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hydrocarbons such as 1-rnethykholanthrene or D!•. Is the present study, tissue culture was used to determine whether the carcinogen-metabolizing enzymc. BP hydronylare, is present in neonatal hurnas foreskis, and whether it is indtcibk in this tissue. The resulHanl d.1a slww that hurnss skin has detectable kvc)s of BP hydroaylase, and that this enzyme is inducibk; nareover, substantial ( iflex- ences in basal and inducible levels of the enzyme were demonstrated This dirterence may be genNically determined. No eotselation was found between the inducibility of hydrosytase activily is the ucowsl.l foreskin and the race or aae of the sather, or the medication jirea so the swother prior to delivery. Th. eszyme system Ihat hydro.ylates /P ne4talnn takotisamide adenine dinuchotide phosphate and s+decvlar oayRew. Eapawte of the akls homoBenates to nit -o0es or CO resulled is little or rw en=ymak atxh•(tia.- It was also shows that irduci- bility of hydroaylase activity was Seater Is bwwss din than in neonatal r vdent skin. The presence of hydroaylase is Mrwas iis and its ability to be inluced may be knportun protective mahaslraas apiwst carcinogenetis in man, since human skin h often esposed to polyeyclk hrdroeatbons in 1he environvnent. However. the eaaa rok of BP hydroay(w is esetisogenesn b slin uncktr. Alvares, A. P.. Leibh, S, Kqrp.r, A., l.evis, W. a.d Coasey. A. H. Drvl 6lr..AoYiw.../ D4pubkw 1(1):1l6-)90, 1973. OtA.r a.Pr+rl r U. 3. Public Health Smioc. Prom Rockefeller l)siveniwy, New Yort, aad the Department of Biochetnistry and Drug Metabolnm, HoAmann-la Roche Ise., Nutley. N. 1. INDUCIBII.fiY OF BENZO(a)PYReNe 11YDROXYIASE IN HUMAN SKIN BY POLYCYCI.IC HYDROCARDONS Beaz.ofabyrenc (BP) hydrotylase activity ia inducibk by polycyclic hydro- orbons is cultures of neonatal bumaa foreskin. This study shows that the eszytne system which hydrosyhdea 11P requires nkoainamide adeniee dinucko- tide phosphate (NADPH ) ssd rsokcular o.ygea, and that its opt:rwwn pH is 7.4. Etposure to carbon nwwaide eoarpktely iaAibita .ydroaytase activity. When skins were ineubaled is a growth rnediurn containing benzia/snthr.cene (BA) two- to taK-fold Iscreaues in the amanl of tsP Mytro.yfase wen observed. Maairrwm enzyme levels wert fousd whes the skis was incsrbated is the presenee of BA for 16 to 24 houn. IsducibYily of hydroaylase activity was Rrealer in huw+as skin thas is neonMal rodent skin. Considerable vuiability ia the basal kvels ssd in the indueibiliry of BP hydro><ylase was observed is foreskirn obtained from 1) subfects. These studies isdicure that human skin can metabolize polycyclic hydrocarbons .sd that the levels of the hydrosylase, as well as the inducibilily of the enryme is skin, may provide a useful mcans foe evaluating individual diAeresces is IM eapaciliey of hurruss to metabdina environmeslJ earcinotens. Alvares, A. P., Kappas. A.. l.evin, W. and Conrxy, A. H. (-Nnl..l rhan...roln~y .n/ TAr.aw..tkr 14( 1):)0-40, 1971. O1h.. .uPport: l/ S Puhlrc lleslrh Service Fram R..trfrtkr tr-rr.o. Nr- Vo.k end the 1)aparrnxnt of Biochemistry •nJ I).vt A1r~.h./....• ILA.n.nn I• Ru1a In. Nurky, N I POLY('HLORINATQD BIPNfNYIS:A NEW TYPE OF INDUCER OF CYTOCHROME P-44t IN THE LIVER TAis study shows that Aroclor 1234, one of the polychlorinated biphenyls mlalures manufactured in the United States, is a potent inducer of the asicro- somal hemoprotcin, cytochrome P-44d, and of beszo(alpyrene hydrotytase and ethylmorphine N-demethylne. 71re COdiflcreece spectrum of miczosoeees frorm rats treated with Arocloe 1254 has an absorption ma.imum aa 44• nrn. With ethylirocyanide as the ligand fu reduced micro.ornes. Arodor 1254 treatasent causes a shift in the 4S3-sm peak to 453 am and increases 1he ratio of aMorb- .nce of 455 nm to that at 430 am from 0.3), obtained with ustrealed rals, to 1.24. These findings are similar to those seen in rats treated with the polycyclic hydrocarbon, 1'methykholathrene, but diAer /roen those that characterize cytochrwne P-450 in control o: phenobarbil.l-lnaled rats. Aroclor 1254 ueat- meM results in a tripling of cytochrosse P-448 content and a I0 fold leacrease in ber.zo(alpyrene hydrosylatio.s. However, it causes a signifkast enhancement of ethylmorphine N-demethylas:. These data wqeN that Aroelor 12S4-Isdueod eytochrome P-448 may be atatyticaNy diRereM from the l-methykholaslhrese- induced P-44tt or that the he+rroproleis(s) induced by Aroclor 1254 may be a mis(ure of cytochrorncs P-41B and P-410 enhibitinR catalytic propenies of both cytochromcs. . / Alvares, A. P.. Bicken, D. R. and Kapyar, A. ProrreAln`s of rAe Narbnal Academy of Sclencer of rhr (InlrrA Sraus of Arnerira 70(S):1121-1)2S, 1973. Ot/iar ar'Porre HoQnun-lA Roche Ine., U. S. Publie Health Servioe, Na- lional Institutes of 1(ealth, and Scaile Family Charitable Trusts. From The Rockefeller Univenily, and the Department of Medicine, Cor.etl University Medical Colkte, New York. EVIDENCE OF A GENETIC RELATIONSIIIP BETWEEN Sl1S('EP'TIBIL• ITY TO 1-METHYL('HOl-ANTHRENE-INDUCED SUBCI/TANEOUS TUMORS AND INDUCIBII.ITY OF ARYL HYDROCARBON HYDROXYLASE • The presence (or inducibility) of aryl hydrocarbon hydroaylae (AIIH) is known to be associated with the cytotoaie action of polycyclic aromatic hydrocarbons. In this uudy, the authors report a close correlation belweeo susceptibility to )-methykholamhrene (1MC)-induced subcutanewu tumors and the genetically meduted presence of AIIH inductwrn. In a 4enclic syslem where AHII induubdlly sepegated at a single autosomal dominant gcne, mice carrying the Aha (or inducibk) sllck were 3-10 times mwe sensitive to M('A turnorigenesis than were their rwninducible (AhJ/AhM) liuermates. In backcro.s animals /(C37B1./6XDBA/2)XDBA/2), 10 of 12 (111l%) mice with tunrrs were AFIFI imlucibk. lAis was sulislicully significant (P <0O2S) (the c.pccad rcnpnnu was 31/% ) and clcarly indicated a rclauix»hrp belwecn this enryn.e system and M('A carcinotenesis. Kouri. R 1: , Ratrie, It. and Whitnure, C E. (RfkroMb-loru-af Au.xlorer) 1 r, 17

/ournal o/ the Norlonal (-anccr Inrrllure 31(1 ):197•200, 1973. From the Ikpanmcnt of ViralAChemicat Oncology. Microbiological Auociatcs. Bethesda. Md. RFl.AT1ONS11IPS BETWEEN ARYL HYDROCARBON HYDROXY:ASE INDUCIBtI ITY AND SENSITIVITY TO CHEMICAI LY INDUCEI7 SUB(-UTANEOUS SARCOMAS IN VARIOUS STRAINS OF MICE This paper reports an observed tauoclation between aryl hydrocarbon hydroaylasc (AHH) ie>,fucibility a.d auroeptibilMy to 7-mNhykholan:hrene (3MC)-induced tumors AmonIf 14 atrains of twice, a dired correlauon was observed between scneitivity to JMCJ.duced Mdcutaneous tumors aid the hepatic inducibility of one of the hydrocarbow-1s.etabolizinR enzyme s)stems, AHH Every sarain showing a c.rciaoRcwic Indea (a measure of sewsitl•rity to chemical carcinogens) >60 was inducibk for AHH and every str>.in Mith an Indcx <)1 was noninducibk. (.'loaer e.aa>inalioe i.volving eight strains iadi- catcd th.u uniw sensitivity was coesislest over a wide range of 3MC cflncea- trations, but was not consistent whcn beao(ak+yrene or 7,12dimdhylb:ntla)- anthracene were used as carcino6ens. Moa suain, that were noninduue k and insensitive to )MC-induced tumon also eahibiwed a high incidence of :ype C RNA virotcne espressioe, as demonstrated by the 6roup-specifk antiteis chu- acleristic of these viruus. On the other hand, suains showin6 a low in..idenct of virogene e.pression were usually inducible for AIIH and sensitive to 3MC- induced tumors lhe resulrs support the idea that certain chemical carc nosens are mtlahoiiully activalcd to a carcinornic inlermcdiate and indicate that the AHH system plays a role in thu activation. Kouri, R. E.. Sakrno, R. A. and Nrhitmire, C. P_ (AfkroDloloticaf Asrociates) lo.rrnd of the Narionol Cancer Irurlrrra S0(2):767-76e, 1973. Other arrprlr Nationd Institutes of Health. From the Department of Virdk'hernkal Oncology. Microbiological Associates, Bethesda, Md. IN VITRO TRANSFORMATION ASSAY OF MAJOR FRACTIONS OF CIGARFTTE SMOKE CONDENSATE (CSC) IN MAMMAIJAN CELI. LINES This study dealing with the transforming activity of 12 rnaior (ractions o( (-SC on ral and mouse cells infecud with C-type RNA tumor v'ruses, and on ummnlectcd hamtter cells corroborates some of the results previously obtained s. TAe same three CSC fractions (1 41'.. in vrvo hy .nMhcr group of inveitrptw weak acids Iphendl. clher'soluble: neuttab, eyclohesancsotubie; newrals, nitro nKihane soluble) slwwed translornwng activily. Whereas two other Iracuom ,.h.KS, cd flcreet411r.ctro.ulrba.rselxtorc, insulubk)~ uxd nl~lrro changes in infeded mouse and nt cells• but none of the fradions altered untnfected mo«.e and rat cells. According to the aahon, these Andinp are coosistent with pre- vious reports that rnouse and rat cells are readily transformed by chemical carcinogens and smoke esuacts when they are preinfected with C-type RNA virusn, whereas cells treated with chemical or virus alone are not uansfora.ed. They suggest, thercforc, that since /n riro assay systems are time coosuming, hn vitro transformation .ystems of the nature they describe have certaio diatind advantages particularly for rapid quantitative assays of putative urcioo6ens in tobacco smoke as well as In orher suspect environnxotal eulcrials. Additional studies are underway to determine the opimum doses of CSC fractions for in- ducing tran.sfornution especially in the infected rnotna cell ayMem. Furthermore, the investiptors oote, subfractionatiow of two especially carcioo6enic fracliona (l.e., phend, ether-sdubk; oeutrals, nituomethane-sdubk) should be done ie order to determine the particularly aaive factor. Rh4n, 1. S. and Huebeer. R. 1. (MkrobloloRkaf Auocieres) lroctel/nRr of the Society /o. ErRerlwtewral Biology a./ Mirdklwe 142 (1) :1001- 1007, 1973. Oth.r arrr.rtr National last;luta of Health. Prom the Departmeot of Viru. Research, Microbiological Associatea, and Viral 'Carcino6enesis Bnsch, Natloaw Cancer leutitule, National Institwes of Ilealtl, Bethada, Md. TRANSFORMATION OP RAT EMBRYO CELLS IN VITRO BY CHEMICAL CARCINOGENS This b a report on nsuks of experiments showing that rat embryo celY can be tranaformed /w rqro by polycyclic aranatic Aydrocubons and that they then product lunots whe. Injected into newbortn rsts. These cells also had tbo following properties: (1) they were earpholo=kaMy .Itered, growing as ro- dornly oriented muhdayers; (2) they showed losr of contact inhibitioe and in- aased growth rates; (7) the cells transformed by )-mcthykholanthrene werv orore resistant to the toxic effects of this carcieoge.; (4) they produoed pro- Qessive(y growing. .erWly transplantable hreottt when Inoculated into newborn rus. Although the exad eroch.nism of this In rlrro transformation procus is still unknown, these data wyest that chemiW oeoogenesL can be studied in cell cultures derived (rorn rat embryos. Studies to further quantuate the chemical /n vlrro tnosformatios of tbe rat embryo cell ayueat described here, are In proprca.. • Rb4n, 1. S. aod Hucbnea. R. 1. (Mkroelololka/ Associrr.) C.wcer R..rrcA )l(4):693-700, 197). OtA.W arr'.rtr National Ca.cer Iwitua. Pros Mkrobioiogkal Assoeiates, and Viral ('ucinoticrwis rsranch, National Ca.oa InMitute, National Institutes of 1(ealth, Bethcsda, Md. 19 IS

26 had viable epilhelium. in which 29 histologic ftalet were identified. Five were paihobt2ic, with squamous melaplasia in two instances and with localized dysplasia .ufTiciendy marked to be considered as possibk carcinoma in rit" in three instances. Of I I) cultured eaplanu, 106 bore viable epithchum in which 110 histotogic states were ideetif(ed. When Initially present, columnar epithclium was retained In about 70% of eaptaets; this retention occurred rnore often if esplants were from whole broechi rather than from biopsies. Nine cultured eaplants showing dysplastic or aquaewua metuplastic epithelium w_re from patients yielding such lesions Ie (reaR nmpiei. Dysplasiat were as highly cellular and replkative after mainteeasc. Is erMwa as they were before incubatioo, suggesting continuity of replicatios ttrrwa8 pleomorphk celb, consistent with potentially preneoplasrie lesions. Squr+sou..xiaplasias were poorly sustained. SweNiek and sioukhing of eoTnul cells s.ete consistent with (dlure of t3e system to sustain this abnormal state or with early phaw in the reversal of jqua.notn meUptnla In mps cvMun. O'Doeoell, T. V., Croc4e., T. T. ewd Nusws L L Cancrr Rein.rcA 7l (1) :78-17, 197). Oth.r .rrr.rtr The American Medlcal Aasoeiation-F.duc.tioe and Research Four.datloe, .ad the U. S. Public Health 3erviot:. From the Card'avascular Research 1.atMute, Cancer Research Ins;itute .ed Departnsca of Medicim. U.iversity of Callforeia School of Med;cine, Sa. Francisco. INTRATRACHeAL INSTILIATION METHOD FOR MOUSE LUNGS The rnouse is an ideal e.perieweatd .e4na) for earcioolIenesis studies .ed ietratradxal instillation is a reliable way to ktroduce carcinogens iero animals. Howerer, becauue of the tenall .ise of the tsotre, ietratncheal instiNatioa treatment of mice is difficult and Is rarely used, thus eacludint .is eacdket caperimental nwdcl. Now, a reliable ia.Lr.cheal iauiqatioe technique haa been developed which permits the repeated sidminiatntioes of prccise volumes of particulale suspension into rna+se luop. 1s this study, benzo(.lpyrene (BP) adsorbed to ferric o:ide was used to tettt the feasibility of the method. The maprity of the animals survived (our weekly trealnsenu. Histological and fresh tissue sections showed extensive peeetntion of both chemicals into the lunk patenchyma; howevcr, while BP was eliminated from the organ rapidly, the ferric oaide wu retained for over 100 days. These dust particles were observed inside mxrophaBn cdlMed arwr.d terminal bronchioles and lymphoid tissues of the lungs. Ho. W. and Furst. A. (Unfrerslry o/ San Fra.rtrco) Owolojey 2 7 : )t11-191, 197). Prom the lostitute of Chcmic.l BiobM, Ueiversity of San Fraacisoo. Sae Frsnciuv LUNG CARCINOOENI?SIS BY BENZPYReNe INSTILLATION Becauu of iu prevaleace in the air, be.no(•)prrene (eP), a carciookeek polrcyciic hydrocarbon produced by the lecanpktI combustion of all orp.k tn.tter, 's .uspected to be oee ef th. uwn o( hurea. lung easocr; but ao far. the use of BP ie eaperinKStal a.irwal reodels has (ailed to provide .wacreu evideece of malignant respiratory tumor forrnatios lealogwu to the neoplarea found in nue. The present report t+urneurizea an attempt to use NIHSwir mice as a modcl in which to study the earcir>oBeaic effects of BP oa' lu.ax. following Ita admieWratio. 6y inlratrached ioui4aioa. Re.uks wllseal that the kthal effects of t/P on this maw atraie are largely related to the frequency of treatment rather dw to the dosage .drninistered. Accardi.8 to the wthors, both the lyntphoid t.rperptasi. ..d foamy tn.uophaBes observed In the BP- treated lunp are Mtributabk to t,he i.vasioa of foreiips Irrit..u. While tAa Irscidence of eeop4sis was 20 tbnes higher thare that sors.ally aoee ia this .utis of miec, tbe resu(tie8 papiltary adesaes were eowsidered beoiBa. It may be, t)seretore, that the chetnic." merelr eeh..cea rhe preaispoaitioe ot thia wnhb lo form the tumor. 1o the authoes' opinion, thw tailrar. ot tsP to i.dtw. waUI- eaocy is thae aeint.y sugoe.ts uver.l poribi" iaerpreutioe.: (1) the etperl- rnenW coaditioru were twt conducive to malignant tureor induction; (2) the aryl hydrocarboa Aydtoaylose enzystaak system of this mouse strain wsitipan against tumor formation; (D) the pulrtwn.ry a.aWmy of die mouu may .or be twitab{e for carci.ogesic rpudies; (4) t/P talo.a may eot be resporaalblo for ma6pur tumor tortaMiok and othet eo(.cton rasay be iavolved. Ho. W. and Funt, A. (U.Irerslry oJ S.ra Fr.nc4ro) hoceel/np oJ the Waraw PA.rws.co(oYr Society 16:146-149, 1973. From the Institute of Chemical Sio{oBy, U.ivvslt7 of Saa Fr.eciseo, Sa. Fraecisco. KARYOTYPIC. VIROLOOIC, AND IMMUNOLOGIC ANALYSES OF TWO CONTINUOUS LYMPHOCYTE LINES ESTABLISHED FROM NEW ZEALAND BLACK MICE: POSSIBLE RELATIONSHIP OP CHROMOSOMAL MOSAICISM TO AUTOIMMUNITY Two separate continuous cultures of lymphold cells were Isolated from tM aplexn and Ilbrosareorea of a(emale New Zealaod black (NZD) nwuse. The cells from thex cultum do nol produtx antinuclear or antierythrocyt" aaI- bodin but syothesize a great deal of virus with the morpho{oBic and bkrclten.ical properties of RNA tumor viruses. Interestio8 karyotypie aboorrnalitka .ud a unique "C-type" virus were noted in both cell lines. The inua v'rus p.rtkks had a buoyant density in aucrose of 1.16 g X crn 8, 70B RNA, and RNA- directed DNA polymcrasc activity. The virus was Infectious for NRK, NZB, (NZB X NZW)P, and (NZW X NZW)P, .rnbryo., aed for ttAtll/c )T) cells, but not for NIH Swiss cells. All celb from established lymphoc7he cul- turu, as well as wme emh.yo cells from NZB mke, showed b.r7otypk abeormahtics. 7he pomibihty of duon.oso.nd mosaiciun is augrwed Ltrnrr, R. .f. er .!. 22 23

hoctrd/np of the N./ond Aa.dnny o/ Sckncn of rht Unlrad Srorrs of Awrtrira 69(10):2965-2969, 1972. Otwr •r' prfr Naioeal Sciext Foundation, U. S. Public Hcatth Service. National fnrtNUtes of Health, Atomic Paergy Commisrion, and National Foundation - M.rch of Dimes. From the Departnxst of Pspcrir.eaul Pathology. Saippt Clini: and Rexarch Foutdation, La lolla, ". CANCEROGPNFS/ NEI PftAMMENTI RP.SPIRATORI tSO-TRAPIANTI DA TOPI 1lAl,/c/Cb/Sa IDRAIJNA-TIPLATTATI Variouw parts of t!e rnpir.rory trset of VALB/c/Cb/Se (aAt.B/c) mice have sfawr ddfereat suscepibilkin b the curcinopesk .ctiou of hydr.zine sulph.te. Thc LreM of tW L.estigNio. wa lo further etamine the modiAca- tiom (ourd in the respiralory lissue of SALD/c mice brieAy treated with hydra- zise suiph.te, whes it wa. Irtroduced into synjeneic hosts. Respiratory tract tsswe fro.r such iaact but previouwly tre.ted virgin mice of both seaes was, dretelore, tra.oplurted into sy.geneie bsls which were in various hormonal uatea. Neither the trachea .or bronchi of the controls or of the hydr.zine- treatod dooors sho.wed aoy important changes. Only two ( 1.2% ) individual dveolar rdrnomu were obser.ed is the pulmonary tiswe uken frorn the con- troh. That t.lee from mice treated with hydrazine sulphate, however, showed alveolar .dtoomaf (211i ), bronehiolu adenomas (119b ), and eareinomu ( 1 S9i ). It in intcresting to note that it takes an average of ee wceks for hydra- tirae-indurxd bronchootar a.knomas to develop, whereas the average time for similarly induoat al.eolu adeoomar is only 40 weeks llruc, the prolonged suevival h.rc of the :rafrs, atuinal af  result of the techniques used in these espetime.rts, allowed tumixt to develop in the bronchidar cpithclium, which (s arp.rrcrly kas suweptibk to hydrazine wlphate than its alveolar counterpart. TAe e.do*eerous .srian ainulation of test mice did not seem to inuease the .aliRaa.ey el tumors i.duced In the grafted tissue. fl,ia.rifioti_ C. ( Stv.rl, L ) L.rari An.row.l. t.roJoorka Pern& 33( I):17-26, 1973. Frosm the Dirisioo of Cancet Reseatch, Usivenity of Pcrullia, Perugia, Italy. IPERTLASIE TIROIDEE L' TUMORI POI.MONARI DA METILTIOURACIIB PJO 190NIAZ1DI3 IN TOPI Ct+A/Cb/Se TAio.r.dl has becs rf+ow• to induee thyroid hyperplasia and tumors in various atzai,e of snke; but among the other derivstlves, none has been shows to pasc.r in oww inhibiting effect on the growth of turnors, either spontaneous or i.duced. in other otgans. 11 has aho bee• showw that varior chemical c.r- uoojens do not accentuate the effect of thiouracil on the thyroid gland. The cvnent nveitiption wsr undertsken in an attempt to eatend Ilre research eon- cuning de influence of the hormonal fsctor on isoniazide (INI-irufuced pulmonary carcisotc"s In mice by etnnining the sctivity of nxthyhblouncil (MT), a thiourea decivative associated with INI. In the intact, untreated, oon. trd, virgin CBA/Cb/Se (CSA) mice, the incidenu of pulmoaary tumo~n was 14% in females, 0% in maki; none of these animals had thyroid \yperplasia. In the MT-trealed group, 2% of the eukes .ad 4% of the females had hag tumors; for thyroid hyperplasia the respective iscidenoe was 0% ..d 4%. TTr INI inczeued the freauency of lung twnorss to 36% in m.ks and 74% In femak+. The combined adminiuratioa of INI and MT Induced ht.g wors (24% in maks, 54% is fennaks) ud thyroid hyperplasias (677F ..d 71x ). 7T.ese results suggest :hat the MT reduord the carcieoge.k actioa of INI wbich in turn favored the lrenislesu of thyroid hyperptsia begun by M'1' 6('EA mice. The author cameot easily e.ptain the reaso. for the interterence betwecn the two substaacen. Biaeiei(ori, C. (Sere.l, L.) L.vo.l Anarorn4. r.raloglc. 1e.vgi. 3)(1) : 27•39, 1973. Prom the Division of Cancu Researzh, Univer.ky of PeruRia, PerugiaItafy. INFLUENZA D1 FATTORI INTRINSECI NeLLA CANCeROOP..NI'Jl POLMONARB DA IDRAZINA NEL TOPO 77This revkw wnmarizea the results of sever.l ieveatig.tlom deall.s with the influence of endogenous ovarian stimulation on hydr>siee sulfate (H3)- ieduced pulmonary carcisogenesis is various uraim of mice. In Ltatl virgin CBA miee, dw incldence of spontaneous pulmonary turnon (p.t.) Is low, but administration of HS in propessively reduced do.n iscreasn It in females more th.o In rn.ka In iotact virgin BAI.e/c mice, 25% of the maks and 4% of the females develop p.t. In some of the esMimental groups reduosd doee. of HS affect the females to a greater degree than the maks, u sryped by the higher iscidence of tumors noted among them. The majority of apo.ta.ear and HS-Inducea p.t. seen were adenomas. In both BAl.B/e sd C,Ht+ r.ia lo various hormonal uates (l.e., breedinit, gon.deetomizsd, (oreed breedi.g, a.d pseudopregnant), sporuancous p.l. were rare; but HS focreased the frequency in all groupr, and Nimulation by endogenous ovarian horrnonts raised ths degree of malignancy as well. The malignaet tumors were carcisornu, o(te* lavadw and met.stasiud through IAe blood streun. According to the .uthor, these results confirm the influence of ovarian hormones on hydrazioe-ieduad pult monary cucinoseeeais In mite as well as Ihe carcinogenic actios of reduoed HS doaes. Biaociflorl, C. (S.r.rl, L.) Rtl.rlone al XX ('onregno Interrealonak Tosco-l'miliano di Pocumotl,kilosl. ( Ravenn 27-2/ Mayio 1972). Rsr.gne di rarolot{a delf Appar.re Rrpp4+ wcb 2):21-)S, 197). Prom the Inslilute of Anatomy srrd Morbid Histology, tlnivenily of Piu, Pi.., and Ihe I)ivirioe of ('ancer Refesrch, Univernty of Pcrugia, Italy. 25 24

ASPFTTI l/t TRASTRUTTURALI DEL CARCINOMA ALVEOLARE DEt POt.MONE A lung neoplasia, which displayed the histological charactcristics of an .Iveolar ull cucuwma, was studied in the ekctron microscope. The general ultraS tructure appeuance of most of the neoplastic cells was simit rr to that of the type-B dveotu cell, aod some contained the typical o.rniophilr- and lamel- lated bodies which arc the distinctive feature of type•B cells. These observations suggest that the neoplasia derives froew the alveolar epithelium, evrn if the dif- fkulty of esplaining the presence of an occasional mucus-secreting cell re+nains. The principal morphologic aspect., the diagnostic problems, and the histogenetis of the alveolar cell urcioonu are discured. Bucciarelli, E. (Severl, L.) l.vorl Ar..r.w.r1. r.foloelc. renyie l2(2):IS-6), 1972. From the Institute of Anatomy ..d Parhologk Histolotgy, Univenity of Perugia, Petugia, Italy. FATTORI EXTRACROMOSOMICI NELLA TUMORIOENESI POI.MONARE SPONTANEA DEL TOPO BALB/c/Cb/Se 1?strachromoaornal facton, such u whole body (rndiatioo, may be involvcA in the spontaneous lung tumorigeoew of BALB/c/Cb/Se (BALB/c) mice. In an attempt to study these lacton, lung tissue from newborn BALh/c mice wau grafted subcuuneously, botb into a poup of adult syogeneic recipients previ- ously eepoud to whole body irradlatroo, and into a similar untreated Qoup. Some of these control mice had been thymeetomise.d at birth. Alveolar aderw- mas were observed only in the lung grafts recovered from the irraduted recipi- enu This suggests that whole body irradiation activates a lung tumor gent io BAt B/c mice. When lung tissue from oewborn BALB/e mice was implanted subcutancoualy into 16- to 2Omo.th-oid ayn2eneic recipienu, only rare {nfts took, none of which showed evidence of alveolar adeooaus. Llowever, when whole blood from 16- to 24mooth-o{d BALB/e mice was injected intraperi- toncally into newborn recipieots of the ame suain, 56.2% of the recipients developed lymphatic kukemia after a tnean latency period of l9'9 days. One of the leukemic animals showed muhipk pulmonary adenomas at awopsy. SQuartial. F. and Bdh, (). B. (Sercrf, L.) Lavo.f Anaomia rarolotlr. rcruei. ))(1):S-1S, 1973. From the L)ivlsloo of Cancer Research, Unlvenity of Perugia. Perugia, Italy. INTRAFISS(IRAL MID-ZONAL ANTHRACOTIC LYMPH NODE PRFSFNTINCi AS A COIN LESION When an asymptornatic pulmonary coin lesion presenu itself in a patknl, the f1rt1 urk of the .rtendlng physician is to determine whether the lesion is henien oa rn.litn.m In rhr ceu reiN.rrrd here•  minimally cakifled midronal p„Ino.nluv n le,n.n rfV-r-r IIrM.twO/ny toH .hatnUU1, proved to he an n,.t( Ihe p.nrin ,if ul.fiuu,in rn Ihu niKlule was not typical of that seen in some of the noncancerous lesioos, and the smJ amount of peripheral cakifkation seen here would cause one to ooasider the possibility of malignant neoplastic disease. Upon' inspection, howevu, the solituy ksion proved to be a well•/ormed anthracotic node without any @ror or histologic characteristics of malignant change. This caae appean to be unique in that a somewhat peripheral (midtarul) benign lymph node, present. inR as a coin leaion, was found to be situated inuanuuratlr radsa tlua intraparenchymally. Rogen, P. M., Ayres, S. M. and Ribaudo, C. A. CAen 61(S): S01-S02 ,11172. Other awrrortr U. S. PubGc Health Servict. From St. Viewaw'. Hoapitd and Medical Ce.ter, New York. ULTILAST1tUCTURAL ASPECTS OF PAPILLARY AND SCLER()SINU CARCINOMAS OF TNE THYROID This electroorokro cwpy study of sia thyroid papillary carcinornrr, fow of which were of the scierodag .ariety, was undertaken in a. attempt to clarify the precise nature of ;he Interstitial material found is the acieroeio{ carci.o mas. The authors report that the neoplastie cells had a highly variable cytoplum even in different areu of a single tumor. Numerous lightly-packed mitochoa- dru and abuadaM eytoplasmie fil.ments were frequent features. There were paralkl, tubular profiles which could represent "paracrystal:' or variants of unooth endoplasmic reliculum. Three of the turnon contained cells with aecretory-type aanules moryhobgiully iod•ntinguishabk from thoee of pam• follicuiar ulls. The characteristic nuclear .acuoles .eeo under the light mkro- acope were found to consist of cytoplasmie evaginations which retained Iheu continuity with the main cytoplasmie mass. In all tunwrs, the interstitiurw con- taincd irregulruly arranted, delicate fl6rils, while collagen Bben wer+ aca.ty. The mkroAbrBs were particularly abundaet In the sderosing urcinornaa where they seemed associated with teduplinted basal laminae around cpithelial and vascular structures. Cellular debris observed io the spaces between basal IanJnae suggests periodic renewal of cell populations in neoplastic papillae as well u in capillaries; basement lamina production .eerna to be a ckuly d'Jlereollaud character of these malignant cells. The authors point out, nwreover, that while reduplicated basal laminae :re a feature common to a variety of repantrve processes, they have also been observed in several other luw-grade malignancies GoafJ, V. E., Oould, N. S. and Benditt, E. P. (Sabbatical stipend recipient) Cancer 29:161)-1625, 1972. Other auprorfe 11 S- Public Lleatth Service. l:rom the 1)cpanments of Pathology. ltnivenity of Washington Sch.wt of Mc01 ciru and ( hJdren's 1luspital. Scaltle. 2fh 27

11. Ileart and Circulation MEASUREMENT OF THE INITIAL RATE OF SERUM CHOLESTEROL ESTERIFICATION This paper presents a method for the measurement of initial rate of serum cholesterol esuriflcetion. The technique b a modifkd version of the assay described originally by Stokke and Norum, a• assay system that allows the combined measurement of keithi. clsoleNerol acyl transfernse (LCAT) and substrate efficiency in plasma or serww sarnpks. Improvements derribed here include the depression of backbtot.rd vahrcs as wdl as an incfcase in the overall efficiency of the procedure. Study of healthy mak humsn subjects revealed that thc Initial rate o( cholesterol esteriflcation increases linearly with the individual's serwn•free choksterd eoMest. [arko. A(: , Rutrnberg, H. L. aaid Soloe, L. A. Suu hrn.ita7 MrAIcinc 7(1) : 17 /-1 8), 197). O1i1er aw'rorr: U. S Pubiic HeaNh Ser.ke. From the Division of Cudiology. Department of Medicine, ettd the Fels Research lestitu(e, Temple Univeesity Health Sciences Center. t'hiladelphia. SERUM ClIOI ESTEROL ESTERIFICATION IN PAT1eNTS WITH CORONARY I(EART DISEASE: IMPORTANCE OF INITIAI. RATE OF ESTERIFICATION EXPRESSED AS A FUNCTION OF FREE C'IIOLFSTEROL Lecithin choiesterol acyl tnsfvrurc (LCAT), the prirnary earyme re- sponsible for estaiilcatioe of free cholesterol in pfasma, may also serve to retard the efiect of forces that favor intra-anerial accumulation of choksterd and the developmcnt of atbaoedcnosis As a preliminary test of this hypothesis. In vitro initial rate of eslerilkatios of cholesterol was eneasurod in the .eta of 12 healthy men and 17 wtee with heakd myocardial infarction. The rates were linear in both group. for ebout 40 twMwtes, with a tendency for duratiow of linearity to be longer the higher the eoncenuation of free choksterd. No obviow relationship awW be demonstrated between the rate of esteri(kation of cholesterol and the level of trittlyceride. When the initial rate of cholesterol esterifkation for each subject was plotted against his respective serum-free cholesterol kvel, the data could be fltted to two straight lines, one for the healthy group and the othet for the coronary group. These two lines demonstrate a significant difference between the two groups Comparison of the data for the percent cholesterol errerUkd per ntinute also shows a tower efiSckncy of cholesterol esterifkNion in the coronary group as compared to that of healthy Individuals. Soloe, L A, Rutrnberg, H L. and Lacko, A. 0. Ar....K+. f(...r lor.w.f a( 2): 15). 161. 197 ). from the I).vu-ow of (lydrofogy. Department of Medicine. Temple University ItraltA Sc.rnces ( eraer. Phdade/phu INFLUENCE OF NICOTINE ON EXPERIMENTAL ATHEROSCLEROSIS AND ITS DL*T[?RMINANTS The aulhon report on their use of coronary an&graphy and appropriate histologic, histochemical and ultrastructural techniques in order to invcdigate the pathologic effects of nicotine on several tabbit orgaas and cardiovascular tluue. For these studies as well as for delenninations of eervm lipids, their test .nimals were subjected to wch determinants of arteriosckrotic heart di.ease (AsHD) as either hypercholeslerokmia or hypertensios, or both; untreated rabbits were uxd as controls. A realistic daily pharmacolofic dose of nicaioe failed to quaMituively or qualitatively affect atherosckrosis of the awta, e.tra- mural and intramural coronary uteries, visceral ksions, or serum lipids. I. either normotensive or bypertensive rabbits whether or not they received suppk- mentary dietary cholesterol. There was so appreciable diAeteoae In the appear- anoe of coronary aaRioRrams obtained frorn nicaine-treated rabbits with and without atherosckrvei.. Anglography did ahow, however, that the hyperte.dve rabbits had kss tortuous eoronary artaies, bistoloRicaUy reflected by Rreater luminal aren tha. are rrxe in noMwlessive animals. Hypertensiott Iwcrcasod the atheroeckrotk prooen in the .arta and ooron.ry arteries of choksacro[-fed rabbits, while sioolise failed to Influence Lduction or maintenance of rtad hypertension. Although the dinical significance of these obscrvationa b u.oer- uin, the euthors point out, they do suuest the .eed for further isetuiry oo.- oer.ing the role of sicotiee in the developme.t of AsHD is man. FtsAe., E. R. er .1. Arrll/ves o/ t'.r/io/oRy 96(1):29t-)01, 1973. From the Department of Pathology and Radioiop, Shadyside Hoepltal, and the Univrtsity of Pi(tsburgh, Pittsburgb. LIPID METAbOLISM IN PERFUSED HUMAN CORONARY ARTERIES 1• thia M vbro esperiroe.t. the awhors deal with lipid syaheals a.d choksterd uptake in atheroscktotk but.a.a eordeary arteries periwad with pulsatik pressure. Roth r`C-acaate and •Hehoksterol were added to the pcr- fusior. fluid. Results show that under these e.perimental eonditiorn, 1M arterial wall fails to synthesir.e chokstetol from aoetate. Whik only very lirnlted .y.- thesis of cholesterol esters from acetate was observed, there was arteriel uptake of free droksterol from the pertusioo plasma. Tl+e addition of nicotine to the perfusion flud did aot influence arterial cholesterol uptake, but did affect the synthesis of lipid from acetate by changing the distribution of 'K:-.cetat. ia phospholipids eod ulglyceridet . Morita, T. and eing, R. /. rrocecdinp o/ rAr Soc4ry for E, ptr(wrenrr e(ofotr an/ Mc/k /we 14(1( 2) : 617-622, 1972. OtA.r awrprlo Kenneth T. and Eiken 1.. Norris Found.tkxr. From the Huntington Memorial Hospilal, Pasaukna, ('elifornia, and Ibc Uol- versity of Southern California, [ os Angeles. 1 22 29

m n m CORONARY Sf OOD FLOW IN RELATION TO ANGINA PE('TORIS An evaluation of methods used in man for the determination of coronary Row is oeoessuy for the critical intapreration of data relating coronary flow to angina perctoris. In genenl, methods for measuring coronary blood flow in man can be divided into (1) methods using diffusible Rases, (2) methods using dif/usibie subsuncn, or subsuncea which actively enter the cell. (3) measure- ment of coronary unus Row by oootinuoua thertnaldution, and (4) methods to measure phauc coronary flow by twea.a of the ultrasonic Doppler flowmeter. Careful analysis shows that prvettdttres which determine nutrient coronary flow are influenced by the preseoee of ttaderperfuaed cardiae muscle. M(a promising ate those noninvasive methods which tdiJitt indicalorn which, during their passa4e through the heart, an acUvely taken up in the myocardiurn. There is w general aRreement concerning coronary blood Ilow ehaafies in angina pectotia and ischernk heart disease. Howe.et, evidenw suggests a dimtnutiou rather than an Increase. In pNients with coronary artery disease, coronary flow faib to mpood ade+>uately to vasodilator drugi A. esp+anation auy lie in the ao-edkd "coronry steal": a decrease In resistaoott of oonoocluded veueh at the pre- npillary k:vel could resuh Is a decreaat la blood flow to muscle supplied by that utery. The Importance of coronary collateral circulation Is &:saibed, nd the development of collaterals from preformed thin-walkd blood vessels is discvssed. Basic principles underlying coronary mkroeirculation, w they affect the osyges supply of the heart musck, an stressed. Sing. R. 1. and Ilellberg, K. Cfrrularbn 46:1146-1154, 1972. OtA.r arrport r Amerkao Medical Asuociatloo - Educatioo and Research Foundatioo and Margaret W. and Herbert Hoover, Jr. Foundation. Prom the Huntingtoo Memorial Ho.pitd, Pasadena, California, and the Ud- versity of Southern Cdifornia, Los Angeles. ME?ASUREMFNT OF CORONARY PLOW IN ISCHEMIC HEART DISEASE In this short review, the authon outline the various methcds developed over the years which have made it possible to study coronary fkrw in normal Iedividtals, in those with coronary artery disease, and in closed cheu esperi- mental animalt; •rtd they describe a number of esperiments as well as their Rfulti A more recent test uses I.oprderehol and correlates the depee of coronary artery disease with the change in nutrient myocardial flow response which follows its Infusion. There appears to be a positive correlation between the severity of coronary artery disease and the response to myocardial blood flow lhe authors also point out the relationship between the coronary mkro- circulation and the metabolic rerJuirements of the heart. Of special signif{cance is the fact that when blood pressure Is lowered by hemorrha4c, only a lew capillaries uc perfuud as the perfusion preuure latls below bO mm H4. Since these capillarar reprrxnt functional shunts, the authon speeulue, a similar dehc ency un rr~+t in heart repons nuurieheJ by atherosclerotic coronary arteries, especially as blood pressure dropa. Clinicdly, this clearly implies that maintenance of blood pressure so as to guarantee adequate mkrocirculatloa. Is most important in order to prevent cardiac necrosis and diminiahed cardiac contractility. eint. R. and Heliberg. K. In: Likoff. W. rt al. (eds.): ArAeroarferosb and C'oronary Hr.n Disease. New York: Orune R Seratton, loe., 1972. pp 146-149. Other arrrortr American Medical Association P_ducatioo and Researc! Fouodatioe, t oe Ayeks County Heart Assoeiatioo, aad the Mavppret W. and Hubert Hoover )r. Fouedation. Prom the HuotioRtoo Memorial Hospital, and the California lostituta of Tech- nolop, Pasadeoa, Cdiforaia, and the Usiversity of Southern C'alifornia School of Medicioe, Los Angeles. CHARACTeRIST1CS OF THE DICROTIC NOTCH OF THE ARTERIAL PULSE WAVE IN CORONARY HEART DISEASE From the oacillometrk studies of othen it appears that the normd patten of the peripheral pulse wave as measured is young healthy childre. abowa •/ ckareut dicrotie notch. With ioaeasioR age a smaller perceouge of perso.s demonstrate this dictotk iacisura. Using floser vaaculopaphy. the merAod de- scribed by Iss, H., Feioberg, A. W. and Cohen, B. W. in 1956, the authors obtained tracings of IfnRer pulse waves on consecutive wbjects in the Ftasly- ham Study during 1963 and 1966. Readable tracior were gotte>l o. 1.778 subjects. FledinRs sbow, that io t.aks the .unsber of "oormals" (Claa 1: deflnite dicrotic notch) haa dropped to lens than 50% by age 45-54 and to less that. 10% by aRe 65-74. DistribtMkrn of tAa prevalence cases of coronary heart disease (CHD) shows aigsifkaatly hiRher perceetaRes of CND ih twb- jects with vasculoRrams with no d'ntinet inciwra (Class IV); the kaa pro• oouoced the incesura th. greater the amount of CHD. V.scubgram daaa ta related to age and blood pressure level. However, In nonhyperteosives the pre- va)eutx of CIID b still found to be related to vasculoRram classes. Cipr.w smoking also shows a weak relationship to vasculogram class, but api. CHD in nonsmokers is found to relate to vascWogram class, indicating that the rcia- tionship is independent of eiprette smoking. Relative weight is inveraely related to vasculogram class for reasons which are not clear. According to the authors, no physiologic reason is known which would lead them to attribute diuppur- ance of the dicrotk notch to the development of ('HD. It is thercfore oooduded that the changes in the appearance of the peripheral pulse wave reflect changes (n the arterial walls, inchding the coronary aAUiea, and may bc a o.euura of the degree of atherosclerosis. D.wArr, T. R.. Tfhornas, H. F_., Jr. and McNarnua, P. M. Anttotory 24(4):244 255. 1973. From the Boston University Medical ('eoter --- Framingham Heart Study. Boston. 71 30 I

EVALUATION AND TREATMENT OF CARDIOGENIC SHOCK This review etsentially reiterates an earlier discussion of the subject pub- lished elsewhere (Mrdic.( Tin.rs 9tf(7):1)7-132, 1970). Here, the awhon describe the diflerent Iypes ol sl+ock, the various clinical maniCeslalions, and how to assess the shock state. They ureas the importance o( eva'uatin6 firway adequacy and gas eschange, acid-base balance, and renal function, as well as the need for continuous mwdtoring of arterial blood pressure; anJ they describe the various techniques invdred. Trealnsesl (and outcome) of ahock depends on whether its origin is suiUly eardioRntie, or whether it resu(u from a d'rseased eoronary bed, or folbws Aeut sur6ery. The aulhas discuss Ihe rationale for the use of vwrprnsartt, alpha- and beu-adre.xrgic agents, )-hydrosytyramine (dopamLr), and tnelhamphetamine, a :alecho(amine- nkasin6 agent, as well r 6/wason, s/aroida, and antibiotics. Muelkr, H. S., Ayrer, S. 61., Mattzara, 1. T., GianneCi, S., )r. and Grace. W. l. Resilrwr and Sr.O Myski.m. FebnsarT 1972. Other srrportr U. S. Public Health Sen(ce. From St. Vincea's Hospital and New York Usivenity School of Medicine. New York. EFFECT OF PtASMA KALLIKREIN ON COAGULATION IN VITRO In this study of one of the at" aloeg the latriosic pathway to blood aoagulatioe, rabbit and humas plasma were usod to determine whether kallikrei. has any cRcct on the promotioo of coagulation in rlrro. Human ot rabbit plasma katlrkrein is highly purified form aecekrated the partial thrombop(astin test of nbbjt, but sot human, plasma Ir a do.edependent fashion. 7Tn clot promoting e/lect of kalldrein was inhibited by preincubation with plasma or by treatment of the enzyme wrth plasma e,-macroglobMdia or soybean inhibiton. Prekallikreis did not substitute for the coagulatio. abnormalties of human plasma defkient is Ilalleman factor, plasma Wroenbop4uie anteoedent, Christmas faetor ar awihemophilic globulin. Wuepper, K. 1). asd Coch..wr, C. Q. Procrrdlnp o/ the Society for Eirer4rsewwf S1oloty r.d Mrdk/ne 141(1): 271-276, 1972. Otheir .rtr.rtt U. S, Public Hea1tA Service. From the Department of EapirirnesW ratho(op, Saipps Clinie and Rcaeatch Foundatio., 1a loqa, Ca1. THE RORSCHACH TEST: AN IMAGE ANALYSIS The Rorxhach scores of 586 healthy young medical studd:nts, who were p.rticipants in a bn=itudinal study of hypertension and coronary disease pre- curson, were studied by mearo of an image analysis. Four perwnallty ratlo[s were identified which aecounted for almost fl)% of the total conarKxr variation: irNclkctual prixlucthvity, form, human rnovemenl, and holism. This provides the clinician or reuarcher with the means to describe individual personality 32 characleristics in terms of four uncorre(ated personality facton rather thas ac- cording to some larger number of interrelated Rorschach variabks. Schori, T. R. aod TAomar. C. a. lou.n.( of Cllnk.( PiycAofory 28(2):195-199, 1972. OtA.r au'prtt Claytoa Fu.d, Nalioad Institute of MesW Hca1tY, and Natiosal Heat1 Institute. From Philip Morrb, U3.A., Rkhrtrond, Va., rd The loboa Hopk4u Udv.nity School of Medic3ne, Baltimore. CARBOXYIIEMOGLOBIN AND THE ACCESS TO OXYGEN: AN EXAMPLE OF HUMAN COUNTEREVOLUTION Access to oxygen is one teeawn* of evoluriowarp station. At tbe top of the evolutionary suk, maronulian oaypee delivery systems eaist for dr rsa/or purpose of providin6 an internal esvirooese.l suflkiently rich is oxygen to permit tissue respiration and the productiote of energy. The respiratory char- acteristic, of herraRlobin, the oxygen carrier of the btood, may be defi,ed by (1) the oay6es upacily, and (2) the shape of the di.sociation curve. Carbosyhemogbbis (COHb) dters tbe oayhemoRlobis dissociatiow arve (s such a manner that oiygew is released to the tissues with great difficuhy aad at a lower oxygen tension. The know. effcets on hean and braia of brearAing low concentrations of carbon rnora.ide are primarily related to this kftward shift and perhaps also to combination with myo6lobin and eerui. Yon- eowuininR enzymes. (lernoRlobinosy6ew eouilibria in the presence of COHb rexmbks the equilibria of rrore pr(mitive forros of hemoglobis asd riw r(se to the wuestios that Ibis decrease is the aceess to oxygen is a forw of eoustertvdutioe. Ayrrs, S. At., Giaenclli, S., )r...d Mudkr, H. ArclUves of Enrkwansenrd He.hA 26(1) :8-1 S, 197). Other arrr.rte U. S. Public Health Servke. From the Department of Medkine and the Cardiopulmonary IAboe.tory. St. Vincent's HoapiW and Medical Center, New York. INFI.UENCE OF CARBON MONOXIDE AND OF HEMODILUTION ON CEREBRAL BLOOD FLOW AND BLOOD GASES IN MAN In thrs Nudy, the influences of moderate carbon rnoooaide eapo.ur. ud hemodilution were compared in an attempl to gain information about the e0ecu of three variabks: the otygen binding capacity of the blood, the ahift of the osyhurwglobin dissociation cuive, and the blood viscosity. ('erebral blood flow (('BF), arlerid and jugular venuu+ pll, P('O„ PO„ O, aatunuos pcroest, s.d lactate concentration wete measured in Ave patients before and after rrwHfe+sre carbon monoside espoaure (mean carboayhemoStobin cuncentratwrn 201(. ) and In another five patients bc(ore and a/ter hemodilution using a sulutton of buaia. 33

albumin The tenon"' intra-artetial injection method was used (or the flow measurcments. The arterial oxygen tension remained constant during :he studies. ( BF increased both a(ter carbon monotide exposure and after hernoJilution. Tlse increase was more pronounced alter carbon monotide exposure. This could be esplained by the shi(t toward the left of the otyhemoglobin dissocLilion curve during carbon monoxide e.pastre. Jugular venous oxygen tension decreased sliRhtty during cubon monoxide exposure but remained constant duing hemo- dilution ('hanges in blood viscosity might contribute to this finding It is eon- cluded that a highly efficient .seeb,araiam maintains the brain's osy len supply during both condrtions. Paulson, 0 B, ParvinL H-H., Ofesa., 1. a.d S4InAo/. E. Journal of Applied Physiology )J(1):111-116, 197). From the Department of Neurology and Clinical Physiology, Bispc9jeril Hos- pitd, and the (kp.rtmeot of Clinical Chesnhlry, Rigshospiukt, (',spenhaRes, l)cemask. 111. The Respiratory System NEUROEPITHEI.IAL BODIES IN THE RESPIRATORY MUCOSA OF VARIOUS MAMMALS: A LIGHT OPTICAL, HISTOCHEMICAL AND UI.TRASTRUCTURAL INVESTIGATION Various electron miaoscopie lechnipues plus several routine, as well as speciflc stains such as silver and Fakk's fluorescent amine, were used to study fetal, neonatal, and adult lunp in rabbits and other mature mammals As in the human infant, each of thesc techniques revealed the presesce of rotramucosal eoepuscles, so-calkd neuroepuhclul bodres, througlxout the imrapulrrsonary airways. These bodies are composed of more or less paratklly orrented, non- edialed, cylindrical ulls which extend from the basement membrane to the airway's luminal surface, displaying prominent cyloplasmic argyrophilia, less pronounced artentaffinity, an intense yellow fluorescence. Electron microscopy shows that these granulated cells eoeuis truiwly two kinds of dcnsecored vesicles, of which the first type are acro(oniw positive, as demonstrated by the • laim-Etcheverry technique. The eeuroepithelial bodies also contain intracorpsn- cular nerve endrngs which create synaptic eed forwutions upon the granulated cells. Although the fwtctions of these woanin-produeing oorpuscks remain ue- scttkd, thex bodies may be related to the reeently reported AFG (arlyrophilic, fiuorescent, and granulated) cells, and are perhaps involved in various mucoW, bronchial, and hronchiolar neurosecretory processes. According to the aWhors, however, they mosl probably rue chemoreceppors, swretch reccpron, and/or tactik receptors modulated by the ee*wral nervous syslem. l..arwrrynr, 1. M., Cokelaere, M. and Tlsnrynck, P. Irnnrhri/r /r.r Zrll/warAunt xnA )WIlrorloPiuAr Anoto.nlc 1)3:369 392, 1972. Orlher .urporf: Nalbnaal Fonds voot Wetenschappelilk (hrderzock (Bclgium ). From the I aborauxy of Pathology and Hislology, Katholickt Univcniteil te I cu.rn Sclxx)7 of McJarnc, 1 ruvcn, Bcltium. I SEROTONIN PRODUCING NEUROEPOTHELIAL BODIF-S IN RABBIT RESPIRATORY MUCOSA The inlrapulmonary lining epithelium of rabbits contains newly ideMUied corpuscks composed of a:gyrophil, arkentaff{., yellosw fluorescent, ultrwrwc- turatly granulated and innervated epilhelial eellular organs. These art proved, by electron microscopic cytochemistry and mkrospectography, to be a source for inlrapulmonary production of serotonin. Probably they art intrapulmoaary neuroreceptor organs modulated by the central nervous system which exhibit local secretory activities. l.rwrrynr, l. M., Cokelaert, M. and Tbeuoytsck, P. Science 1 10:110-11), 1973. Otb.r arPprtr Natioe.al Fonds voor Wetenscluppclijk Oodcr:oek (Belgium). From the tabrwatory of Tathology, and Hislolop, Katholkke Univcnitck te I.cuven School of Medicine, Leuvee, Belgium. THE ULTRASTRUCTURE OF LYMPHATIC VALVES IN THE ADULT RABBIT LUNG Four adult rabbils were used in this study of the ultrnwuctural features of lymphatic vducs. Electron microscopic investigation revealed that the pulmonary lymphatic valves are not simple duplicates of the lymphatic vessel waB; they have an identifiable structure of their own. The valves consist of an unimer- rupted central connective lissue core, covered ora both sides with a single layer of flattened endolhelial celb. Near the valve i insertion in the lymphatic verel wall, the connective lissue core reveals a distinct thickening being composed mainly of collagen bundles. Elsewhere it contains mainly elastic fibers and Ane fllamenu, enclosing also sdne rather peculiar connective tissue cells. Nervous nd muscular elements were not observed. The endothelium is conlinuoui and eahibits no open junclions. The valvular basemen( membrane is better developed than in lymphatic capillaries. The enddhelial cells contain numerous cytoplasmic filansents which might be endowed with contractile ptoperties. The ultrastruc- tural features sugtesl that the function of the lymphatic valves is mainly passlve. They are firmty inserted in the lymphatic vessel wall by collagen llben and their moving parts are slender and elutic. Their endothelium appears relativdy impermeable and is firmly attached to the sublacent connective tissue. Lnuwtrynt, 1. M. and Boussauw, L. Zriuclhrl/r /ib Zr/1/ocxAunp.nd Mkror4oplarAr Anaromle 11):149-16J1, 197). Fronr the Ikpartnsent of Flistoltrgy and Palholoty, Katholieke Univcrsitet t/s leuven School of Medicme, Ituven, Belgium. STRIATED FILAMENTOUS BUNDLES ASS(K'IATED WITH CENTRIOI ES IN PULMONARY LYMPHATIC ENbOiflel.lAL ('eLlS In the r.bbit, the cndothcli.l cttts of pulmonary lymphatic vcsscls and valves generally contain two centsioks situated between the nucleus and the (]olti appararus, which are almost invariably assocuud with ouc to s(vctd 14 35

slriated hundtes Qf two to sis Alaments. These Alamentous bundles reveal a cross banding of alternating Ane (d0-100 A) electron dense bands and much broader clear ones with a variabk pcriodicily (600 900 A). The lu+gitudinally oriented filaments seen within the clear bands .re about 40 A in di.meler. The bundles re attached to the ccntriole at either or both ends, nd sxnelimes in the middle. Although their actual function Is unknown, the authcrs speculate that these uriated bundles might be vestigial roorlNS (rom ndimen:ary cilia of lymphatic endothelial cells. Their actual significance, howevcr, remairn to be i.vestigaled. L.uwrryrnr, /. AI and l3oussauw. L lorrnd of f/lrnssrrucrure Rc.e.rcA 42:2S-2fa, 1973. From the l.aboratory of Pathology .ed Hhtoiop, K.tholicke UuivcrsiteN te Leuven School of Medicine, I.euverti Befsisre. FILAMENTS IN FIflROBLAST IN PULMONARY ALVQOI-AJI WALL The /unp were inAated with 2% 6fvut.Wehyde, pori-A:ed with I% osmium tetroside and processed for electron microscopy. The eell body and processes of the alveolar Abrobfast an loca(ed In the interalveolar septum. These cells oonl.ia lipid dropiets which are eapccially twnserous In newborn and young mice. Small bundles of drtue filaments arm formed in the cytopl.srn adjacent to the nucleus oc in the process away frorm the cell body. In the protr-isded wall of the alveolar duct, a AlameNcorstai,ing process may be located t,tRether with supporting connective tissue flben. The ILaments usually run a strorghl parallel course in the cyloplasmrc procrss In the alveolar wall, a Abroblast process very often ends around a capillary outside the basal lamina of the endothclial eclls. The Alaments in such a procen run in a curved fashion following the contour of the capillary walls. The anatomical ananRement of the Alamcnts in the abeoblasts in the alveolar uea wucsts supportive and contractile functions ie the Alarneots. Hung, K.-S., Hertweek, M. 3., Hardy, l. D. .nd Lowll, C. G. /.: Arceeeaus, C. l, f ed ): lOrA Anwwal rrocrrdinrt of rAe Elecrron Mkros- eopy Sockry of Amerk., f.or Ante/v, 1972. Otti.r .r'porti Environmental Protection Agency. Hughes Employees Give Once Club, and Hastings Fund of the Univenity of Southern California. From the Dep.rtments of Anatomy and Pathoiogy. University of Southern California School of Medicine, L.os Angeks. INNFRVATION OF PULMONARY ALVEOI I OF THE MOIISE Il1NO: AN FI E(TRON MICROSCOPIC STUDY Whrn rhry rrurhed the nerve supply to the alveolar duct+ and alveoli of m..uu• lunli rrn,lrr the r/rru.rn mrcruscupc, thc .uthrws norcd that in the •I.r../u J...ir iLrrr -rrr u.u.lly rxr.r burxllrf rrrntrfling of at many as nine 1r, unmyelinated asons surrounded by connective tiwue Aben In the latcntitium surrounding Ihe openinRs of the alveoli. In the alveolar walls, taeeve rwrdlee consisting of as many as Hve unmyclioaled aaom were located in the intersUtiurm between pneumocytes and the npillaries. TAe unmyetin.ted aaoer cootai.ed neurotubules and some mitochordri., and were partially or compktdy wr- rounded by Schw.n. cells. Two distinct types of enlarged nerve endi.p were identiAable. The Arst contained nuny small milochondria and was either uso ciated with the type I pneswnocyte a fowrd alose ie the interstitiurn. The second was packed with numerous IarRe, densecore vesides and was in close cootacs with the type 11 Pneunwcyte. It b suRRes(ed that the fIM type of codlag Is ses.sory while the second is motor in 4rrdio.. Huog, K.-S, Hertweck, M. 3., Hardy, l. D. and LowN, C. G. TAc A ns.rk.n lown.d of A n.rorwy 133 ( 4): 477-4%, 1972. (HAor awrr.rtt PaviroemeMa) Prolection A6escy .nd Hastinp Fou.datio. Fund of the Udversity of Soulheen CalifonJa. From the Departteests of Aauomy. Pathology .ed Medicioe, U.)versity of Southern C.liforw School of Medicine, Los Angeles. ELECTRON MICROSCOPIC Of3SERVATIONS OF NERVE ENDINGS IN THE ALVEOLAR WALLS OF MOUSE LUNGS The nerves .nd their eodinp ie the alveolar walls of moux lu.p wers studied with the eleetroe microscope. Methods used lor this eaamination wen those used routinely for the study of awm+J lung structure and the effacu ot inhdation of air pollut.ots, influenta vituocs, or both, os the respirauxy trad of mice. Of the 40 rniu whose lungs were eaamined, 12 were oonveWio.d and two were germ(tet controls, while Ihe other 26 had bcen used is vatious inhalation e.perimenu. Groups of unmyelina(ed aaons surrounded by Schwane cells were located in the inlentilium in the walls o( the alveolar ducts .ed alveoli. The sons coot.ined many neurotubuies and some mitocho.dria. Two types of enlarged nerve endings were IdentiAed. The Arst type had many sstaM mitochondria and was either closely associated with the type I peeumocyte or located a)poe in the interstitium. The second type was Aikd with lar{e, deo.e- cored vesicles and was txat the type 11 pneum(c:yte. It is suggested that the Arst type of coding is sensory and the second type is maor in function. Hung, K.-S, Hcrtwcck, M. S.,,Hardy, l. 1). aod Loaull. C. O. Anrcnran Review of Rrrolratory !)urmt 101(2):32tr-3)), 197). Othor .uP'ortt Environnxntal Protection ARency, HuRhes Empioyeea (llv. Once (-lub, and Hastinp Foundation Fund of the l)nrversity of SoWher• C.lifornia. From Ihe t)cpartmcnes of Anatomy. Pathology and Mcdrerne, l/nivaslty of Southern California Schoof of Medreine, l os Angeles 37 I