarw)rx 2, fauvirkJ es%cntially no siRnal to the I ekctron carlure detector. The tase with which )-(3-pyriJyl )-y nrelhylam inuhutyric acid can he converted to cotinine aplaats ar aflrrrJ a haais tur Ihe quanlilative determination of the melhylamino aciJ- (lrR.r Rrantora: American Medical Association FJucatirrn and Research VunJ, anti Amcrican lobacco Company. "OBSFRVATIONS ON SOME FFFECTS OF 7 FfE SO1)1( IM SAIA SOF ('ERI'A1N MON(x'ARBOXYLIC ACIDS ON ESfABLIS111iI) (-1:1.1. I.INFS." Br 1)onaA1 M. Pace, Phl), Byron Th. Aftonomos, Alice F1liott, and Steven G.mmcr, Institute for ('ellular Research, 1)epartnrcnt of 7rwtluRy and PhysirdoRy. Univcrsity of Nebraska, l.incoln ('anadran lou.nul of Rioahnrsirlry 4S/I:t11•tiR, January 1967. ((:rantee: Pace) Some of Ihe steam•v.+latile organic acids fotmd in f>,rllulyd air and lohaccn smoke were sNKbed to obtain information reRardinR their wnirity in cells cultivated in vitro. Ouantitalive and qualitative determinations were made of the action of the salts of 10 rnonocartxraylic acids (formate, acetate, propionate, huty- r tle, vakrate, caproale, cxnanthrlale, capryl.le, caprate and hen7oate ) on severa) established cell lines (Hel.a, strain L, human lung and human skin). All of these compounds at a concentration of'10 mg 9'.% were toxic to the cell lines tested with the eace(Nion of fnrmate, acetate and (xrouate on strain l., and of valerate and caprylate on human lung. At a concentratian of I mg %, on the other hand, all the compounds either stimufatrd prolifen- Iion or had no significant effeet eacept eaproate and t.rntuale, which were toxic to human lung and human skin eells, respectively. ()d4er grantor: U. S. Public Ileallh Service. "CNLOROGFNIC ACIDS AND R.EI.ATED DFPSII)FS." fly Urnest Sondheimer, Phl), [)epartmenl of Chemistfy, State Univcrsity ('a1kRc of Forestry, Syracuse (Jnivetsity, New York. The Roranicaf Rrvrrw )0/4:667- 712, (><t.-Ikc. 1964. In this review paper, the ehemistry, natural dislrihutiun, birxynthesis and important properties of the ehloroRcnie acids and their rclaled Jepsides are discussed. "771E DEf/;RM/NATION OF 1) QUINIC ANt) I)S1IIKIMI(' A('ll)S BY MI('ROIIIOL(X;tCAL ASSAY IN 111E ('l1ARA('1 (:RI'lA I I()N OF ( IILORO(i1:NIC ACIDS ANI) RELA'Ifit) ('OMPO(INI)S" Ity (kralJ ('arkman and Frnesl Sondheimer, Phl), Ikparlnrcnt uf ( hemistry, Stalc ( tniversity ('olleRe nf Forestry. Syracuse l lnivcrsily, New York I'hvro chemistry 4:77J-775, 1965. (Grantee: Sondheimer ) In this reprrrt, a mkrohintogical assay for the quanlHa/ivr, strrros/rr(ihc tktermina/iun of microRram quantities of h quinic and t) shrkuuic arids is described and the application of the prncedurc to structural work with chlorogenic acid and related drpsides is demonstrated An ArroAm rrr arru- Rrnrt mu/an1, chown previously to tu suitable for mKruhioltrRicat assays of quinic and shikimic acids, was used in these lesls. ttt 51

~ ~ ...,a I IX. I'h(irmn(•(rloRy NrUI 1'Ryrlllr-Pferrrrrrrtr•rtlrrRy "RI:LFiAS1: OF S IIYhROXY I RYPTAMIN/; FROM ISU1 A l1 1) I)(X; IN I I?Sf INF IlY NI('OI INF. "Ily I F. IFurkc and 1 P 1ong, Phi),1)rlTtrt ment of PharmacoloRy, (-o1kRe of Mrdicine, I Inivcrsity of Ir,w;r, Irrwa ( ity. Brrrirh Iournnt r,/ !'Irnrnrn<nLrRr ond ('hrrnnrhr.n/rv 11) 2 22'! 219, lunc 1967 ((iranter I onR) NiccNint and dimethylphenylpiptrarinium (I)MPP). Mrth powerful stimulants of aulonomic RanRlia, significantly cnhanctd relraae rtf S hy- drocytryptamine (S II f) into the venous effluent of perfuscd dog intestinal scRmenls and Iso stimulated the intestinal struMTrh musck On the rrther hand, the tnxxTth muack atimulatinR and S III rckasinR Irrofrrtirs nf nicotine and A( h were aiRnificanlly anuRonirr•d by atrrqrint. When isolated Intestinal stRmenls were pcrfused with (-a frre solu- tirTn, spasmoRcnic respnnses to nicotine were cnmpklcly elimin.ltcd and the respc.nus of the inlcstinal muscle to 5 Ff f and morphine were greatly reduced llFxTn investigation of the actinn r.f ('6 (henamcthrTnium), a selective and prTlcnt RanFIKTnic blocking aRrnt, it was seen that C6 (lid nrTt antaRonire the increasc in rntcciinal mntility by nicotine and 1)MPP; in fact, crTntrary lo eapcctations, there was a non siRnitnanl increase in the rtapcTnac to nicotine afler C6 treatnscnt floth nicntinc and 1)MPP were significantly anlaRnnired on the isrTlatcd intestinal seclirm hy S(NI micrnRram iknc•s of nicrNint. Possibilities rc considcrrd that nicotine and 1)MPP could enhance S-11h releasc and motility in this prcparalinn by stimulation rTf exlraRanRli- onic ncrvous struclures, by direct aclinn rm the chulinerRic recrplort ar, perhaps nwre hkcly, by stimulating a prq+ulatir+n nf ganglion trlls *hich are exceplionally resistant tn ('6 blockade. Other Rrentnr.: Amcrican Medical Association -- FducatirTn and Research Foundation and the ll. S. Public Ifealth Service "E?FTF?CT OF GROUP SI7.F AND CAGE 1)I?SIGN ON VOLl1NTARY RIINNIN(l A('FIVII'Y OF AMPHFI-AMINI:-'IRFATI-'U MI(7?" Ry Duane (3 Wrnrcl, Phl), rnd 1.. 1.. Elrnadie, 1)ivision of PharmacohTRy. Schord of Pharmacy, 7he lIniver,;ily nf Kansaa, I.awrence. Arrhivrs Inrrr- norionolrt de Pharmocod ynomir r( de 7 hlrapir 159/ 1: 154 1(A), 1966. ((7rantct: Wenrel) llx intcrrelationship ot group sire and care design in the mcacurement of voluntary runninR activity nf mice was studied. Mak albino (Y1V mice were placed in activity cages (nr a rrnc and onc- hdf hour period of acclimtiration after which eithcr d amlrhrt:rmmc (ir sa linc srdutinn was administcred inlralxritnnc:dly, and voluntary tunninR acliv- ity was recorded fr.r 60 minutes ( irnuFvs of Iwn, thrre, (our, and five cnn(rrTl or exrerirsTental mice per Rroup were tested in sinRlc t.eam (unrcllrcted), sinRlr t.raOn rrflrrtrrt nnd tnpIr hr.irn phntrr•krtrir acnvity unit tlrsiRns. 52 Rcsults showed thar, with the three cage desiRns cmphrycd, cage design and group size effected variability to only a limited extent. lluwcver, sensi livity to incre:rses in voluntary running activity was found to hc closely related to both design and group sire. With all three desiRns, a relatively low number of cnunts were obtained with groups of two ur three animals, but the triple bcanr cage design was more efficient than either of the single beam cage designs for measurcment of the higher nunsber of counts obtained with four or fivc animals per group. ()thrr Rrentnrr National Science Foundation. "SF'IMl/l-Al'ORY P.FTI?CTOF NI('O77NE ON lllh METANO1 ISM OF MI:.PROIIAMA 1 F.." fly I)uane (i. Wtnrel, Phl), and Larry 1.. I)roadic, l)ivisinn of 1'harmacoloRy and 7-oaicoloRy. Sthtrul of Pharmacy, Ihc Ilni vcnity of Kansas, lawrence. ToricolrTRy and Applied Phomaroluty B/):455-459, May 1966. (Orantte: Wenrtl) The effect of semichronk nkotine administration ulxxT the in viro response lo, and the metabolism of, nxprobamate is presented in Ihis paper. Thirty male mice Iraincd lo balance on a"ro(arod" were used to measure the duration of atatia produced by the inlraperitnneal injection of 2(K) mR/kR of mcprohamale, lhe administration of 2.2R mRikR/day of nicotine alkaloid in drinkin¢ water caused an immediate and siRnificant decrease in the period of laxu produced by the mepmbamnte. A simdar, allhouRh Iesser, effect resulted from the administration of mcprubamate alone at 2 day intervals. SloppinR the nicotine treatment restored alaaic tinxs to the uriR- inal levels. Nicotine, administered In vivo, enhanced the in virru melabolisnt of meprobamate br mouse liver hotnogenate, an effect which was apparently nne of enzyme induction since the administration of ethionine blocked the effect. Other Rrantorr National Science Foundation. "INFI-l1FN('E? (N: PROPRANt7Lt7F.ON FIFMO1)YNAMI(' ('IIAN(iFS AND PLASMA ('AlF:('WOLAMINE LF?VELS FOt.LOWIN(: ('IGAR FiI-1 F SMOKIN(i ANI) NICOl INE " fly Thomas ('. Wcstfall, PhU. I' It ('ipolloni, and A. C. Fdmundowict, 1)cpartmtnls of F'harmacrrluRy anJ Medicine, West Virginia l/niversity Medical ('cnter, MurRantnwrT 7'roHVrd- inR.r of the Srk i(ty for Etprrimtn(ol Biolagy and Mrdir nu 12 1/1 : 1 74 179. (klober 1966. "A('('UMUI.A/1ON OF NURPPINI:PFIRINF. IN RAI IISSttI: Pul LOWING IRI'AIMFNI' Wlll1 7FIRF1? 111?IA AItRI•NI-R(GIl' AN TA(iONISIS" fly llxTmas ('. Wcstfall, Phl), I)clrmtrnrnt rr/ Pharma coloRy, llnivernilr of Virginia School nf MedKlnr, (lIarhHlrsvllle Irr hnvr lnrrrnarion.ilrr di fharmocudynomir N dr 7hlrrTpir 167i I(r9 79, May 1967. ((;ranlrc: Wcatfall) 53

Thrse papers prescnt twrr diflcrrnl asl.rcts of the eRects nf hrta- mdrencrRic anlaRrrnists uryrn carduvvasculan crmorlynamics and catcthrrla- minc levels in the Plasma and trasues of latxxattny animals. 1be first paper details a audy of the cRcct or prr,pranolul, a hrta- adrenerRic antaRrrnnt, on the hcrn(><fynamic and catechnlaminc relcasin6 PnvPcrlics (.f ciRarctte smoke inhdalion and nicotine adminislration in the doR Cigarette smoke inhalatlon or intr-avtnous infusion of nicoline pro- duced a marked increase in cardiac outE+u1, slrnke volume, arterid blrrx) pressure and (Aasma eF+incE+(srine and nrxepinehhrine kvcls with a rcfk t decrease in heart rate in the rrw)rphine-pentnhart.ital ancstheticcd dog. Fol- NrwinR hrra adrenerRic bkukade wilh 0 2 mR/kR (arhnanolrr) inlravenr.usly,. cigarette smnke inhalation and nicotine Infusion resulted in  nrarkcd aher- atirxr o( cardiac oulPut, stroke volurne, hean ralc and mean arterial pressure without significant changes in eaval plasma ealecholamine kvels. It is concluekd that beta adrenerRie blockade produced by prnprannk>t r1<.es not modify the release o( catecholamines from the adrenal glands of rN,Rs in resf.r,nse to smrrkinR anJ nicotine and that the "unmasking" of alpha rcccPlrtt aclivity causes a marked increase in systcmalic (uriPherat resistance and comPrices k1t ventricular function lhe eflect of lhrre of the newcr hrtaadrencrRie antaRonisls (prone- thalnl. PrtrPrannAd and iproveratril) on the enr),rgrnuus and infueion kvcls of norclrinephrine (NF) in rat tissues is the burdcn of the second study. Pn>[tethalol produced a significant tkereasr in endogen(ws levels and a significant inhibition of the accumulatirm or uptake trf infused NFF into the heart in the anesthetired ral 1 hcse two rr(xervalions were scrn only at doaes larger than necessary to block the h.ra adrencrgic receptor and are prob- ably unrelated to the blocking Profxrties of the thu6 Prnpranr,lol (ailed to aller either the endo-genous amine level or the optake of infused NI~, while iProveralril produced a significant decrease in cndnRenous levrls hut only a slight and insiRnifxanl inhibition of uptake of NF. OtAer Rrantor.r West Virginia llcart Association and the Natirmal Fleart Institule X. Pregnancy Studies "S1Ot)IFS ON NIC'OTINF. ABSORPTION I)IIRINO PRF(:NANCY. I I.l)„F(1R PRFi(7NANTANhNUNPRFGNANT RAIS." Hy 1 Fdward King, AM, and R Frederick Aecker, Phl), I)eparlmcnl of Anatrtmy, I at>,.ra- tory nf Prrinaul Studrcs, Uuke tlniversily MrJital ('enter, Uurharn, Nrnth (-atoiina. Amrriran Jnurnd of Ohrtrtrirs anA(iYnnvrlrrRy VS/4 ti(IR 514. )une 1966. "SftI0tI SON NI('OTINF ARSORPTION I)(iRING PRfGNAN('Y II IIII I 11 I('IS OI A( IiII III nV1' I)Oti/ S UN MOIIIF R ANI) I NEONA7 FS " Ily R. F. Bccker and 1. F. Kin6. Amnir an lonunal n/ Uh,rrr. ncJ and (:yn.rrrlrrRy 95/4:515-522. June 1966. (Grantec: Ikcker / Ihese two studies deal with nicotine absorption during pregnancy and its eflecl upon mother and neonate. Initially, the 50 per cent lethal dose of nicotine for pregnant and non- pregnant femalc rats of the (hborne-Mersdel slrain and for neonates of this slrain was determined before estimating doses that couM he administered in chronic studies All rats were injccled subcutaneously with heavy drrses ol a 2 per cenl solution of •+ure nicotine. Pregnant rats received dte druR on Ihe twenty first day, one aay before eaPected delivery. 1 he following valucs were obtained: Oatxxne-Merwkl rats l-E)„ (mR/kR) Pregnant adul(s, 140 l0 150 darI of age 27 4 NonE+re6nant females, 140 to ISO days of age 33 S Neonates, 6 to 24 hours old 14 55 Pregnant rats tended to die significantly later than nunprcRnant rats, but their tolerance for nicotine was considerably less Alar, pregnant versu% nempre6nanl dillerences in respect to tokrance for nicutine wcre thc rcvcrsc of Ih.ne consistently encountered with barbiturates. In the second study, primipara pregnant rats, 140- 151) days uld, rcccivrd a single heavy subcutaneous injection of nicotine on the Iwcnlyhrsl day uf preRnancy. Pregnant rats responded diflerently from nonPrcRnant femalcs the same aRe, similarly treated. 'Ihe pregnant animals Irrlerated Icss druR and hyperventilated eacessively whik body temlrcralure Jcpressitrn was not as marked as in the nonpregnant rat. Many of the treated animals failed to build dequalc nests or to takc proper care of their young. Uclivcry was d.layed 2 to 4 days fayonJ trrm, the young Icnded to be lighter in weight than normal, and the yuunR survlvcd Poorly through the• first critical 4R h8urs of life. l he data Ivcscntcd hcrc do not su(qxrrt the idea of an e.lrernely rapW elimination of nicotrnc Irum tissues when it is present in rsear-klhal amounts. (lth.r Rrantorr l)uke University Research Council. X1. Other Studiea "F.XIFNSION OF FLF('TRON AFFINITIES AND IUNI7AI1(/N PO 'I F.NI IAI SO/-' AROMATIC F1YUR(X'ARHONS." Fty Rall.h S. 1lecker, rhU, and UJward Chcn, 1)eputment of ('hemislry, (/nivcrsiry rrt Etouctun, Icitas The Jou.naf ut Chrmira! )'hy,ir, 4S/7:2401 2411), ()ktutrr 11066 ((iramee: Ilrc4cr ) 1he elecuon affinilies of 14 aromatic hydnocarlwrns arr rclwrr/ed in this paper. Uala reported here and earlier show that it ic Iwra~ihlc ru determine molccular ekctroneRativilics ( X='. i( irrni)ation Iwrrcntial I electron affinity and that these are esuntially cunslant for the arumauc SS Sq

r I hydrocarbons. From the mokcular elcctr(1ncRativily values eilhcr ekctron affinity (F A. ) or Ihc ionitstion ptrtentia) ( I P/ can he dcterminud, depend- ing upon which is knnwn. lherc eaistt a linear relationship bNween F~. A. and the ener6y of the /!., transilicm (ll.,-hv„) fcX the hydrocarbons studied. Fronl val- ues,  large number of F-.A. values can be prediclcd. It dncs not appear reasonable to relate the inlercept resulting from estrapolation of the afore- mentioned plot to hv= O to the .•ork function of graphite. Ilased on the measured ek<Iroo afflnitks, k!s possibk to deduce a relationship with methyl affinities and caku/a1e AF?„/ between neutral hydrocatM/ns and their nxxxlncRalive k/ns. ('erlain thcorclk.l approaches can he suca:cssfully employed to estimatc ekctroe .fi{nitks of aromatic hydrncarlx/ns Ot/1er Rran(.rr U.S. Publk lkalth Servke Rccipicnts of (;rarits I ullllwing is a list of all recipients of Rranlt approved by the Sl icnlilhc Advisory Filrard since initial grants were made in late 1954 Srane ul nce projecls havc been completed. CRANiFF. ANI) INS1iITIrT10N PR(UF(T Tfil.P. ( I ARI N( 1= M A(:RI SS, M 1) ('hr./, MtasuremeM of Ihe funcli..nal solui of (orAun.n.ole. /.A.n.rrrr, VNtr.nm tht human htart by frtttutncY spcr Admnmar.lnrn ('enlcr, 1 os Anrrks; Irum •nalysn uf its rrh.auonrt tnr.tr An.nr.rt ( frnrul Pr.r/trww n/ Arr/.. .rn., Ilni.rnn) ul' ('.Idorni., Im ' Antelts ANtllONY A AIRANFSF, Pnf), /h. rr.bv, Nwr.nn..n an/ M.trA.rlic f7.. i.nnb /h.r.r..n, llx Rur1t Rthahihl.. turn (enter, Whde Plains, N. Y. AN11IONY P AMAROSE PN 1), F R- M S, Anrrranf Prn/.u.v, Drr.rtrntnl n/ Uhrt.hu r an/ (irn..uln~~, The AIbany Medreal ( ollege of l/niun (/ni .enilr, Albany, N. Y. F 1 AN(;l I AKOS. M 1), PH O, Pro/nr.rr ../ Phrrnrl..fy, Roslon llm.ersrty tich.wd of Mtdicine. Roston lhe eflrcl of nicotint on prolcm and amino acid melah.h.m rn humaof FRecl of nicotine on human mtlat><rh.m of amino acids fhron.mon.e palltrm in palknl..rrlh car amun. of Ihc lunt, helore, durina, and aher Irealrotnl Rtkax of calectwdaminea ho.n the iw Lced htarl I) MI/RRAY ANGF.VINF, M h, P.o Pathoh.aic anatomic +lu.t) of crllutu /rnn. .r/ rorl..rloRrllni.rrsilr o/ Wnch.naes in human Monchi cnmin Medical Schoot, Madison: IX)MIN(:O M AVIAIX). M D, Pro/.r- Jnr n/ Pho•ma.dnR1, t/nianitti of Ptnm)Iv.ni. School of Medicine. Phil.dtlphu STFPIIFN M AYRFS Mr1, ni.eccnr, ('orJrnpufnr..nn.~ l.Aor.nrr~, SI Vin FRecs of nicoline and cigarette snw.lint on neuroaenic mech.msms in Ihe lunt Tolerance of IunRs lo lobacw with special reference In~ .imon.ry emphyurna and •ascular occlunre lesions Measurement of .Lrobr .rlenal ndrurn drRtrrm-r hy a.t chrnmalop.phr ctnl'c Itrnpnal, New Yrwl (lly. Tht ditlnsing t.pacit) of the .Iveolar mtmbrane in pdr.wrnar) emphysema Retaion of air pnllulw.n to deak.pmrnr of chronK PUInN/na1) dlsLte TTe eRerts of ineaaurrd small mrerms of c.rhutr htnwrflohin on r.rJwrt.rwra tury funcliun in man rt. In tr m m m J F.. 1RrhFRIK H HAN(1, MI), l../...•~ anJ ( hurrman /Lperrm.n/ n/ P.th.rM.d..Ry, the Inhm Iloplim llmvtrsi/y. S[A.Md of /iyR-cnt and Pnhtic /lt.llh. R.himrwe 7 Inler.clion of virures with muro.s of she rcqwrNU/) IraU, and I/K tRc./ nf v.ru Ir.n In (unclia)n nf Ihc muc.Krlnrr rY• Itm l.~ Ch

(:RANiFF. ANI) tNITtilrTIhN RRUI)A 0 RARNI S. M 1), Pn 1). P.r. /nrn. In~.harr) n/ PAlu.d..tr, ( oMraJn Ct.rr (/mvrraty, 1 nrt ( nlhns / RFI)t Rt( K W RARNFS, 1., M I), Pa I) , Arrrr..lr Prnfen.rr of Aerdwine and IArurln~n.l t Arwrrurt, Jnhrs Ih.pllm tlnrvtnd) ScMnl of Mtdr c.rw, Rallrnnnt. MJ (nnw Prolnsor of Mrdreal Srance, Rrown (Jmvennti, Prnv.dtnce, R I I T(- SARNFS, 1)Sc, Rrer.rrA Srlrn nrr. Ph.ladetphia Stut Hospnal, Phrla. dtlphra R/ RF1/1 RI( K Rt ( KFR, Pa I) . Au.r rwrr rrn/rrrnr n/ Awer.•w.y .wd flurr lor, I.hrralory of Ptr.nalal ticrtnre. 1)ult Umverat) Mrd.cal ( tnltr, Itur ham, N (' RAI P/1 S R1 ( KI R Pu 1) , rrr./rrror ../ ( hrwruur. llnnrrsrtY of /lr.uunn Ilawlnn, tecas SAMll/l Rf l I f T. M/l , nirrrt..r, ni vrri..w of (w.dn.fner, Philadelphu (;tn eral 1hnp.lal R 11/1AGA1, Pu1), Anhr.w/ rrr./nn.r /n I'hnrnrar.l.re., Ne. Yorl Mtdred ( rdlt/rt, New lornl t I S^RI RIAN( I11(1R1. M 1) ILvlri.•n PR()JF(T Tt11 F. A! piakminlnRy of hrnA cancer I taminal.on of such faclnrs as .nhentancr, audrpsf rerynJS on rtlallvec, rtsrdtnct in unlavocahk atmocphrrr, wmlint cond.uons rtlalivt to hedlh hatards, personal haMls, pail rllnrsxr, etc S The role of the dtcrease in luherculnsis fw the rise of lung cancer, emphysema and myocardial inl.rction The rok of hYptrplasia in Insue rtspnnse 1n chrnn.c dam.Re lbe tRecl of inhalalion of ciRarrtte smo\e Und injrcted nKMint / on karning con. drlinned refk.ct rn rals nd on the .cQuired neurotic hrad Iwitth in isoIaled mke Pmsrhk eflecls of malernal intake of nKOhnt uprm the Jeveloprnt Irlus anrl nrnnalr A sWdy with Ihe ra aml a.unta pi/ An rnvnutalhnn of s~{e clral paramrlers of arnn1a/1c hYdrrKarnl.m A spectral in.tsliRalion of rnrnalic hy dn.earhom and their cr•mpletet wilh proteins lhe eflect of nicotine on cardiac irrilalinn in the presence of rtscrprne, and the ef fccl of nicotine on cnronar~ hlrsrvd flow ot dop wilh eoronarP irnufRciencF FRecls of nicotine on Ihe mtxphologr of eoronary arlerks and aorla; Rbrinnlylic eRects of nicMine on hrman and ani mat plasmr; eRecH of cessnrnn of tnsolinR on terum ehnksttrol tevel' al ehrnwic smoltrs: Ihe tRec Is of ciparrlle amole on /rre tally acid Itvrls of sah jtcts .ilh myocarJul inranlinm The tflecl of nicoline on varinus param- tlen of cardiovascular funclinn Iht mrrhanr.m of mcncira inducrd re lease o/ ulrcho/.mints t unR Iumr.rrRrnrais by isnnurid I IN1I1, n. mrril.~ldr hsArarrnt vrlrha/r (h-s / .n.l .Lr~..r~.rc n/ hldr.nnr Nrw (w. r (:RANIFF ANI) tN41111/1t(/N 11Y1 AN A Rt( KI RMAN, M 1), Atrrr r nr.r ( Irnn nl /'rr./r.c.n n/ Afrdn rnr, •nd At VAN I RARA1 H, M 1), frrn o.lr,uu rn Alr/nrnr, ( nikttt of PhyJ tians anJ Surfienns, (folumhia llnivtr suY. ( dund.ra (Imvtrsny Rtstarch \trvwt. (.utdwalrr Mtnmorial /lnsprlal New Yorl RI( IIARU I RIN(i, M 1), Prr./rnnr of AIrJn.nr nw,l ( hnoman, llrpwrtnrrnr r./ AlrJrr rnr, Wayne Stale llmvauly 1 nlle/le uf Med.crne, 1)elroil I 111 1) /i Rtl( K. M S, Prl1), .frn6// (wnr rr Rr vrur h Sr renriU, Roswtll Phr l Memnrial Insldult, Rudo[ical Slalrnn. SprinRvdlr, N Y (ste Mnore) HI-RMAN V R//FNIO, Pwl), Hr.d, ( hnmv.v anJ Rr.hhrwriur~ nr(..rrr wvnr, \pindlrn.p Research ('enler, I tt inRlnn. Krnlurlr 1AM1 ti I R(tNNI R, Pn 1) • rrnfrrrnr r./ Ilr.rl..~.. 1 ahforma Inslnult uf lech nnlr,ey, Pa...kna WAI 11 R M R(K)KFR, Pn 1>, hr./rrrr•r nnrl Ilrn,l. Irrpwr.nrnr ..l Ihnrmn..~l IluwarJ (Jnirresdy. WashinRrnn 1) 1 PRIIIF(T TIt1.F: lenlia) carcinnRrns for the human /ung (IN11 L h s/ have hren JtmansLaled in prtvMNH etpermanli on miu 1he ainms of Ihrs prr.jtc1 .re1 lo study whether Ihe carcim.gemc actnun of IN11 ae.l hs will tale place in apecrrs uf lahoralory animats olher than meet, anJ It 10 sludy whether dhtr denrvah.es of hydrauine are c.rcrnugemc lor mnt Nnn irritant ciprelle smnlrnR with ob servalions nn the carf.Mm munntide cnra-enlralion of arlerial h1.waJ anJ alvrot.r Rat d/tr troulinR wnh rnhala /iun and afl(r rwrn rahalalic.n •rnolrng Ihe r/1ec1 of a non rnhalhnR Irchmet.w u( titarelle srnoling on Ibe carhan monoq ide h/rKw! kvels anJ venlilalrv) func lion of healthy tuhjecti aml palitnts with chronic respiralory drxase The eflecl of smoLing r.n the craunary blood flow ancl cerlarn phasas of myo cardial melaAolisnm in palirnls wlh arlctio.c/erolk or hyperlrnuve urdr osatcular disease Sludits In cellul.r physiology of Lrarl musck Measurement of coronary bAax) fNrw by rntant of raJioaclrvaltd alM.min Tlte effect of smn\ing on coronary hlrw.d 1bw (n patients with artern.x/ernuc heart diseast an.l the eflrcl uf mcoline on slor.ge of amines in heart muule Measurement of conmary hhrw) 1h.w wilh a system using coinciJence cuunlins Ihe eRecl of nicolint and chanRe rn heart late on carduc meu(.dum arwl related whjecls Sludiet on cardiac mrlaM.hsm with spe cial ttferenet In rns.•rardral aru.ns InvtsliAaliun of Il.t hi.dnRu.l eflrctr uf cigarellt smuYt An ini/ul NuJy of the rRrcl nf mrrlrl hrr ruhc als in carr inuArnru. 1 nryrnaUc shr.ly uf mrrhylar.,n rr.. rn.n. rn plant Lcwr Snrdirs on Ihe Mssihlt srnutu.rn.n of Ihr vtalular mrchamsm 1., carrhr.lemrnr. (n1luw.nR nu.,hnt a~laumur.ru.n ~ v iN 59 ~

CRAN1fF. ANI) INtllilr1t1/N 101161 G Nl1w/ R Y, PM ly , rrVrr rdr Rrt rdr.r laA.•rnr.ry, (hrmhr.y llrpe•I mrnr Nutth ( .rohn• CINt ( ollrAt, R./eqh Inn+ I elr.murd OPtran.nt anJ PrrKedurts tMrtrr, Ikpertmenl of l/tadlh, I ducaunn and Wrl/are. Se thrsJs, Msrylaml/ (41111 1 RI Y I PRINKMAN, M p, As s.nrnr. rrn/ru.+ al A/rdr.rnr, W.ynr S1a1r 1/nrvrrtrly Schoc.l of Mtdicrnr, Iknoil /1ARRARA II RR/1WN, Pwl), Rrrrer.A rr.r/ru.r r•I f.prnnvnref lrr.Amr.t. ( a/dornrt 1.dlr ft of Mtd.(rnr, I ns /1ngeles 1OSI / RR(II1 K, P041). P.nJrta.r and ( An Irrlv.l.nrwr of rryrb.rl..fr / rhyh 1lmvrrsdy, Rrlhkhtm_ Pa SIIF Rl/( KINGFIAM, M I) , Aruuswr Lnlnrnr n/ rrd..r.r.. ( ulumhu (In. •trcrh. ( nllryt of Phyuruns •n,l Sur ftt.ro, Nrw lnrl 1 ny R/~NI^MIN HI~RR/1WS M I1, An... •rr !'rn/nr•r n/ AIrJ....r linr.n..r. of ( hnafn. ( hn.fo I M S(T1'1, M I), ( Mr/ rnrh..t..tnr• l os AnRelrs ('ounly Nrnp.l.l, I rn Anfek,. I ahfmn,. RI('/IARh lf t1YFRRI/M. Pt/l), r.n /rttor of CArmlrrry, Michipn S,aue ltmatsily, Fa.l 1 .nsing S1S1FR M FMIIY ('AFIIII, Pnll, ( harm.n, ( Arnt/tby flrr.ctmrnr, Refis ('olkfc, Weston, Man WII I IAM // (ARNI S, M 1) , r.nf.rr.•. n/ r.rhol•.tr. l/nrartuy of I/uh ( ul koe of Mr.hcrnr. Sefl 1.1r ( rly , MAR(11K N c'ARRUII, /., Pu1) ( 6.r/ f/n . o/ rAernw..l.•ft l hr h-oldak /ll.np.r.l / rwrer. (h...Urn N IF PRIIIF(T Tf11 F. II/F .nd tndrin reuJuts in crRarnrrr smule T)tt rfirr/ n( crgarrlle amolrnR on the ulna nnttn.u.(..c slrtrtlure ul the laon clu.l muttna N.ac.linr an.1 tmnlrq tRr.rt un tlrclrn tntrphaln.ram torrrlan .~f /+h..r..r emolw.nsl rrtpumr.rnr.s srwl .nu.l prrcrplmn m c.ls R.n{nfiral tharsclerislus tuf men and /htir sntnlrnf haMts Sludrts on the drvtlopmenl and h.uloRt ul Iunf nu/attanl lh.u.cut tnmplun.t rn hrnmt oh+lruc u.t Innt dr.raw A tnrrtl.hnn n/ stvtrny of symplomt nl tMumt nMln.el.ve tunR dntase wrlh en.uonmrnlat frctors P.rholnfre snalom.c slndy nf celtular chanfes rn human hronchi Study of 'Ir.ce mtlal sloraRt of pulmon •ry .nJ Irver tissut hy spectrollr.phrc and chemical rnelhcn/s Hiosynlhesrs of the pyrid.nt rinf of nnro line ('omp.riu.n of an[lylical mtlMds by Jtltrmining the pertrnt rtcovery of .rsenic added at known It•els 1o lu h.cco s.mples and a brnad survty ol the arDnnnl of arstn/l prr.tnl in In h.cco sarnples /rom  -rde v.riely of stwrcef P.I/w.InAu rnalnmrc th.J.n nf trllul.r r h.urrt rn human hrurn 1.1 ( tnnal ntrvna. sYslrm tvnleJ rAm... and .ro..nary hh-l n..w srrhy t I:RANIFF AN[) INTl1ilITIf1N I 1 01411 1/ ( 1 R I( I-I K), Pw 1) , rrn/r. .•.r n/ Rurhrmm~y and Nar.m..n Ilmttruly of Putrlu Rko, Schrwl 01 Medrerne, San lu.n (lorrnerly Profn- t,.t of Nrnchemalry, Iofdh.m Uni.ersily, Ncw York) NAIfFR M( FI(/PRA, Pw U, Aas.nl.cr Ptn/runr o/ ( Armrnry, the Agrstrdlur.l nd lr(hnn.l (b1kift of North ( ardrne, (:reetnMtro. Wtl 1 1AM U( 1 ARK, Ptt 1), ( hnl..l Arurrnrr rrnfrnnr nf PAtnulaerur ( hrmnny• I/mrrrsrl ol l'.Idorma Mrdn al ( rnrrr, I ns Xnork• IIANS 1( I ARKF, 1)Sc., rrn/ru..r o/ Ru.r Armuu r, ( olumMa llni.ersity (ol lege o/ PhysKram .rd Sur ftons, New Vurl l lelired, see Gabch.ll ), /AY 1) ('l)1 I MAN, M 1) 1 Srrnnn Hr./ Perrphrr.l Vscular IaboratorY, llni srndy Ihnpdal, floslon. I)ANIFI ((/111 N, I) V M, M P 11 , Aa. sulnn/ rr.r/.u.rr oJ Vrrrr/na.y ErrdrrnL n1..Ay .nJ ruAl.r Hr.kA. School of Velerinary MeJicine, l/ni.enAy of Penncylvanu. Phdsdtlphi.. 1111 IIIS II ('(1MR/1F, 1. , M I)., I)lrrr. rr.r ('n.Jrn.n..uler RrcrmtA /nrrhulr, 1lmvtrsdy c,/ ( alrfntnu MtJKrI ( enler, San 1 rsntisco. I1/-AN M( ()NN(1RS, M/), AurMfslr Irl.r.rn.. lrrpmrmrnr n/ I.A..n+r..ry Alydu rnr, Sr Mary s H.npi1.1. M.dr v.n, Wraurnin Pllfl IP ( Ix)PI R, M 1), Chief. Surfl..f Irru.r, Verrran. Admrniatalinn 11.n piut, I(ron., N Y,( Irnr.al rrn/nr.n PROIF(T lftl.f: A study of tarly t hcmrul ( han frs .n the lungs of lumur hearrng rat and mr(e The drpedaion of 1/1/1, 11)F- and Urt/ Jrrn in the at.relle rn..n.uum and srJcslream smules I Rrcl of mtobnc aml rtlaled subaamcs nn •nnnt levtls in Ibe r.rrvuus syslrm Prottolytic .chvlhes of the w/.ile h1ouJ cclle of men and the eflrcl un whrle blood cell aclivrttes, of carumraem, nultilion .nJ olher influentes The effecl of R.uwolfl..nd (7uanelhidrnt Icnltclsol.mnt drpkhng or bk.cking •igtnls) on the syn,palltelic vasrKon slriclion induced by Inh.cco smolrng sad by environmenlal hot)r cooling TTst tok of cutetM.l.mrne relrat frum the .drenal mtdulta rn causing the ctr eul.lory eflrtn seen during tubacco .rc.oking Tobacco snw.ling in human auhjocH dur. inM beta receptor bltact.de To survty radiosc.p hically Ihe lunlfs of all dop pattinR IhrtroRh the velcrrnary elinks and Mnpil.l nl the Vniversrly of Prnnsylv.ni• Velerin.ry StMrol in order 1o delermine the prevalence of pulrnon.ry ahnorm.tities delectable by lhis /nelhod- • comp araivt pulmon •ty disease a/udy lo Jrflc.r IAe pal/rtm ol respirawy dist.se in •nimah in limately shaing m.ri s en.inonmtnl and provide inlormauon on the tRecls of sit pollulion lhe eRecl of smoling up..n airw.y rtsnl •nce Analysis of e.x hislories on rmphysern• A sludy of the •llrtsuons in the hum.n hcc.ncM.l wall oaru.rrng with qrng wnh par/itu/ar e.nph.sus nn rlasrlc lu sue thanges and as.auled chanfes in the Mortt hisl lumen sire A slndy of the tflrtn uf cifarellt smulrn~ un Ievrls 411 11alric acrd, pepsm, an./ woprptin .7• _~ /.11 61

CRANIFF AND 1N1iTT1/T1ON ol ~r.rer~I. Alberl Frnstein Medical ( ollelle. Hrnn (/nrrntrly r..•lr.N•r n/ ( lrnrrnl l/o,lon (lni.ervly Schonl of Medreine .nd ( Are( of SNrrr rnl te.rur.nd I)rr.l.rr nf Sr.rifqs/ RrtrarrA lnA..r.rr.r•r, Vrler.n, AdminHU.IN•n /InsMl.l, PrnrN)ence. R I ) IOIIN F (RAI(iHFAI), Mt), Arvrl. .te a rerA.rl.•tr. ll.r..rd Medie.l Schnol, ll.nlon RORFRT I ('RAIN, P.rD, Auirl.nr Irn/en.n rr/ S.rr.d.rA1. tinivtrsrly of ( hrc.Ro Isn 1' Kslrl T lIM(1TFIY ('R(>t KFR, M f), P.n/tr- ni, of A(rdreinr, f)rp.rlmenr of lnrrrn.l Afedr.rn., tlm.tnny of (.hfrnrn. MrJ ic.l ( enter. S.n I r.nci,co CF/'ll F ( ROSS, Rrse.rch Ikp.rtmenl_ SI lvseph Ihnlwl.l Rmh.n1, ( .Idrrr ni (we s.li4hury/ AIRFRJ 1)AM(IN M/), Prtl), Aun Innl rr.r/rrNrr of A(rdrrsf AnrA•nryrl nl)'. hr/ar/mrwr.•f lndN,ni.l 11sR,rnr, Ilu..rd Stlwr,l uf Public Ileallh, Mnlnn R F 1)AWSON, Pn 1) , formtrly P.n/n rnr n/ Roranr. ( olumbb• lini.er,dy, New Yort. ANI/RFW S 1)IRNFR, Pt/D., Free— Inr, /rycArr RrrrorrA, lhe Age ( enter of New Fngl.nd. Inc., Hc,slon, Mas+ I,te Whislin) I~f)WARI) F. IX)MINl7. M D. Frn/rrr.n rr/ rA..m.cnlnr,, Ilnirtrsily of Mich igan, Ann Arhnr. RAI P/I t. fX)RI MAN. t+rr f). IHrtc/nr n/ IiA..r.Lrrrrl, W/NerMel Iou/xt./rlrn (r~ 1 Ptrrmrnl.l Rwrbgy, Sh.r.,lmrr , M.s 1 nor sl Cynlt. ( urpnr.linn, P.Ir, Alto, ( .hf sre MtNlstn) )AAU ', I It)'AR, Prn )) Annrsnr Prn I.r..,. ../ t4..l.•r. N.Il.cnune ( ollta 1....r..~Ilr Ar PR(UF(T TT11 F. A sl„dy of Ihe enecl nr ttlr.rH ..f 1nh.c cn on cuhurrs u/ Imm..r anJ rwxnul cells. Anrm.l Ir.rttPl.nt, nf lumnr li, sue from 1r,a1/e cU11Urr, Sludy of coml.ined tRecl of rnjrcled vir.l •ge/1ts •rxl env/mnmrnlsl 1•cIM,, in elw)ing ca.clrw,ilem and tob.cco smn\e, ow the Ir.chroAronchul Iree and prdIrson.ry p.renehrms of r.prrimenl.l •wim.ls .nd on Irs,ues in orit.n culture S/udks on Ihe combined rRec Is n/ inlluen is .irust. .nd sulphar diociJe on lung pNhnsitrwis in Syruw h.mltrs Riolony .nd cytnM`.thk eRect+ of re,pir. brT and oncolienrc vuuvs in Organ cwharri of human resprrelory Ir.cl lis.ue Social and p,ycholoRk.l correl.les of .do{Nion and dr,conlinuabn of cill.r elle snxr\rng Riobgic .cli.ily of lob.cco Lr on reepi- raory muco.a of rn.knH, canrnes and Ivrmae, /n organ cullure; a hi.loloolic •nd .ulm.drngnphic sludy I Retl, of ,mnkinR and of nicnhue nn Ihe hr.rl and cuculelron An udrstraire ,ludr erwly 1orm, ,mn\inR, .rxl .Ir.•hnl tnnsumplN,n Among Italian Amtrra.n men An inrertiRNrrrn nf the rntt.Mdi,m of p)ridrnt cumpnunJ, in she Inh.ceo pl.nl P,ycMdnRur.t and beh.vior.l chsr.cleri, bcs of rnhsttr, .mun8 srnnAtn I Rtch of tobacco ,mn1e .rd nicoline on Iht central nrrrouf sy,lem Fv.luair.n of /nh.cco cnn.umplian on Ihe h.m n/ m, u/me or nu oluv mrl• )wrhlt, rn 1+•le RurJ, .n.1 ..rl.rm m~n nuJe conltnl of hlr..d Nnrnicnlinr rnmtninn .rn) rr.ullinss Prff nKnl ch.nRri in ctrl.rn ..ntht, nf r„h..cn (12 CRANTFF. AN/) IN4TITtT1(1N RI( IIARI) /1 I ARI F, M 1) , ('Aie/, Iul. ~r.rnur t F unr nnn I wla•rolort. Arrirr.nr Prn/rrt.v ol Aftdrrrne, tlnirenily of ( hlcrllsr,, ( hKrl(A i(t11N W 1(KSIFIN M1), Arrulanr Pr.r/rrvn r./ In/rrnel MtdN mr, ( ollrste nf Medrerne, Sr.le (lniversi/y of Iowa. low.( rly R Il('FIF1., RS, l)1)S, f)lrrclnr. Inul rNre of S/nmlr.rlnAN/I Rta.nA, Salclat Re,r.urcrs 1 oundainn, C.mArN1olt, Mas HYMAN FNGFI RFR(7, M D, Alrend. ing, 1Aaitlon, ( ed.ts of I eb.non llor pil.l, l.os Angelts. CARI 1nN K FRI('KSON, PM D., Ar• rrunnr Profrlrn, of IA.rnvcnlnfr .nd Jndtul..~r, Schr,ol of Ph.rm.cy, lhe t/ni.enily of K.ns.s, lA.renct. WAI.IFR R FSSMAN, Pw t), rrnJrrror of P.yrhnlnR., (Juecns ('olkge of Ihe ( ily of New Yorl Flushlng. NANS 1.. FAI.K, Pu f), Senlne Rrre.nrA ArnNiale, nrpar/mrnl of LrAnlr.F,, t/niversity of Soulherw California Sr hrwd of Mtdicine, 1 0. Angeles (now Ilr.d, (hrmi,tty Srclion, (.rcinottenc u, Sludies Rrnch, National ('.nier ImtUlule, Helhexle, Md / DANA I I ARNSW(IR1/1, M 1), Nrnr) A Utrre. I'n./...,.. .,I II rRrrnt .nd Ill r.rr.. uI (Jnn.rmr l(rslrA trrrNn, ILrr.rJ I/mversuy, ('.rnhndtt, M.+, I ste I leah and Mc Arthur ) 1 RANK (' I FR(t1/SON, I. , M 1) , ( Am.nron. Itrpnamrnl n/ rAa.mm.•/ r.er, Albany I N )' 1 Medrul (ullrfrt PR(UF.(T TITtI. Fap.nded.n.lysi, of Prdmnn.ry, /nnruon dae using computer lechnryoes Resprmxs of Ihr periphrr.l veins in man to Ihe inh.venous .dminislr.Iron o1 nicotine FnM blood M1ow responses to smnling in Ihe prr+ence of hyperliprmi. nd by pertension Mtl.b.lit' iMtrrel.lk.n.hiry, Irelween to b.ceo .mo\e and 1he human nxxdh SrnoltinR •nd Ihe Ihromhnsfs of hum.n blood: meeh.nism and prcvenlion Meeh.nism of k.rning f.ci/il.lirx, by nkaino Sludies of nkoline .ctron upcm memury tor,.ohda ion FR.m/n.1qn of ciRerrlle paper .m1 ril.r ellt \nqle tnnJemaes fnr •rIM1a1K polycyclic hydroc.rhnn, A compl.lirm of fluore,rencr s(rUrs ul pnlycyclk •romaic hydrr.c.rhons and closely relaed cnm/~wml, wl.ich ere of inltresl in Ihe ,IrNly u/ .ir prdlul.nH, and eig.relle smu\e in rel.lion to lung cancer elinbly lhe eReclt of loh.cco smote corNtansalt on Ihe deferoe mech.rn,nn of the ra • in delosi8c.li..n of p.,lycyclrc uomalc hyd;ra.rhons .m: the cumptlilive in Mhilinn belween the p.Jycyrlic hydru c.rb.m In condensate with rrprd to eaeinotenrsis lhe physk.l •nd chtmiul prnptrlirs ol mucus ur.der r.ormal runJrlrnn, .nd following c.p.nure tu .erowl irciunr, Prrson.lily •nd ,mn~rn~ in tnlltRt Ilr.A uars. a Fllttrn yr.r fulla.- up uuJr FRecls of Ir,l.uro unole up.rn Ihr (urx hon of Ihr cudrn....ulv r.rrm m •nrn+.l, •nJ m.n 61

1 CRANIFF. AND IN4TFT1R1(yN T IIF(/1K1RF N f INI FY, M 11 , A n.vr at, P.../rrt.N nf A(rJnrnr, 1he l/mar v(y of New Me.,co %cho.d of Mrdr<Ine, AlhuQuerQue WII 11AM I 11C1111FIN, M f). (under 1he direction nf SAMUFI- 1.. ANUFI.- MAN, M 11 , M P 11 ('ornm:nawer of Ile.llh). ( Arr/ rpr~rnuo7nlir(, Cb(- c.lo 14..rd of Ife.lth R(1SSF1 1. S 1ISFIFR, M I), ('A/r/ Mr/- l.d Et.minrr, Slw/e of M.r)Lndt Pro- fruar nf f r1r.f A(rlklnr, l/niversitf of M.ryl.nd Medical School, R.hin.ore lt 1/ RFf l)1 AN/yFR. M 1), f)brrl•. of ('nnrrr Rr.r.rrA, Mount lion llry pil.l and Medical ( eMtr, San Fr.n esco Ideceased, sn French) / RFI)FRI( K A F RI N('/l, A R, D/rrr- h.r of (-.n.rr (ArnuMAr..Iy Rr...rrA, MnuM 7a.(( 11r..p.t.1 and Medrr.l ( en(rr, San / r.ner.co Isrt f rerd Lndel ) )A( K I R/(IN11, M I) , Arrirtnn( Pn1fn n.. r./ "d,.rr. Mrdlc.l ( ollr/e of Vnpnl.. Rlthm..nJ (i /1 F R/f hF11., M D, Srnlor Rrrr.rrA A(tolr.cr, (anrrr RefrrrA /nlr/r.nr, New I~nll.nd 1)racones. Floepil.l, Rcn- lon ARTFIl1R F(1RSf, Pr(I), Dl.rc(nr, in (frrrrr of (-Armw.t RioloRy. l)ni•ersitry of S.n 1-r.nci.co UF(1RGF. (1 Y, M fl, f)brr(nr I.wvr IM.vll ( .nrrr Rrrr.•Ih fiA ora.ny; Ana r.rr rrn/rrro, of .tr.- jrr7, Irrhm Iluplin( l/ni.ersitY Schnol of Mrd/une, 11.Ihmort, Md PR(y1FCT T17T F. 111t'cl of cig.rene smnlinR nn Irprds and morpMdngy ol •l.rnl.r IIn.nR nulrrral and m.cropA.Rrf P.Iho phys.dnRy of lung in /eriallic pa IKnl/ Palholngic .nalomic +tuAy of cellular ch.ngts in human Mon(hi F.perlrntnls nn /ht p-f.hle r.rtira.len{t and (Ma1clM.ttnlC .(INIn of ll.h.cco products ( .rcinnsenicity, eocuclnogenkily .nd an/l carclnnRrnKlly t)1 drrlary fKt(/1• in rrl.lion lo p.dm(m.rY lumors Pol ul.k inttr(clatlombip of tol.acco h.sc. and dret.ry f.ctors (hemicd cludiec on pyrktine h.w rncluding ni.crn .n.lnp ( nrrrlan+n of mullitrchnic.l prncedurrs performed on the ptripl.rral cnculalion nl nurm.l /ndiv.Ju.lt /n rtcumfrM and erect p.mlnon..nd afler rcercr.e Ixf(we and after sham and lluel snw.lind A study of the eflects of rilvetle srnoklng on the peripheral cnculation of imli •idush wnh •ryrrlMrIerMl7 ohliltrwn( and other peripheral v.xul.r dise.ses. ultilirin/ mldnlrchnic.l procedurn Tfie pNhoffenesn of human M.ddrr e.n cer A controlled study in e..lute the effect of .dministr.lion of Ir.ce mel.ls (wilh or with.>,II e."ure to ciprrc e smole 1 on 1he incidtnce of p.Jm.mary .deno m.s in Susin A mice Nickel in relNirm to the smokint and lung cancer problem /r1lo.rhMps fnr HudyinR Ihr (uhure of hum.n long h(arr •nd t/a rflrcl( uf Inrwn .r.,t p.nvhk (.rurwr~rnit elrnl( upnn fu(h tnsne ( h.r.cleri.Uls of normal (rll lrnwth In cullurc in rflalon lo in.ai.e C1re111- onu, r(pru.lly in Ihe lung h4 I:RANTF.F. ANI) INTIff)-IfTTON 7/1OMAS M(i(K'KF., M 1), Auorlerr Prnfrarrn of rrrrrnrr.r Mr/rrrnr .nl ( ommum(y llr.l(A. New leney Sltle ('olkfte of Medicine and Iknlnuy, ler- sey (1(y. N. 1(nmr wl SLIe Uni.eraitp of N Y, 11p.ute Medical ('enler ) PA111. GUI DHARFR, 1)DS., Auor/as rro/raa..r of rrrodnnrolofl, Il.rv.rd School of Ikntal Medicine, Bolow. 1)AVII) M GOt I)FNBFR(i, Sc D, M D , Hre/, /)rp.rrn(rnr o/C'lrn4.l.n/ t (Prrrwrrnrd (Inr../.>!r, ChirvrRische Khnd, I/niver.ity of Filaqew NYrw- berry, West (krm.wy. IFONII)1? GOIDSIFIN, I)3c., Rr- ar.n h S( lrnriur, errr.r o/ Rrar.r.A !n Nrrrnl..ry .nI rqcAl.rry, NrwroPAwr. m.rolnrp Sernm.. New lerxy Neuro- p"ychiark Imlilu/e, Princt/on I R A (3URF., M 1), rro/rrsor of P.rAol. oRY, Ibuon (lnivtrsit] School of Med- kine: CA/r/ of l.Mr.(ory Srrrirr, Velerwns Adminitlrwliow Ilospil.l, West Roebury, Ms/ (7FR1R(/DF. Y G(YTTS('l1All., PI(D, Ar(ue.nr rrofrrfor of Rio.Arnv(rry. I)ep.nmrnr of r.rholoq .nl A(4n. Arnlotf, l he Rockefelkr Iwstilule Iw Medicwl Rese.rch, New Yo.l. (ser ('l.rke ) A CI ARK (iRIFFIN, Pn D, Nr.f of sio.Armiprrr OrP.rrnwwr, M O. Aw- derson 1lospitsl wnd 7unwr Institute. l)ni.eruty of Teau Medical ('enter, l lmnlon ARTIIUR I.. (IROS.S, M S., Srninr f11o chrmi.l, Southwes( Rex.rch Institute. S.n AMonio, le.af M(yRTON I UR(KSMAN, PH L)., M D., A.rrar.rr (Irmrd rro/ruor of Mr/r(rnr, Univenily of Cwliforniw Medical ('enler, I oa Angeles. ('ARI C. (iR1/1171T, h( D., M D, Aaao- r.nrr in rAyaiw.lotl and IA.rn.wrolcqf, (Ini.er+ilr of Penws)l.ani. (:r.du.te Schonl nf Medrerne, PAil.delphi. (now I rcl.uer in Phys.o4.sy. Uwaerdly of /h.ng K..ng) I RANK 1' (71/111R1/, Pr( 1), Pro/n.a., and FRNFSI NO/K)SON, Py(1), Ar- nnwn( Rrrr.nA Prn/runr, I)rp.rln.en( r./ (•.nrnn..,fnRr. North ('.rolma Stae ( olkgc, Rdrilh t RWN(T 7111.Y. A study of the nasal and ph.ryngr.l ba( leri.l flurw of amukcn, rrm smolen and e.snnobtrs lTse produclinn of wnlihodny 10 lob.cco smole condensw4 w smo4e in .nrm.l, wnd hum.ro Hclerdr.mpl.nlatinn sludres with human /uns cancer A audy of bioekc(rie dlflrrences helwern wicoline habituated nd nrn haMtualed orR.nisms by use of high energy fhint phae eompounds lTre iwRuenct of ewvi(onent.l f.clnrs ow arleri.d Intim.l conaituents and fuwc linm Inltr.c/bns of .rleri.l acid mucopolye.c eharides Proleolytk wctivitirs of the while binod eells of man wnJ the eflec/ on whi(r blood cell w(livrlies uf c.ram.ltm, no Iritiun and Mher inffuentes The effect of e.p<nure lo tisurlle smolt on the inductnrn of cwncrr by chemical compounJs The correlation of wctlnnitnle in body 1luids to tobacco us.Rr 7he eRecl nf fmnlinR un certain Lstnc functions Phwrm.eologie sruJy o/ rutotmr and re laled •IY.k.ids Rio(ulia.l ouJ.ri.m uf r.rh.mur ir.w.ll cidts 65

(:RANIFF. ANI) IN~TTTtITN1N 11 R IIA11O M h rrn/rrvv of rha.. rne.n/..ey, Mrd•cal ( olkltt nf Vrrff.nia. R.chmnnd 1Jere.vd, see I arx.n) F 1 IIAI)1)Y, M1), PNI), lr../rtanr and / An.nren f)rre.rmrwl of PAydnf. nRt. Itni.rrdly of (Nlahcrna Medical ( enler, (1\tahnma ( rry (no, at Mrh. Ipn Suet llnraroty, 1 014 1ar.lnt, Mnhl 1(/51'P/I /1 /IA/ KFNC('111FI , M f), /now at Mtdeal I)ep artmenl, Sandoe Ph.rm.ttuhra/s, San I rarui.co, (abl 1 RI( IIARI) I 11AVF1., MO, Auhr.n( r.n/rnnr n/ Mrd.. a.r, Univtrsily of ( atdornia Mtdreal School. t.n / ran c/Ko FIFRRFRT R NAWIHORNF, M 1), ( henn.en, flr(•rrrmrnl of {rrrrry. Ilm veruty of Penntylvanra Uraduale School of Mrdaine. PhJadetphra (-I.ARK W /IFA111, Alyd.unr end hur.hn n/ NrebA t..r urr, lults (tnr.er..lv, MrdfnrJ M... Iste 1 arn-onh and Mt Ar.hur / NORMAN W 111IMS)RA, Prrl) 4, r.r.mrr Pn./rrr... of rntAnlort end frl rrrn.r, Iln.er RrharwN 1 ahnarnry, I)rpac/menl ut Psychotogy, (Inr.rrtrly of Soulh I1alnta, Vermilhon PAIII /NF. 11/171 R, P.t /1., Rrrra.rA Arn.ialr rn (rrnfnr) and (yrncArmlrrty, San I ranci.co Imtilult of Mcdi e.l Sciences, San Irancisco Isre Rkh ards) I AWRI'N( F 1. IIfSIFR, 1. , M h, rr.•/rrr... end ( hevman, Drparhwrnf of (IAurr.lr r ewI (: ynrr.dn~e, M[Jicat ( nllter of 5.>,.Ih (lrnlina, ( harttalnn IRRF ItIR11S 11O1/, Prrf), MI), r.n/..,n, end ( Aei.n.an, fp,ld..n of In. h.ern. R..ren A Medical ( nllrrt nf Vueima, Rrchm..nJ PRINF(T Tfll F Prrparalion Inr puMrcafu.n of a Mr.l nn Iht M.doR.c a+pecc. n/ rohacco anJ smnlmt I ocd tflectH of the inhalation o/ lohacco smole ury.n the fwdmonary, p;nphrrat and cornnary vaxul.r (ad. Mt.suren.enl of cnronary Llrvrd f4r. cardiac worl and tardr.c o.)jen arwt earl.rhyJtlte metal..Mm In rwunwNtn .ivt wbtrtls before and after /nrr• ancwn nkMlne and alrer snr.(mf Nandud crgucl/es A aludr of the eRects of smoking ar.d nicolrne .dministralion on sympalhn M1ren.l funclion and latuy acid meta- Lolnm Alttmpls to induct prlmonary nroplasm in eeperuntnld anrmds by ecp..cure of the IratheoMonchial tyclem lo ln hacco smo\e 1•rrannal.ly and smokrng in (nlleRt Rr.d u.lt. a h/rrrn ytsr L.ILw up clndy 1 flrUa nf am-IrnR nn .nalarntJ fwrfnrrn 6.,e in a vmulaleJ drr..nR raal A comp.rati.e study of early hisluM.licat and I/N^ chanFes in the epidermn of Iwo strains of mice (('17 Hlacks and Swiss Webslers) after daily apphca tions of whok cip/e11e +mnAe cnn denvle I.wone and combined with erolon nil/ and the carcrm.Rem 20 mc/hykM.l.n/hrent and 1,4 benrpy rene The relaliomhip of Ihe use of lohacco product+ 1o the oulcnmt ol preRnancy Riuchtmi.al sluJre- ul .nurw anJ 11, inltrmedrale rne1.1+.b1e, anJ their el (e/ts up.n crrrMal .ulum.mic mtthan isms Ceretnal aulon..mie changes prrductd by Irrhaccn arnult, nn.Nrne or colrmnt, a mtuf•..hlt uf niconne 6 (, (:RANTFF ANf) INTTfTI(TION RIItCF11 1 111)1 MAN, M p, rrn/rt. r..- and I(rad. nrlw.r.nrnr e/ ParA.d. nev, I rnutrana Slafe IlnivenitT School of Medrtrne, New ()rlnm. Ideceased, sre Mc(ill) and SImns) 01 F A H(11 1fRMANN, M D, Rr• lear. A Sr rrnnrl, LnAund I~Anrafnr7, I/nivenity ..1 Notre Danse, Nolre 1)amt, Ind I R1 1)1)Y II()MM/R(:F R, M 1), rrrd. drn/ and Rir Rcstat(h Imlitutt, Inc , ( amMidge, Mau. RORFRT W 11U1 1, PN 1) , P.n/rrwsr of Rr.d.rrrral Srrrnrrr, Florida Slatt t/ni. versity, /alahasaee. OFORGF IA( ORSON, M h, Prn/ra.nr and ifrad ../ Radrolnty, I/nietrsilT of Suulhrrn ('alilornia School of Medi eine, 1 os AnReks. /fRRY IfART /A(;ORSON, MI), l)L rntur n/ Fartr.npAyrkrfuty, New Yort Fye and I ar In6rmuf, New York. 1111 fUS II 1A(Y)RSON II, M 1), Ar.r. r ra/r rrn/rru.r of Sr.Rrry and Dbrt Inr of Sr.Rhal RenraaA, ('dk/e of Mrdi.. eine, Ilnivec+ily of Vermnnl. Rurhnil. lon (No+ Ihreclor of lunqr and Vas eldar Restueh, Mt Sinai l/ospilal, New Yorl, N Y ) MIIRRAY 1? IARVIK, PH I), Ara.rlerr P.nfrffn, of PAo-nlnRt, Alherl Finslern ('rdltge of Medreine, Stona, N V ()CWA11) R /(IN/S, M 1), SI 1 u\e's Ih.apiral, New Y.x1. 67 PR(UF.(T 7fT1.F. P.Ihologic anatomic study of crllydar changes in human hront hi T)re influence of tobacco smoling on Kult myocardial infarumn A An inveslig.lion of the in aarn Ir.m /ormation of sermfrte mammlun ctlls by chemical eutinogem S An invesliffalion of the reFaliomhip o/ kulemutlencsis to ant•ernic uunula,r.n Studies on eareinottentsis arnl Ihe biu assay of carelnuffenK agenls ('omparaliee sludies of e8ects of vari.ws loh.cco srnole condensates on st<rm o/ R1Ke Sfslemie eRtay of three tobacco smole eondtnaales SioloRical eRec(s of cipre/le smo\e Phdodynamie .elivNion of carcinogenic hydrocarlpns: la) stanJardinauon of assay lechnipues ulilumit protoroa, (b) {nveaiplitm of the mtchannms of aeliva/iun •r.d reyrmx to arnmNic careieogens by prolnrna The influtnct tul certain rnvironn.enlal /ac/ws in Ihe genrrrs of ne..plactic dise.se in tuhercuhnrs palienls and rn children A cornpuia.n of ekclrorttinn~rapAy n • meam of evaluaUng the rfltcl ol vasoeomtrklor Jrup u(r.n cerehnl and relinal circulauun wuh aAtr Iech niquts for Ihn delernunal.on 1 ung homnlran.plan/athnn Prlo/ sludy of Aahilu.hnn 1.. m.nnnt by mtanm of rlaaus n.urAey. ('art..n muno.rdt up.1e anJ drRrnnrn capacity in thrlJrrn /hrs rest, IngrlAtr with tMhrn, v.AI be uaJ lo t..dudt pulmonary (unctiun in chddrrn clart me at Iht earbrH aoe ol co..pecalron lhr. t.alualw.n of pdnumary (urwurwr .rll he alybrJ to rumnd thJdren, IMrst

I CRANTFF, ANt) IN4tTTlyT10N ANI)R/ W A KANI)(ITC('ll, PN 1), Arurrwr llwt.n•r .•/ Rrwrrch, Rn.coe P I.(l.on Menw+tr.I I.hutalory, P.r Ilar/r+t, Me ARNO11) R KAPI AN, PNI), fNttcror. liMn.r.wy •I Afrdu.l (:rnrn" t. (kst land Psych,alr.c INnstrnule and Flo.pil.l I/RAI( /1 KASPARIAN, M h, Auur •nr 14.n r.n, ( ( ih+.• Iwy lnlhM/M /n Alr/r..nt, //ahne mann Medical (olkrt and /hwpdal, Phd.dtlphra F 1 IHI/ K A 1 7. Pa 1) , 1 u.r r.lr r.nrr,r,•r of S.wrnf..rt Ilm.eruly of ( h«.60 Ittt (ram) S11IR1 FY I KAl/t 1 MAN, M 1), At x•.isN rrnlrn..r n/ r.rh,.L.rr. It.•+n stalr Mtdreal ( rnrrr Sulc 1/n.arsny of Nrw Y..1, lolrtw+llyn AN( FI KF Y5, Pn h, rrn/r,xa n/ rhyt 1.darnd 7ry(rrnt .n/ l)brrbrt, t.A nrun•.y n/ rhy,inlnri..l N.rwnr, lfnivtrsny of Minnewla School of ruht.c Ileallh, Minneapolis /l)5FPI1 S. KIRSNFR, M f), Prn/tunr t•/ 1lfrdu.nr. Ilnrvtrsdy of ( Mcar.. School of McdKlne. P/-.It R 11 KNAPP, M I). Rrstarh r+o /t/..w n/ PI,IAMI.y, Pntton (/M.erslly StA..d of Medal.r, Poao. KFNNI I11 P. KNII/)1SON, M 1) , A, p.l.nl ( Aw/, liAtw.rotr .Srtt4r, Vtl- tnm Administntr,n Ilos~ lal, Scatlle. wa,h r.ar.r.n. ,•I r.rh.Uni ad M..h.nr•.n M.d,.rl 4h.r.l V.IIV PRIIIF(T TTTT.F. with asthma, hronchitr., or chronic pncamnnia, .hrch condrtr.m wtre n,b .equenl In infections of all I.nd.. Paslrc- ul.rly thox uused hy kmwn vnal arenls. To dettrmine to whal ttltnt Iobacco 'lar' tnwnks Ihe Klwnnl carclrr,Rtmc hydrn earhom in the slrn and other I,nues F aaminalk.n of Ihe estenl ol, arwd con N/IU1re1al bacis for. cnr,rt.tu+ns he twetn Ihe followiq I 1/ lasle Ihtesh oMa lot qumrr.r and 6 n prutttr+++/1rMnur Krt, (7) cotnldulrwlal pt.l,sp.sdwn (o pahok.r.c varublrs, 1/1 r~t.•r/ual dJftrences in smul.nr pr..lrats, and 111 food dicti\es Thr eflrrl of tobacco smnlmr nn /ht cdr her of the cornnny ulerres S.au1 and (nycholnru.l cnmlramis on IM Iranrlarnn of r+rwr.rs .nrn .cnon The c.st of cq.rrnt rmn\rnr ln rn.tahralc the p.IM+rtntns of ure Ih.nt rnd.ard lunr .dtn..mas in mict. .rttrPtally Ihe rltnlrlxarn.n nf Iht cells which rra rue 11) the dtnon.as. an.) the Pne rtructurd chanres in lht+t all% durinr ntoplsna (eR prohftralion In luer following ev- einorerr. ('huaclerislics of tnen, includinr smok inr, in po(wlalions ddlt.inr in the in cidcnce of coronary htarl disease TAe eflect of lohacco smolinr upon hasal raslric /tcrrlrnea in man Insedigatinn of prrsnnalily ftalurts as soeuted with ru,tmes of srnol.ntl hthaviot Palholoric ananmk study of crllul.r chanres In human Mon(hi CRANTl.F AND tN1TTTIJTqN ALVIN I K()%AK, Pnl), .luociert r'raltn.n o/ ( hrmul.y. Washinrlon Square ('ollere, New Yorl Vn,versily, New Yorl K()PURT A K(/IIN, M f)., All Souh 11os{ital, Motrraown, N I and Aaao- cietr rro/rnnr, Drvinon of Nrrro- ,urrny, (Itparlmrnr of Srrrrry, 1'lew lorsey Slate ('ulkre of Mcdreine, )cr- ay(ily,N I MARVIN KI)S('/INf R, M 1), rto/r,x,r of r.rholnr7, New Yor1 (lnivenily ('ollere of Medarnr; [)Itrrrtr o/ r. tA.dnry, Ptllevut /losptlal, Ntw Yo.k. ( IIARI IS W. 1 A PFI I t:, Pt11), Ar dll.nt rro/t,rar of E.nrbonment.l II yrrrnr, btPmrmrnr of Irr.rwrra MrA.crnr, letlenon Medical C'olkge, Philadelphia (deceascd) T11OMAS C I AtPPIY, M D, Pro/r»or of raholory, Nonhwes/rrn Vnivenily Mtdical ScMxd; ('A.irnvn, f)rParl- mrnr of ralholnry, Wesley Memorial Flwpiul, ( hkaru. PAVL S I.ARSON Prr D., N..r rro/ra- ao, n/ rA..,notohnfy. Medical Colkre of Virrinia, Richmond. (scc 11a.lf and McKennis/ R(X:I R K I ARSI)N, M 1) ,( Aitf of AfrJuinr, amt )US1 PH R Mt1 11N lI(', 1'r/l) , ,Irurrolr rra/runr nf AI oL•Ry, I rnm l ounly Ilu.pilal. I rtsno. ( ah/urnia (:(ISIAVF A t AI/RI Nl/, M D, A, ,ocarlr rtnfr,uw n/ A(rJurnr .ns l),rrt lot Orrrunn n/ Rt,rue,net hraa,t,. New )rrsey SrHe ('olltre of Medicine. )ersry (ity, N 1. PROIF(T T111.F. Thc isolation and idtnlifkahnn nt ce.t.in lowcrlvdrnr curnpuncnls of uruene nnoke Possible effects of smu\rnr and oituene upon cerebral ciuula(iun Pahokqic an.lurnic study uf trllular ehanges in human bronchi PRecl of ciptreut .mukc on pulnn.nuy ckaraa Ptlholook -_ anatomic study of cellular chanres in human bront h. Clasi6c.tion, p.ognosis and etiologic lac lors of primary lumorf, o/ the lung Fvdu.t{on of morplw,lurie chanres in Irachtobronchi.l lice in pabcn(s from aekcled study lro-up (Set I ishbei.) CornP.rison of ehanres in Irachrobronchul epithelium In snM+lcrs and non smolrts, with speeial te/crence to lung earelnornn in nnn snr+kers Prep.r.tion /ot publicahun of a book on the biolork aspccts u/ Iob.uo and amotl.g Fnaymak ttanrformalionr of nicoline and relNed compounds The possibk effect of tnhacco smule and nicoline on axorbic acid tnetIr.hsm Subsidy requiremenl by Ihe Williams A Wilkins l'ompany lur publrcallon of a wpplemenl to Ihe morr+rcaph, "to hac co" Mrchanisms of resulantr lo p.dmunsry pathorens in mice up.ncd ru cy.renr nnolt To lesl more Ihtwourhly the hypothesis /hal the sustrplrMhly to dr.rlup o. naN to devtlop emphyam. In rrnultr. i. fcratkally dtlrrm.ntd Sludits In bronchitis a tor,tlNed inresn ralion of (a) Ihe efletl (d rmulmr on the hatterndory uf the rrfp+ua•ry u.ar of hum.n., and Ih/ Urt erlttr ul ur. rrl/t .mult .nd tullur k.uudr I.u /r.l 69

I CRANIIF ANh INSTf11rTIt1N ( 1'( It IF 1 Fll( 11t f NRfRG1 R, PN 1) , IIraJ llrrwrrnrrwf n/ ( ybrhrw.nrrr, Swrs. Invlnult ..f / .nctt Rrse.rch, .nJ rn•/rn..r, a.wxiNtd wflh Ihe Mhhc.l ScMx./, I/nivtrdly of l.usanne, SwnrerlanJ f/rxmtrly SrnAr RrdrrRrrf.wJ ( Lrnurr Si.. Menx.ri.l I aFnralorie), Pr.wds /LnpH.l, Rr(..Ibnr, Maii / AV1 R11 I A I It ROW, M 1),( l/rpeunvwl nl r.thnlnRl. Y.k tlmver, uly [cMr.l of Med.crne. Nfw 1L.en, ( nnn I S11 N fl I IN/KFT11, M 1), Pu 1). Ar rnr.r.r rr..fn...r nf turRrrr. Iln/vrrcdy of Mlnnrv.la Medr(.l %eMrd, .nd tr.rI rh)u.raw. Su•tual Srrrr.r, Vrltr.n. AdmrmrtrHrnn Ilucpit.s, Mrnnraprdrr Inow .1 SI In.ephl Ilo.p.1.1, St P.ul Minn I R(yRFRT II I INNFII., Prl t), An,x/err PrnfeUnt of ( hrnulny, (Inlve/aly ol Verr.x+nl. Rurlrnt/on (now al Nalfnnal Sc ience I oundalion, Washin/lon, 1) ( / NFRRFRTL 1(1MRARb,M1),MP11, Rrx.rch tmlilule, Ne. FnRl.nd (k.(nneu llcnpilsl, Soslnn I P 1ON(7, Prl t), rro/raror of Pharme rolnRl. Slale l/nivenily of Iowa (ollerye of Medicine, low. ('ilf. CIAYTON G IOOStt, Pw/), M1), Ilnrnr.Rr rrr.fruot of A(eduinr awd ParhnluRr. (/ni.enil) of Southern C.li. l.xnu Sclxx)1 nf Medreine, t d AnRt/es IN)NA11) n It)1/RIA, M1), ArwKl.rr r.nfrr..r, ln A(rdr.rnr. (.wr.rta tlnl.tr . uty MrJ.(.1 ( olltae, Ne. York KI NNI 111 M/ RRI11 I YN( 11. M 1), tir 11 1 1 n_ f h.wr.rl..r and r.nlrrrn. .•f I'.rrl•.•l•vr .r.d 111R1)F A Mr IVI R. NI 1 t A r.. w. Pr../r..r nl rarhnlnt r. PR(ylF(T Tf11 F. lul.nl I on Ihe clrvmR of hacJrna frnrn Ihe rr.pualnry Ir..ta nf amall .mmal, Inl/cf, ral)1 Fflecl uf cqtarerte smr.le nn pulmonary rrs/\lante lu Infe(IN/n The eflrcl of ciRartlle +mo1e on Ihe n.lure .nd funclron of Ihe al.col.r m.cra ph.Rt (.) mohditahon; 1h/ mel.hnlic .cUvqy; (c) ph.Vxytic .chrily; •nd (d) bsclerkrl.lic hactericdal c.pacily A cnrrtlatd hianlogical, rytnlo~ictd arxt (yl.r.hrmrcal snxly .f Ihe Ira.hrrs bronahral trK uf nurr eywntd /r..l@a rt/le suno\e The m/etrtlalron helwten iullucnta virvs infecliorn, e.penure to cil;a(ttlt smnlt •nd olhtr faclors in Ihe developmenl of pulmonary and hroncl.ial k.ions in mice To InvnliRae Ihe formatian of pulmon •ry surfacunl in fetal anim.ls •rd ill presence in Ihe nt.(.rrn Measuremtnl of Iht drffrrtnlial Mrx.d M.w in Ihe m.mmat.an IunR during Ihe .cuar ptrnwl of imn\t mhal.lnrn usinR Ihr nprn (hesl annnal and Ihe mtlh.xl .nJ prrncrp4 of R.mm. tmnlmR r.du. .c Irve IradeJ micru•plhtres T)x otWaion of nic..tint by gasr.xn o.ygenmeehanism, producfs and tr rltlr(a The wloaidalicx) of nicMine FpldfminlngK.I ftlClols in long (ancrr ('.rdinvascul.r proprrli" of nicn/ine Further st.x/ies corscerning Ihe sympatho mirnelic .ctiont of niC(wlrne I unR lie.ut re.cliorn Io airborne chemical •nd hmlogic.d aRenls $lud.rr nn mirMr.rint in 1n6.r.o hnvirnnmenl.l /aclors and pulmon.r) Ars t.ct I A+Ir.us JnV It ArIKa/n .nJ tu ucc rnogtm, vir.l .nd (hrmrt.l 70 I (:RANtFF ANI) tN11f/IR1()N Mtdxal ( nlltet of Sxl/h ('uolma, f harlferun INI S MANI)I , Pn 1), Anirranf Prufr) ..rr uf Rr..rhrnuurt, (crllere of Physi- cunc ar.d SurIenns, ( olumbi• (Imver- +rly, New Yort. 1(1/1N 11 MAN/1O11) 1. , 1) M f), Prn- fru..r and hurrrnr of PathnlnRy •wd r).nI f)r..tn..rn, New ttr.ey ('ullrye of Me.bcrnr and Iknhilrr. leney t ny t)AVII) F MANN, 1., Pnf), Murlatr Prn/r.r.rr u/ Pha.marnfnRt. Temple llniver.dy Scho.d of Ph.rmacy. Phd.- delphu 1O11N P. MAN(/S, M h, /nrtructrv /n 1'rroluRv anJ I(.rfninlnfr. Medreal ( nlltge uf Gndh (arolina, ('hsrkslon < IIRISI()PHFR M. MARTIN. M 1), inrmrrlr Atciamnf rrnfraanr of A(rdi rmr and 1hrr.ror, Drv4inn of In/rr. fiaru I)nrarrt, N. I Sl.le (-ollege of Mrdxine, lcrxy City, N I. (Nu., •1 (:fo1RflUwn Ilniv. School of Med.. W..h, 1) ( ) 11(1NA111 1 MASSARO, M[)., Aaaorl- eu /'rr.frru.r of Mrditlnr, 1)rde Uni. vrr.ily Medical (eMer, 1)urh.m, Not1h ('arolhn• ('11AR1 FS (' McART111/R, Prl 1) , rrv.lrr.lr•Riv fn rhr f/n/rrra.ry Hrdrh Srrurrr_ Il.rvard Vnivtrsily, (ambrrdge, Mass (ae Ileah •nd I ovrm worlh 1 ( IIARI I S R MtCANTS, PN 1), AMSo ..nrr Prnfru..r n/ tnrb. ScMxrl of Aprl cullurt Nnrllv ( •rulina $lale f olk~r, R.kqh IIFNRY C MtG11 t, 1., M I/, ,IrrrnR Ilrad, llrpnrn.rrnf nl ParhalnRr. I orn si.na tilale Itnivtrsurry Sch.x.l nf Mt.si arnr, Nfw /)rleans Isre llolman and Suong) 71 PRINF(-F 1111 F. T).e role .d herr.h/.ry t/a.ra.r mhd.dnr delxrency in Iht fliulu~y uf p.dmunuy erophyaem. Tn sludy Ihe purpnrltd rrlalionshrp hc Iwern smolrnR and chanlts in human 01-.1 buue rw vn.r by roulint mica• ctMy. ddlerenU1 slarn,ng, and mnln Ietplllxtlflfl nK1IMMl., and lo furlhtl t..mint c1a1r.1/..11y Iwu arrts ul data prevtnlly in thf princrp.l rnveslyauur. puaenion Fflecl of lobacco sm..he anJ lobac.o rea iduts on melhylclx/1an/Me.a inducrd skin t.rcinr.Rtnt.r. m rm.e T1K 1epNNM1n nf Ihe vararus suhcef'.dar nto~ la)~lic parlKltl by ull. hlualrun nvelh.xls vul Iheu chaa(Itr4alron in t.b(walory .nmu/s •nJ rn buue cul lutes of v.riuus cell line, Possible /n/e1aclN.ns of vir,rses and st,l, aancn in luhac.o smnle con.knule Compar_jNve nci.l prev.ltnce of chronic btonchilis Alvev.lar cellr prrNtin and glycoproltin bhnynlhe,is Pro/ein aynlhesis and vcrtlH.n by Ir..ht.l n1U(M• S.x'ial and perv.nal Jtrermu.anls of vmut in@ hehavi.x The s.xi.l medulran nf smoling twhsvim •A-rsrnic (onlenl ul wnls anJ al.wuplmn Lt Iht tob.ccn planl the eflrcl• ol tnvunnrnrnral /..n.r. nn devrlopment n/ .Ihrr...rtrr..a. ., it ve.ItJ by au/np.y nf a.uJ.nl .ur.m.

CRANTFP. ANf) INTTfT1/T1(NV ItFNRY 1) MrIN'T(K/1, M D, Prn/rrrnr o/ Afrdurnr.nd llrrrrr.. C.rdlnvarrr tar I.Anrorury, bule llnivtruly Mtdicd ('enrer, 1)urh.m, N C. FI)WARI) McKFF, M 1), Prn/r.sor.nd Arrrnf ('A.irwun, and WILLIAM M. I)AVIS, M 1), Rrrr.crA Atnttwt, Dr• p.rn.rnl nf P.rAotofy, Medical ('olk fe of South ('.rolm., ('h.rkstow (see Pral ihoma) KF.1 l Y T Me KFP, M 1), As.ort.rr Prn• (rnar of M.dl.lnr, Medical ( o1kffr of Snulh ( .ro/rn.. ( h.rkNOn IIFRR/RI MtKFNNIS,I.,PNh,Prn• /rnn. n/ PA.rn..rnlofl, Medical (ofkfe of Vir f.nn, Richmord t.ee 1 arr+n 1 VI('tOR A McKltSl( K, M h, Pro/et trr n/ A(rdrrnrIrh RI( IIARU M (ilK)IfMAN M 1), lrlln, rn A(rdl nnr, Inhm /"ins ll.r.rr.ity ScMr.l of Mednrnr, R.Irunore. Md RI)SS 1. Mtl I'AN, M 1), Ars..4.1r Prn Jruur n/ A(rdhrlnr, 1 mory llm.ersdy School ol Mcditrnc. Atlanta Wtl11AM F McNARY,1..Psr t),AUn- ci.rr Prnfrtan nl An.a•nry. &ston l/niarsity ScM.>t nf Medkine, Rc+ston NFAI I McNIVFN, PN b, T)x Wn.oes ler found.tion lo. Faperimenl.l Riot- ofy. Shrc.•sbory, M.n Isce Do.fm.n/ llll IA MFYFR, PM 1) , Arwri.rr Profrt. lor n/ 0,01 P.rA.dcryly, Vni.enity of Ilhnois ('nikfe of Iknllstry, ('hic.p RPRNARI) I MII IFR, S3, M 1), Ar nrr.nr Prn/rrw+r. The Daniel Rw h In- slitute of Anatomy of the /tfferson Medical ('o11eIle, Phil.defphi.. )AMFS O. M11..1 P.R, M.1), PN n. Prn- /runr of f lrcAra.r .nd Ir1rAoJnft. .wd frFrrrln., A(r.r.l IlydrA Rcrr.rrA lnrtrrrlr, l)m.rrsiry of Mrchy.n, Ann Alhot /111(3/1 MONTGOMFRY, M /), Arcnrl err Pr../run. nl Afrdarnr, (1m.eraty nf Prnmsl.-. MrdKSI 4hocd, Plnl. drlrh.. PRI)1FCT TTTI.C A study of the eRecls of hyperhsric o.y ifenaion on cornnuy .rlery dnr.x rn tht tsperimentsl animal and man C.rciwftenesis in Ihe Lhorstory •nim.l a cornp.rixm of species re+pnnse to N..d.rducd sitts of .pplicn on S/ud7 of lung funclbn in snwdcrs .nd non s/nolk ers PneymNk u.mformainn. of mcnNnr and related con.pounds A eombinerd fenrtk, physiotolic, clinical and epdemroluf+e study of Ruer fer'. dntsse A study of Rurr frr's diwar .nr+nl the /t.nh ethnic poups in Israel Inh.(co .nd co.prhtion A sl.rdy of frnncc f.clnrr in vsscul.r dnr.ct To m.le rrcordinfs of rwnm.l .nd r.IM. M~pc hrr.Ih sc>•.nls Tht hisloMgy, Mstnchtm.nry and ultro srructure (of norm.7 and d,srwd lunf Nicotine and its mHS1+oGtes in hnd) ffuids of srrn.lers An ord cytnlofk .nd emolers study of nnn ,moters An In.eaiplMn of the hlmd surMy of inelal.tk and primary mdi{nsnl lurnors of the Iung TAe heh.viorsl efltcts of smr,lmg under slrtss Influence nf tobacco snw+ling on the hh.nA fh.• of slrn snd nf nuntlrs nl tsrrrmdrn in symratheclomiled and umrmrarhrclnmiltd suhle<ts 72 (:RANTFF. ANI) INSTTTVTI(yN P(1'R MONTGOMI RY, )., M 1), Pro. /nrnr n/ P.rAr.f. F). nd ROI I.ANI) C. RI YNq1 US M 1) , Aa.ut.nt Prn/rt. nv oJ Prrh.d+.fy, llnrversily of ie.s, Soulh.eslern Medical School, Dslla GFORCF F M(()RF, P/r 1) M n, pl- trrlnr Ra.all Psrk Mtn,qri.l Im1i lute, Rofldn, N V (see Roc1/ KFNNFlN M Mt)SFR, M[), Attbr.nr Pr+./ru,w nf A(rdrrinr, (kpsc/ovn llnisersily Medical School, Waninflon, 1) ('. IIl1Rl FY 1 FF. M(1Tt FY, M D, Prn/rt- a.+r of A(rdrernr and thretror, C.rdlm Rnprrernry I nAnren»y, l/rsicersil' of Southern (shfurni. School of Medieine, t.of Anfelts I'I)MONI) ANTONY MI/RPIIY, M h, Sc I), Mrn.ro/r Prnfraww of SlotlnNs. rrca .nd Alydurnr l/nivcrtily of Color. .do Medical ( enter, Uenver. WII.1 IAM S MIIRRAY, Sc 1), Srnlo. Stn# Srirnfiv fmrturr, RMtoe S. /sclu.n Memnri.l I sboraory, R.r Har. bor, Me. hONAI t) M PA('F, PH 1), ProJrtanf of PAyliul.-Rr .nd l)irrcrnr, Inurrr/r /or ( rllufe• Rnr.rcA, l/niversily of Ntbr.dts, I incoln 73 PRoIP('Y ifTT.l. Influence of nicn/ine li v/ .nd Inh.cco smolin` ow hk+oJ flow in human slrn and sleklsl muscle Invesliplion of the rote of the nutlrnlui in the normd and Ihe m.lifnsnl cell Nuclear ch.ngcs produced by chcmrc.l c.rcinogens An investif.llon of the physiuh.fic.l ef fecls of direcl inhdstion of lobacco smoke by l.boraory .nim.ls .nd the study of the biological respon.e ol Lbd./rNy .nim.b to conlmu..ut in loesllon of dret tobacco prtrluct rnn lures FRects of acute and chronic cie.retle srnoking upon flMinolylic .clivily •nd blood coagulation in m.n Srnn\er•t.o.rmoler diRerences In .cti... lion of flbrinolylic and cosful.tinn sys. ttres A sludy of the eRects of srnnling un pul mon.ry function Il is prore»ed to .rnr1 out In detail an .p proprutt me.m nf drtrrmmmit Ihe dur- Nan of surviv.l of the hum.n plstelel The produclion nf lienelically ennrrnlled •mm.ls and lornors for use in r.rcri mental research on loh.ccn in relation to health Studies of the mammary lurnnr rrumnt into 4udities of •.rnn lile ptim,rlr, under v.rying hormonal •nJ fonR conditions Cenelk atudies of crcirn)frne.n Fellowship for Ir.ininf in tissue tullure techniques Study of the effects of Ir.h.ecn smnle conNiluenls on v.rious su.cns of Imut celh cultuv.ted in .u.n In.eni11Ni.n, on rcrpir.rmn .mf flyro (y.i., •. ..ell •s prwuhle c/uonu....m.l v.n.Nn.ne in tsl.l.lrshed tell Lnte .hu1h h.ve been eupustd to ciAsrcrrt rrnn\e nd single consliluents of smnlr Investifaionf on rRrrh nf r.rrrnnfrnf .nd study uf Ihe rf)tit uI rlh.rw.l •nd

CRAN7FF. AND 1N1TTTtrTInN ALSFRT S PAI MFR, Pw D, and N()R• MAN W 11l-tMSTRA PNU, Au4e• .nd pro/r,w..s of pta1to(ory. Driatertnvnr nf p,yc Anfrrql. Univtrdl' o(SOMb /)ehaa. Vtrmill.ow (1)r. Palrntr wos at the (rwiversay of Tokdo, OA1o) R(XF MARIF t AN()M)RN, R 3, M 3, A ssitt.wr F rw.d Te. Awololf(e/ .wd [ tv • Irrrr, tlrp..tw.rwt of Food Stlrwtr .wI TetAwoloPf, l)rrlverr(T of (aldorwla, 1)•.I., Calcfornia MARY STFARNS PARSNLeY, ht D., A,r/N.wr Pr../rnoe of Aw.rowsy (e Ofn arvir, .wd GtwrroloFy, ('olkpc of Phrykians nd Sur/eowa, ('olumbia Univerwly, Ne. Ya1. PDWARD W PFI IKAN. M 1), (-h.lr- pA.rw..rnL.~y n.an .wd Ptofrm+r of •n/ E.prrlwcrwt.f TArrepertkr, floston Universily ScMw( of Medicine. Roslon OTAKAR /. PVI I AK, M D, IM h, F-trtrdrt D/rrrro., bover Medical Re. seuch ('enler, Inc., I)over, IkI MORRIS POI.IARD, hID., f)bntor, Ln(.Ynd Laborarory, Universily of Nolre Uuwe, Ind C. M. POMFRAT, Psl D., Dbrcror e/ lkrL.(Ita/ Rrit..rA, Pasadena Founda- liow Inr Medical Research. Pasadena, Cali/ (deceased) S N PRADIIAN, M D, Pn D., rro/r.rot of f•Aarrw.rolo~y, 1lowud (lwivee.i// ('olkle of Medicine. Wa.Mnl;ton. D C. N R. PRAT7 THOMAS, M 1), Dr.n .n/ prolrr.or of PatAolory, MtdKal ('olk~e of Soulh Caroliwa, Chatksron (see f~ McKee/ MARTIN 3 PROT1F1, R.S,. IfOS, ( hrr/. ffrpa.rn.rnr o/ Or.l p.rh.J..Oft. Ntwarh ( r1y flnspital, Ne.erl, N/ PR(UF(T TTTI.Fr carclnoren" on physfok.lic.l- mel.lr,hc, and morpf.oloRKa) changti in dipN+id ceRs undrr aerobk snd anaeruMc con ditiona Personalily correlales of smoting and low smokrng in adolescenls Iwlerac/lowa of rystalory, olfactnty, uc Ilkt and lhermal N/mrdr anurn~ smolen aw~ wOw .nN,.er. FRecl of comliluerMS of tobacco smoke on wamal and malignant human resplra. tory epitheliurw rw vitro Sludies of slruclure.aclivily relationships among drugs which aflecl nkolrnesensilrve physiobffical mechanisms Possible effecl of tobacco derivalives on arlerial and rnyocardlal Irssue cullures ('hemkal and viral eareinotenesis In the auenk ("(;erm/ree") animal Fellowships /or aludylng the culture of hutnan lung lissue and the cflecls of known andpo~srbk earciwn~enk agenls Ypow auch 1{ssuc FReh of nkdlne on bchavfor Palhologk - anatomic study of cellular changes In human hronchi Applkalbn of a new bioaa.aT technique In teaminalkrn of cigarette amole con densates /ot possible carcinorm Carclnoffenesis In Ihe laboratory animal: a cornparisow of species rtsponse to slandardi,rd silts of appGcal.on A cornparalive sludy of Ihe effects of ) melhylchulanlhrent nd cigarelle smoke cnnaknsale apphrd to Iht nral lissues of Swiss mree I 1( R ) cnnJi I.ontd with alcohol and/or c.rlwm Icnachlmrde 74 (:RANTF.F ANI) INSITTTTTMN WAI TFR RFI)IS('l/, M 1), Auoci.n P.n/rr+ar of ('bnuaf Mrfirlnr, Ner Yort TJnivenily School of Medkine, and NY1/ Rtxarch Strvice- (ibMwaler Memorial /lmpplal, New York Iste Sulebertler) IH)I1AR1' A RFIMANN, M 1), Proft,. So. o/ MrL. rnr, //ahnenunw Medical ('ollefie and /lospilal, Philadelphia. VI('TOR R1/ 11AR1)d, N D., CA/r/ of SurRrry, Presbyterian Medical Center. San Franci.co, ('di/. (set Ileiner) R. 11 RIGDON, M D, pro/eunr of p.• rllnlnpy and Uirrrto., Lii-Orao.y of Ecpetrmtnr.f l.rhology, llnitersily of Tesas Medical flrawch, O.Iseslon. SYUNFY C. R ITTENRFRO, !hr D, Pro- ltunr of Sactrrlololl. University of Southern Ca6fornla, 1 oe Aneeks. I(XFP11 /1 R(XiFRS, M D., Hd' Name of lesus Ilo.pilal, (ladsdew, Alab.ma. RFNS(1N R ROF, M 1), A,xal.rr r.n. /eu..e of .trrirry, flrparrmrnr of Sur• 1 rrl I)nivery y of ('alrfornia School of Medklne, Saw Frawciseo. ClIARLFS I.. ROSP, A M., Srwlor Dlrre. to., Veterans Admiroslra/aw, (hdpa~ IieM ('linic, Iloslon, Mass RFNIAMIN A RI/RIN, Irrl), A,r4r. .nr prufnr.n of pnAllr /Ir.1tA •n/ P.t.rnrlrr A(rlr.inr- Reylor, (/nivenity C"u1/rRe of Medicine. /louslon. Tetas. (n+w Men.ltr, NrnM.lical Producls 1k vtlupm tnl, Wyeth I.hnaluties, /'h~la delphia ) PR(Ut(T 7111.F. A comparative study of the cffecu of in ductd liver damage on the develr.pmenl of lumors of Ihe oral mrKo+ and .\in /ollowin` Ihe applicalwxl of tobacco Lr in inbred Swis WtMltr mke Vascular resporses to tobacco smoking in paienla with .ascular disease Vascular Mpowat~ Of the.I111 mKrotlrcuIation and cercbral circulation to to bacco snroling in rnan T)re ef(ecl of lobacco srr.olinR on pbys{o IDgIc and pharrllKolowc •asotlMMor aliwwN TAt ptsibk eRcet of tobacco or nkdlne iwperiodre disorders, a newly recognrred syndrome A comparative study of the effects of whole and fracliond ctlt.cts of crp rNte smoke and thux of \noww tar- elnosena on (1) the cytology and nu. clear 1)NA content of eprdcrmis in various strains of mice and/or (2) the tytoloBy and nuclear UNA content of 10011 and epirhelium of the brorKhral Irte of mice and hamskrs P-lleela of tobacco smoke condensale ..e the resp~ralory Iracl and other tinues of the ducl T)x bacterial degradation of nicotine swd related eoenPrti.nds The objective of the project rt the elucidation of the Mlerreediary melabohsm of nkoline osidatbw A alY/y, of the Incidenc+r of f.tal heart .1laeks, strolits .n.l pulrnc.nary embobrm M PYlmonary emphysema Study of the action of negatively (harltd ions on Iracheobronchral citiary aclnrn in Ihe human patient Social predictors of k+nrvily An~ evdu.lion of Itr phrrw+nKnnn of lumor growth enh.nctmrnl es an uvy for carcinogens amona the Ldycy.lic hydroe.uhons and rtl.red c.wnl.wrr/s 75

CRANTFF AND INSTTTCJTN)N 11/'NRY I RUSSFK, MI), FA('P, (-nnlultnwr rw ('erdrnrauulnr 1lnrafr, (1 S P..blic Fltallh Servicc Nn.pr/at, snd rrrndrnr, 1 ht Rucsttt I nundalnn, Inc, Srsten Idand, N Y. W I I I IAM (). RUSSFI.1, M D., ParAolo- ~w rn rhirJ, M 1) Andersow Hospilall .nd Turna Imtilult, (/nlversily of leess Medkst ('enler, Iloawlo.. PF1FR F SAIKSIIRY, MD, Pn. D. Hral, /wVwtnr Trrarmrnr ('twrvr, SarM loxph flo.pitrl, /Iurbsnl, ('alif Ide ceased - see ( roes) PA(/1. O SAI TMAN, ht D, An/lrawr Prn/trra of f/MwArndpr) (laivtrsily of Stwlhern ('alifornla Scl.ool of Med kine, l.o. Anleks III R/('11 11 S('l1AFPP1, M 1). D/rrrra of Nrr.npAa.rw.rnln*1 , Mson Rtsesrth In+thtutt. M'orcesltr, Mnc.chu Kllt At VIN R S( IIMII)T, PN T), 1>i,nr.•. of ( nunvhwe, lultr I/mvtrnt~. A/rA ford, M.n ISAAC SCNU(IR, h 1) S, PN 1) , 1) Sc , Pro/rnnt nf IIN.dnjt and ErnArrnfnjre awl flraw. Uni.trsily of tllino:s (olkFe of IkMistry, ('hk.p (decrssedl MA(IRICP. S SF(IAL, M D, ( llnlcal Ptn(rna n/ Afrdlclnt, lufls Oniver- sily School of Medicine. Soslon, M.ss ; [hrrrra, Ihrjo.rrwrrwt of IwAalarinw TAtrapy. Ik++lon ('11) Tlo+pilsl ('AR1. (' SFI TTI R, Pw 1), Rvr.atrA 1 rllnw /n PArdh a/ AnrMopnl..t), Ilsr vard (Inntrvly, ( .mbridge, M.u . .nd I)epsrtmenl of Nulritron, Ilarverd Cclwrd nf Pnblrc IIt.Ith, Rn.lnn PROIFCT TIT1 F. tnlerreldiomhip (.elwrcn emotinnal slre+s (occupalinnal), tobacco con.umpliun and cornn.rr be.rl di.e.v Strcfs reaclinm In snw.lers and non srnolers as delermincd by urinary cele cholaminc eecrelion P.IbloTic -.nalomic tludr of cellular cAanges in human hronchr Infh/enct of nkoline and c.lecholsmines upon coronary vacMnornr lonw in nor. lnil .nd erherosclerrwk dop The entymalk mechsnicm for the d.rl Raalow of ( Ur by lohacco Snnre aspects of mino acid melabolism iwlob.cco kaves Invnliplion of the doect stimul.lion of p.rasympahelie nerve Irrmnals by l.kotine NKo11rK •dln/n{tlr.InM to rotlral •rea of the cat Maineflats upon FF(; .nd .ulonlrmK rystem Slud) of .rtifhrde. Inward, a. wtll rt es tenl, 1)pe ar.d hnlury ul. Inhuco smol rnR in ...hrnl cnlltgt pprpularrnn Sludy of r..mt rd Iht rrlannn.h.r. rd smnlrnR .nJ rr.n t n.1.nR n, f.rm.lr hr.r.wy. ttpt o/ utunJuy uh.w.hnR, aradtmu rnler trts •caJtmn •th.ramrnl, n,l, rrnial rrl.bomhrpr thsracltncbc. Ihaologic chen/es in Ihe or.l, pharyngtal end na.al Ir»uts of esptrimrnlal sni mats •rx1 humans subjcclyd to tobacco smole FRecls of ci/.ntle smolinA on IunA func lion in normal suAjeels •nd patrenls wilh cerl.in re.piralory dise.st condiliorn Relslionship of eigarelle smoking to cMorJc lobslruclnel pulnx.nary em physem• An inlegraled study of ancillsry .nd newly developed p.r.melerc to delineate the diRerenl 1)pes of the chronic bronchitis s)ndre.me and their evslualion (hronk Monchilis rnhlirs Mrwphnk,Ay em1 srn.AinA In tol/tAe Frsdu sle.- a filleen year fullnw up study lluvsrd lohm Iloptirn sludy of hrndy frwm es rtl.ttd to sm..\rnll, and the 76 CRANTFF ANt/1N4T1T(fTN)N I 1/('IO SFVFRI, M f), Dlrrrtor. Inxl. lurr oJ AlaAid Aw.mn.y and lfistolopy. Dntirion of ('anr, tr Rr,rocA, UrrvtnNy of Perugi., Perup., Italy. CIIARI FS P. SHFRWOOD, M D, Ar. aluant Pro/rllnr nJ Radiologl. Umvec- sily of Rochester School of Medicine and Iknlistry, Roches/er, N Y. 6AVID 1-. SIM()N, M D., In,nwror in Abdirlnr and Frllor /n Cardlo.otr• far RrseaucA. University of CiKionali C'olkge of Medicine .wd ('.rdi.e 1.6. oraory, (-incinnali Gcner.l Nospiul. OFNP. M SMI TII, Prl D., A,d,eent Prn. /r»ar nJ Ptrr, ho/orr, Narv.rd Medre.l School, Massachuselu Generd Ilospi 1.1, Boslon. TO(JIS A SOIOFF, M t)., Prn/r„a of ('6nira/ Mrdrrrnr and CAar/. Diruinn of ('ardrnlot), 'Tempk Universily Med kal ( en/er, Phil.delphi.. SIIFI Itt)N C. SOMMFRS, M D., Pro/ra- snr of Parholofl. (blkge of Phrsici.ns and Suw~tom, Columbia Uruversily, New Yru1. FRNFSF SONDFfFIMFR, PI/ D, Pro- Jrl><rr of Planr elncArwrilrry, Slate I/n/venuy ('otlege of /oreslry .1 S)rr cuse ()nivenily, Syr.cuse, N Y. T. M. SONNFRORN, PM 1), Dbr/n- rruArd Srrricr Pro/etta of Toolorf. 'rdian. Onivenily, hloorn{nIfcon. SAM SOROF, PN 1), Hrad, Drpr. o/ Afarromolrrr/er CArmi,rry, The Insli- lule lor Csncer Research, Phil.delphi., Pa. AI FXANDFR SP(K'K, S S, M D Al• aitrant Prn/r.v.r of Prd/ar.k,, tTw(e Univershy Mrdre.l (tnltr, /)urhsrq No.lh (lrolins. FRFI)FRI(-K I STARF M 1), Ph/1), Ptofrrenr of Nurridon ll.r..rd School of Public 1leallh, Boslon. 77 PR()1F(T T111.F. precursorn of hYperleniion and coro nary artery disease An approach to the sludy of inlern.l f.c locs in lung carcrrrrller.eus InOurrwe of hwmones Invcsliffaion Into the na(ursl history of c.rcrnoma of the lung wilh parlicul.r reference to the r.d.opaphrc appe.r •nce of sucA oces.es, Ihe e.rhesl tnanifeslalictn o~c.ncer or1 chesl X r.y plw/otraphs and the tabulation of Ihc relNk+nship of .molinit habds and occupalan wilh 1t.c ir.cidtr.ce of lung cancer The tffecls of chewing tobacco on the c.rdiov.scular system of man The tRecb of pipt emofting and cig.r snlo~inR on Ihe csrd.ovascutu s)stem of nun The rel.tions between s.noling and ptr sonahly The eRecl of tobacco imnlins on sur facl.nl, specdkletly acrdr, cardiac pet (ormsnce nd mtlal.drvn of .drpcnt lissut Ilosl feclors in chronic pmlmonsry inflamm.lion, enrphysenr• and lun/ cencer Tbe purifkuion .nd struclure detrrmina lir.n of comfrrunds c1,.xly releled lo chbrogtnic acid ChtciinIt •nd ealendrnll the Slcphamr Puawrrrrrwr lesl for careinogenrcily ('Lemical and physk.l sludirs nf the lissue pruleins invulved in chemrxal c.rcinoattntsis The Influence of ci/arelte srnole on cihary .cUvi/y •nd histology of the Iraeheu Aronc hral Irre u/ Iht r ahbd Feperimenl.l Hudres of c.ncrr rdrhtma • new Irthnique 10 wr if ..rwNn '1sn' eelr.cttd from Iohacco may in cite the forma/ion of luns lumorr

(:RANTIP AND INTTTTVTI()N C. IIAROI I) STFFI FP, M n, Dlrerrar of (.A..relorlr,, MerMd-sl /k.phel, Mernphe, Ten.. lACK P. TTRONO, M t), Auoriere rrofetuu of r.rAolon. Loulsler Swe lJniverfi// School of MedKrae, Ne. Orkens (.ee 11o1cn...nd McOin) MARION 9 SU12ePR(1PR, M D., Lo- fenoe .nd (-Adrn.ew, Drp.rfn.ewt of Drrw..foG.gy .wd Srph/fo/.yl. Ne. Yorl ()niver.ity tlelkeve Me~kel Ctw- Lr, Nt. Ynctt Irellred, .ee Redi.cA) RP.NATO 1-AOIURI, hr D. Asorllere lrofrtxrr of PncAofo*/, GroL.dv School of Irsiners Alnclnlsrr.rkrn. Ilere.rd llni.et.irt. 1kao.. CAROIINP SPOF11 TTIOMA3. M 1), Assorierr Irolruor of Mr/klwr. Iohw, ltopkine UnI.er.ity School of Mrdi clne. e.ltlmorc, Md IP,ROMP. P. THOMA3 I1t.D, PrOlrssar of S..If.ry En~wrrc+wp, U.letr.lt) of C.Nforwie, Ser eky. TTSSUP Cl1LTURP. AS.S()CI'ATION IAMP.S P r T'OMAN, f'rr D. Pro/n.or ew/ (Adrww of 1'A.r.w.rofort, (Tdeep Medk.l ScAonl. Inetilule fnr Medicd Re.rerch PR(UP)CT TTT1.1. The inRurnce of cipreue emore inh.le lion on hisrnl.+Rk ch.nges pruduced by Mlreeenous heeechkwoAuocohulene in r.u Tlw e*ecra of envlrowrnenlel f.clon on deabpnrem of .Iherosckrosi. m re- v..Ipd by .wop.y of accident v.cl,ns In.ewl~Mion of the eRecMs of tobacco o. the huws.w e.eeulY .fsrem, b.sed ow the fact I/W eert.rn tobacco eRecre .re due .o efkrRk w.eeprA.itnT of .peeiRc l.dl.ldu.h r.ther Ih.w to ohli- A.loilh bek prodvrte in lob.cco .nrrAe, ..d Ihd petknrs .irh ncclwi.e .ue.rly di.ea.es testwnd d.Rrremtr than haMhy wnden CrMk.l revkw of l/teraure on p+/cAd- on of swo\.ne r - i TAe e1orniAcenCe of diRereM Individu.l p.Uerrr of clrculelor) response to cie .rerle .woll ine Srudin of 1>rnnk dillerences bet.een sw.oA er. .nd r.nn .nwkers Srudie, o1 peychok+tkel diRerenres be. t.et/1 .IrrM en and non .nrOker1 •f .ho.. by comperison of /lrure dr... Mp IrrclqbRlul cA.r.clerMko of heahhr yount .du)u .nd their bbko}k.l Ire- Vtlea{on; a eorNbwun/t study In depth, .hh rqecl.l reference to Ihe Mecue+or" of Afpeneneios .nd cvron.r)' he.rt ds- e..n nnd le nnwlln$ h.bite A ee.dT of tle precorson o[ hyperteweion .nd eoron.ry dlne..e The de.elopmest of o nrkrohlot"kel eeeKwing eywew for .r./ of elrborne c.reinofer. To nnM In e.1.b1i.AInR of .ummer 1r.lw- Ing course in rb.wn cuhure lechn~ques at Unl.er.ity of Cobr.da Medic.l Scrool. Denver Colorado. and Unleee- .Ny of Wi.co.njw Meeh.nisme of Ihe prrMnr(.pk eRecu of n/cvlIne Tpe Mudr of .clbne of nkodlne urcwr cen rr.t srn.p.es and M. coneLtH'd .hh Ihe nw.h.n..m of .clw+n of het{..ior..Ilt .1..r diup 11 1 (:RAN-T7C AND INTTT1VTTpN IANIT TRAVFI 1., M D, Assorf.rr Pro- frssor of CNni(d rAvrnvco%n, Coe- nell Uni.enily Medical ('olkge, Ne. Yo.t. 1 1 E SIIA TSAI, hM n, Rr,e.rcA Asorl- Ne, Dep.rrnrrnr of r.rAolop, Yale I/nieenilr School of Medkine, New H..en. ROMPO A Vll>nNP, M D, Anocide rrofe»or of r.rAnln.7, Y.k Uwleerslty Scrwol of Medkine, Ne. Il..ew. P. 1). WARNPR, M t), rrofeuvr of Pa- rAr.f,yl, S/.1e (tnl.ershy of Iowa ('ol kn of Medkine, lo.. ('Ny. SIIIFf.DS WARRP.N, M D, D/.rrsae of 1.1nr.rae/rs, Cancer Resr.rrA lw,rl. frrr, Ne. Pngl.nd Ik.co.er Hoepltel Soetow. . SARRARA K WAT3ON, Pw D., Asdw- .nr S.Herlolo1l,e, M.nachu.Hls (lew- er.l Ho.pil.t; ReseorA A»r.ri.N, Ik- pertn.enl of Sec(eriolop .wd Iwrwr.- ok4., H.rv.rd Medical $thool. IOHN S. WAUGH, Pn.D., he/roor ef CAewdsery, KP.RRY W. IIOWPRS, rw D.. A»banr rro/rrwor of CArwrb- ". Mnaschwelb t.elNdo of TecA- nologp, C.mbridge. RICHARD L. WPCII3I.eR, M.D.• CRwI r.t lAy,(ofa*In, Moae4on !1~ .t Institute of Re.eerch, Pitt.b.rgh, ~e. A. WFINSTO(-K, hr [)., RrsearrA Sb cAewd.r, [Jfr Srlenrs D/rbfon, ItT Re- search Inalilute, Chk\p- RUSSF.I.L W. WPI.LP.R, M.D P.rllolo- fbr, Men.ori.l /lo.plt.l el CAtsler (buntf, West ('hesler, Pa.; Assorl.rr tro/rssor of r.rAolr.gy, H.hnewr.nw Medical ('o1kNr. rhll.delphl.. SIMON 11. WFNf)PR, rw D. Rrsr.rA rrnfrrsoe of 11/nc he.wlsrr., U.Ler.iry of Oll.l.u.n.. Norn..w. 79 PRUJECT TTT1.I. FRec(e of nicotine In the rabbit with fe- perirwentd coronary elherosckn»ie St.dy, on the ec1i.My of hiw/dlnc docsbo.- )le.e dutln. /he de.eloprnenr phase of collateral ckctilalk+w in the lung of the nt with Ngaed pulmonary .r/rry 1liwochen.lslr~ of ePlrhell.l rnuclrr In c.r- cinoenq of rhe luwe raholoorfc-.nerornk study ch.qee to hunr.w bror.chi of cellular Cornl.tioo of bronchi.l e{rithell.l ch.nille. WMh cornpor.Me ch.nges M dher o.- hrr-a pahobgic-.n.lon.k rudy 71141, .ateew of wret.a.de of c.rcinwne of the h.y Iw ru.n H{.top.tAoloty of human luns e.wce. t.rrwwoblk and .Irolo.k erudke on the role ef In/lucn[s arus in m.lign.nl cell L.nefortwMion F1eclrow epin reeon.nce ' to.cnp~ of p.rnnr.lnelk .pecies ri.ebk fror» tob.cco and related systems PRect of dgerette .n.ollnif on cerebral blood *o., cerebral r.et.bolie.n, bl.od IlruK+. blood o/1, arterial pulse pres Mre cr.e., ekNroc.rdloRr.me, and e{ec(roeiroephJnRe.nr Ff/ee(M of lob, oo n..ote on nllul.r re.- Nnaoicoa P.1bloRle--.naomk study of cellular ch.np In human bronchi A tleeted, relended .nd derelkd rudt of human bronch/.l n.uco+. A r+r.111Y1ve and ,u.ndr.tire study of the .rdl.ldu.l pohphen.d c..nrrnl .I • elpreae tobacco and the earr%e and 'l.ri rew.h/nR Irore clprene .n..lwp .nd •.1eo study of rhe /are of rhrx cornpounde h the .nlm.l reeprulnr) ererem TTre IdenNBcaion of Individuel p.J)phe

I CRANTFF ANI) 1NtTfTltT1ON 1)IIANF O WIN7l'I, Ptrl), Pro/etroe Schrnd of Ph.rm.cT. Ilnrrtr.rty of Kan.as, l..rence 711OMAS (' WFCTI A11, Pw h, Arrfrr en/ Lofe.cw n/ IA..wwn(n11. l/ni.crsdy of Vrrg•nia, ( harlatec.Jk, Vn. gin7. I•Rfl)IRI('K P WIIISKIN,M1),('M, Ouerr.r, nr.nl.,w nf IIr.IrA and Pr. tnwe6rrr Far•bA.rrw., Iht Age ( rnlrr of New 1)ibrar 1 I ngland. Inc , flcxrnn leee R(Xi1 R I W11 I IAMS, Prr 1), L..fncnr of ( Armnr.y .n/ f)i.rrrn., ( larrow I 1 nrn/annn Put Aew.rr.l Iwrnrore, i ht l/rn.crsn) of le..e. Austin I 1 I I)WIN W(X)1), M 1), lwrr.r.rn. In Afrd.crwr, Mtdreine, Boaon llni.enilY Schnd of /lrnron Inow Profec.or of Medicine, Mcd.c.l ('olkgt of laortia. Aurlcla I SI/MNFR W(K)1), 111 , M D, Anluanr IrnJclu•t of r.rMlotl. Drlvrlmcnt of Lch.rfnty, )ohnm /loptina lJnm.cmil), 1(allrmore, Md. /OIIN P WYATT, M.1), lroleuot of LrM•JoRe. S(. I ouis llniversily ScAoul of Medreine. St loufs, Mo (now Pro (e.v.r and [Nreclor. Ikp artment of PNho{oRY. Ilm.ersily of Manhob.. Winnrpeg, ( .nada ) PRO)F.(T TTII FF nolic cornp..unds preunl in the .moite frnm cisaretle. and the p•cpat.hon, whtre Iravhle, of rhex compounds for suuaLcr on Iheir melabolnm and pnnibk eRecl on human heallh FRecl of crgarelle smoke snd ds compa ncnls on frte pro6ne in animal lissue tulturet lhc delerminalion of the thrunk effect, of nr.llr .dminMered nicoline on aerum cl.rkslerol and pfw..phnhprds. the ekclrrasrd..yrapMc n+pnme lo ereono.rwe, and the .aaculac parhololf of chulenero/ fed uhMl. A sl.dfi of .nlih)pcrltn.l.c sttl.llT of nkwrn. Aclios o( nkoline on sulxellular dislrl- bulion of culcchol.minec anf aeroloniw in br.in and he.rl PrIM sludr of amc>•Ing habils of Age ('emtr membtrs An invtsriRatron of biixhemical hclors arvxraied nh rnuepr.hrhly to Iung clncer 'The effect of prolnnped ianlinn of lobacco smoke..nd of pr,Ajjed .Mlin. ence fr.wn Ihe uu o/ tobacco o• the reripheral v.scular respor~e Io .cule mhala/ion of lobacco +ml~t in man Esalu.tinn of e1.as.asic rKlor7, sucA as occupational h.ruds .nd h.bits, and pahnlogic peculiarities in the Iong• term surviv.l of pNientU following re. aeclion /or bronchornie carcinoma An In.eUigation Into the nature of the pigmenlary kriorn in centribhular em. physema Rl/ 0

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