Tobacco Documents Online

I V. 1'tyr lrrr-~rlr y.irrl uKerrrl InvediRatlnns aimed at descrihinR differences between smrrkcrs and nnrrsmnkcrt and atso relatcd to the nranncr of smnkinR, have cnntimred with increasing attention. ('ommittecs of the Scientific Advis.ay 1loard, wnrkinR with cullaMnNtinR consullants, have underlakcn ill review the e.istinR literature that may he pertinent to the situation and to hold periodic mectinRn for consideration of work in progress. A preliminary anthropomctrk study of smnkern and nnn-smokers, conducted to determine whether there is any significant constitutional dif- ference as reflected in body build, has been published. A correlalion be- tween  particular pattern of anatomical trails and heavy smokinR was diccovered, and it was deemed to he of suQ'icknt magnitude to jusffy an enlargement of the study to include a larger populatinn of sludentt at f hrvard and Johns f Ic.pkins Univcrsitics. Other traits that reflect hio- IoRical make up are also to he included in these studies, and nther kinds of pnpulatinns, including a Rroup of relatively nldcr pcrsons. Are undcr invettiRatit,n. V. Talrrrr•rvr (:/rPrnr.lry Reports in this field include hirxhcmic:d invcstigations of nicotine formation in plants, the course of nicotine nuidatinn by haclcria, the kinetics of nicntine nxidatinn by air. the idenlificatinn of previuudy un- idcntified camfnmcntt of tohaccn cnuokc, and the fate of certain insccticide resitfucs. Uf particularly direct pertinence are the newly reporlcd ohscrvatinns on the course of nictrline melahcrlicrn by mammals, which have m,w been extendcd In man. ihe formation and etcrelinn of O cntininc as a major melahnlite have been confirmed and the study ill pharmacoktRic effects of this metaholite has been undertaken as a contribution ill the undcrdinding of nicotine cffects. Prrxfucts from the further mclilw+lism of (-)-cotinine have also been isolated and identified by rignrnus methods. N.rn linok I:ooer• R'orfd Lirrrnrurr on Tn6nrro nrs. f.arsnn, IIaaR, and SilvcHe tif the Medical ('tdlcre nf VirFinia, culrninatinR  project assisled hrt a number rd years by the ticicntific Advisory nrrartl, have cnmplrtcd a IwMlk titlcd "Inh:rccrr I:xl+crimcnt:r) and ('linical Studics " the Mwrk. RIX) frar.cs in Icnyth, is a crrmprchcn-tive account of the wt.rld liletnltue and it F,:r.ed rrn sturly r+f mrrre th:ur h,(NN) nrtitlcs pvf.li.hrd in alw+ut 1,71N/ it+unutls lhis majra nrhlitimn In the tcirntific nnrl rnrdical literattnc on h-h:rc'crr, wlhirh i% ill hr IruhtiOhrd in rarly 1961. /nrrnri.r. Irr Lr rrl vrry I-tryl nt.i~t.~nrr Irr rnvrUry:rtrrrn in the /irlrl As a crdlateral activily, thcce scienlisas havc al.rr laurluccd a« rics uf compr(hcnsivc, critical rcviews on a variety of specific sul.jccls hearing uprm tobacco use and huntan health. Four such reviews which have ap- l.cnred durinR the year are summarized in the ahslracts. F'4f.rr.•ari1r f rnRrnm '1 he ?'.I R.C. mcdical student felluwship program was aRiin in effcct durinR the year. I his program has been renewed each year since 19.55 when il was originated upon recommendation by the Scientific Adviany Iloard to ctimulate interest in basic research among mcdkal studcntc. Suhjects for study are selected by the students in cunsullatiun with their advisnrs. Recipients of the fellnwships are chosen by the deans of the medical schnnls and the research is done during summcr or rrther off- Icrm pericxls under the supervision of eapericnccrl scicntials- Several hundrerl young men and women have participated in the fxtrKram in thc h:nt siR years. I Q 21 1' 71/ ~ r1

Tnltle• of ornirnir Annnl+ ttf the New York Arnrlr•mv +tf tit i~rtrr•N Sclrirnrlu•r 27, 1900 1'ar1 1. 71tt• Alr•nrl.linn .nd Fair of Nirntinr lnrr.rrlurtrrry RrmnrAt. fly ('arl 1. WigRcrt. Nicntinr and Il. Rrrtnnira! Sourrri.• Hy R. F. t7awtrrn, Maric I Srtll, and h R. Chritlman. .fbtnrprion of Nirurinr /rnm t'arirnu Siirs.• fly )anet 'fravcll .Ih.r.orrlinn of Nirnrrnr t/ndrr i'oriorrt C'ondilrnnt nl Tnhnrrn i/sr.• fly P. S Larton. 7hr F:+rrrrir.n and MrroArdism of Nicntinr.• fly Ilcncctt McKcnnit Jr. 1'.rt 11. 1'}..rna.roloRlr.l Arllnna of Nirnlinr rnr) Toherro 5mnAe Cnmpnnrnrt nf /'lhnrntnrntrrAic lnfrrrtt in Tnhnrrrr S.rrrrAr fly (' 1 Kcntlcr, 7lrr l4rnrnrnrnhrgirnt .Ictinnt of Nirnlinr.• fly fttliut 11. Crtn+rt.c, Ir. 7 hr A4n lrnnitrrt rrf (:onXtinnir Rt.H rImlr I'rndln rrf hv Nn nrrnr • !ly I:tlward W Pclikan. i(rtinn r+l NirnNnr nn the ltrnrl fly 1 I larnld lturn. 7hr l*/Int .r/ Nirr.nnr und SmnAiyR rrn lirr .Cri rrtirrn n/ I l.frnrhlrrinr. fly I)inicl T. Watls. I'.rl 111. The InQuenrr n( Nirnlinr enrl CnrukinR nn the Prril.hr•r.I (.irrnlStion Thr Artirrn nf Nirrrlinr nrt rhr I'rri(rbrrnt Cirreulrrrlrrrr. fly ) IL:trrdJ Iturn 7ltr Arnrr (i/frr t nf ( ignrrffr CrnrrAnlg rm rhr ItrKitrrl ( m ulrnrrrn rrr llrutth anJ t)rtrorr.• fly Jack I:rctmrl and (l:tirc Ward Infhrrm r nJ Nir nlrnr nn tlrr /tfrrr J) IrrN rr) KrtlmR .CArfrlnl Muv Ir• unJ llrr f)iXitt in NrrrnrulSnhjrrrt.• 11y Ilnn+ Rrtttcnslcin, (ict,ryc f'rircc, 1i11icr Rl1tt, I1Tvltl f fltlCr, antl Ilnl;h I`/rtnlprmcry. Ft f/rrt nf SrnrrAmg nn thr 1'rriphrrnl ('irr rdation in It.rrnurn w /' nrirnrunrnrn/ 7rrnrrrnlnrr.• fly 1. Fdwin Wrxu1 7 hr ./r t.rr F./Trc t a/ ('hrrt•inR 7 nhar r n nnd SrrrnA inR in llrrlrNrurt il.rrrJ, • Hy David (.. Simnn and Arnuld IRlaocr. Rrrynrntrt n/ rhr I'rrilrhrnA Vrirrt in Af~nr Irr tlrr tnlrnt'rnnut A,lrninitrnrtinn n/ Nirrrtinr • fly )rthn W Vcktlcin and A. W. Ih,rtlcy. 7'rrhacr u!1 vfrrrtrntirivity.• fly Vinccnl l. Fontnna. 7rrharr.. fttrrrtrnnrivilv 1'rrq+l+rrui ( irrntnrnrv Irnt+firath-tt • fly W RcJitch, K. Mcckclcr• 1V ttruwn, and ). M. Stcclc 1'wrl IV. Aclinn of Nirotinr .trrl SrnokinR on ('nrnn.ry f1rrnleliun I'llvtirdrqt• of thr ('rrrrrnarv t irr rr)ntinrr 11y 17r.na1r1 I:. (itcl'P ('ur lrnr !/)rr I t../ Irrlrar rrrnrrrrr v~rMnrrl lrrrrr trrmr rr/ Nrr un.rr ' !ly S.unutc) Ilcllct, rarnt•t W Wt••1, ;tntl S:rnliayn VGurnr.rn 1 r tirrnt n/ Nu rrlnrr nnr( .irnrr.A/nR rn (.1r.ntrrry ( err trhrrr..n urtrl Al-r rn,li.rt !)rl-rr.r Iluh:nrrnn t1y (irr.rlrl A Ktcn nnd Ilrcr•rtr.tc i( 51.t'n,..l •,~....rr.l I.r . r...r,r 1„ .ht tr.,.n rh. t.,rm... Irrdu,hr r o..u..itv. Crrrnnnrv Rlnnd Flnw and Cardioc Oxygen MMoholi.rm nnrinR icntinr- lnrlnrrrl lnrrrn.rrt in Left Vrntriculor. Work.• fly Ivan r. 11v urte, A. Jane Williams, Louis Potsicter, l. E.Schmitthenner, J. It. Ilafkenschiel, and Cecilia Riegel. FjJrrl nJ ('ianrrttr Smoking on Coronary Circulatinn and C'ordioc Work in /'alirnrr with Arteriotclrrotic Coronary Distasr.• Ily Timothy 1. Rcgan, flarper K. Hellems, and Richard 1. fling. Tobncrrr SmnkinR, the F_lrctrocordiograrn, ond Angina Prctori.r. fly ltertil von Ahn. Par1 V. P.nel nlsru..lon Significance of Flrcrrocordiogrophic and Botlirtorordingrophir C'hanRrr Indncrrf by Smoking. Isaac Starr, moderator. Participants: Frank W. Oavis, Jr., flflrje Ejrup, and John 1. Kelly. )r. P.rt V1. (llher A.Lre1a of thr Ph.rrn.eolop of Nirotinr.nr) Sn.oUlnR Thr F(frct nn Rats of Chronic Exposure to Claartttr SmrrAe.• [ly I1. B. IIaaR, P. S. t.arson, and J. It. Weatherby. Chronic Nirntinr I'nitoninir• By Clinton I1. Thitnes. Nicotinr nnd SmaAinR on rhr poa Bolli.ttocordiogram, By Aldo N. Corbascio and James W. West. Effect of Cigarette SmoAlnx on the /nfroocufar Blood Volume, By Victor G. rcllows and Jerome W. Bettman. Circulatory Rrsponrrt to Smoking Lt Healthy Young Mrn.• fly Caroline Iledell 771omas and Edmund A. Murphy. Compnrisrn of C'ordiovascufor and Related Chornctrri.tir•f in /tnbitual Smokrrs and Nontmoktrs.* By Ilenry Blaekburn,losef Ilrozek, llenry 1.. Taylor, and Ancel Keys. P.r/ VII. F.fRrrra of Nicolinr.nd SnroklnR In C,.rrliov..rul.r his..rders Cardiac F,Brrtr of Nicotine in the Rabbit with Exprrimrntal Coronary Athrrnsrlrrotit.• By Janet Travell. Seymour 11. Rirvler, and 1)~inthy Karp. The Chrnnic F.Brcrs of Orally Administered Nicotine in Cho/r.ttrrol-Frd Rahhira.• ESy Duane 0. Wenzel. Jasbir SinRh Kamal, and James A. Turner. Thr CardirwntrutOr F(jrctt of SmokinR with Special Reference to Nyper- trncirrn. fly Cirace M. Roth and Richard M. Shick. Fflrrt nf Nirnrinr on the C.»r>nory Blor.d Flow in the l'rr.rrncr of Corcrnory Innrf/irirncy' .fn F.~tprrinerntal .Sltldy in /)n>tt.• Ily Samuel flellet, Jamct W. West, 1JRo C. Manmli, Ot(o F. Mutler, antl f'arrlo Rosti. 7'reharr-n rItlrrFy in Coronary Ar(rry !)iseasr. Ity lttserh I4arkavy and lily 1'rrfm.,n. ('rrl V /11. /'anrl Ili.ru..lt.n h:(/rrYt rrf SrnnAinR in /!lfrntrt a/ thr /'rriphrral 1'atrntnr Svvrrrt 1i A Iiinrt, 1r , nnMlrralnr Pnrticiltanlt: Fttwin Wt>,rr1, Ilup}h t,trrntprrotrry, (iracc M. Rolh, and Rrrttrrt It. Gr.rtr •Af.iard t+y . Rr.nt in •iA trom the lnh.crn tndu.ny Rr.r.rch ('ommitlit. r' 2 ) ,1

/ Ahstracts of Rc-ports Fach tcci(.icnt nf a Tnhacco Industry Rcscarch ('r+rnmiltce gront-in• aid is resrtmcihle (ar the initial preo;rntation at puhlicalirm of the results o( his research in scientifie meetinf!s or in aptin,priate scientifrc joutnals F-nlhrwing arc rhstricls, approved by the aulhurs, uf rescarch reptrrts, with ackmrwlcttgrnenl of surptal frnm the T.1 R.(•., Ihal have a(,(+carcd in scicnlific jt,urnals since the last Report and lhrnuph (h:to(xr 1960. Titles td earlicr pal,crs by granlees abstracted in prt:viuuS Re(•t+rts rd Ihe Scicntifsc hireclor are listed at Ihe end of Ihis section. 1 he n,rne of the scienlisl to whrrm thc T I R C. grant was made is Riven in (+ircnlhescs whcrc required. These ahstracts have heen K+nuped under six hendinRs: 1. Cancer Research; I1. Iluman I.unF Studies; 1(I 1(tart and ('irculatinn; IV. 1'sycho- physitrh.Rica1; V. I obacco (•hcmistry; and Vl. Ulhtr Studics. I. ('ar+rer Kr.Pnrrlt "A S7UO1' OF 1II1? SfiNSl1IVIJY Of l1(1? MO(ISF, FORPSlOMA(-II TOWAIi,I) ( I?ItfAIN 1`OLY('Y( LI( IIYf)RO('ARIIONS" fly Fred r. ht.ck ftnd I1r,up,l ss W, King, (tuswtll Park Mrrut,rial Institutt Itinlt.gical $I:rtit,n, Sl•rinpvrltt•, Ncw Yrirk. Irrrrrnnf nf rlrr Nnlrnnnf ( nrrrrr frrrtrhNr. Volume 21. py,rs 911.1419. Oclo)rcr 1')59 (1 1 R('. Franlct: Ot+ck) / urpn.. n/ .trrrh rOurinR pi1r,t st++rlhct nf thc rflccls of ci).irrtle smnke crrndcnsatc nn Ilhc rnr,u.c Ir irr, r vl•nrlr rnt nrnnla r n( I,:rlnllnrn:ra wcrc rrlr- served in the fprcalnrn,u h of ('S1111 nnr r,ahr, h h,rrl hct•n •'p.nn,cd•• rmce with ahuul l S mr. trl 7,1? dnr,ctlrN lt.,nit,rt.rnrhr:rtcnc (I)MIIA), suR Retting that the (rncttnm.ach ntr}•I,r crvr :ts a IcM attc It,t scrrrninF weakly cafcinrrrenic hyr(rrK:,r)n,ns, 1 n mvrNq•,rlc Ilttc 1,rncrl,ilily, Ihc ct(cclt r.t orally administtrtd I)M11A anrl 1.mtlhylthrrl~nthrcnc (M('), and alsn hcnz(a)anthr:rccnc (IIA), were srurlicd ProrrAnrr.: (•51111. mice wcrt dcrtivcd of (rant (nr 24 hr+uts and then intuhated IhrmrFh the earphygus, each aninial receiving 1).1 ml. (.f heavy mineral oil ct.n,nininr 1) S nrp rrf tcs/ crrrrnf+twnd Rtpcatcd drrsts were given ltt some at inlcrvnl-t n( 3 trt 7 tl:ryt, arN( tllc 1mn1:1ls were nlatntlmed without (urthtr trcalmcnt until F~Hric palailitrmas were found ct.nsistcnlly amtanR the nnimala that died 1)A111A :rrul M(' prrnrps reqnircd a I+erhat t,t R In IO mr.nlhs, and the IIA series were kilicd a(ICr 16 nrnnths, althnuRh lumnrs had not been found in the (wnt rnrrrtcm nratcrial avail:rhle. Finr(inRr: A sinRlc intrig:r.tric alq.licatinn of (1 5 mg tr( titht•r 1)MI(A ar M('Ravc riar tn a trrres(tun:rch Innrr» intillcncc ro( RS^,:~ and %1"S,, rr-,hcc- tivcly Multifrlc a f(+licalinns IrH:rlinf! A rrr R rnr! I,rrHluctd (•:qrillran:ra in all 44 treated animilt an l carcinrnnas in G Amrrnr 7 7 mice reccivinl-. 4 rrt R mr. o( RA hr ttrrm,rth h,ht, 2 dcvchqacd 11a),ilhrmls uf thc Grrtalrun:rth aftrr ((, n11,ntIt1, h,N m, Ntmtns -V(•rr:1tcrl +nu,nf. Zrr nricc 1trilcA t,ncc will. (1 ~ mr. r+t ItA Ihc rl,rt. inrlicn/r•rt Ih:tt Iht nnrnac frnral,.rnnth is mrnr arn.rthvc trr tin/;/r :,t•I•hr.rlr rna nf tartit-rrns Ih:,n Ihc akin "1-ttMOR-I1OSl• RF?I•AIIONSIIIPS STUb1FiF) IN 1'l7RU, RXPFiR1- JNI S W1111 1'ISSl1E SI,I('fS " fly l.enpnld R. ('ercccdn, Sister Marian use Smith, and Jesus Vicenle. F)eparlmcnt of Itiuchcmistry, ftrrdham (lniversity, New York City; Department of Biochemistry and Nutrititrn. Schtarl of Mcdicine, Univcrsity t.( P1teHo Rico, San )uan; and ('olleRe nf Saint Iai?a(xth, ('anvent Slalitrn, New Jersey. RirrrArmicnl nnd Rirrrhy.riret Rrrrnrch ('ummunirnrinn,r, Vol. 3, pages 32R-332, Seplcrnher 1960, (T.I.R.C Rranrce: Cerecedo) Prtrpnr• of .nrdy: Previtws studies have shown that the presence of a tumor causes cer,am chemical chanRes in the host tissues at a distance from the tumar, which are reverscd when the tumor reRresses. This work undertook Ihc stucty of the ineorptxation of thymidine-11' into deaxyriho- nucleic acid (1)NA), and of adenitx-R-Cr4 into DNA and ribnnuclcie acid (RNA), in slices of tissues of normal and tumor hearinR rals. Prnr.rlnrr: Lungs, liver, spleen, and kidneys were eatirpatcd from rats hearin the Walker 256 carcinnsnrcoma and Ihe Jensen sarcoma, and from muntaTrats, ant( tissue slices madc, llx Incorporation of adeninc R-t't4 and Ilrymidinc 11' inlrr /tfie 1)NA of lissues nf Ihe normal rals and carcinoma bearing rats, was detcrmined by radioactivity cnunler. FlndinR.: Slices of liver, spken, and (ang of rals hcaring Ihe Walker tumnr incrnrtrratcd Ihymidinc into DNA Io a nrarkcdty Frcatcr e>ttcnt than did the sliccs of correspondinR normal tissues, whereas Ihe kidney did nnl ,htrw any change. Similar resu(IS were obtained in rats bearing the Jensen snrct+ma c><ccpl that chan(;cs in the spleen were more pronounced In the ex(+erimenls with adenine in rals hearing the Walker tuntt,r, Ihe DNA in the liver, splecn, and lung shnwed greater activity while the kidney did not show any change. In rals with the Jensen sarcnma, the tumnr caused an increase in the activity of the 1)NA of the liver, splten, antl lung. As Iu the RNA, both tumors caused a sliRht rise in Ihe activity of the liver. In other lissucs, a drop in lhe activity was usually ohxtved. 'l he pattern (if thymittine and ndcnine incnr)axation in vitro by Ihe orRans of norma/ and lumnr- hearinR ra1s, especially by Ihe liver and spleen, are in harmony with Ihe results whiclr ("crrceda el al 11959) trhserved in vivrr, l1t/rrr Krnnror.: U.S. Public FFeallh Servke and the Damon Runyon Memarial Fund. '•I:FFF(T OF AIR I'OLI•IITANTS ON CII.IATfiI) MU('(/S S(f('Rl?"f- (N(i 1?PI ( I 11: I,Il1M.•' (1y Ikrla M. Tremet, ('h F. , Ilans 1. 1•:rlk, Ph 1)., and Pcntl Ktrtin, M.1)., 1k'partment td Pathnlngy. Univtrsily nf Stnnhcrn C:dilrrrnia, Srhrwrl of Medicine and Los AnReks ('trunly ( icncr:rl I lrrs(rilal. lnrrrn.rl n/ Ihr Nntinnal Cnntrr Intrirulr, Vol. 2,1, pages 979-99A, Nrrvcm hcr 1959. •'ITIT(T Or ('1(rAR1:7-fE SMOKE ANI) ITS ('ONSf I7t11:NTS ON (-1(.IA1(1) Mtl(lIti Sl'('RI?1IN(i f:1'11111:a,ItIM " fly Il:rns /. Fall, ItrHa M 1 rrmrr, rand Paul Kt+lin. Inurnnf trf (Irc Nntirrnaf ('anrrr frr4rirurr, Vtr1 21, paRrs'IVV 1012, Ntwemhtr 1959 (T1 R('. Rututcc Falk ) I'r.rp...p n( rnrdl.r: 1lndtr ntumal ctrmljlinns. Ihc rlrrw vd thr nrucnus tlream In tht• rr.(ritahrry lracl (+revent. Ihe atcumul~tirrn u( (,arlictulatt matter trn the rr.lnratt,ry epitficliunt. T he maverttcnl of Ihis strcam it relatrd 25

I t m N N t• .i D to two factnra: thc whip-like action nf the cilia, which provitlec the propellinR fnrce, and the amnunt and cnnaittcncy of thc rnucuc. 1 hcae studicc wcre inttituted with the ultimate aim nf yuantitatinR the inhibitory efTects of in- hated tuhctancet on ciliary activity and flow nf Ihe mucous stream. The first paper ia cunctrncd with the develnpntent and atandarJiFatinn of methods for rlclcrmination of the eflectt om mocous now of exprxure to irritantc in the pnllutcd a/mntphere and with correlation of the physiologic findings with mrxphnlnpic chanRet of the retpiratory cpithclium 1 he sccnnd paper com- pares the cffects of cigarette smoke with the retpnnse to irritanh in polluted air. Pro.r..Er.r..: The measurement of mucous flow wat first undertaken with the uce of eateriorircd and in sinr tracheohronchial scgmenlt in anesthetiYcd rats or rahbits; paraltel studiec were performed nn icntated trachcohronchial segmenta from the same animals. II was stxm found that Ihe data were com parahle trnlh qualitatively and yuantitatively. Further work was done on Ihe ecr+lthagcal tract o( the frnR, which waa technically Icta cnmplicated, becauae envirnnmental agcntt crnrld he inUrxluced at rtxrm tempcrature Ilere alco, it was fnrmd that the qnaitative findings were similar and et<tra- polatat.ility nf data wat not aRtctcd In the firtt p.iE.cr, the animal tpcciment were expnccd to the test acrmnh undcr cnnatant conditient by twn mcth<x1s-one a"hy-pact" mcthrK) whirh attempted to dnf+licatc in vivrr cnnditicros of ex(aicure th:N cUtl in thc majnr part of the tr.chenhrnnchiil Iree. the other f,y impinrinR the aernorlt dncclly nn atlectcd arraa in tndcr Irt duplicate in vivrr cnnditinna occurrinR al hifurc.-itinna nnd anRnl:rtinna of the recpiratory tract. -1 hc rate of flow am1 nthrr phyainlnRic and hictrtlrrp,ic chinFct were tlctcrmincd, and conditioni prior trr exprranres were utcd ac cnntrnlt In the accnnd study, file ctpcrimcntt were reErcatcd with c iRarctte smoke. 'Ihc smr.kc wat dilutcd in a mixinR chamher, and a por1 r,n was pasted over the tistrrc by eilher file inr .ingerncnt or t,y-~'ast method. Furthcr Icsts were marle hy applying micro rlrnp qu,ntitjca of water sr+luhle com- pnncnlt of ciRarette srnoke to the dnwnarream end of the ciliated epithclium .pecinrens. FlndlnR.: The initial recpnncc of the cpecimcns nf epithelium to natural antt artificial cmrrg, mmnircd hexcne-2 (in lieu (if gasnlinc), and nlher individual and allied cnmfxoundt uaually waa a Iransient increate in mucnuc flnw, ratc, which wat rapidly sut.crccdcd by a tlnwdnwn in the flow rale of rnucut, followed hy slow recovery tn the hace line rate. 1 he efT!ct was fundamentally nnntprcifre since ettcntially unrelitcd cheniicnl conrrnunds cnuld prndnce the enet-tt Atan, the rrefalnce wis nnt cpeciet qucr.rc. lhe initi:rl increaae in (low rate varird in intentity with the ral+rrnlre a(-ent, whereat the dowing and recnvrry perirxla were relatively crrnttant, mr+re f+eraiatrnt, and larrely indcpendrnt n/ the Iect aPent I)irecl impingement nf file lett a/cnts pnNluceJ a more r+van/ilivtly intenat, thnnFh yrrnlitativeiy similir, rcelttrnte aa trrnyrnrrd In t'rr hy Qaat mrthrwl ('hnnprt in cnnaittrncy nf Ihr nnrcut nltn r.ccuntrl, anrl will Lt r•vahlnird in Lrtrr wnrk. Mrrrphrdrrric chrrhra rrvrnlcll a mnrkrd inrrrnae in file rrnnrt.rr rnrl :x tiortv r-t thr I•rdMrl rrllt '1 hr intcntily rd hittrt- I,.,rh.l,prr r Ir rr~y.. p.rr.dlrlrrt rhr rnrrntrtv ol thr .rhnrrrrn-il I~hyairrln0ic r.rl. n.. In the tet•s with cigarette tmoke, brief stimulation of epithelial flow dso was fnlluwed by inhibition and recovery pericx)t. The impingement melhnd eliciled Ihe strongts( original stimvlalinn, hut the inhibition effecl was most intente after the aqueous solution test, and recovery never returned to the basc line flow rate when this method was used. I)asically, cigarette smoke in all ils various fractions, as well as in its entirety, primarily decreased the rate of mucous flow after a short pre- liminary acceleration. The deceleratinn persisted for • considetahte period and was relatively conttant for both whole smoke and its various com- r nets. Filtration resulted in a smoke which had little or no altering effect yond a brief initial acceleration. The elicitation of a response to both air pollution and cigarette smoke establithes that from a phytiokrRic point of view a hayard existt during eaposure tn virtually all measurable concentrations of these agents. T1,ese repetitive ctudies are believed to parallel the human situation. Orlr.r Rrnnror.: U.S. Public Ileal•h Service and American Cancer Society. "A (Y)RRF.I.n1Th IIISTUI.(X71CAL, CYTO1.(7GICn1., ANI) ('Yl'(1- ('11EMI('ALSIUI)Y OF lllEi TRA('1EIiUI1RUNC'FllAl. 1R1?13 ANI) LUNGS OF MI('1; I;XPOSI?1) TO CI(iARE?TTIi SM(1K1;. Ill. (iN- A1,1'E:RFI) IN('11)I:N('F- ()F (iRt7SS1.Y VISI111.1? AI)I:N()MAT()(IS LUNG TIIMORS IN FEMALF. ('P MI('F AF1FR PROI.ON(:FI) I:X- POSURC '1O ('1(:AR[:TTEi SMOKE." fly Rudolf I.euchlcnherRer, M 1), and Cccitie Leuchtenberger, Ph.n., The Children's C'ancer Rctearch Foundation and Department of Pathology, The ('hitdren's tlospital, Itoalon. Matc.; and William Zebrun, M.1)., and Patricia Shaffcr, Ikpart- mcnt of Pathology, Wectcrn Reterve University. Cleveland, Uhin. Cancer. Volume 13, pages 956 95e, Scpt.-Ckt. 1960. (T.I.R.C. grantee: ('ecilie 1-euchlenberger ) Purpo.- o/ .tudy: In the course of the aulhors * majrx crxrelated study of the sequence of events in the respiratory tract of mice after exposure to cigarette smnke, attention wat also given to the adennmatnut lung tumors so freyuenlly nbserved in ceranin strains of mice. This repnrl dealc with the incidence of grotsly visible adenomatnus tumors in the IunRs of ex- perimental mice and in non-eaposed controls. Pror.de.r.: A total of 397 female CFr mice were examined I death, between three and 28 months of aRe, of which 166 were non e><pnted controls and 211 hnd been exposed daily to the smoke of r,ne-hnlf to eight cigarettes, at hnurly intervals, for perirKls ranging from t7 to 600 dnys. 'Ilre mice were not smoked un week-ends anrl hnlidays At certain pcrirrlr after eRf+rtturq the e><pcrimental mice and thcir conarnlt were killed nnd Ihe Froatiy vieihle ademrmatrmrt tumurs were rrcnrckd. FPnrUnRr: Nn ttntistical difference w•t fnrmd in the frrqucncy of the lung tumnrs I-elwren the cnnrrnlt and the etpraed nrice. Ahout nne third nf thc mice in IHrth grmrps had tunuut rnnKinR /xtwern I and (A mrn in tire I tie hicluluRical tcaturca nlan were very airnilar in tMNh Rruuht file tumrat nunl frcqurntly arcn were lanlyn adenrrmas. Whrrr tnnttrdc and cRpnacrl mfie were urnngrd nccrnding Irr file nft at wlrich turnnrc were nhacrved, a rtlatinnahip httween a/~c :rnd Immor incident'e w;rc alqiarent Wilh the ewceptinn Ih:rt Ihe ewlalSrJ n11Cr rr.iched 27

an incidence of 40°,''~ at aRcs of R in 10 months, compared to that at 11 to 14 rnonths in the controls, the plotted curves for cnntroh and e><poscd mice are vcrr similar for all aRes. When mice were grouped according to length of time of etf.nsure In cigarette smnke, it can he seen that at I I to 211 months nf age there was cssentially the same frcy ucncy of adennmatnus lung tumnrs when e><posed to smoke for 17 to 99 days and for IIK) to 199 days, while Ihe tumor fre- qucncy in mice c><(+~~scd from 200 to 6(K) days incrca.ed to 66^~. Ilnwevcr, it thould he nnteJ that non-txposed controls of the same age also had a higher tumnr inciclcnce - namely, 56% - than that found in mice expnscd for 17 to 199 (lays. Whether e>< ~sure to cigarette smoke may snmctimes accelcrate the development of I},e tumcws cannot he answered at this time. In view of the small samplcs, more experiments with larger numbers of mice should he carried out in order to determine whether such a difference is significant. "STUn1ES ON TIfF. EFFECTS OF ACETAI.DF:FIYF)F? ON TISSUE CELI S('lll-TIVAT C:f) IN V1TRO." Fiy l)onald M. Pace and Alice Elliott. Institute for Cellular Research, l)niversity of Nebraska, l.inculn. Concrr Rrrramrh, Vnl. 2/l, pages R6R-R7S, luly 1960. (T 1 R.('. Rrantcc: Pace) Purpo.e o/ arudy: lhere is considerable interest in the possihle toxicity, carcmo~e nicily nr cocarcinngenkity.o/ the constiluents of tobacco smoke, in which acetaldehyde occurs in concentrations of 0 9R to 1.31 mg. per ciaarelle, depending upon the kind of lohacco. This invesli6ation was untler- talen to accerlain Ihe short- and lonR-lerm efTects of this substance upon several types of tissue cells cultivated in vitro. Procedur.: Four cell lines were used: Farle's strain 1. cells, mouse liver epilhclial cells, human skin cells, and llcLa cells. Routine suh-cultures were made once a week for the firat two 1lrains and snmetimes each 3 or 4 days in the latter two Ohservations on the toxicity and poscihle influence of acetaldehyde ulxm rate of proliferation were made pericxlically, usually 4R hours after replication. (kcasioncJly during the shurt-tcrm espcrirnents, and in all except the firsl series of long-term eaperiments, the percentage of viable cells in a culture inoculum was ascertained. Purpoae of .nrdi..r In the course of in vitro development of moo mam- skin cells exposed to 2.0 mg. acetaldehyde per ml. seemed to resemhle those of the control, except for a definite granulation and vacuolizatinn, but care- ful exunination showed that the cells were dead. The cells began to rcund up and detach within a half hour when e><posed to R 0 mg. acetaldehyde. lhus, these two concenlrations pmved toxic to the cells in a matter of hours in the lesscr and oi minutes in tFx stronger concenrratinrtm. A scc<md series, expnsinR skin. IkLa and liver cells in 1.0 and 001 mg. acctaldehyde, also shnwed toxic effects In a matter of hnurs in the larger cnncentratir,n, as did  third series usinR concentratinns af 0 5 and 0.OS mR respectively. On the bnsis of the short-ternt findinRs, 001 nrR and /) O5 nrR con- centUations of acelaldehyde were ch~nen for the honR lerm stodie., f.cinI~ the least to.k in effect At these enneentrntions cell prnliferaNnn nl'l.e.ned In he rnxmnl nr was arhrally stimulated (rRee d lcrr the liver crlls in 11()S rnR /ml ), IcajinR tc, thr.e quettinns- I)ors srit stinwlatlnn cc+ntinur at IimR e /he crll+ arr relwned7 1)u Ihe celle return to their neurnal rate erf gmwth and then cnnlinue to prnliferate as though nn acetaldrhyde were Kresent7 Is there 3 gradual accumulative effect of the suhstancc that may inder later gruwth? Frrrm the results it is evident Iha10 05 ms. acetaWchytk per ml is toxic to the liver crlh. 'I he 1. and (IcLa cells prnliferated well, at least for the firlt f,~w weeks, hul cells e><pnsed to this concentratinn never incrcascd as much as the cnntrols. After a period of several mnnahs, however, the acetaldehyde hecr.mes inhihitnry, and the cul/ures may (lie out Lr;cluse nf its presencc. It aIcn appe,rs as though those cells which shnwcd the e/fecls u rcetaldchyde accumulatinn recover if placed in normal nutrient medium, nless the limc of e.rosure to this substance had been excessive. nt6.r Rrernrnr: 11. S. Public Health Service. "ON Tllr CIIRf)MOSOMF: NUMFIERS OF FII/MAN AMNION ('rLIS IN PRIMARY ANI) STRAIN ('ll1.Tl1RFS." fly Y. 11. Nakanishi, M V. Fernandes, M. Mizutani and C. M. Pomerat, Trssue Culture I ehoratnry, heparlmcnt of Anatnmy. Univenity of Texas Medical Rranch, ralveston. Tuos R.yarrra c.n Rinl.,)ryand Mrdirinc, Vol. 17, pages 345-353, hall 1959. :SMOKfi (Y)NI)IiNSATFS ON I.l1NQ CF?LI S IN TISSUE ('lI1.TU Rf.TURf WIT11 SPF('IA1. RF.FF.RfiN('F: '1O CIIROMOSOMAL ('IfAN(:F:S.'Ily Yrdr 11. Nnkani.hi, Mawhiro Mizutani and C. M. 1'umcr:rl. l'riur Rr- rnrrt rrn ItinlcrXy ond Mrrlirinr. Vol. 17, pagcs 542-59I1, Winter 1959. "1TIE DEVEI.OPMENT OF A KITTEN Ll1NG CT?l.l. SfRA1N AND 1TS C11ROMOSUMI:S." By Yuh H. Nakanishi. 7.rittrhri/r /iir 7.rl/f.x- .lchrrnA, Vol. 51, pages 13R-ISt, 1960. "TI1E nfiVELOPMENT OF A NEAR-1)IPLO1D IN VITRO STRAIN F:ROM A SMOKE-(Y)NbF3NSATE INI)I1('EI) MOUSE Tl1MOR." fly Masahiro Mizutani, Yasushi Uhnuki, Y. 11. Nakanishi and C. M. Pnmcrat Tr tnt Ren.rrrs nn Riofogy and Mrdirint, Vol. I R, pages 455-469. Fnll 1960. ((T.I.R.C. grantee: Pomerat) 1•nrpc... oJ .rndlsr In the cource of in vitro development uf mnst mam- malian cell strains of both normal and malignant ori6in, chromosome mmncers havt been found to undergo changes from diploidy Io a helero- ploid state. Such Iransfnrmatinns are associated with slruclural chanRes in addilinn to the nunrerkai increase of chromosomes. Fstahlishcd cell strains invite quantit:rtive studies on the eRect of chemicals suspected of influencing the chrrnnusnm:J complex. AccordinRly. Ihe work included ntlcmpls to develop erithelial lung slrains with and without the presence nf suhstances in tnhacco smnke cnndensates. Such nuhstances and hcnzryrene were em- phrycd to dctennine whether the chromosnmal ccpfiguratn.n of an csta- hlished IunR strain could be altered. rrorr.rur..: 1n the fir.t st-udyrlacental tissue fnrm a healthy woman was ohlained. 'I he trst nhjects used eonsiated of Ihree ty('rs cr/ mm~iun cell dcrivatives, lxciuse mmninn cell strains are consideted In Ix partic'ul:uly usrful for virnhor~ical sludica and rnar he aRected t.y irrndialii~n ns well 'Ilre ccll culhuci were trypsinized nml ehrnmosnrnet were ccrunted f.dluw- inR a Inotracted qeries of auh-cultures In /he srccornd dudr (un/ tissues frnm a 215 tnwmth nratc humnn frtus and frortm ncwtb,,rn to Gcur-weck-ctld kittens were ulcd as tesl matcriats; I m 28 29 X, N 0

r I i I I e.flants were stt up In eultnrc hnllles with the uce tit avian pIa•:ma clots, to which EaRle't mcdium with 111"F hnrse sctum was addcd. 'I wo kinds of smale c-t,ndcnsales were u%ed to tcsl the cclls, as was hcnzpyrene alone and htnrLyrenc in contbinatinn with a smt,ke condensate. '1 he third study presents a more detailed account tit Ihe kitten Iung experinrents. The fourth study was concerned with similar exreriments with a cell strain from a(''H male mouse carrying a suhcutaneuus tumor induced following injectit,n of ciRaretle smoke eondensates. FinfirInR.: In the first study, the chromosome counts of human amnion eelh obtained in freshly isolated elements before culture were 42. 48 and 55. The ntost frequent numbers in 25-day primary tissue culture prepara- tiorn were 46 (25'7F ) and 4R (21%). C'ounts made from cells nf trypsin- ized cultures fined on the 351h day of incubation (2nd suh-culture) had a range from 60 rn 77 with a peak at 67. Cclls in the 401h sub culture (191 days from tht initial trypsinizalion) shnwed a range fn,m SR to 90 with a peak at 66 In Ihe latest ohscrvatiuns in the R4th suh culture (664 days) n( a trypsinizcd culture nf amninn tiesue without crubryt,nic e>tlracl the most freyurnl chrnmusr,rne nurnlrr was )5 (h2%) in a narrower range of 69 to 7R• In the sccnnd study. Iwo epithclia( ccli strains were cstahlished from the lung of the male fetus, one 'rum cells in the presence of a cigarette smoke condensate (fIL.-S) and alSr,lher front an untreated control (IIL.C). At the outcct, the most freqnent chrrrmosnme numhers showed a shift to lower valucs in treated cuftures, then a widened ehromosnme sreclnrm developed to a staFe tit "great spread" in hnth treated and et,ntrol cullures. Finally, a narrow f.eak of hercrnplr,ids bccamc estahlished et 77 (FII_--C) and 76 (111-S) The NI: C strain was chatlenEed with two fractinns nf smoke conden- sale together with acetrxu and untreatcd conlrols, as well as wilh benzpyrene alone and with hcnzpyrene plus one t,f the smoke fractions. In the two controls in each changed environment the modal value was constantly at 77 for each observation from the 61st to the 81'st subcultures (during 95 dars). In conlrast, the new modal value of 76 chromusnmes was estnh- lished after the appearance of dicentrie chromosomes in snme pa.ssages. It will be necessary to recheck whether pretreatment with the smoke con- dcnnte is significantly important in the estahlishmcnl of a cell strain and whether the chromosomal chanRes are associated with malignant conversions. In the third sludy, the most frequent chromosome number in the primary culture of kitten IunB lissuc svas 3R (in 6R^,'n of Ihe cclls). With either Ihe increasing numbers of suh cullures or thc l+trirK/ of cultivation, chromtnome ntnnhers shnwed a decrease of diplr,ids and an incrcase of Iririlr,ids t,r tetra(,Irrids 1 he Ialest uhacrvatir,n on the chrtunrrsr,rne numhc•rs trf the srriin tm Ihe 41 Ith tlay after the I,rinm:uy cullure druwtd Ihat Ihe mnst frcyuent chtnmtnnrne mmihtrs wrrt '11) ( 22'Y. ) and '7] (2(i % ) Ohservatiun r+f milr,tic activity r,t trlls in Ihc .trnin tultnrrs hy I,ha.c nJcrr~~tr.l,y %hr,wcd a riiinr. Inolifcr:rli„n in,tcR durino thc t,rat acvcn d:,ys nftcr inrK ulatinn Ir, rhr (ra,rrh itarly thc ruir,in:rl n,ornr Irrn,nr wa-, irlrntifr-r1 as A Icirnnyrr~arcran:,, a lunrr,r of 11rc vura,th mucclc titKrs conlaining im(.cr- i fectiy differentiated embryonic cells. The induced lumors showed no in- vasir.n and spreading AuI grew under the skin, st,metimes to a size larger than the hnst itself, withotd invasion. Tlu most frequent chrumosomal cnunl frr,m prim:rry eaplanls of this tumor was found to be 41 (42`9i. ) and hyp.,tetrapluid numbers ranged from 74 to 77 (2490 ). In IJrYo two number distributinns were found, one in the diploid range (40-43) and the other in the tetrapluid range (74-R2), suggesting that the e.planls contained mixed cell lines Following the 161h sub-culture the modal value for Ihe chromtnnmes seemed to persist t 39, with a narrow range of distributicxt fmm 3R It, 42. This mrxlal value has remained withrwt shift to date (63rd sub-culture). No evidence krr the heleroploid transformation of chromo- somes was nbserved. In order to ascertain whether or mrt this fnouse tumor strain waa malignanl, cells from several of the sub-cultures were inoculated into male ("Fl mice. In four separate tests with varying procedures the results were negative three months or more after inoculation, "[:FFIi(-I OF'[OIIA( C'OC'ONf)ENSATEON RESPIRAlYIRYIRACf (1F WI11T F, f'fiKIN 1)O('KS." Dy R. 11. Ripdnn, M.1) , Professor ol 1'athnluRy. Vniversity of 'feaas Medical Ilranch, (Dalveslon. ./rr-hiva of PorhnfrrRy. Vol. 69, pages SS-6J. January 1960. Prrrpo.r of .rudy: In previous work lhe author investigated the mech• anism of removal of fluid and particulate matter front the respiratory tract of while Pekin ducks, and found that liquid petrotatum and India ink entered the lungs and air sacs and remained there for varying periods of time. A study of the effects of tobaccn'eondensate on the respiratory tract was undertaktn in view of e><perimenlal studies by others of the effects of application of tobacco condensates and inhalation of cigarette smoke on various species of birds and mammals. Three ml. of cigaretle smoke condensate were added to 19 ml. of liquid pelrolatum, and one-half milliliter of this mixture was put Into the trachea nf young adult ducks once each day, except for holidnys, for a maxinrum of 1301imes. Histological studies of the Iracheas frunt 99 normal ducks, 26 Siven petrolatum alone, and 26 given the tobacco condensate mi><lure, were made at varying intervals following trcatrnenl, FlnrfJnR.r An acute and chronic reaction occurred in the trachea of a few of the birds instilled with the tobacco condensate mixture. A similar re- action, however, was present in normal birds and In some of those receivin6 only the petrolatum. Either Ihe tobacco mixture was phaRocylosed, tit it passed hetween the epilhelial eells lining the respiratory tract tn reach the adjacent srrama, and subseyuently it enlercd Ihe lymphatic and blood vessels, nnrmal channe(s of etiminotiun of inholed suhstnnces. 'lhere was nothing in this slurly tn suggest neoplasia. An unetpcc'ted findinR was the tKt'urrrnre of arnqIuiJ like malcrial in the liver tit three tit nine ducks given th tnhaccr, cmultneate for the lanFest (,trirats - 1 111 injectiuns in all nylrlidusis has not Leen assrKiated wilh ey,nettc smukinR in any rd Ihe 1 nnan stnti.tical studies Irh.. R.n..r..r r 1I S 1'uhlic Ilt:1slh Scrvice. "111f: 1 11 I('I (W 1•11: IIIY1 ('llOI ANIIIRI:NIE ON 1111? GASIR(/- IN I FS1 I N A I. I RA('1 0 1: T11F 1)(1('K." Ily 12 11 1(ipdrht, M 1) , 1'ro- K 3I t> 7(1 ro

feseor of Pathology, University nf T'exae Medical flranch, (7alvcctnn. Trtos Rrrnrtt nrr ItinfnRv nnd lllydirinr, Vol. IR, pagrs 275-2R1. Sumrner 196t1. Purporr of .rudyr Past erperimenls have shown that variations in the occurrence of inerhylcholanthrene-incluced tomrrrs do occur in rlifferent tit- sues in a sinRle hcnt, that sonie recearchers have produced tumors in an animal while others have nnt, and that there is need for an e><perimental approach tn the prnhkm of enrcinogenesis in rach hosl and in each tissue. lhis study was underlaken lo determine the hnmrn response of ducks to the oral administratinn of mcthylcholanthrene. Pror.drrr.r Twenty-one •fecks ged 19 days were given 7.5 mg. of methlylcholanthrcne sua(+endcd in I nrilliliter of liquid petrolatum daily for 30 days, at the rate of frve each week. A second group of I 1 ducks were given 311 mg. of mclhykhotanthrene crystals miRCd with 270 mg. of fluur in a gclatine capaule, at over-all rates which supplicd 600 mg., 1200 mg. and I RIN) mR. of inethylcholanthrene respectively to three prrwps c.f birds. I)irds died or were sacrificed from the 2R7th day on and the intestinal tracts were examincd. Ffndi'nR.: No tumors appeared in the gasln, inteatinel Iracls of any of the ducks -ihe melhylchrdanlhrene crystals were shown to t+e rapidly e><crcl d, and the ahsence (tf nrnplaeia may he e>tplained hy this failure rif ahsty~itian of the carcinogen. 1 he ttudy emrhasizes Ihal narplacros accepted o he hasrt nf "a.anciation" with a carcimogcnic agent always she~ultl he itically evaluated. Othrr Rrnntnr: II S Puhlic Ileallh Service. "(X'Cl1RRrN('E: ANI) ROI.F. OF GI.YCO(iUN IN TIIf: Fr ITIIf:I.tUM OF IIIf: AI.VI?<)I.AR Mlf('USA AND OF '1111i Al IA('III?1) (iIN(;IVA " Ily lo,eph P. Weinm:rnn, Julia Meycr, Uururhy Mardfin and M. Wcist, 1)ivisitrn of Oral ('athrdrrry, (Inivcrsity of Illinois. ('rdlcge of 1)cntistry, ( hicaRo, Illinnis. Arnrrir nn Inrnrrul rr( ,1 nnrumy, Vol. 104, pages 3RI-4112. May 1959- "f)F(iRf:F OF KFRATIN17.A11ON ANI) G1.Y(Y)(;fiN ('ONIfiNT IN l llf; I/NINfI.AMI:I) AND INI 1.nMlil) (i1N(;IVA ANI) AI.VfiOI.AR Mtl(Y)SA." fly M f). Weics, 1 P. Wcinmann, and 1. Mcyer. lorrrnnf rrf Pr.inJrmrnlrrRy, Vol. 30, pagcc 2(IR-21 R, July 1959. (T.I.R.C grantee: Dr. Isaac Sch!.ur) Prrrlrn.r of .tudlr.: Recent ttudicc of thc free gingiva have investigated file e(lcctt rd in0ammation on keratininrtion and glycogen dcpositiun, and have slresud file Lrcl that variable rtefreee uf keratinitatirtn may occur in the sanx specimen in different pvts ul the free gingiva. Theu sludies crtm- parc the diRerent regions of the free gingiva, the attached ginRiva, and the alver+lar mucuta of uninflamed sf,ecimens with retpecl tn de ry,rce uf keralin- izatiun and contenl trf RlycoRcn, and tfinvrdipale Ihe interrelatitrns hrtwren infl:unrnatirrn, kcratiniratinn, and Rlycr.rrn in thr.c rrgirms, Prr.rrdnrra ~ Ilil.rtct'tal hiepsic+ uf Ringiva anrl alrvrrlnr ,nn(nvr were rrth- laincrl ltrrm 52 mrn 27 71) years of nre Mrnl yd file nrcrt wrrc riF.rrrtlc srnrtkrrs, anmr utcd other furnn trf t.4,acco, nm1 n frw wcrc mm .nu+lrtt (;lyct~Frn wa. r.tim:rlctl u.)nr. file prrimlic end ntid Sthifl mrrh-I cr-n Irollcrl b~ rh:rttatr diOcttirrn; rlryrccs rit kcr:rtinir:rtir-n were dclrrrnincJ rn N M1J using 1lenslcy's specificalions of Mallory's connective tissue stain; inflam- matirrn was evalualed from the density of inflanrnratory cell infiltration in the connective liscue underlyin/t a given epithelial region; and cell size was estim:rted frum the cell density estahlished by cell counts. FJndinR.: In the absence of inllammation. the tendency for keraliniza- tion shows a regional gradient, being least marked in the crest region and most ntarkcd in the attached gingiva. Likewise, a regional gradient in incidence and concenlralitxr of glycogen was noted, the deposilion being nrost marked at the crem and least marked in the attached gingiva. Study of inflamed rrRinns showed that in0ammalion reduces the tendency for kera- linization and increases the tendency for deposltk>n ol slycogen. t he alveolar mucosa Iras a nnn-keratinizing epithelium and contains glycogen in all specimene. Keratinization and glycogen content are inversely related in un- in/lamed Pingivat regions, more markedly in inflamed Rin~ival regions and mrnt arke~lly in Ilre alveolar mucosa. The glycogen depostls in the alvenlar m sa may have a structural function in maintaining the intcgrily of the Is Ot/r.r Rranr.rrr U.S. f ublic Hcalth Service. I 11. llumon /,ftnR Studica "p11YSIOL(K)ICAI. RfiSfARCII IN ('lIRt7N1(' PULMONARY bIS- EASE: AN I:VALUAI'IUN OF ALVEOLAR AERATION, OXYGEN ANI) CARIION nI()XIt)f3 l'RANSFI:R ANI) '1111; PULMONARY ('IRCUI.A 1 ION." Ily llurley L. Motley. M.1)., I.'(^('1 ,('ardio-Respiratury Latx.ratruy, University of Stwthern California Schtxrl of Medicine, Los Angeles. /)irrovs n/ the Chcst. Vof. 311. pages 250-26(/. September 1960. Purpo.e of .tudy: There is great need at Ilrc present time for further studies on file pulmonary circulation In chronic pulmonary disease. An adeyuate clinical evaluation of pulmonar~ function alsn requires measure- menls on 1he venlilalory stalus, and on the transfer of onyFcn and cartxrn dioRide in Ihe lungs. Single tests of lung function on a single acpecl of the question are un-mliefactory. Important aspects of recent physiological re- search in chest medicine will be reviewed. Prorrdrare end jrn.finR.: Measurements relating to alveolar aeratinn in- clude spimgrann of tolal, titned, mid-ettriratory and nta>cimal breathing capacity; rc.idual air; intrapulmonary mvng; evaluation of brrrnchnspraam; and special devices for air flow which measure the rapidity with which air can he exhated from the lungt, amt.nR other variables. Significant infornra- lion on air Irapping is pruvided from the shape of the recorded spirogram Itacing. '1he maraimal ttrealhing capacity pnwi>les significant infurmatirrn un file fxlhrwt acliun of Ihe ehesl and lun ~t in addition tn file IimeJ vital c:rp:rcily mr.nurerncnta. Ilrnnchocpasm it lxst evalualed Itcfnrc and after aAminialratirrn rtf a hrunchrKtilalur druR. Residuul nir mrncurement and Ies1s of tnrrnpulmunnry mi.inR are vrr~' hnl+rut.rnt in the evaluatiun of IanF furrctitrn. In fuur ye:va' etlxrirnce wit11 an improvcJ hclimu t'hncd cFrt uq nrethrwt mrae nc(urnte rrculrs ruc uhl:rinrd in .evrrc rml+hysenra r:r.ca Ihnn with file oxyrcn chr.cJ circuil, unless a nilrugcn mctcr is uscd Irr m+milur Ihe nitmRen wathrnit Re6duil 33 • 12

.z ~ .~.. ~ Sh, ' air has been a mnH scnsilive tcd to detcct ch:rn}!cs in pulmnn,ry slalus, hul it may hc correlated poorly with the chest menlRenogtarn. lhr nitr(+pcn washout on oxygen breathing is n most sensitive test for the cvaluati(rn of intrapulmnnnry mixing in the IunRt, and reve:rls most graphicalty the prescncc of e ltcnsive nhstructi(.n in many of the smallesl respiratory airways in asthma and emphycema. "1 hc curvc of nitrtrgcn cx- halation with the sinple deep breath of oxygen and the nitrogen meter has not been found satisfactory in quantitative evatuation of inirehulmonary miRing. The nitrogen single deep breath test has been ohservcd to irnprnve after breathing an irritant such as cigarette smnke and to worsen after ad- nrinistration of a hronchodilator, just the reverse ot the vital capacity measurements taken at the same time. Valuahle information has been derived from sludies of the pressure volume rclationship of the lung (compliance studies), which are fxst cnr- relaled clinically with total vital capacity. For satisfactory clinical evalua- Iion, however, the compliancc lesl does not appear to provide any more siFnificanl infrrtmati~rn Ihan is obtained from lhr spirnRram. Adequacy of oxygen and carbon dinxidc transfer is evalualed pri- marily front arterial blood oxygen saturation and carMm dir+xidc cnnlcnt at rest and with excrcisc. These and many other aspccts of recent pulmnnary research will serve to fill the nce(Ffar accurate pulmonary function tcsting, for better diign(nis and Ircatmcnl, and should he uscd along with If`e his- tnry, the physical and Ihe rnenlRcnological cxaminalion. '1 he rulmomary physiningisl must cmplny an adcquatc battery nf tests wcll clandarJi?ed and suitahlc flrr muline utc umlcr a11 hcalth conJilinns, an(I Ihc infruma- liry( sn ohtaincd in turn must he imrilaclcd corrc(tly as well at theine pendahle Orh.r Rrnnh.r: 11 S f uhllc Ilralth Scrvlcc 111. Ihnrf anr! (:irrltlrffirrn "T 11F. MY(X'ARI)IAL Mf 1 Al1OLISM OF FR11("fOSli " fly Willi,m 11. L)anfurlh, M 1) ,( harlcs f:. I logancamp, M I) , Fred 11 Nallard, M I) , and Richard 1. IIinR, M.l)., Washingt(m University School of Medicine. St. I.ouis, Mo. American lournol n/ rhe Aledirol .Srirnrrt, Vol. 219. Lagcs 477-4R4, October 1959. (T.I R('. grantee: HinR•) f urpn.r of atudy: In view of research which shows that the muscular suhstancc of the hcart has the ability to ulilize a wide variety nf f(wrdstulfs, depending to a larre extent on their availahility, a study was unllcrtakcn to dclermine whether the myocardium extracts siRnificant quantitics of fructnse and whether this carhohydrate aflecls the myrxardial ulilvatiun of tither subslrates. Pror.dur..: ('athrters were placed in Ihe c(ur+nary sinuscs of eleven human palients (Iwu diaf>etics, threr with milral Uctnntis, onr wrlh aurlic insnfl}cicncy, nne with re('enl fxricnrditi., two wilh unc.lrlaint•d c"nr.cslive hrar( fnilurr nnd lo withuul (Ieleetrd heart Ihtr.rse) In a f:rstinv, statc (hc(nrr iniulln adlniniuraliun lo the (IINI-('tlct). n11rf1al hI1M/(I was r.htaintil '1)r thnr i. n- 1''ntr%.nr nf Mt-liiinr rn,l ( -harm.n, t)tp.rlnkM of Mrdicine, W.tnt %,.,r I'n..r.uty (0/rRt ol Mn6iinr, Ut~rn~l, Miih 14 t r I an1l cnronary blood tlaw was determined. Artcrial anJ ctrnmary sinus samples for fruclose, glucrne, pyruvate. Iaclyle, and kctoncs were obtained simullancrrudy, and the average of two cr.nscculive blood samples nrca- sured. A priming dose of fructose, varying between I S and 41) g., was adminislered, and intravenous infusion of 10% fructose in saline was maintained cunstantly. Sampling was carried out twice during the course of the infusion and the substrates were again measured. Six aneslhetizcd doga were calheteriud via the coronary sinus nd the femoral artery, and also received 10% fructose in saline at a rate calculated to deliver 0.5 g. per kg. body weight in 30 minutes. FlndlnR.: With initial arterial and coronary sinus levels of fruclose at zero, arterial fruclose kvels rose slightly between the two samplings in four palienls and fell in five of them, while arterial glucose rose in all palients, varying cnnsiderably from one to another. [flood pyruvate levels rose in the majority of palients, but not in the diabetics, and there was variation in other measurements. Most of the dur showed a slight positive myocardial fructcne balance during lire frucUru rnfusion, and one showed a slight negative balance at the tirne of M+th samplinRs. In two doRs the coronary simrs concentration of fructose was greater than that in the artery five minules after strrpping infusion. Negative myocardial balances of fnrctnse were detecled in other animals I S and 30 minules afler the onset of infusion. It is possihle that the variable results were due to movement of fruchne in and nut of the heart muscle as the resull of changes in plasnm concenua- lion of Ihis carhohydrate, but other factors such as variatinns in cardiac activity cannot he excluded. The tesulls showed that myocardial utiliralinn of Rlucose, pyruvafe, lactate and kelone bodies were not noticeably affected by ruclrne in normals or diabetics. rRrr Rrnnrnr.r U.S. Puhlic fkallh Service, l-ife Insurance Medical escarch Fund, American Ileart Association, and Hurronghs. Wellcome and ('o., Inc. "Mf:TAfl()I.IC ('fIANGES IN IIF-ART MUS('LF f)IIRIN('r ANOXIA." fly (:erhard Mich:d, Siegfried Naegle, William 11. 1)anforth, Fred U. Rallard, and Richard 1. Ring, Department of Medicine, WashinRtr.n t)niversil~ School of Medicine. St. l.ouis, Mo. Anrrrican lnurnof of l'hy.rinlngy, Vol. 197. pages 1147-1151. I)ecenther 1959. (T.IR.C. Rranlce: Ring) Purpo.e of .rrrd,r: Studies of metabolism in the heart muscle following a perial nt anoxia have demonstrated impaired oxygen uptake if caronary pcrfusion is interrupled for more than two bours, and such hearts nlso pro- dnce significanl amnunts of lactic acid despite normal nvailahility of oxygen. Ifence rt w.rs decided to study changes in nryncardial metahnlism in greater rktnil durinR ann.ia, particularly in respcct of altcratinns in concentradons uf t•.lycor.cn, high ener(ty phcnphales and pyridine nucleutides following rkath (if Ihc tcsl aninral. rrnrrdrrr.: Following anesthes6 the chetls of 12 rnnn/rcl dtrRs were ulrcned, tlrr Ixricardium incitcd, fhe anrta xevered, and nlNwl h:rll ul Ihc left vrntuiclc rrmuvcd After a ptritxl of one half, one, nr two hnurs, another specimen ut 1he Icfl ventricle was removed for analysis. 35

!`•IndinR.: Anttcia pntiluccd concittcnt ch:tnfrt in :dl suhctanccs studied. 1)iphnclrhr,ryridine nuclet+titlc (1)1'N) IICI'rC:KCtI in a11 cxrcrimenlt; re- duccJ diphttci.htrryritline nuclctttirlc (I)f N1I) intr%~atcd shghlly, stt that a thtrr in ctmthinct) v,tnre -ccnrrerl, r,rticrnarly in the acontl la+ur (ilycttRcn strtret in antttic heart nmacle tlitaprearcd raridly and chnwed a prrtFreative deidctitm aftcr t)carh. 1 hete stwliet illuttrale tlr:rt ttxYgcn lack Ie:rJt to rapid dephutrhrtryt:,tinn of high enerR phrnphate cr~mftrndt and to Ihc suh- sequ nt frnnrath+n ttf intuRanie p~mphorus. O.r Rrnn-nr.; II S. Puhlic Ilealth Service. I ifc Inturance McJical Re- earch 1 und, An,etican Ffearl Ass(xiatinn, and IlurrttuFhe. Wcllcttnre and ('o., Inc. "MY(>CARI)IA1. FXTRACTION OF Rh" IN TIIF. RARf1IT." ny Robert F. Mack, hivid U. NoIting, ("harics f?. Ihtgancamp, and Richard 1. fling. 1)epartment of Medicine. Wathingtnn llniversity Schtwtl of Medi- eine, St I.rroit, Mu. .finerican Irmrnnl of P/r)•dtrhrXy, Vol. I97, pages 1173-1177, 1)ecemher 1959. (T.I R.C. (i'tantce: fling) Purpn.e o/ .tu.lr: lhe isolnpe of Ruhidium (RM") it widely uad in hinlnFic:d aludict I.cc:tnte of its armilarity to pttlaatium. lihe ul+take ttf thit calittn by heirt muarle tnggcsted to tdher ex)a•rirncntert a metlatd of yuan- litatively tlelcrrnininR blrxXt flrrw, but the prescnt authnrt trhtervcd no np- parenl rclilirmthift between theaylwn cvente in dnR studict. lherefttre, furlhcr evalualittn of this facUtr was undc-taken in r:thhitc. f-nrr.fnre: 1'erfnaittn was begun immediately after exlractinn on isttlated rabbit hcirla with warmcd uRyRcnated rahhit hhwtd containing Ira(ec of Rh"". ('ardiac cnnlractir.ns rctumal promptly. and the rnrtflnw hhrtal front the heart was cnllectrd, nmeasuretl and the plaarn:r cnncentratitTn of Rh•4 determined 1'erfucit.n was ct,nlinucd for 21) rnin,det, fx•rnrittinR cr+mp: riam of values for myocnrdial extractitm al a wide variety of now tates, both early and lite in the experiment. FrnrlinR. : '1 he mcan value for myocardial extractirm of Rh", during the firct len minutct of infusitrn it all r:tles of now w:rt 41.1% r 9 13. a value similar to that tthscrved by the authnn in dng eRhcrimentt (46'7 ), which seemingly Ixae no rclalinnchir to either ctmcenlr:Hitrn or now rate. Ilow- ever, the present inveatiRatinn dcmttnctratet a relatirtnchir not only between the myneardial exaractirm and the rate nf flttw, but also between Ihe myn- cardial ettractittn and the Icngth of time of (htw, since extraction perc'entaRe was tiFnificantly lower durinR the l:dcr fxntitm of pcrfutirm at a wide variety rrf now tatet It it ctrnceiv:rhle that varinhility in myttcardi.d or lat a elecutdyte content in the etl+crimenlal animals may lie rcal+ttmif.le litr e wide range of cxtraclitm vahres determined, eh~r Rrnnf.rrrt 11 S. Pahtic Ileallh Service. I ife Invnancr Medital Re- sr.trch Furttl, Amt-rican I lcart Attrtciititrn, and I h-llm:rnn I.al(trt hc, Inc "MY(N'ARI)IA1. MIJAHOI.ISM 01 VAI"1Y A('ll)S." Ily I rrd II Itall:rrd, Willtam 11 I-;tnfnrlh, SierfrlcJ Nary;lc :vttl 16th:nd I Itinr, 1)c (t:rrlmt•ntt If Mcdit inr, Wathingtnn I lnivct~ity nnrl W,tyrnc Sl.rlc I lnrvcr+uy Itturrrtrl if ( 111n.nl LnvttJrnlr.r.r, Vul 1't, It.rl'ct 1I1-121, May 196d0 1 I I It (' pr:rnrcc Ilinr) I'rn l~. .. ..l •rr..l• N- nr rcu i"h ILy ,.Ihrr .uillmt~ h:ra 01-n Ihat ( I the princip:,l, lipid fraction of platma Mncerned with the transpnrt and metahrdism of fatty acids is the ncxusterified or frec fatty acid (1•I•A) frac- tinn, and that the heart uses a amcitkrahle amt+unt of FFA. 'Ihe pretent study was undertaken to determine further The role of (atly acidt in rnyo- cardial metahnlism. Prored..r..e Coronary sinus and arterial blood samples were obtained simultaneously by catheter front human subjecls and determination made of bkxxl flnw, 6lucnse, tutal fatly acids (TFA ), and FFA. The patients had hypertensive, rlxumatic or arteriosckrotie heart disease but were not in congcslive heart failure. Fasting individuals were tested and then given orally two ounces of a fat emulsion containing 199f, saturated and BI% unsaturated fatly acids, and metabolic studies were carried out three or four hours later when little or no lipemia remained. After blood sampling from the initial studics, 1(1 mg. of aqueous heparin were given intravenously and repeat metabolic studies were conducted 20 minutes later. Two sels of ex~xriments were performed in dogs:myocardial utilization Of fany acids was determined in fasting dogs before and 20 minutes after hepnrin injectiun, while a second Froup was given l.ipnmul three hours txfnre it timilar cycle of determinalmns; in this group coronary hltKrd flow was measured during laclescence and after clearing of the plasma with heparin. FlnrlinR.: The data on myocardial metabolism of fatty acids by fasting man and dog reveal that FFA average 6% of the mean arterial level of '1 FA in the human and about 3% in the dog. In the fasting human the mean myncardial extraction of FFA accounts for 42% of the TTA elttrac- tion and the esteriGed fraclion makes up the balance; in the dog the FFA fraction accounts for only 23% of the total fatty acidt extracted. The oxygen extraction rotios were 264% and 65')4. retpectivcly, confirming other experiments which s)H>w, that in the fasting slate most of the energy in the heart is derived from fat metabolism. Ingestiun of a fat meal increased both platma concentration and myocardial extraction of FFA. Fleparin induced a fall in plasma concenlra- lion of TFA and an increase in enncenlntion of FFA. TICe studies demon- strate that esterified fatly acids account for more than half of the total fats extracted by the myncardium. Myocardial extraction (if fFA usually de- pen It upon (he arterial concentration or Ihis fraction. •r RrnnL.r.: U.S. Public Heallh Serviee, I.ife Inturance Medical Re- . arch Fund, and American Ifeart Association. "F.FFfi("1' OIT ISC'IIFM1A AND R[:OXYGiiNA11ON ON 61.Y('O1.- Yl1C RF ' A(-flON AND AOENOSINEI Rll'11OSPIIA'1 F. IN IIFAR I' MILS('l.E." fly William If. f)anforth, M I)., Siegfried Naegle, M 1). and R. 1. llinP, M.1) , 1)eparlmcntt of Mcdicine, Wr}thinghm I lniver.ilr antl Wayne Stale Onivertily• (-irrufatlrrn Rr.rrarrh, Vtrlume R, ItaRes 965971, Scl'tenrher It)6(1 ( 1I R('. grnnlee: IIinR) Purpnre of •tu.ly: I'rcvlput wrtrk by the nuthttrs tlenutnatralcd that mytrcarrlirrl 1•Iyrr+r.cn fallt, while hiflt ener(y Irhrrtithatet :utd tdhrr crnn pttunrla vary in eirtut directinn, durin~ the f1tat two hnura nt inJuccd rnytt- cardial iachemia in dn(;t. lhix wtuk it cttncernctl with detailet( c'hanFet in 1,, 37

17) 70 ..i. ~ the glycnlytic palhway uf heart muscle during 15 minutes (if anaernhiosis and when the ischrmie heart it again perfused with osyFenated hlood. /'rnredrrrtt Samples of myucardium frum mongrel dnRs were taken before removal of the heart and placed in an oxyRelt frce saline bath. Saline was nuthed through the left coronary bed through a sulured eannula to prevent formation nf micrnthrombi, and a second sanrl.le of myocardium was taken after 15 minutes of anoxia. The coronary system was then perfused with well oxyRcnatcd hlra+d and further samples obtained from a previously undamafred section of the left ventricle. The method of sampling miRht tend to hiat the results, since parts of the myocardium distant from the large coronary vesselt mutt he taken Rrst, but this should not aRect glycogen delerminalions. Several other related tetts were nrade, including some with perfusion of blood directly from a donor dog. Find7nR.: During the IS minute period of anoxia the fall in glycngen was as expected, and there was an increau in hexosemnnophosphale (IIMf ) and in lactic acid. 'f here was no accumulatirm (if fructose 1, h diphncfihatr, dihydnr.yacetone phtxphate, or ryruvate. Adennsinctriphrnrihate (A'f r) declinrd at etf.rctrd When the annxic hearts were rrrfuted. there was an initial adynarnic rAa~e ( I to 2 minutes ) followed by fihrillatinn nr irreRular, ineRective ventricul:n cantractiont ('hanRes in rnyrxardial Rlycngen eon- eenlratitrns were incnnttant ('oneentratinn of IIMP declined rapidly lo nrar normal levcls at the end of Ave minutet. ('nncentratinn of A f P rose (lorinR the firtt twn minutct; when K('1 wat adrtcd to the pcrfuainn nuid, A T P concentration reached the initial level in 4 to 10 minutes; in exf+eri- ments in which the heart was alhrwerl tn heat (rr to fihrillatc, no consittent directinnil trcnrl in A I 1 could t.c rlitccrncrl after thc first 2 minutrt Snme tMl of the f.crfusinn itsclf mutt be invoked to explain the decline in IIMP with enntinued Rlycngcnolytis lthh.r Rrnntnr.: II S Puhlic Ilralth Strvice, I.ife Insurance Medical Re- seareh Fund, American llearl Ast(.ciation, flurnruRhs, Wellcrrme nnd (-n , Ine., and AhMrtt I ahc+ratnriet "f OSSIIILIi MF(-IIANISM OF TIIF, f)f?('I.INF. IN Mfi('IIANI('Al. fiPEICIFNCY OF 7IIF. ISOI.AT I?1) IIEART." fly K Knko, 1. 1). ('hnudhury, and R 1. (ling, Department of Medicine, Wayne State lIni- vertity Co11eFe nf Medicine. fktrnit, Mich. Journal nl I'harmarnh+Ry and Erprrimrnhd i hrraprurirJ, Vol. 1111, pages 46 54, Septemhcr 1900. (T I.R.C. grantee: fling) rurlrn.r n/ rrndyr 11 is the purl.rnc of thit paper to describe eRpcri- ments dealing with mrchanisms nf the decline in nrechanical efficiency of the isnlatrd heart and with the r.rtsihle innuencc of liver and spleen in altering its mechanical efficiency f'rnrr.fur.: ('trrnnary nnw, glnrnte. Iactite and kctnne ht>,1ict were de- termined in clnsed chest dngt by cathetrrs into the crnonary sinut and the riRht ventricle aml in isolated hearrt by hearl-lun/ tirrlraratinn In etprri- tnentt in whi.h livrr nrtd tl.tcen were intluded in thc pcrflnirrn cirtuit, thete rrrRans werr qrritkty renurvcd hrrrn a rhrnrrt nnirnnl nml irntnrJlatrly (on nrcted to thr circnil rrt the hcart IunR Incriratirrn, whn h had hern ohci atinR frrr 41, minutrt ( lthcr etl.erimrnts crnntr;nrd contr:rt Idity rd nr trmrymin 1,311411 hrnn %laontanrrrutly faiGnR artd nnrmal hrartt JR i FlndlnR.: In the closed chest eaperiments oxygen and glucose ueage fell significantly and lactate and ketone bodies also decreased. There was no significant change in the oaygen eatractinn ratio of glucose, lactate and ketone h<wlies of the isolated heart as compared to the heart in JfrY. The eRecS of the inchrsion of the liver and spleen was a significant decline in myocardial oxygen consumption, hut myocardial usages of glueose, lactate and ketone txxlks were not aRected; the oxygen extraction ratio of ketone bodies did rite, however. Contractility of actomyosin bands prepared from hearts failing in the heart-lung preparation was nrN impaired. Cardiac autput, left ventricular work, and myocardial effickncy de- clined significantly in all tests. Inclusion of liver and spleen in the perfusion circuit raised myocardial efficiency by lowering the o><yren usage of the heart. The heart rate deelined. Addition of small quantaies of nnre~tine- phrine and dnpamine to the perfusion fluid increaced myocardial efficiency wilhnut significantly altering heart rate. Following the onsel of operation of the heart-IunE prcparation. the concentration of catechnlamines in the pcrfutale gradually diminkhed. This trend could be partly reversed by rnclusion of liver and spleen into the perfnsion circuit. I)t . Rrnnrnr.r l/ S. Public llealth Service, l.ife Inturance Medical Re- rch Fund. American llearl Assoeiation, Burtrrrghs, Wellcnme and ('o., Inc , and Abbott f.ahrxatorks. "IMPORTAN('E OF CHGMICAL TRANSMISSION IN CARf)IOL(XiY ANl) NE(JROPIIARMACOL(XiY." Ify Richard 1. flinR, M f)., Wayne State Univertity College of Medicine, Detroit, Mich. Archivet nf Internal Mrdfrrnr. Vnl. 1(14, paRes,658-671, October 1939. "TIIf: IIfART IN CONGESTIVE FAIL(1RE." By Richard 1. Bing, M.l)., Wayne State University C'ollege of Medicine, Detroit, Mich. Trtas Starc lournal (i/ A/rAirinr, Vol. 55. pages 9J1-9)6. December 1959. "Mf:TAII()I.ISM OF TIIF 11l'sART IN FAII.URE." fly William I1. Dan- furth, M.1)., F. H. Ilallard, M.1)., K. Kako, M.D., I. b. Choudhury. M.l)., and R. 1. fling. M.D., Department of Medicine, Washinglon University SchrNrl nf Medicine, St. Louis, Mo. Circulation. Vol. 21, pages 112-123. January 1960. "PIIYSIOl-(XiY Ot' TIIP_ MYOCARDIUM." By Richard 1. IlinR, M.1)., Wayne Slate University ('olle e of Medicine, Octroit, Mich,; and William II. I)anforUr, M I). and Fre~ H. Hallard, M 1)., Washington (lniversity Schrx+l of Medicine, St. Louis, Mo. Journal of the American A4rdirnl At7n- rinrirrn, Vol. 172. January JU, 1960. ppages 41R-444. (T'.I R C. grantee: IIinR) T hesr frrur studies are revkws of recent research hy the authors and nlhert contribuling to knowledge of the hcart in health and disease. The (ir.r paper ttresset Ihe equal importanee uf ehemical Iransrnillers such Af acelytchrrhne nrrd nr.repinephrine in both circulatory and ncurophysinlnRical evenlt Ilrr tmmnu,n denominatur is the innrrvatinn of Ihe hrarl and .crilrthcral 611,40 vetsrls hy the autonnmie nervnus tyslem 'I1rr phytirrlnRicnl Ihasit nf rxcitatirrn ntul mhihitinn trf the centtal nervnut system it Ihrn rccrrpniird m a matter of uniyue interest to the earAinhrRist. lhe most attractive aslxcl of the mutual antagonitm nr synrrRism of 39