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lar lo tlwx obtained with MCA alone. Since the highest spccinc activity of AIIN occun IS hours after TCDD treatment, it is evident that elevated AHH activity by itself is not a requirement for enhanced tumor ausceMibility. F.s- peciany interesting are the tqectrum of metabolites formed and the kinetics of entrme formation during the tlnt 48 hours of T('Ot)rRected At1H induction. The available data suggest that it is during these fint IS hours of treatment that the neoplaslic event is flsed. The genetic data presented here also augr.t that even though the level of AHH plays a dom((t.M role in MCA- and HP-induced cancen, other genes art abo ef/eNint cancer wnt:eptibiliry. Immune competence could be another influencing (aclor. 1s addition, there probably are subtle dif- ferenees in the way the various strains met.bolae poycrclic aromatic hydro- catbats (PAH) even within Ihe "inducible" and 'noninducib{e" clusincalion. Studr of these diRerenees should yield valuabk information on the actual stepr invd.cd in the activation of PAII to their prosimal carcino`enic /orm. lhe hrft model srskm used hen pro.ides the t.nans to observe hydrocarbon me- tabolism and carcinotienesis In the &ame tiasue and thw should prove aduabk lor studying the tnechanism of tumor production by at least one class of chernL eal urtinofeas, the PAH. Roari. R. E. (AlkroMoloskd Asrsor(ret, /nr.) 1.: Freudewthal, R. 1. and lones, P. W. (cds.): rol)nrrl.ar Aromark Hydro- carbonr: CAewt4ny. Mt•r.boliswt, .nd C.rrinojernrsts. New Yort<: Raven Presa, 1976, rol. 1, pp. 139-151. Other n.pp.rts National Cancer Institute. Protw tM Department of Biochemical Oncoiogy, Microbiological Anociates, I.e., Sethesda, Md. ON 771E PROTEOI.YTIC INHISITURY EFFECT OF HUMAN FOETAL AND NEOPLASTIC T7SSUES 'fln Prokase Inhibitory activity of human fetal and neoplastic tistw:s was Mrdkd by tweant of the 11beM slide sandwich technique, a hislachemkal tech- npu. /or localizing BbrinolYsir inhibitors which uses flbrin r a substrate. Be- sides 12-22-..eek fetuses, their placentas and deeidua, the material esamiaed in- duded Mrea ovarian earcirwmas and metastatic tissue from the peritoneal cavity. On dides M.t covered by a layer of plasmirwgen-free Bbro6e.a and thtvmbirs. theta iecubated at 1' C and eovered again by a layer of urotina/e or human pl..min. the thrmnus, placenta and decidua consistently showed a suvng inhibilory effect on both plasmin and urokinase. while Bver, pancreas, adrenah. and spleen deenorsstrsled orny modente activity. Myocardium and re.al oortert rescted only weakly to nwderdey with urokinase and not at all with plasmin. The renal tnedulla, Mng. Momach. and aorta had no inhibitory effect. The ovarian cartinanas had a medium Inhibitory e8ed. but their peri- loned tnetastasn had nate. The hitherto unknown inhibitory activity of the th]rmr .trengthens the a.sumed connection between the /Wrinolytk and In+- muno{ogic .yssewn. lUa fael thM fetal h.ete. stomach, renal meduila, and aorta did wo1 displa7 iwAiMtory .cti.lt7 is wot considered conclusive of a lack of in- Mbibn i these tit.ucs /lowever, it is suue.Icd that the absence of proleo- lytic inhibitors in the metastscs might tefiect o morr aUresoive stage of tumot growth. Fornasari, P. M., PandolA, M. and Astedt, S. (K.Jfader, S.) Thrombosfs Resesc/i E:S29-S3fi, 1976. Other support: Swedish illedica) Research Council. From Ihe Departmcnt of Clinical Mediciae Adc.fo Ferratr, University of Pavia, Pavia. Italy; the Coagulation Laboratory, kTtp.rtmeM of Opthalmology and De- partment of lirnecolog1 and Ob•tclrics. University of Luaf, Allmanna Sjuk- huset, Mahnti, Sweden. ('LINICAL 11@MATOLOOiCAk. PROORESSION OF IIEREDITARY LYMPHGttAkCOMA IN RASBITS There Ia eotaiderabb diversity Iu dNa on the clinical progrnaion of ympho..rcana (1i.) botb betweew ad within species. He.e, hematoloBic pa- nrnelers were used to tNUdT 34 rs6bNs wilh herMitary ymphotancoma (/WAa) in order 1o determine W elLleai ~ropesaiow under controlled genetic eoadl- tiona. In these anirndn, d:at6ts in hesrro6,rawt erythropoietic cells followed a fairly well defined dinleal oarsr of nboul ons and a h.lt month's duration. Packed cell .ohnne, rott blood oepr+ (R11Cb) count and hemoglobin contew dl dropped. Osmotic frtqlitP i.ue..ed. Sased on these data, the apeculatioe is thN both twppesfow of ery6ropoeisia turd increased hetnoi7sis occur. Theo. Is no queslior4, howe.er, tltM both peripheral and bone rnanow granulocyln are deptesacd very early la Mo eewsa of ahe d'aease. probably quite sorne time befote the RSCs tue uRecMed. lt Is etMhw.led tlut the btal course of the ympho- aaroana, based on ehat>.a In tbe 6rasuloqr/a rather than on those in the Roca akvne, is perhaps r tsrudt r twiee aa bn6. 7ltese conclusions would be in accord with reports of nitsilar obsttrvatitms in tee cat and in humans. For eaampk, whik mattrow Ie.olsenteM Y/witiaM7 ras in Hodeekin's disease, a Coomba positive hraroytie awetwia b peseM in ib late Napa just as has been observed in the rabbit; and th. Mability, of the total kukocyte count observed here until very terminal Maon wetm teached aped with yet another report on Ilodgkin s disease. Fox, R. R., Norberg, R. P. aed Meler. N. The lo«inal o/ Hered/ry 67:376-I90, 1976. Other nrpports Natioral i.Milufsa of Health. Prom The lackson Laboratory,l/ar Harbor. Me. TRANSPLACP.NTAL CARCINOOENIC P.FFP,CTS OF COMB1NFrl TREATMEPfT OF ETHYLUREA AND SODIUM Nil R11 E IN RABBITS The Iranaplacental induction of primary tenal tumors by the adminisualioa of (<1hy1-1-uiUO.ourea (ENU) lo rabbits has been previously demonstrated. 19 1tl

-i1Thia paper now reports that the oral administration of ethylurea (EU) plus aodiurn nitrite (N.NO!) to rabbits pregnant 17-t9 days also induces primary renal tunwrs in the progeny with approsimately the same latency as tumura in- duoed by ENU. Neither EU nor NaNO, alone is sufficient for tumor inductinn; no tumors were induced in the one-year-old offspring of rabbits given EU (0/12) or N.NOi (0/1a) separalely. However, the combined treatment in- duoes tumors. The present esperimenlal results show that of 20 WFl/1 progeny that survived one month, sin developed primary renal tumors at a mean sge of 3.e±0.e nwnth.. In contrast 1o strain Wfl/l. AX/J progeny developed no tumor. (0/8) during the Arsl year of life frvrw EU plus N.NO=. This differ- eoce is probably due to a strain effect Alao, one of two surviving IIIVO/1 progeny developed a renat tumor at 1.25 nwoths of age. In al( Inslances, the ttrtwrs were renal tubular eysladerwrnas, cysladenocarcinomas, or nephrobtas- Ionrs, which appeared to develop within unaR renal cortical cysts. The data for stniw WH/1 were In accord with a previous report of primary renal tumors in- dutxd in progeny by the administralion of ENU to rabbits pregnant 10 days. Apparently, the combined treatment of rabbits with EU and N.NOs led to the formation In v/ro of ENU. Pot, R. R., Diwan, S. A. and Mekr. H. lownd o/ the Navbwa/ Cwrer hurUrre S9( 2):127-I29, 1977. OtAer eai' prtr National Cancer Institute. Public Health Service Division of Rese.reh Resources and Hyccl Inc. From The lackson lahoratory, Bar Ilarbor, Me. OENET7C DIFFFRENCFS IN THP. INDUCTION OF COLORP.CTAI- TVMORS BY 1,2-DIMETHYLHYDRAZINE IN INBRED MICP_ The symmetrical cornpound, 1,2dimethylhydrarine (DMH) Is one of the tnoN potenM and reliable carcinogens foe the induction in rodents of colorectal Itrnors, which aro histologically similar to the ones In man. While several aRenb have been implicated in the devekopmeM of these tumors in humans and animals, environmental factors have been suggested as the major determinants: tlr susoeptibility to spontaneous and induced eobroctal tumors is also thought to be governed by hercd". This Arst report on a systematic study of the role of kenetic factors is the indultion of these tumas in mice and- its associated biochemical and immunoloak tnechanisms, shows that se.erd of the inbred strains (or genotype.) are differentially susceptible to the devetopment of DMH- Induoed eolorectal tumors. When AKR//, SWR/1, P/1, CS7B1-/61, and OR tnkr were treated once a s.eek for 20 weeks with 15 mg DMH/kg body wei`ht, ooloretiyd ade+wmr or welldiRerentiated adenocatcinomas were found In fl)9L of the SWR/l, 90% of the P/1, and.alf, of the cs7BV61 mice that survived 22 or rnore weeks after the Arst injection. None were observed in AKR/1 mice. In whkh, however. the incidence of kukemias was comnan. While almost aM of the OR mice developed anat squamous cell earcinoma+, this type of /umor was not found in any of the CS781./6) animal.. The SWRIJ mice dereh.ped kukemias and putewmary adcrwrnas in addition to the colorectal tumor+. Mul- tipk tumon of diverse types were also common in P/1 mice. lheae resulls sug- kest thal the host ,kenotype oe• nquse strain ia crucial in determining the dif- ferential response to DMI(-induoed c.rcinoAenayia. Diwan, B. L., Meler, )f. and Blacksnatt. K-1? lorrna/ o/ the Neriond Cancer Iwrt)trte 39(2) :133-1Sts, 1977. Ot6er support: Leukemia Society of Meerrca, Inc. From Meby (aboratories, Ine., SpringAeld, Va. and The lackson Laboratory, Bar Harbor, Me. (lEN(rllC DIITERENCES Ihi NENZO{cr/PYRENE CARCIN(X)1?NIC INDEX IN VIVO AND IN MOI;SECYTOCHROME P,ISO-:dED1A7ED BENZO/a/PYRENE METABOlJ7E BINDINO TO DNA IN VITRO f ertain polycyclic aromatic hydroearbo.a indutx Ihe de wovo synthesis of cytochrome Prd30 In resporrive animals ud increase the activities of at least ten mictosomal nwnooslAewaaes InchsdieA aryl hydrocarbon hydrosylase, the enzyme system know~w to metabolite benso(e/pyrsne (BP). In the study pre.ented here. BP was adminislerrod to different subNnes of the inbred mouse strains CIH. C37BIJ6 and flBA/2, and column chromatography was used to seek a correlation between Ihe qwnAitative change in the site or shape ol any peak formed In vitro and Mnqr formation in .iro. Nine peaks, indicating BP metabolites bound Jn vitro /o DNA swckoaides, were reproducibly identified. When either the C3H or CS7BL/6 strain was eompared with the DBA/2 slrain, a positive general correlation wp fou.d between the carcinogenic index In vivo and each of three determiuatios is vttro: 1he size of light of the nine peaks. the hepatk aryl hydrocarbon hydroaylae activity and the total hepatic cylo- ehrorne P450 content. Peaks D. E. H, and I demonstraled relative differences among the three straim Ihat were In Ihe suune direction as the carcinogenic indea in vitro. Ilovrerer, when C7H Aioa were compared with C57BIJ6 mice, no quantitative eorrelatiow waa found bNween the carcinogenic inde and any of the three !n vitro n+ea+wemt.b. Hena, the total quantity of nuckoside-BP rnetabofiles in each of the alee peaka was not necessarily associated with bio- logical activity (l.e., eanoer bs Hwl, and aq statistically significant relationship was shown to esist between BPdeitiated tunwtilienesis Gn vlvo and the nucko- sWe-BP melabolNes generdcd /n sams. Nebert, D. W., Boobis, A. R., Yaji, H., lerina, D. M., apd Kouri, R. P. (Mkroblologkd Associ'Nwes. Inc.) ln: lallow. D. l., Koesis, 1. 1., Snyder, R. and Vainio, If. (eds ): Biolosl.d Reactive )nternrrdleren, New York: Plenum Press, 1977, pp. 125-145. Otbee sMppHr National Cancer Institute. From the Sections on PharmacokenNin and Molecular Teratology and O.ida-. tion Mechanisms, National Instilutes of Itealth, Bcthesda- Md, and the Ik- parlment of Biochemical ()neolop, Mkrpbiological Arsociates, Inc., Bethcsda, Md. I 20 21

7-MFTIIYL('HOLANTIIRENE-INDl1CF.D MONOOXYOENASt? (O-DEETHYLATION) ACTIVITY OF HUMAN LYMPHOCYTFS la th-s study, a dirtct fhrorescence assay for O-deethylation of ethosyre- uoru/lo was used to quanlitate mised-funclion oaidase activity in miloten-acti- vated human lymphocytes. Whik etho.yresorvlM Odeethylase .divity r:m6ed (rom low to nondetectable In noninduced, milogen-activaled celb, it was read- Yy observed In )-methykholanthrene-ind.ced, mitogen-activsted lympho:ytes. Results showed that the enryme activity was 4pendcnt on ast.y lime, number of ymphocytes and the presrnet of te1uoed 1ieiAinamide .denine dinucwotide phosplrle. It was also reproducibly delected whett duplicate samples of ~Aood from ons individual wcre cultured and assayed at the same time, hot quite 9.riabk when these procedures wen done on dilferent days. Since the assay preaeo/ed her. is direct (requirirK oo estraction Neya). sensitive and amenable to Womation, and ainee ethoatyre.o.uliw may be specifically metabolin d by only cytochron.e P-IIt1, this chemical may ser.r as an eAadve alternate sub- Nrsita to benzo(.lpyrene for dekrmininR mbted-frnclion osidase activity is humao tisus. turt., M. D., Mayer, R. T. asd Kouri, R. E. (Mkrobiolotkd Associ.les, lwc.) Gncer Rex.rrA )7:164-46), 1977. Oth.r a.rP.rf r National Cancer Instilute- Prom the Sioehemislry Dep.r(ment, University of Te:aa Health Science Center. D.Ras, dre United S1nes Department of Agriculture Research Serrice, College Statio., Tea., and the 1)epartment o( Biochemical Oncobp, Microbiob6ical As.oeiales, loc., Sethesda. Md. 11. The Re,pirewtory System BRONCHIAL CYTOLOOIC CHANOES DURINO CARDIOPULMONARY BYPASS: IRON TRANSPORT BY ItIS71OCYTES IN LOW FLOW STATES Although In previous studies more iron-l.den histiocyles ha.e been ser. 1. (1) Me tr.clroobronchW secretions of patients in hcrnorths6ic shock and (2) lh. hu+p of rab bled b hemorrhagic shock thaw in their n:spectire cor- tespordinR cowtrob, so esplawalion for these obxr.ations wr ever established. In this studythe bronchial set:retions of 12 open-heart sur=ery p.tknts under ardioprdma+ary bypa+a wen awyed in specimens obtained (1) bnmediately after onset of aaeslhesia: (2) during eatracorpoteal circulatioa: and O) alter lermin.tion of cardiopulmonary bypass. While in an earlier study the mean per- oratalle of iron laden hiatiocyte. (PIIFe) of 10 patients In hemorrhagic shock waa 12.1±1.4, here the p11Fa rvae from 13.6t60 after Intubatbn to 19.6t6.t atter ooe hour on bypas with virtually arrested pulmonary blood fiow, .and remained close lo the letter . ~hro one hour ofler pulmonary circulation was re- stored. All lhese Rndinp droa' th.l o sluggish or arrested pulmonary circulation allows large numbers of iron-tadea bistiocytes to appear in the tracheobronchial tnee. During cardiopulmonarr brp.fs. only the pulmonary circulation wflers, whik'ehe systemic blood eow is also reduced in shock. It seems, therefore, that PHFe is inversely proportiont+) to tltt pulmonary blood Ilov,, and that hypoper- fusioe, accumulation of mNa(roNA¢c aed t.Yitrg pH at the lissue level probably account for the pHFe dndiep. Friedman-Mor, L, C/i.fon, I., ZLrnoorf, H., wd (orkin, L R. The /ourwd o/ Trauma 16(10) •t1SJ18, 1976. OfRer ao'r..Ir U. S. Publk HeaaA Service. From the Ikpartment of Anertiwiplogy, New York U.sivenily Medical Center, New York, and the Departm:a/ of Anesthesiology. Albert Einstee College of Medicine, lhe Srona, N. Y. TISSUE PRINTS FOR STUDIES ON IRON, PAT, AND METHYL-METHACRYIATE (MMA) UPTAKE BY Ii1ST1OCYfES In this preliminary report b 11w edilors, the authors describe Iheir reta- lively suecessful use of tiswe prints ln.ltad of paraffin sections for various hslochemical Mudies. Based on their sroed for a method bolh cheaper and faster than the usual hislologic sections, they have obtained escelknt lissue prints from rat and dog traehe., hrp, kidney, spleen, liver, lhymus, and in- lestines. The technique essentially eo.shled of sequeoliaNy psessin6 areas of the evenly cut and b/otteA organ uwtTaa .pi.st a series of microscopic slides, and immediately Gaiat the priM drus obtained with a water-soluble spray /laalire. These were tlree stained by /h. Pap..icolwu, Prwsiarn blue or Sudan IV methods. In otder 1o bs satil.bls for I/lietaaopr, however, this type of ma- laial mus/ be composed of ealrathM, preferaby, nwnocellular, layers which faciMale cotrrting, .nd snwt faiWdly reproduce 1he configuration of the original lissue. While ,udr 1Mwte pri.b should not invariably replace hisloloRic sections, which stiN best represerM We actual tirue slruclure, they do have a place in laboratory and cYak.l silwtitw where a fast, reasonably accurate and ineapensi.e specimen is deaired Friedman-Mor, L, CA.lon. L, Orkia, L R., a.d Turndorf, H. Acr. Cyrolosk. 21( 2):1 d4-1 K, 1977. Frorn the Departmcnts of Anesthesiolop, New York University Medical Center. New York. and IM ARbert Eloaleio College of Medicine, The 8rona, N. Y. TNE INTERACI7ON OF Q-1-ANTTTRYPSIN W1T11 SrJLllel.8 AND SEPHAROSE-SOUND ELASTASE - AAInIty ehrorn.topaphy .nd pdy.crllamide gel ekctrophoresis in the ptetencie and absence of sodium dodtcyl sulfate were used to e.amine the 21 22

prvducts of a-l-antitrypsin and elastase interaction. Five substances can be identifkd by gel electrophoresis. Two of these are e-l-antitrypsinelastase ccxn- pkses with molecular wei6hts of 7),R00 and 3lt.)00 dalton units. Two others ate identital to the trajments of .-1-antitrypsin which are removable from a Sepharose-bound elastase column immediately after its application to ite col- umn. The larger of these components weighs about 50.000 dallons, reacis with .-1-aMitrypsin anliserum and is not aa eniyme inhibitor. Amino acid asalria shows that these two produets together an similar in composition to a-l-anti- trypsin. The fifth product is probably a fradrtent of .-I-antilrypsin missinil from the low molecular weight oontpkx. The elaaast can be separated trorn a-1- .utitrypsin In the complex by twild nrdoophilie attack. Small quantities of the inhibilor ean be ehrted frorw the elastass aRi.ity column by phenyl-methane sulfonrl Ihsoride. The data suRjest that elaqase may split three bonds on .-I- antilrypsir.. One such attack cleaves the krhibitor iNO two inactive frai.nenb while the other two produoa oowtpkses whose combined molecular wright is lower thu that of the sum of the react..ts. • Lo, T. N.. CaArn. A. S. and lames. H. L IiocAin.ka er AbpJiyrka Acaa 433:344-136, 1976. O/Aer aappartr National Ileart and Lun6lrtitute. From the Dep.rtment of Medicine. San Francisco Qeneral Hospital; tt-e Pul- nsonary Specialiud Cemer of Research. and the Cardiovascular Research In- atitute, Univetsity ol California. San Francaco; sod the Department of Medi- eiee, Temple University Health Sciences ('enier. Philadelphia. PREVAI.ENCE OF AI.PHA 1-ANTITRYPSIN PI TYPES AMONO NEWBORN INFANYS OF DIFFERENT E7/1NIC BACKOROUNDS Crossed lnwnunoeketrophoresis (Fagerhol-Laurell) was used to study seta fran 1.010 umbilical cotda In a systematic attempt to screen newborn inlauts for abnormal phenotypes of alpha-l-antitrypsin (a-I-AT) whose presence may be associated wilh potentidly lethal hepatic disease early in life and with ero- phTsema in early adulthood. A variant of the normal M patterw which is rare- ly found in later life was commonly detected in the neonates. Tbis "aep" p.t- tern, characterited by a shift of the relative amounts of peotein in the major peaks of the M patless. was fooad regardledr of taoe in 96% of newborns but in only 9.9% of infanb one nwnth 1o two yean of age aed in 18% of childree two to less years old. Maiot ethnic diRerences. howevet, were noted in the prevalenon.f o( abnormal phenotypes for this eayme Inhibitor. The oon-M phenotypes were sipubcantly more prevaknt in I/ispanic (11.00% ) than ie black (2.92%) or white (3.63%) intanb. The MS phenotype was found in 6.7% of the Hispank, 1.3% of the black and 3.9% of the white group. lbe MZ phenotype was found in 2.8. 0.7 and 1.0%, respectively. When M and non-M infanb were compated. tnean vdues of .-1-AT were higher in M than M nas-M in(anls in dl three poups aed significantly so in fhe white and llis- panie {roups. Ilowever, deeressed kvels of .-2-mscroRlobslin In M oompared with non M Inlanb were statistically sigmllcant lor all thnce troupa. lbese se- sults clearly demonstrate the iofiuence of ethnicity on the distribution of a-I- AT Pi phenotype4 amoo# newborso infants. Eranr, y. E. et d. The lournd o/ Pediaric190(4):621-624, 1977. Other support: Brooklyn Lung Association. From the Department of P.dialtia, lewistt Hospital and Medical Center of tooklyn, Brooklyn, N. Y. 1N1't.Ui?N('E Of' A('tfl E PXt"O6URE TO CIQAREITE SMOKI! ON THP. ALVEULAR MACdA?G.AOB SYSTEM Techniques for QuaNitatin6:.eR deposition of bacteria and alveolar macro- phake harvest were used in +,is study of (he response of the alveolar macro- pAaee system eo the inhalation of viable bacteria and cigarette smoke. 71" studies were performed wtde:• bwl eowd'Niona, dter the inhalation of cigarette nnoke, and after eapowre b baclerial aeroaots and cigarette smoke in sequence. Macrophage yields were ineeeased 1.1, 1.2 and 1.5 times hasal levels by es- posure Io cigarette smoke ak.wa for one, two and four hours, respectively. The inhalation of SrapArlororcrs ern.n (or 30 minWes induced a 2.4-fold increase in macrophage numbers. Within iS minuW a/ter bacterial deposition, macro- phase yields dropped ll%, but elevated kvdt were restored at 30 minules and then maintained for the remainder of the four-hour test period. Cigarette smoke introduced immediately after baclerid challenge and maintained lor up•to four hours did not aller tha m.esoph.6e se.ponre provoked by pulmonary deposi- tion of staphylococci. lo additioq, smoke inhalation had no eftect on the « 1- lular characleristics of hnq har.ests or on the viability of alveolar macrophages. Grerwert, 1. 1. TRe'lorrwal o/ Laboraror7.w/ Gbs4+d dlydkJwe t9(6) :1213-1224, 1977. From the Queens Hospi'tal Cenler AtlWatiaa of Lons Island /ewish-Ilillsids Medical Center. ()ueero, N. Y. i AIRWAY RESPONSE TO SHORT-TERM INHALATION OP TOBACCO SMOKE. LACK OF RACIAL DIFFERENCES Scattered studies imply lhal b/ack snwken develop neither the chanees ia pulmonary funetient usually seeu in while smoken not as much chroruc ob- strvctive pulmonary diseae, although their smoking habits are simdar. Since lhia suggests that bl.ck individuals may be "ptWeeted" from the consequences of smoking which lead to deterioration of pulmonary lunction, it is possibla 24 25

that they respond differently to cigarette smoke inhalation. It has already bees dwws that hereditary (acton art estremeiy important in the palhoRenesis of chronic obstructive pulmonary dixax associated with smoking. In spite of the lack of evidence linking the response to short-term inhalation of cigarette smoke to the long-term conscQuences of unokint, this report e.amines the air- way ndponsea to short tenn inhalation of cigarette smoke in healthy black .ub- jecta. Ttwr.ck gas .olume, airway resiNance, maximum espiratory flow rates, and elosin6 volume were measured is 12 headthy blrck volunteers befcre and after smokinA a cigarette. A siptiAcasl re&ctios in airway conductance and midexpiratory flow rate was found ./Nr .ewkieA. Since these results ue simi- lar to those previously obaer.ed in w)ri•e arbjecK the authors concluk that aJrway response to ahort-1mn inhalNios of cigarette smoke Is indeperskM of rsm. StiM uskows• however, is whether the annaieW bronchoconslriction caused by snwking eontribnes Is aq maamer b the development of chronic cbatrue- tl.e Pda.o.ar7 die.se. T..eirs d. Sllvti A. M. asd H.n.ad, P. CAsr 71(2):1)9-141, 1977. Pras OtorBNows Unl.ank7 Scboola of Medicine a.d Destistr7, Washirr6tos, D. G THB EFFECT ON P.XPIRATORY FLOW RATES OF SMOKING THREE CIOARETTES IN RAPID SUCCESSION 1s t5i. Mudy, ses healthy volunteers (ail heavy srnoken) smokei three ciprettea at the rNe of tes puffs/Ave rninutes, wilh Ave misutes for mea+ure- arta, between cigarettes. Maximal and partial espiratory flow rates were noted before srnokinA, after smoki.8 each o/ the three ciprettes, and one hoau after tnakis8 the last cigarette. Frorn the partid spiroAram, forced instanuercar /ow wr resd after 30 peoeest (PFEFSO%) and 75 percent (PFEF7'%) of the origisal forced vital eap.city (FVC), obtained during the initial screening of dw subject. Subsequently. /ve tnaoeuven to determine the forced eapiratory fiow were performed from total lung upaciy (TLC). Conventiona, spiro- metrie data sbo..ed sipiiAcant changes in mean espiratory flows; a response that was rnuimd atter the Ars1 ciAarctte. Changes In the partial e.piratory Aow rtttes, PPEF73% and PFEFS0IG, were almost three times higher tbas the ehaqea is matimal espirNory flow Narted from TLC. These results show that s.n.wcmeM of partial ntpintory Ao.r might be a far mae useful irdicalor ot Irritant e4ecb on airwats than .nd7sis of the maximal espirator7 Aow- volune carre. In tact, the authors suggest here that partial e:piratory flow atrt•ea be used aa a luo6/rrllant acreeninA 1est. H.noeA. r. sad Tavtira ds Silva. A. M. Clltrr'f2(3):61O6f1. 1977. Pro.w the tlrp.rtn.rnes of Mrsrolney and Reorhy.ice and of Medicine. (Jtorde- ywn Usr...ntt Stlm.4% of Medaane .nJ 11cotutry. Washington. 1) ('. THE EFFECT OF PROLACTIN ON THE ",.EC/T11fN CON7 ENT OF FETAL RABBIT LUNO Lung surfactant defkieac! b/6s prirsar7 causative factor in the respiratory distress syndrome of the newbors and in probably due to immaturity of the biochemical pathways rerpuosibk [or th's phospholipid's synthesis. A number of hormones, includiot oohiooNeruida, thyroxin and probably estrokens. in- Auenoe this process. The k-a-s.ewd, however, may act Indirectly through the stimulation of fetal prot.ct a secretion .ad, actudly, fetal prolactin kvels have been found to rise sharply before as iscnxx in pu:monary aurfactant kvcls. TKs study, 1Aerefore, seetn b de/ertnina tl[r effect of prolactia administrat'an on the pfwspholipid kveM is fetd rabbit lunp. After two dars, intramusculu injection of ovine prolaetio (I ta8) Into 2Lday rabbit tetuaa did indeed in- crease the total lung pho.{'LoYp',d ..d IedehM consent by • statistically highly aigni/kant (P<oAol ) amewt oo oorwp.red to the eoMrol group. Dip.lmitoyl- kcithin, the chief swf.es aMiw pwtpsest o/ hra8 watactal, constituted 67% of the IuwA lecithin fraclka h tsn trealed fetuaa an opposed to 44% of the oornparabk fractios in dK oosUrol.. No et.tistieally significant diRerenoes in body weight and ks6th. M>t weiBht,lw8 so body weight ratio, or DNA, pro- leis and water corMest were fo..d betwees the treated and control fetusn. Be- fore the e0ed of prolaetiti .drsisMrNio. on fetal hnu sur(actant levels can be fully evaluated, however, the pApsiologie /etal serwn prolactin kveb must be established. Abo to be asanered It whether prol.ctin bids as specifically to the fetal lung as N does b a r4.taba of other tiouea, and whether it dfects eke- trolyte aeeretios by the dvtolar oe1M. (A direct relationship between potassium •ad sur(actant seeretios kNe trscht.l /lrid hr been shown in fetal lambs.) Neverthelesu, the reaults obtained here suggest the possibility that prolactin is a phYsiologie trigger /ot Mu[aetast suLLuration, in support of indirect evidence .iready compiled. HanrosA. M. sd Naeroih, P. The lorrnd of CBnkd /wsmlraHew l9:1002-1005, 1977. Ot6e..orprtr National Heart, Lsr%.ad Blood Institute. From the Department of Physiology and Biophy.ics, Georgetown Univenity Schools of Medicine and Destistn, WashinAton, D. C. INCREASE IN TRACHEAL GLYCOPROTP.IN SYNTI/ISIS WITH ESTROGEN ADMINISTRATION Ovarioctomised nts, 12S-1S0 B in wei6ht, were used in this Itempt to determine whether estrogen .drwMiMrNion causes any change in glycopoWein synthesis in the rat trachea. Starting two weeks a/ter operation• the rats were given in}'~ iom of 23.0p~ of 17/1-tatr.diol for eight days and were sacrilked on the ninth day. Af1er a)-hr. Irrcubation period with /r'C) 6tucosamine. tracheal epithelial (ractions from treated animaia showed a 20% increase in uptake of radioactiviy into acid-insolubk material. 7be concentrstion of tree minvwpars was not affected by estroges administralioa. In view of previous dala ahowing 27 26

that D-illuoosamine is mostly incorporated into Rlycoprotein by trachea, and of the prexnt data sho.ring increased uptake of 114CI tlucosamine in tracheal epitheliwnn without any debctabk alteration In aminowsar pools, the authors conclude that estrogen can cause an increase in alycoprolein synthesis in air- way epithelium as has been pre:wusly shown in the female genital orgiins. Yeaser. H., lr., Shechter. Y. and H.nwrh. M. rroreed/np of the Society for Eipe.lnsrnt.l eidoty and Medkine 133:113- 117, 1977. OtAer.orrsrtr Aenerica. Lung Association. Prom tha Departmenu of Medicine and Physiolopr and Biophysics. (7eorge- Io... Uni.Krsity School of Medicine, Washington, D. C. OLYCOPROTEIN SP-t:'RETION BY TRACHEAL FXPLAPTi'S CULTURED FROM RATS EXPOSED TO OZONE While ozone is known to be an important atmospheric pollutant, li:tk re- search haa been done so far on Its biochemical eRecb on airway tiswse tnetabo- litrts. In this study o/ the effects of ozone, tracheal explants from rats etposed b 0.8 ppm (1.9 mg/m') of or.one eight hours per day for one to 90 days were kotubded in culture with ghrco.amine labeled with 1rC or'H. Compared with tracheaa /roen eontrol rats that had breathed only ffltered air under otherwise idealkal eorditiom, these explants demonstrated a decreased rate of slyco- protein secretion for exposure Intervals of as long as one week, folbwN by a tebound 1o a. Increased rate o( glycoprotein secretion for at least 12 weeks of continued eapowrre 1o ozone. DNailed study of the behavior of labekd glyco- proteins from the culture medium by chromatography on odumns of HioOd A-ISOm d~rmor1trated that the ratio of the bw to high molecular weight peaks 1.peued wkea there wr an Increased rate of SI)rooproteis secrelioo. 'tbs is IM Arsl teport of a direct biocAanicd effect iedviced by omne on airway me- t.bolist.. Tht .uthors. b.aittB their aswmptkaas on several Indirect lines •af evi- Iesc+n, toilsest that the cbaaBes in gIycoproMe necre/ory rate /n vitro mav have a tuwctknnal (enzymatic) be.M rather than aw teutomic (sttnctwal) one. I.e., be utated by tevenibk chanBes in enayme ooncentr.tiom rather than by eeBu- I.r hnerplasi.. 1/ this hypothai. Is true, it offen a promising new concept to be ea.plored in relation to possible therapy of diasascs Involvin6 bypenet retion of teucve withln large .irw.ys. Lask 1. A., /enninp, M. D., Sehwartsy L W. and Croa. C. E. Anre.kw Re.Iew of Retph+.tary Diseau 116(1) •693-70), 1977. OtAar.r/r..tr National Institutcs of Health. P.nvironmental Prohxtion A6ency, and PnerOrY Reaearch awd Developmrnt Administration. From the ('allfoeni. Priw.N. Research ('enler and the [kpartmenl of Internal Medicine. Univenwy o1 C'drorai,a, Davrs. I CHROMATE INHtBt17ON OF METADDLISM BY RAT TRACHEAL EXPLANTS Using sensitive biochemical lecbniques available in their laboratory, the present authors examined the tracheal e:pla.t model as  method for deter- mining threshhold levels of chromate-ioduced toxicity. For these tesu, rat tracheal eaplanu were Incubated in tisue culture medium containing various eoucenlrations of Na*CrOs. There was a boae-eelaled inhibition of mucus tlyco- protein secretion by the atplanb at all concentrations of Na,CrO, evaluated betwtee O.OI mM .nd 2•16mM. Rou of amount of slyooprolein secreted rer.us log of chrornate concentration suggested tMt there were two types of inhibition oecurring, one of which wat only observed at higher (>O.3 mM) conccotra- tiorn of NsCrO.. Also, et eo.ceNratiom of 0.05 mM and above, Inhibition of precursor (D-I•111-tluoo..mia.) ttWake and coocurrent morphologic damage in the epithelium of the tr.clred slices wen obeervrd. The histopathologic end- inp inchdcd damage to c9i.:ed eells, severe epilhelia) desQu.matron and severe cell nuclear pykrasis. The rett.#.a preaetNed i. Ihs paper show an excellent cor- relation between the oonam(raion of thromate required to elicit moryholoilical- 1y, observ.bk damage s(1 tlre oonomaralions at whicb tlucvaamine uptake by tracheal dioea is siprfica-Al7 iahibiled. They also suggest a hitherto unreoo6- nited mode of actiow of eiror.Mn io., l.e., iehibition of Rlycoprotein secretion at concentrations IhN do got elidt arorpAolotie damage. It seems, therefore, that deteretination of glyooptotweitn tucteiiow by tracheal explants oQen a nessi- tive, quantitative teehniqrnr tor attsd7inR the eQecu of soluble air and water pollutants on airway metr.baYsts. Lrt, /. A. N.l. (Cnus:, C. E.) L.Boraory InvesdNtlesr )7()):27i-279. 1977. Otber nrrpr•tr Fn.io.o..td Prokeetba Agency. From tha California PritaaM Research Cesler, University of Caliloroia, Davis. LACK OF CORRE.I.ATION BL*iWEEN OLUTATHIONE PEROXIDASE ACIIVITIES AND SU9CEPTIBILff'Y TO !is TOXICIIY IN RAT LUNGS The suggestion that 6MadAone (OSH) peroaidase is potentially impor- tant in the hing anlioaidant de(etta: taecAanism stems from two significant types of observations: (1) after rrsposws b various types of o.idanta, cytosoiic frac- uwss detived from lung AomolienNa oodein hiRher kveb o( OSli pero.idasc, perhaps induced by the otiJanl oe products of oxidation processes; (2) dietary selenium defickac7, which deerrtra OSH peroaidaae activity in lung tissue by as much tr 80%. appean to enhance hrad tissue susceptibility to hypero,ia and 1o paraquat, a herbicide whow toxic effects upon the lung may be cained by pro•oaidant mechanisms. le order to further /est the 3hypahesis that lung (lSH peroaidw activity reflects the eapacities of the pulmonary antioxidant dclense system. 0, loaicity was studkd in rw under eondilions whereby the dekteriow effects of exposure to 90% Os at atmospheric pressure for three to four days could be modi8ed by administration of anli-infiammatory qents. the dala .ug- rt( that in this eaperlmeMal tnode/ of U, to.icity there is sa consistent rda- tionship between OSH peroaidase activity and protection; nor is there any ap- S 2S 29

pareat co.relation betwcen such enzyme activity and the susceptibility of lung tirue to O.-induced damage. 71+ese rrsults, ho..ever, do show that prior aad/or ooncomitant admini.tratioa of anti-infi.mmatory compounds may rtodify hrel ousocptibtliq to o.idant Injury. It is concluded tha1, at least in this one arodd of oxidaet-induud lung danuge, susceptibility to oxidant injury does not appear related to the OSH perosidase activity in lung homokeoates. Cnw, C. E. and Last. I. A. Rtsr/eA Corwwrnk.rforv M Chrwdcd r.Aofop and lA.rm.cobn 17()): 417-416. 1977. t0th., ar'r.rfr U. S. Public Health Senios. Ftaw the Dep.rtmeet of Istenul Medicine, School of Medicine and ('ali[ornla Pri.uM Research CeNcr, University ol California. Davi.. PULMONARY L'NDOTHP-L1AL CELLS 7hb esltyr.ive re.ie.e surnnar(m the aoerespiralory fundions of the put- taa..ry endwhclial eelb. While they pos.rw many of the same proper,:es n the oonWwrors endothelium of other vascular bed., the eelb are unique in their strsteilic pe.itiow within the circulatory system. They are at the last point where 1be composition of arterial blood can be nadified, which is critical for both blood psa and nonvolatile solutes such as hormones. The pulmonary endo- dielial cells may aiso be unioue for what they do not do. Thu., perhaps mw. than asy other or6an. the lunp murt allow the unhindered passage of hormones rerJuired by peripheral tiaues. In fact, they do not degrade an6iotemins 11 and 111, asd they probably do not cku insulin to any si6nificant extent o` eliminate olytoci., .uopreasin. epinephrine, histamine, or substance P. Although MiY relaN.ely little is knowt about the ability of pulmonary endothelial cells to syutbesiaa brn+aws or so modify preformed oew or prolw.ntooes, the peculiar ph7sblopq of the lungs suaests that there may be unusual means of influencing ehe net raults of the metabolic activides of these cells. Pulmonary blood flow e.d /bw distribution are eotrepka functions of many (actms, such as posture, eaercise, airway patency, inhalantr. and others, and it would not be surprisin6 so tlnA dut 1br hormond composition of uwi.l blood is closely related so the o.enM perfoenueee of (he luup thennelva. The role of redwhelia/ cells in prooesaln6 chylankwro and iw clearing free fatt7 acids. prvsla6landins and re- lased nubstaeoea, sr well as in synthesizing prostagludirr, 1n oWlieed. Tlreir ef- ted on oo.pdatioa and /Ibrlnol7sis through the conversion of plasmino6ea so pjrmie aed the activity of thrornlwplastin and other (scion .re also discussed. r are Ihe selective procea+i.it of biogenic aeimes, and d+e metabolism of the .udeotides. kieina and angiourrins. Ryan, I. W. a.d Ryw, U. S. reAen.Now PrerreMngs 36(t)) :268)-2691, 1977. Otl6or s.'P.rtr U. S. Public Health Servia, the Hartford Foundation, and 1M American He.rt Aroclatios. Prwn tbe Dep.rtmenl of Medkine. University of Miami School of Medicine. Miami, Fla ALVEOLAR CIEARANCE AND'iliE ROLE OP THE PULMONARY LYMPHATICS An attempt is made le tyis re.kw paper b develop a synoptic schert» of the various alveolar ckarweob mecbr.isma, with special emphasis on the put- monary lymphatic system. Aarortg t`a 295 literature references cited here, ao elaborate and synthelitarg ekxMoa microscopy studies were found concerning the multiple cellular and moephologie (atlws tbat regulate alveolar clearance. Although a eomprefien.ivr .i'ew of ete.rtaea, wroehanisnta mi6ht be drawn up based on the compilation of :ortsutly e>tisliq studies and hppotbc.es, these In- vestiptors (using the rewdb of their dNailed etperiarental electron microscopy - studies investiptin6 the various a.peeta of alveolar clearance wbiM uain6 carboo and fertitia aa tracen, and a e.i" NuQy of the literature) ouUir.e Ihe follow- ing synoptic scheree of alwaLr tiearaaea involving: (1) the tracheobronchid trea with the mucociliary eeealMor awd with e.doeylods and difiestioe by non- ciliated broechiot.. spitheNal x#.: (2) eadoeyto.is and di6eniow by the a1- veolar macrophaM which kaw 6Se alwolr lumen via the airways; (3) enda eylosi. and digestion by the ceutKiphMie grawulocTtes, which leave the alveolar Iwnew via lhe akwaps: (4) ;+halloeylow by the large alveolar (type 11) epi- thelia( cells: (5) eedocyloda and .ilher digestioa or transcellular transport to the iMentiliwn by smdl alreolar epilbelid oeMr (6) the pulmonary Mood capillaries and micropinocylo.is and either digestion or cytopempsis by the blood capillary endotheN.t eupa: (7) the pulmonary lymphatics with the open intercellular endotheB.l ju.eoiona (rwais road) and endocytosis and digestion (or eytopempsis7) by the lyrwphatic eadoMeli.l oelb at Ihe luminal or abiumi- nal surface, and (S) etadoryLosi and digestion by the interstitial macropha6es, which leave the lungs via khe lymphatics. Fin.My, the relative Importance of Ihese various clearance ways aid clearance snechanams is undoubtedly depen- dent in each particular Insta.os oo t!a phYsioochetnical and biologic character- btio of the contaminating particles. The aolubilit7 of the inhakd particlrs M apparently of paramount irnportattoe In thia respect because the wk played by particle sdabilizatios ponAly prs.idn an aeawer to the intriguing problem of 1M variability of the de.r..a respoaM on studying diRerent Inhaled or in- stilled materials. I Lrwtryn., !. A(. and Dae+t, l. H. Anreric.n Rer4w o/ Respiratory D4ter 1 t S(1) :62S-6e1, 1977. Odher nrprorfr NationadFoub.oor Welensth.ppelijk Onderwck (9el6ium). Fnom the Laboratory of Padrolop and Hidology, Katholieke Universiteit te Leuvee School of Mediclne. Leu.ea, delsium. NEUROEPI'il1EL1AL BODIES: IMPLICATIONS FOR LUNO FUNCtION Neurocpilhelial bodies, the autlar's tentative name for certain particular cellular corpu.ck., have been well idrMUkd (n an Integrated mkroseopical. hi.toehemical, ullrutructura/, and microspeetrographic Investigation. 7hese neuroepithelial bodies (NE_0.), which occur widely in the mammalian lung, are m 30

intr.em.coaaty located. innenated and coatain denx-cored cellular co4puscks. Scrial aections rc.eal the ultrWructure of the innervalion of these corpuscks to be very compkx, since eumeroua unmyclinated nerve fibers are prdrnt and various ty}+es of moryholo6ically aRerent-like and efferetN-like nerve endings can be observed. The cytoplasm of the NEBs reacb positively to Sok:s lead benuloaplie stain for the identilication of endocrine celb secreting pol•tpeptide hormones or amines, and the uncorrected as well as the corrected valuts of the Ruorestxnce emitted by these eslls wtaich the spectral characteristics of pure auobnie. When subjedcd to sarioar dedees of hypoaia, the Golgi ,:otnpiex 1a the NESa of neonatal rabbib beoorwes temarkaby active. producieg many ptognrwkr. In a Ouick wrmm.tiow, the anthor qstes that NESs prvbaMy pos- sw .erioua aecretory functionr, eodt.ialing not only vasomotion but .dio other brwrnhial sad bronchiolar hwrctitnn, twcA as muco..l secrNion, smooth muscle /oea a.d (nte6ration of the acti.itin of the ou/monary unillobuks. L..wer7av. 1. M. Ie: Moore, R. D. (td.): Lrns Mrwalow .nl r6e herewrlow of Hyaflne MenrM.nr Dtruasr, Report of Ihe Se.aMiet6 Raaa t'.,onference on Pediatric Re- searek Cohrnbru. Ohio: Rou laboratorie., 1976. pp. 16-21. OA.r s.pp.rtr NubnadFoods.oor WtletuchappelijkOnder:rxk Ptar tbe Department of Patholop. Katholieke Uni.ersheie it i.euren„ l.euvee, •d6its.. IN712AT MONARY NEUROPPfTtIPL1AL BODIES IN NEWBORN RABBITS. OF HYPOXIA, HYPF.ROXIA, HYPERCAPNIA, NICOTINE. RESERPINI; L.DOPA AND 3-HTT Light tnkrosoop, , mitrospectrographyc morphomctry, and electron microo- acwpr rsed to etamine .eowafal neurvepithelisl bodies (NEM) under various eapetln+cnul conditions abow thst: (1) while the NEM appear Mructur.ty .orrnd, acune h7Poals deueaan amine /hrorescenx iwlemiryr and increases secre- bry e=ocytosis of den.e oore .esicks (DCVs): (2) hypereapnia has /6e aame eLeet+k but the core of DCVs (rapneeliser (3) h10eroaia does not appear to dlect eithar /luorescewae or esoeqtaais signi/kandy; (4) adndnYtratton of bio- lienio ea+inea such as 3-HlT and LDOPA produces high Intensity fhrorcscence, indicaUng their uptake by the corpuscular «Ib; (3) reserpiwe c.use" amine de- pktba, with a decrease of NES Mroresoenoe end an ritrastructural pillor of the [X.'Vs; (6) ietratrssheaMy administered niootine ia .ceotnpanied by de- eraaaed 1luore.cenoe and distinct eaocytosif of fra. meMed DCVs. The NP-M' reacdow 1o flypoaia and hypercapnia suggests that, in addition to being centrd a.d per{Oheral chenwreroeplors. they snsy a6o be inlrapulmonary oncs, inducing a rellet reaction through the release of DCVs at sensitive corpuscular nerre ewdinp and via the central ner.ous system. ln addHlon. the NESs may have a local intrapdmonary e4reet by directly modu4ting the hrpo.ie and hplxr- e.pnk pulmonary v..ooartrktioe. By ahuntirg blood from poorly ventilated arer to better aerated ond, this mechanism may be Important in the alreralioe of the lung veotilatN.rt/perfusioo ratio. Larwerynr. 1. M. 3r ./. Celf and Tirrrr ReiearrA 1a2(4):423-440, 1977. Other support: Nationaai Foods voor WekaschappeGjk Onderzoek (Belgium). From the Laboratory of Hislopatholopr, Kathotiek Uoiversilcit te I.euveo School of Medicine. Leuven, 3elgium. EXPERIMENTAI. EMPHYSE11ia NDUCED WITH PURIFIED HUMAN NEUTROPHIL ELASTASB: TISSUE LOCwLIZATION OF THE INSTILLED PRO7ZASB Human neulrophilie PoKwrorpMerdear kukoeyles (PMN) contain rela- tively large .mounts of an e',aatue whics he. recently been implicnted as a mediator of lung damap k oerlaie Reneticsllr-wrceptib/e individuals. 'tbs present report describes the rawdM of experiments in which purified humas PMN elastase wr instilled iulu dog haap. Rindinp show that this enrqme, acting alone, was capable of rnpidly Mducin6 ernphrsenulous lesions in isolated lungs ex slrr atd in intaet lua6s /n .Ire. 1n edditiow, /ror.en sections of treaKd and control lunp ..ere eaamMred for the preaewee of PMN elastase by the in- direct immunoperoaidase melbd trieR a mo.ospeei/lc rabbit antiaerum against PMN elrtase as the PrimarP stain. i.i6M wacro.oopr revealed dast.se bound to connective tiswrc le the trealed Mtnp, is ebae Protimity to aldeh7de-fuchsin- counteralaieed elsstin. A.iedMr e:ptxiateet winR dog bnp /n vi.w nQaie demoa+trated elastae in sroeiatbo vidt aoenecti.e tiaue ekments in the ksion area. Pan of the Instilled /rotsne could be dewronslrated within alveolar macro- phages. In addition, eletteota /ekeoaoopr aoshbined with inxnunoperoaidass staining revealed a dired aMacMrc.t of Me insliMed enzyme 1o elastin wilhie alveolar sepa. These reseU. show t,hM hunmae PMN elastase penetrated the dog alveolar epitheYal layer after ekwey MWiM.liow and that the enzyme attached to Interslitial elwin inducinR ItiMolo6k changes eanparabk to those seen In human emphysema. The hnpMcatien" of tMye Andinp for the pathoRenesis of pulmonary emphysema In ew, ...aits IM raulla ol/uture Mudio. lanofl. A.. S1osn, S., Welnl.rM Q., Daadsno, V., Sandhaus, R. A.. Elias, l. and Kimhel, P. Anwrkan Rerlrw o! Rt#p/n.rory Dhwar 115:461-175. 1977. OtAer.rpportr U. S. PubMe Hedth Servbe, Oeneral Research Support Funds, and intensal IuodiaR frora eM Franklin Institute Research Laborrariea. From the DcpsrtmeM of Patholo6f 3/aM Uni.enUy of New York .t Stony Nrook, Stonr srook. N. Y.; tha Pulmonary Dbea+e Section and Resiarch 1.- boratories, Albert Einmtein Medical Ceeter, Philadelphia; Iha Franklin Institute Research L.boratoriei, Philadelphia. I 32 33

111. Heart and Circul.tion TIIE EFFECT OF INDOMETHACIN, 6•IiYDROXYDOPAMINP., SARALASIN, AND HEMORRHAUE ON RENAL HEMODYNAMICS 'iAL paper describes the ellects of prolonged hemorrhagic hypotensicn and reiefu.ion of blood upon the renal circulation of anesthetized cats. Abo, three different drup, Mdomethacia, saralaain, an4 !f-bydroaydopunine (6-011 DA), wen Ri.es in order to is.estipM tbeir apetaal pharmacological action,. Foe ebL Nudy, plastic micrwpheres wera traed b atwwr D1ood Ibw pertuai;tT Ihe entk* kidney r well aa the outer oortat, isser eortea aad nteduila of tlhe kid- .ey. Cardiac o.tput was deternised with a Doppler llo.w probe, and tot A and regional flows were calculated. Resuha stwwed that following hem«.hage, aortk pwsse (AP), cardiac owpW (CO). total renal flow (TRF), and outer eorti- eal Sow declined significantly while the i.ner cortical and medultary fk w eit- yrered as a pementqe of TRP inctered significantly. Redittributios of blood Aow (rvrn outer oorlex to irer cortec asd medulla occurred during hemo Thaee asd after adminitratios of ssniarie and 6-OH-DA, while bdoenetbacie ( id eot aher istrne.al Aovw distrieMio.. Total reeal eow iocreased afler minfusion of blood and rrala,in, but decreased dter indomethacir it did no1 chanE~ after oocw ti-OH-DA. Thesa resuits show that ehanTes is toW atd intrarenal Qo.w Isdepe.dcnty asd are probabfp due to d/lereet mecbanisms. Fl.cber. R., Reda, S., Sar.na, J. S. M., and ding. R. l. The lowrwd of Cpska/ rA.r+wsc+oion 17( i):3-12, 1977. Other awrltortr Hoover Foundation. Norris Foundation and Wright Founda- tio.. From the Hurdn6toa Institute of Applied Medical Research and Huntington Memorial Hospital. P.sadena. Cal., the California Institute of Technoiory, Pw- deoa„ sod tha University of Southern Cddornia, Los Angeles. REFLEX SUPPRESSION OP RENIN RELEASE BY VENTRICULAR RECEPTORS WITH VAGAL AFFERENTS Se.eni teports iedkaN that cudiopsimonary reoeptors participate in the retkx coeud of sttul .aacvlar tai.taace sad of eenis rekase ntediated through clasRea ir teead t+ytnp.thetie nerve activity. intracoronarp in}ection of vera- trwn aRaloidt stimubtes .estrku(ar reoeptors through vagal aRerenu4, resultinR Is brsdreardia and hypoletnio.. Tt>H study eaamined the role of veratrum- se..itire ventricular reocpbrs In the control of renis secretioa in eight cMora- lose-aaesthethed dogs. Eaperimentaly-productd hemorrhage (10 ml/kg) caused a siptiAcaM Mcresa. M the rek..e of reais. but arterial presaure and R..1 blood Bow did not chaap siptiAcanty. The in}edios of cryptensmine (2 pi/kti), a veratrrm alkatoid, inb tbe main left coronary artery virtuallT abolished the augmented release of reaie, which teN Delow control kvels withim fow minuw twm the inieetiow. Blood pressure was significantly lower a/ter tha iajection, drvpping trorn 130 mmltg b 111 mnJig, but ehanges Is renal blood flow were not significant. Vagolomy abolished lhis refk suppression of rrais rekase. Thae data indicate that activation of ventricular receptors with vagal aRereots rdktty inhibits tite oecretba of oct*. The out:wr suggests that io addition to atrial and vestriwlc,r reoeplon, vagally innerroted pulmonary receptors may abo contribute to tBe t~ooic inSiiSitioo of the .aaomotor center. Tlanrs, M. D. An.er(can /osrn.i of PArtiolop -_33(2):Hitl-K:fi4, 1977. Other w'prtr National Isiti{ yaem of HeaM(a. Frore the Depanmest of Plyeb `.op sad Siopl7sks„ Mayo Clioic and Mayo Fouedation, Rochester, Mir. s1OCHEMICAL AND CONTRnC11LE PROPERTIES OF HA1RT MUSCLE AFTER PR(wON02 J ALCOHOL ADMINISTRATION Tt it+ report eorrelaees clay ;w 1n cardiac metabolism asd myocardial ooo- tractii9t7 in dop maintained o.t 'yooid for 29 moaM.. QyceriaNed beart muscle flbers were u.ed so stu&- ruryotardld contractility /n vitro with an ap- p.rHw designed b reootd botoctrie asd i.oloaie aoetraetiorn. Muimal tension developed (r.), nwinwtn r.1e of Ie..iom de.ebped (dp/dt nua). dme to ipeak temioa (r,) and tbe toroa .eloeity reldiossbip (V..) were the param- eten measured. These .alsa wc;tr t.cb.yed after prolonged alcohol admin's- tration etcepl tor the V... wbis3 waa dtaifkaMlY bwer than in the controls. Biochemical studies revealed triR4leaM depesic, of the mNochondrial respira- tion, diminished wcwplarndc relk+itrr caiciww uptake aad bindin6, lower erdoRenow calcium ooeknt, arrl decrered activity of intranitochondrid isoci- trak dehydrogeom (NAD-ICCH) is tlw heart muscle of akohol-tres/ed asi- mah. Howe.er, at the erd of the iat ptriod. e.ea during anRiotensis infusion, these dogs did not demonstrate t+ny airiAcaMy diflereet hemodynamic changes in dro than were noted in tbe oottlral sn{ttrit. These results suggest that, with- out any apparent hemodys.mk allerationa M N.o. Ihe corAr ttile appar_tus of the heart muscle eapoaed to akohoi w ae.er2 te maaimai isometric tension while being deficient ia the rw of erso.er of ts,eehanical work. Either the /n Hro measuremeots ue .ot wdkicaty sesrNiw to identity a small reduction in coptractilNy, or the intact mYocardiww it esdowed with certain compensatory mechanems that can overooms subtle eAasRem delectalrie only Jn ritro. The knesed isocitrate dehydrqesaa. activity may te0ect NADH inhibition, while the dimisi.Aed calcium upake a.d bi.di.R u wett as endoReeous content may IedicNe a defect in its transport a.d isltaoeMular ratorage. However, whether the contractile changes observed fn dtro resuR from the direct actios of alcohol on the interaction of contractile poWei.s or neAeet etbanoi-induced biochemiul chan&s remains to be deteneised. Sanna, 1. S. M., Ikeda, S., FLebar, R., Manryama. Y., Weiuhaar, R. and s,nt. R. l. JoM.n.l o/ Molerrf.r an1 Ceildi Cqrlolop t:931-972, 1976. Other sr' rtr National lestiWtes of Heallh, The Iloover Foundat'an, and the Norris oundatbn. From Huntington Menarid Hospital asd the H+ntinttos Institute of Applied Medical Research, Pas.dena, the Usiversity of Southcrn C'alifornia, Lo. As- jde.. aed the California Institute of Technology. Pa.adena, Cal. 34 35

REVERS181LITY OF MITOCHONDRIAL AND CONTRACTILE CHANGES IN T11E MYOCARDIUM AFTER CESSATION OF PROLONGED ETHANOL INTAKE Although many studies eaist tyins tont-term akoho/ consamplion to spe- cilk clinical and biochemical changes in the myocardium, relativtly little in- formation is avaitabk about the eRects of eessation upon these same parameters. The eurrenl clinical impression is that abstinence from alcohol reverses the ef- fects of prolonged coraumpiun, but hidthemieal data to support tf ese clinical findinp have been missing. For tbis study, therefore, mitochondrial respiration and /w rhro contractility of 617cerinated heart muscle /iben were chosen aa biochemical indeaes for rero.ery because several reports have demonstrated significant changes iu thae variables after chronic alcohol intakt. Measure- tnenls were made in rab coeuuming 25% ethanol daily for four, iix or eight weeks. Analysis revealed a paduN reduction in the ma.imd rate a/ isometrk teasion deveiopment (dP/dt,,,,), the ma.imal developed tension (i',) and the velocity of shortening N uro load (V_.). The time to peak tension (t.) padu- ally increased and mitotlsardrial respiration steadily decreased with lon=er pe- siods of ethanol injestion. These effects occurred earlier and to a 6nater degree with 6/utanule as aubstr.k than with suecin.le, which aNroduces electrons through ait. 11. l.ater, after eight weeks of ethanol conwanption, sotne IeN rab were given a nonalcoholic diet to assesa the etTects of abstinence o«t Ihese two variables. Four weeks after removal of ethanol from the diet, the uoMraclilily of glycerinated hcart muscle flhen was still significantly diminished. However, after eight weeks, even though dP/dt_„ was still reduced by M11. V,,,,, P, and /. had returned eisentialty to eontrol levels Miloehondrial respnation, also, had nearly returned to control values after eiRht weeks of abstinenee. TTse re- sults In this report demoantrate that the decline in both mitochondrial respira- tiow and /w .lao contractility can be arrested after cessation of etM.al inuke. Z1we results at the cellular level Iend to support the clinical findings that at certain Nages the eRects of chronic alcoholism on the heart can be arrested and reversed by abstinence. Weishur, R., Sarma, 1. S. M., Maruyama, Y., Fischer, R.. Bertu6iia, S., and d/wc, R. /. The Anrerlr.w lorrwl o/C.rJblotr 10:336-162, 1977. OtAW wpp+rtr U. S. Public Health Service, Hoover Foundation and Norcia Farnd.tion. Fe+oet the Huntington hrtitute of Applied Medical Research and Huntingtoe Memorial Hospital. Pasadena. Cal., the California Institute of Technolo6y, Pasa- dt:e., and the University of Southern Cdrfornia, Los An6eks. REGIONAL SLOOD FLOW. CONTRACTII.ITY AND METABOLISM IN EARLY MYOCARDIAL INFARCTION This report deals with the early effects of regional myocardial infarctinn on coronary Mir.d fl..w, the In ra.o c.rN..(tdt state. foarcrdysn and mNo- ttw.ndr,.l rt.p.r.i.•.. (.tvrn.wnlallr, swhemea was mdbated by ligating the ktr ma.n .uwer.w .k..erwlonif ,.N4.narV .ller?. and the nselahobc eflects Of ot- clusion were studied in both iatlnttted and waJnfarctcd areas of the dog he.rt. Measurements were made at I ood 3 hrs. alter onset of ischemia. Regional coronary bkood flow waa wasured ks iofaretcd, swninfarped and border/iae re6icxis using radioactive rniceoapAtres. Blood flow through the iahemic area was reduced by an average of 69% after I hr. of ischemia, and by 75% after 3 hn. lAe subendocardium of twlt botderliue region also revealed a si6nifkantly reduced blood flow afler 3 hrs. Miloehoedria isolated from the ischemic region of the heart eahibiled a aubaltrMial decnuse in the rate of respiration, and mirwr reductions in the eou71ir12 betweei oii3.ilive ptasphorYlatioa and electron Iransport, as well n in the :urtoied of ADP phosphor7lated per oay6en reduced. Levels of hesose nwnophcaphNea were elevated I and 3 hrs. afta ischemia was Initiated. At the saaw p3rne, the oonott.tration of frvctose-1,6diphtnphale declined markedly, rrAecthr{t (nh;oilia, of (lyeolyse at the phosphofructokinast level. ('oncentrations of ths - de.odw. yhosphate nwiclies, as well as crHlina pho+phate, were reduced, ohRk lkvels of treo faty acida were elevated i. ischemie tissue. The /w .ftro (iowtne(iiy of 6/ycetinaled ischemk muscle Bben was also depressed. SipifiurN tM.ges wers found in maaimal tension develop- ment, mauim.l rate of leas'aa de.elop.eM. time to peak tension, and shorten- in6 velocity at zero k4ad. IM ost of the elun6es brought on by regional ischemia occurred within the Rts1 hrar after i>lptiosi. and remained essentially constant thereafter. I Weishaar, R.. Sar.oa,1. 3. V., Marvy.rna, Y.. F'acher, R., and dlnt,A. J. CarJiolot7 62:2-20, 1977. Otlirr.apperfr U. 3. PuWk Health Service. Hoover Foundation and Norris Fundat+on. From the Huntington InstkWe of Applied Medical Research and Iluntinpon Memorial Hospital. Pasadena, GL, and 1he University of Southern Ca/ifornia School of Medicine, Le. Anjelea. REGIONAL MYOCARDIAL BLOOD FLOW DURING NICOTINE INFUSION: EFFECTS OF BETA ADRENEROIC BLOCKADE AND ACUTE CORONARY ARTERY OCCLUSION The influence of bere adrewerfk reoeptors apon the cardiovascular re- sponse to nicotine was etamined by delerminin6 the response to nicotine before and after Arrs adrener6ie blockade with propnnolol. For this sludy, 20 anesthe- ti:ed, open-chest dogs with norsnal coronary circulation (NCC) and 20 with acute occlusion of the left ankrior descending coronary artery (I.AIX)) were evaluated. Regional blood /low wa. estimated by administration of 7•10r diameter radioactive mierosplseres ktMO 1hs left atrium. Nicotine infusion re- stdted in elevation of the aysteswk nrterW and left atrial pre..nres in all dnRs, but left Nrial pressure increaKd to • much greater eatent In animals with I.ADO. TUe coronary arteriovenow di//erence in pOs decreased with nicMine infusion. Coronary vasodilation oacurred (n normal myoa.rdium bu1, in ischrmic mroeardium, blood flow /ncreased only proportionallr to anrtic pressure. Nico- line caused ventricular arrhfthmin In dop with I.AU) but not in dop with NCC. After treatment with propranolol, left atrial blood pressure rose, whereas 37 16