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( SIMON H. WENDER. PH D.. Re>rrch lru/n.or of Atochemiitry. UniversiNy of Oqlsbaawa, Norrear< DUANE O. WENIEL, PH D.. rro/ruor .wd Ch.um.w of rhrmescolop M/ Ta.icofotl, Tbe University of Kasis.. School of Pfermacy, L.rrence. FREDERICK F. WHISKIN, M D_ Di- rrdo,. Dtririow of Health .wI hrso.- .Gty Eqrdterirm. The Age Ce.w af Nc. England. /wc, 11oe1o.. ROOER 1. WILLIAMS. M D. rroless.r of Chtmur.yDtrfctOr. Clqtoww ow- /aiow /tochemir.l luu&wr. T1e UWsi- vcrsitf of Tessk Austin. i DANIEL H. WISEMAN. M D., AuiN- .wt l.o/eiwr of reli.nk.. Uwivetsity o( Souwiserw C.li(orsia; ChNbew i D!- ririow. Los Angeles Counly Oenerd HosplaL Los Angeles. 1. EDWIN WOOD. M D., lnnructo. Iw Mrlic4.r. lostoa Uaiversir~,5cbol of Medicine. Soaon. SUMNER WOOD. la. M D_ Aulu.nt ho/es.or of ruAofoir. TM IoMs Hootwu Urversiry School of Medi- ei.e, BaMir.ore. JOHN P. WYATT, M.D_ rro%aor of I«holoSr. Louis Uwivcrwr Sclool ot Medai:r. St. Lor.ie. INDEX OF PRINCIPAL INVESTIGATORS ~ Avisdo. D. 1N., 33 eeQ, s. and Roac, C. L. 62.63 Benedict. W. P., 14 Bial, R. 1., 35, 36. 37. 3/ Homburger. F., 15 Lauweryn., ). M., 27. 21, 29 Lerner. R. A.. 16.61 Looeli, C. O., 30, 32 Camero0. S. P.. 4?. 46 Caslro, A.. $3, 56 Chabn,1., 24 Cocbraoe,C. U.,11, 40.41.42.57.38o39 Lynch. H. T.. 63 Meier, H., 19, 22 NeuraW, Q. B.. 20 Rasmureo. R. E.. 20 Co6c., A. B., 24, 23 Rose. C. L. 63 Cross, C. e., 30 Dowsey, H. F., 39 Friedrnaq O. D., 64, 63 FudesberL ll. H., 39.60 Pun1, A.. 23, 24 Rubie, R. P., 48,49 Ryan. U. S.. 50 Sloane. N. i1., 21 Siatl., T. A.. 50. S/, 32 Travis.l., 33. 34 Ooldstci., L. 41 Ouaraerl,l. 1., 31 HarooaA, P., 26, 42, 43 Veseq, F. S., 57 Vidif, S., 61 Wentel, D. O., 43, 44. 53. 54 Helawra, N. W., 47 WAitraire, C. 1-, 22 82 /3

i n.turally occurring proicinase inhibiton, and specifkity for synthetic substrates. 7 he nm.epr difference between the two proteaxs, other Ihan the lack of elaslo- lytic acuvrly by human protease E. seems to be in their ionic characters. Por- cone clastase is a cationic enzyme while human proteaae E appears to be anionic in nature. The drsvmdarities concerning elaslolytic activity and ionic character appear to be directly telated. These studies also show that althouth human protease E lacks the ability to digest the structural protein clastis, its biological sitnifkance as a digestive enzyme is scarcely allcred. Mallory. P. A. and Travlr~, l. SiorAemirtry 11(1):722-770, 1975. Other arrporfr National Inultuleaof Health. From the Department of Biochewristrp. U•iversity of Georgia. Athens. INHIBITION SPECTRA OF THC HUMAN PANCREATIC ENDOPEPTIDASES The purpose of this study was to establish accurate and concise data con- cerning the effect of seve• naturally occurri•g protcinase inhibitors on the human pancreatic cedopcp,dases, catiosic trypain, anionic trypsin, chyrndryp- sin 1, chymotryp.in 11, and protease E(an elast•se-like protease). lhe inhibi- Ion listcd in order of their decreasing effectiveness were a-l-proteinase inhibi- tor (•-1-antitryp.in). Iwna bean tryp.i• inhrbitor, soybean trypain inhibitor. Bowman-Birk (soybean) inhibitor, Kunits pancreatic trypain inhibitor, porcio• Kazal inhibitor, and chicken ovomucoid. The relative orders of resistance to these inhibitors indicate that human protease E dernonstrues the least swcepli- bility while anionic trypsin is most susceptible. The complete order fot the human pancreatic proteases with respect 1o reaistaoce to .aturally occur- rin6 wthiWors is human proteasc E> chyrnwrypais 11 >chynatrypsin 1 >cationic trypsin >atwonic trypsin. TD• contribution of each of these pro- lcolytic enzymes to the total proteolYtic activity of crude pancreatic eatracts was also investigated using specific active-site direcled rea6ents. The general arend borne out in these data shows that the human pancreatic proteases lend to be kss sensitive to naturally occurring i•hibiton than their homologous enzyme couMtrparts of the lower specin Thua, according to the atthors, any human nuttNional significance previously atlached to these inhibdors must be reevaluated with respect to their specific Inhibition of human pancreatic pro- teasea. Maliory, P. A. and Tr.vis, l. The Am.ric.n /ournel o/ CNnka/ Nrrririon 28a2l-s )0, 1975. Other support: National InNitutes of Health. From the laeparuncnl of Biochemistry. University of Ueorgi., Atb!os I INTRATRACHEAL INSTILLATION OF ASBESTOS IN MICE Here the authors report on a simpk technique developed for iaMilli•g aa, beatos frhers directly into mouse lunp. Using inlratracheal inqillatioo, the ie- vestiprura placed measured amounts of asbeslos dust into the lunp of 2- momh old NIHSwisa and C37e1/6 mice. The asbestos 6bers could be detected by negative phase contrast microscopy raaminalion of the Nained alidea. This study showed that although the iatratr•cheal method is not identicai to iah.la- tion, it is an effective method for placing • quaatitaliv amount of aabestos dust directly into mouse hmp. 1/ does appear that the asbestos fibers remain in the lunp aod act as a pulmonary irrilanl. The health of the tested animals deteriorated as a result of the treatment with asbesto.. Eaperimenta are •ow underway in the investigators' laboratories to determine the clearance rate of the asbestos and th• long-term eQecta of the asbeatoa treatments. Wilooa, K., Marar.a., W. aod Funt, A. (Uwirerriry o/ Sae Fr.nclrco). Proceedings of rAe Western rAarw..cdoPy Soc4ry 17:217-2J0, 1971. From the Inatitute of Chemical Siolopr, University of San Fraociaco, Sa. Francisco. I I I. Ne.rl .wd CJreaT.tion CARDIOOENIC SIIOCIC - ITS MECHANISM AND TRL'AT1rtENT CardioBc.k shock ia a 1•ttn used to de.is.ate the ocarr»ao, of th• si•ck syodromo by reuon of pimary cardiac dyafu•ctio.. Here, r in b.wot.b6ic abock, tbere ia a dimi•uliot in ooroaary /bw •sd a reductioe 1n myocardW o:y6ee usa6e, as well as myocardial ischemia and aaoaia, which renrt 1n tha central and peripheral changes which are defined aa `dwck.' T1a Litid bio- chemical changes ia Ma heart muscle is eardiogenie shock are a projecl{os of thosa encouetered I• myocardial infaretioa Various studies show that bio~ ehereical changes in eardlogenic .hock and myocardial idaretioa aQec1 certain enzyme srstema as well as mitocbondri•1 functioa and eadtatioa~oar.ctba coupling of the myocardium. Thia was dernonNrated by a diminution In mito- chondrial respiratory function aaid by a decreaso in cakium uptake aod binding in freshly infarHed areas. lhe hemodyo.mic chan=ea in cardioscoic d.ock lie primarily In diminished compliance and reduced e/'eclion fraction. Cardiac out- put and coronary ilow are reduced. TredmeN of cardioloenic slw.ck has ber• disappointing when purely medical mcana ue empbyed. None of the alpha- or beta-adreoeryic drugs has beea able to appreciably decrease the hrgla mor- 35 ~ 34

THE ROLE OF THE HOST IN THE DEVELOPMENT OF IN YIVO MODL'IS FOR CARCINOGENESIS SIUDII:S This paper reviews the factors which the invesliptors feel play a role in the selection of the best possible animal model systems for respratory carcino- genesis. Their discussion of the inbred mouse system used in their studies, in spite of various anatomic disadvantages, presents several aspects of isost control over susceptibility. The topics dealt with are: (1) susclptibility to chemical carcinogens; (2) chemical carcinogen reetabolism; (3) viral etiology of cancer; (4) tumor immunology; (S) other 9esetk controls of neoplastic developmenl; aod (6) cells at risk to earcinogerw and DNA repair. The development of cancer depcnds upon the integrated response of the host to the carcinogen and to the initial transformation event. Genetic factors determine the host's po- tential to respond to chemical and vitd earcinogens, whde endogenous and esogenous environmental factors influence the realization of the genetic poten- tial. In chemical carcinogenesis, for etampk, it has been shown that aryl hydrocarboo hydrosylase (AlIH) i.dueibilny is under genetic control, but tumors will occur, a1beM to a kesser degree and after a longer delay, when large do.es of polycyclic aromatic hydrocarbons (pA11) are admmistered to nonisducibie mice. Induction of AHH by noncarcitotenic materials may also influenee the effects of PAH carciroitens. In viral earcirwtienesis, evidence porsu to genetic transmiasaw o/ the RNA oneo6enie vintscs with eapression of the viral itenorne under host control. Once the initial cells have been trans- formed by chemical or vird inductioo, the devefopment of cancer is dependent on the host response. This is under nusnerow influences with immunosurveil- lance probably the flnt line of defeare against these transrormed cells. Genetic control of immunocompetence is evidenced by the variety of responses to va- rious antigeoic stimuli in genotyprcally different strains of mice. Immunosup• preasive effects of carcrno4en., drup, infections, and other factors appear to make possible the initial act of establishing clones of transformed cells by overriding the immunocompetence of the hosl. Other variables related to die1, aging, suesa, and more, affect the host control over the carcinogenic event and may be related to the increasing susceptibility to carcinogens and/or the in- crease in "spo.unewus tunars" incidence. The authon hope their studies will establish the integrated bost raipooea to the events occurring in respiratory carcieo6enaia. Whiunire, C. E., Densoise, C. F. and Kouri, R. E. (MkroMoloskd Aisociater) In: Karbe. E. and Park. 1. F. (eds.): Eiperirnrraral Lrnr Cancer. C.rcino- rewesL and Iio+r..ys, New York: Sprieprt-Verfa6, 1974, pp. 2047. Otiirer .urprt: National Cancer Institute. From the Deparuneot of Eaperineotal Oncolory, ViralChemie:al Carcino- geaaia Section. Mrcrobiolo6ieal Asaociates, l.e., Bethesda, Md. TRANSPI.ACPNTAL INDUCTION OF PRIMARY RENAL IUMORS IN RABBIIS IREATED WITH 1-ETHYL-NITRUSOUREA Newbo.n and young (C311aA)F, mice treated with 1-eth)l nitrosourea (1:Nt1) dcvelop pnmary tumon of the kidney as wcll as othcr organs Re• portcd here a the laeyue.l aad almost exclusive induction of rend tubular cystadcnomaa a cysudc.ucarcrorau ts two slraw of rabbits by ttansplaccotd I administration of ENU; this agent also cau.es tumors similar to the Wi4e.• type. Pregnanl rabbits of the two partially inbred strains 111 and WII were given a single inlraperitoneal dose of ENU (60 mg/kg) in trioctanoin on day le of gestation. Controls received solvent alone on the same day. Of the (S strain 111 progeny that survived more than eight weeks, 14 developed primary renal tumon at a mean age of 3.3 months. Five other strain III propeey diod trom other cnna at an early age. In eontra.t, only three of the seven uraia WII offspring wrvivinp more tlun eight weeks developed renal tumors after about the same latency period (3.9 rnooths). In each strain, either read tubu- lar cystadcnomas or mixed nephroblastornas appeared to develop within small renal cortical cysts, which in strain 111 may be explained by the high Irequeocy of a recessive gene (rc) for renal cysts. Is strain WH, however, they were induud by ENU. This differential strain incidence suggests that the pre.eeu of the rc/rc genotype for cyst formatioa increases susceptibility to reaal tumor ioductioas by ENU. Foa, R. R., Diwas, B. A. and Meirr. H. lowwd o/ the N.rbw.f C.ncer lnrdtute 34(6) • 1439-14/!I, 1975. OtA.r asr'rortr Natioad Canxr Institute and Hycel Inc. From The )ackao. Laboratory. Bar Hatbor, Me. PULMONARY CARCINOGENESIS BY TWO ARYL NYDROCARBOW ON THREE MOUSE STRAINS 'Mat the susceptibility to polycydie hydrocarbon carcirsoileoa.ia is rddd to ioducibke aryl hydroearbon hydroayksse (AHH) is the current oo.eept luted here on three different mouse strains. Beaw(a)pytcne (B.P) and )•wtetiyt- cholaruhrene (3-MC) suspended ie a 6e1Nia aolutioa were inatilked katr.uacrr ally into the luop of these a.irnaM. The CS7B1/61, the raadorn-kwd NIH- Swi.s/Mai, and the DBA/21 strains were selected for their respecdvety Nik, vuiabk, and low AH1t ioducibility. Tbe 3-MC was more carcisopic and loaic thaa B.P to 1he NIH-Sww/Mai a.d C3711A/61, but had keaa toak d.et on the DBA/21 mioe. The NIH-S.rir/Mai bad the highest total kaa6 tw.a i.cideoce and 1he C37M/61 1he lowest. 7La eAeclive cumulative card.o6eak do.e of 3-MC appeared lo be 2 ny. Regardless of their hepatic AHH acti.ities. ar mioa were equally tesisust to pulnw.ary aquarrsotu cell carcieoaa i.dirc- tion by both chemicals. In the (hree atrai..` the 3-MC induced only a undl perotrtta6e of Mia snali6aancy in the young addts. It did, however, produw a higher iecidenoe in 1he mature CS7B1/61 animals. The rates o/ cardaoseaa+is and lung clearance o/ carcinogens observed ie'this study suggest ebN in tb moaue, target tissue AIIII may be a more relubk indicator of .usoeptibilily to polycyc8e hydrocarbon eareiarolieneais tham hepatic AIIII, and tha rola of At/lt in tumor /ormation may be secondary to genetic, physiologic or vMsl f actas. Ho, W., Wikoa, K. and Funl, A. ([/nl.vralry o/ San Fr.wrlrco) le: Karbe. E. and Park, 1. P. (eds.): Flrrrtwrenref lant C.ncrr. C.rr/wo- g.nrs/t.nd Alo.rsqs. New York: Speiniter-Vertag, 1974, pp. 62-71. From the In.titute of ('bemical Biology, Univcnity of San Pranckhoo, Su Fraecisco. 23 22

graphic characleristics of the bronchial and pulmonary vessels are recollected briefly. The discussion devoted to the lymphaties focuses on their most distal inlrapulmooary endinp, aaenely, the jusu•alveolar lymphalics. According to electron microscopy studies. Ihe ullrestruclure of the pulmonary lymphatic capillaries is compatible with great permeability and active transport. Most iolrapulmooary lymphatic valves appear to be mooocuspid rather than bicuspid as wmrnooly suggested. (,wwer7wt.1. u. Acre C"oloske Suppl. 19:137-167, 1971. Otlbr aup/.ertr Natiowaal Poeds.oor Welewchsppelijk Ondcrzwk (Belgium). From the Laboratory of Pathoioq at.d Histolop. Katholieke aloiven8eit a Leuven School of Medicise. Lewves. Wgiuat. NEUROEPITNELLAL BODIES IN THB HUMAN CHILD AND ADULT LUNO This study attempes to establish whether the neuroepithelial bodies (NEB'a) previously demoestrated ia the htnp of varioua mammals including adult rabbits and human infanty, penid Into adulthood in man. Lung tissue was ob- uined from five children and 12 adults during thoracotomy and immediately Aaed in Bouin's Aud. Alternate aerul aectans were stained wi,h hematosylie sod eosi4 with Van Campeohout's modified Bodian silver proaeinate method, or Orimeliui silver nitrate technique. Mocro.copy reveakd typical NFB's in the broachid, bronchiolar, and even the alveolar epithelium of these human lunp. As in the other specie.. 1he.e corpwcular bodies consisted of ovoid to triangu- lar groups of celb, 20 1o 40 fwide st,d 15 p hi6h, intercalaud within the respiratory mucoss. The cells thettuelves were nonciliated, and rather large (6 p X IS p) with a ckar, slightly eosinopbilic and distinctly argyrophylic cylo- plwe, a.d eatended from the basemeM membr.ee to the airway lutnee. They were usually close Io at kast one cspillary in the underlying lamios propris• Although the function of theae corpuscles remains unsettled the suthon eut- 6est that the NEB's may constitute u iNrapulrrwnary. hyposia-scnaitive ocuro- (chemo)reuptor system modulated by the central nervous system that might influence the pulmonary vasocon.trktor response under both oormal and psthob6ic cucunuta.cee. L.rweryiv, l. A!. aad doddeeris, P. Anw.kew Review o/ Rerplretory Disease 11(4):169476, 1975. Other erprortr Natioeaal Fonda voor Oes+oakuodi6 Weleaachappclijk Ondcr- xock, Belpum. Prom the I shoratory of Hiatopatbobgy. Katbolicke Uoivenileit te L.euvea, Iruvee. Belgium I NEUROEPITHELIAL BODIES IN MAMMALIAN RESPIRATORY MU('OSA: LIGHT OPTICAL, HISLOCHEMI('AL AND ULTRASTRUCTURAL STUDIES Having previously reported on the occurrence of ocuroepithelial bodka (NEB's) in human infants, the authors now describe analogous structures throughout the respiratory mucosa of various mammals (rabbit, cµ lion, monkey, rock-badjer, pig, hedse-hog)• Studies combininS light opics, micro- spectrography, cytochemislry. and eketroe microacopy show thr,l these newly identified corpuscles in the intrapulnanary lining of epithelium of letal, soo- natd and adult mammals are eompoacd of ararrophik, arsentallin, yellow Auo- resceet, ultras/nrclwrUy granulated, and innervated epithelial cellular orgar 11 is aujillerted that these NEB's probably have an ietrapulnwnary, recepor lunc- Iion which is modulated by the central nervous system and wbich apparsstly liberates various.ub.toaKes withiw the IunR, one being aerotoeio. L.rweryx., l. U. eN d. Chest 63(Apcil Suppl.):22S29S, 1974. OtA.r supports Naaoaaal Foeds voor Weteaycbappelijk Oedersoek (BsL Ou°t)- Frora the Laboratory of Pathology and Histobp. Katbolicke UdvenrMek u Len.ven School of Medicise, Leuveq Belgiur.. AOOREOATIONS OF DENSE ORANULPS IN MITOCIIONDRIA OF ACTIVE PULMONARY LYMPHATIC ENDOTHELIAL CELLS Since it i. weU kuows that eww active aitochoadria display aa olwed ene atructure, these i.veslisaors decided 1o ex anine pulmonary lymphatic eo- dothelial cells i. light of the possible associalioa of their ckara.oe sdidtia with changes in their wtitochondrial morphology. F.aperirnea.lly, a/o/a/ of 16 neonatal rabbits received itlr.trscheal iaMiMations of /errilin or earbon p.r- ticks: three corresponding animals were kept ae cootrda. At low mapiBcNios and after Trumps' /lsatioe and staitdng. lung tiswe aeclions showed electroe deruie. round so oval dots (diuneter N141100 A) in the mitochondtid teatris of the pulmonary endolAelial cells which had absorbed /erriti.. Though It waa diflkult to aacertain the eaact number of grsnulsr aggregations per maocbo.- drioa, it appeared largest is the lymphatic eedothelial cells which contai.ed the most ferritin. Similar aggreptions of detne Rraaulea were not found in wito- choodria of lymphatic endolhelial cells Irom control animals, nor wern they seen in the group of animals that had beee innillated with earboe prrtkke. Alihough Ihe precise .ature of the demonstrated granuks remains ueeaplainad, it is suggested that these aprejations are related to an increase of the endo- thelial cell metabolism which was stimulated by the er.docytoeia and d'yatiw of the ferritie particln. L.wwrrywr. /. 6I. aod Bsert, l. Erperlrnd. 71(7):6)9-612, 197J. From the Katholieke Universiteit te I euvee School of Medicioe, Leuvea, Bellium. 28 29

of research. Becau.e of concern with human wefl-being, studies are being done with human subjects when possible. P.pidemiological studies especially must relate to human populations. In other sludia, animal models musr be used to reveal information to augment our knowkdge of the etiology and pathotenesis of those aging-associated diseases of the pulmonary and cardiovaacr l.t systems. WLLLIAM U. CjAUtNEl, PH.D. Scientific D rector Studies Related to Respiratory Function and Chronic Pulmonary Diseases The Council's 1973 Report presented general concepts and plans wldcrfr a~k the research program in respir.tory function and disease. Along these lina, a dozen projeNs in a number of research inslitutes were maintained duri.t tb year just ended, with collateral support by ccatact studies for equipment dc rdopment .nd mcthodolopr. ...5~ ~ I I Anb..el Stadie. On.olving /w6.l.tbw Bspo.ure. In four uudip anirnah wete exposed chrvnically, by iahalation, b arnb widely present in hu.o.a environments. One inveeiplor, who had developed methods for a+easur(q prlrno.a.t functions in rnioe, .uboclcd anirn.ls of two aulies so cigarette snloke inWatioo daily for five lo ke weeks. Nigh- .nd bw-aiootine reference ciprell.s were used to eomp.re the eQects of di0etw nicotine levels in ueokes otherwis varry similar. Effects of whok, fresh snwke inhalation were similarly eanpued wMf, those of the p.•vapor ph.sn alone. Th. latter, being substantially fns hoao particulates, contains only trnces of nicotine. Measurernents of functional residual capacity of the hxys shvoed thr emphysema wan nut produoed. 7Ue Nrws diAered in sa.eeptibilNy b Mcrearw in pulmonary resistance lbroeebp.t.wl, whieh was elieited by wbfr snwte and 1o sane extent aho by the pll-v.por phase, but both str.bn d.reb4ed almost contpiete toN:rancrt within uw weeks. A deerew in puMnon.ry oontpli aaoe was reported to be aasoci./ed with Ave- to ka-week inhalation af staok- from the hi6h-nieotins reference eipretle, by1 this was not eliciled by tb ps vapor phase alone. FJlects of acetaldehrde, nerokin and staatole, whic, an low kvel, but in other eaMeats knoww lo be chemically activs, ooatpone.b of tb pwvapor phase, were measured in separate bu1 parallel eapetintents. Me.nwhik, becawe of suqestions is the literature that cumulative tracr of inhakd cadmium might be a factor in the etiology of entphysema, a stud) similar to that jusl described was begu. with cigarettes "prirnod' with Ih.e levels of added cadmium compounds. Because fly ash and nitrogen diotide are found in the atmospheres of wan; cities where chronic pulnaw.r~ .itments are prevaknt, .norher investigator eo posed ham.lera for ptolon~od periods to atmospheres containing thw oom pounds. 11e too had w impressive series of physiological and mwphob6ical ta methods applicable to the hamaer, an animal regarded from other studies a being relatively susceptible to h.n6 damage. The animals were exposed chrow cslly for about 14 mondu either to dust aloee, to dw1 wNh niuo4ea diaaid. o to amMent air. Srwne of the animals wen teeapoeed to ambient air .br fo twoweeks following the othereaposures. After aacrifke, measurements were made of atalic compliance of tha lunt 7 I

i other noninvasive method (systolic time intervals) were measured. Separation of the two groups was accomplished better by eN.CO Q•Doppkr peak than by systolic time intervals. It would aeem, there(ore, that ef:CO Q-Doppter peak is a useful inde: to evaluate the myocardial contractile state since thu iodea is readily obtained nooinv.aivcly. Lahikawa. K.. su fRs. H.. Sarma, R., 7illoaer. H.. Fauvel, l: M., Oetzeo. l. H.. loa.w., J. L sod OJng. R. !. l.pwe+e H.art lorrwd 16(1) •22-35, 1973. Oth.r..rr.rtr Wri6bt Fouodatiau an/ tb Hoover Foundation. From the Hu.ti.Itoo Menrorid Hoapitd, t•a..berra, Cal.. th. Urvcnitr of Snuthcrs Califoniia. Loa Ao6elea, aod Kltl! Uoiv.rsiry School of bledicioe. Os.tt, l.p... and tri•Ilycerides, snd plwpholipids was measured, no influence of CO os lipid synthesis in the arterial wall could be demonstrated. In contrut, arterieft corich were exposed to CO showed a higher uptake of cholesterol than their respondint controla. The concentration of CO in the per(usate did not alter the degree of cholesterol uptake. These results are in general agreement with those of others who found that CO .i6nidcantly increases the permeabifiry of endotbelial membranes. S.rma, l. S. M., Tillmanna, H., Ikeda, S. and eGrt, R. /. AtA<roackrouls 22:193-19i, 1975. Ot6.r srrp.rtr Norria Foundatioo. Frova Huntington Memwial Hospital and the California Institute of Teo1- ook+Ry, !`...dena, Cd., aod the Uoivenily of Soulbero Califoroia, los Aaplas. COINCIDENCE AND NONCOINCIDENCE COUNTINO (a'Rb asd'aK): A COMPARATIVE STUDY The vae of r+dioerrclidea for beart 1.u1i+6 4a bees iecreadnl over the last few yean. We moM frequently used iwtopes beinR sK and more recently a'Rb. 'i1Thr neport compares the accuracy of ims6iq asd resolution obtained with tDeae isotopes by coincidence and wacoi.cidcrx counting of phantom preparstioas and i.olated, infarct,ed dog bearta Special emphasis was placed o0 the deRrea of resolution. Ttse results clearly demonstrate the auperiority of coincidesoe counting with a resolution of 0 S cm. Noncoincidence counting failed to reveal even nzable defects in the radioactive source. Furthernwre, since "K decays only by nelatron ema.ion and thus cannot be used for co- incidence counueg. it appears that •'Rb - which also ha. a,horter hal( life. Is more easily produced, and 'a Ic.a eape.rive - is the more deaerabk isotope to uae for ibis procedure. Deds, S., Dukeo. ll., Tillmaoon, H. sod lf/wg, R. /. /orrwd oJ Nrck.r Afcdklnt 16(7):65/-661, 1975. OtA.r.r"+rtr Hovver Fouodatlon a.d tb Norria Fautdatio.. From tba Hwtiepo. Memorial Hoapitd, Pardeaa. Cal., and the Uoiveniry of Soutbeo Califoroia, Lo. AeRelea. T'HE EFFECT OP CARBON MONOXIDE ON IJPID METABOLISM OF HUMAN CORONARY ARTERIES Carboo naoooalda (CO) eapowut kw beao Yoplicated before io the In- crwe of lipid aocumulation in the arterirs of hum.os and Ai~m~aL_ oa this study deaiisl with cholesterol uptake aod lipid ayotheai. y arteria were perfused In vitro willt blood containing high or low coocentra- tioas of Ct). Upid .yntheas io tbe srteriat walb was investigated by iocorpora- 1K+n of ('•CIK'etaic. and cholesterol uptake was studied by using 1'11/cho- katerol as a uacer When the synthesis of eboleaterol. eboleaterol ester, d!- l/NIFORMITY OP TRANSMURAL PERFUSION IN ANESTHti*T1ZeD DOGS WITti MAXIMALLY DILATED CORONARY CIRCULATION In this traaamural pertusion study, wsonary, blood flow (COF) wr .eaa- ured ekctromqteetic.lly, ..d regional myocardial blood Aow ( MBP) wr cors- quted from ti..ue upakp of 7-10 /a radioactive .ricroaphcre.. Metabolic di4- tioi ol the oorooary elreulatroe wY induced by occluding thc coronary artery for 10 or 90 aecords, and pharm.colollic dilatioo was induced by kafu.M1 pspaverine into the arsery. In aeveo dop. diAerealy labeled mkroapheres were administered before coronary artery occhrcion, at the peak reactive hyperank response to a 10•aecond coronary arlery occhrion, and early io thm riai.R phase of the hyperemic reapore followinR a 90-aeoood coronary artery occlruipo. MBF was distributed uniformly across the left ventricular free wall before oa clusion and at a peak hyperemia alter Ihe 10-seoond ooclusioa, but early 1n the hyperemic responae b the 90-seeond occluaioo CBP preferentially perfused aubepicsrdial tiasue. In a.other group of seven dop, microspberea were ad- ministered be(oi•e coro.ary artery occhnion, al the peak hyperemic Oow after a 90-second occluslon, sod at the peak flow during local iotracoronary iofu.ioo of pap.verine. Tbe left veotricutar free wall was uniformly perfused under each condition. However, in 12 vetrted, RbriMating hearts with coronary dreulalioea dilated maximally by perfusion with venous blood containing either pep.vetloe or adenoaine, left veotriadar blood flow was preferentially directed to the wrb- endocardium. The wthon conclude thN the eoronary circulstioa of t,8 oor- mally functioning canine heart can dilate maximally without causing relative wbendocardisl iachemis because of a gradient of vaacularitr that favors tha wbendocudium ard coropenaatea (or systolic fbw limitatio. io that rrAba Downry, H. F. .t d. . CLerJ.tlon RriercA 37:111-117, 1973. O'A.r suF'ertr Cardiology Fuod and The Amerkao Heart Association Tam Aftuiate, Inc. From the Cardiopulmooary Institute at Methodi.t Ho.pital and the [kpot• rneas of Phy.wb6y and Internal Medicine, Univenity of Tea.s Healtt, Sde.w. Ceeter, Dailaa. 38 39

THE DFSTRUCTION OF TYPE 2 PNEUMOCYTES 8Y AIRBORNE INFLUENZA PR!-A VIRUS; ITS EFFECT ON SURFACTANT AND LECITHIN CONTENT OF TNE PNEUMONIC LESIONS OF MICE Siooe the broochid membranes as weq n the alveolar type 2 poeumo- cytn of mice are destroyed by dtborne inlluenra PRd-A virus, it seemed worlhwisik to study the effect of this destruction on the surlactaot and pho.- pbolipid (lecithin) content of noda[.e1ed and infected lobes in relation to the onset of in/eclion. Electron ank"aco" of tbe kings of miee which received sublethal doses of sirborsa PRt-A rirw revealed that the virus ptopapted io ciliated and nonciliated bronc6ia) oelr r well aa is types I an3 2 alveolar pncun.ocytes and destroyed them. T1s repserati.t broachid n.embrana were meuplastic and pew peripheraMr kab the wnoundiy alveolar ducts a.d alveoli to focw epitrelial nodules eawYy obaruclioa aad ool/ape of the ia- volved Iobes. The devr{oprncm of Iu.R lesions correlated neptively with pho.. pbolipo leveb sinoe dipalmiloyl kcitbia kvds decreased dgoificantty with in- crcased oo.solidatio.. The diAerencn behreen tba kscitbia content of sos- coruolidated and co.adidated tlous was greatest eight to 10 days or anom after the o..et of iafectioa Tbs 8ntrsrclioa of qp. 2 paesrmoc7tes by the is- Ifuen:a virus and their failure to repe.crate is 1lourbt to account for 1he low phorpbolipid kveY in the involved bbes, and is thua co.sidered sa important uuw of poMialh.cwl eollapse is nria. These obsenatioas support the view ahat type 2 poeunwcytea atr a nuor aouroa of wwAactast le maarmatias hwp. l.oadl, C. O. er al. CAest 67S (Feb. Suppl.):7S-14S. 1973. OtA.r..pp+rtr Esviroeme.Na! Protection Agency. Howard Hughes Empby- ee. Give Oac. Club and Ha.tiop Foundubo. Fund of the University of South- era Cdiforda. From th. Departments of Patbobp aed Medicine. University of Southern California School of MedirJn.. Lfla AnReles. BIOCHEMICAL AND MORPHOLOGICAL ALTERATIONS IN THE LUNG FOLIk)WINU OZONE EXPOSURE CoaccMratio.s of oely 0.4 pprr of oroaa (Oc) rnwY cause changes is hu+{ nirway reaiuanoa is buauaa, and only a few paAs per rnillioo may eaum aevere pulmonary edesna aed pathologic cbaep is rau, mioe. rdrbits. and ~uiera pigs. lhe precise mdecular rnechanisres of lung iojury are slill ua- knowa, ho.revcr. Y is the possible roM of preventive and/or therapeutic inter- venti4MU Naperimental esposure of rata and monkeys showa that Oc can alleet iwo duunct acpecie of pulmwnary tissue melsbolum: (1) shorl-lerm. high- k.el ecl+utc+ ..u.e .cuw JocruNStive changes such ae sulfhydryl (SiH) osi- J.u„a soJ .,1 rwt•na s.u.u~ca. and (21 whacute. low level ci- posures cause adaptive enhancement of reducing compounds and incrcase of enzyme activities. Acute eaposures (2-1 ppm for 2-d hrs) lower nonprolero wl(hydryl (NPSH) levels by as much s 30% a11er sie houn, an effect whKh leads to diminished levels of cellular reducing compounds or enzyme inAibilioa, but which may be transient and reversibk under appropriate conditrons. Lung mitochondrial and microsomal fractions showed significant concomitant SN loss and depression of marker en:ynw activity. Low-level eaposune of tbe animals (0.2-0 i ppm for 2-7 days) did not produce net Sit o.idation or di- sulfide formation, but imlead increased h.ng NPSH and (iSH kvcls by up to 50%. These compounds, involved in cell divisiom and repair, may also suppk- ment lung antiosidant defense mechaniun.. The activity of esurymca eooocsaed with NADPH production and disuldde reductiom also increaaed. u did abst of mitochondrial and microsomal marker enzymes. Correlated morphololie studies showed byperplasia of epitheliW and interstitial eelh, aa well r u 1.- creased number of macropbRes and kukocyw in the eewual retioas of tke pulnwoary acl.L Do Lucia. A. 1., Mustats. M. U., Croar, C. E., Pkapper, C. O., Dunlwortkv O. LL and Tykr, W. Ankrk.n Iwrtltaue of CMwrkd EnliteerY Syrnprlcun Strlu 71(117):91100, 1973. (Air: rart I, toll.tlow Control.nd Cltan Enrrll•) OtA.r .r'prir U. S. Public H.aw Ser,rb a.d tbe Califor.ia Air Re.oup. Deprutwteat. From the Udrenity o( Califorwia, Davi.. CLEARANCE OF INHALED BACTERIA FROM THE MURINE RESPIRATORY TRACT The muoociliary app.ratus and alteolar wucropbape eyNenm oonqrir tb major resident defense mechaeisme of the respiratory tracl alaiesc inhaled Is- asanate and 'wfectioua agenu. This study eaaadaes the response o( 1lan d. feoae mecbani.nn 1o inhaled Sty4ylococrcu arre.u wN6 the aid of IeJaiqrw permitting paired Nudies of tracheal a.d Iuas clearance of bacteria a.d .ath- ods for invealiluins ceMular defense in Ire rwpiraory Iracl. S. .rrnu wr rapidly cleared from the trachea of reion dler aeroaol irnpladation (lHl 1s 15 misutes, 3.% in 30 atinwes, 72% ie I bour, ts% (. 2 kwurs, a.d 95% in 4 hours). Lung ckaranee„ although equally e8ec/'we, was not as rapid ()11i In 13 minutea, 44% in )) rninutea, 33% i. I bow, 74% ia 2 boun, and N% in 4 bours). The wmben of alveolar rnacrvpbaRes har.eated fro.n 1h. aaurir lunp were meawred under bntl conditions and dter chalk.l, by aaperi_ rnental conditions. Eapowrs so aeroaolirtd phoaphaw-buAered awpenab.s of viable S. errrrt had a deAnile effect os macr,Aphale numbers. Inun.diately after eaposure (0 time), macrophape counts wrer. Increased 2.0 tisira basal levels. Macrophqe yields at 0 time were turther Increased 2.6, 2.4 a.d 2.3 times basal levels by the deposqion of 19,000, 131.000 aed 211.000 vi.bl. Naphylococci, reapeclively. ibia magnitude of Increase over basal yl.ids was taken as an indea of macrophaae mobiliralioo. These results denaasuata the individual participation and combined efficacy of t6s mucocdiary .nd aiwdar 30 I

PRINCIPAL INVYJi1GATOR OR INSitilII10N RRANISLAV VIDi~_ D.S.. rro/ta.ar of Awuo+wy. Oeoraeto.. U.iwrwy Scbools of Mcdou.e eed Deriarr. werw.a,oo. D.C. IRENE Y. WANG. Pw D. A..iawn Re- surcA CAewua. Cancer ke+earci IrBL Iwe awd Hooper F~rd.~w~ Uaver- ~nr of Celd«wie Sctqd o/ 14e_ idw- , Sr Fre.eiecs. (Now Aadwwr rnJer ior ol /a.wrrwology and MicroAieloq. Medic.l Ua.er.iwy of SowA Cara/f.k CMrkqo..) OEOROE WEINNAUM• Pw D_ lfwc4 rwnAr. rufw.ow..y Dw.r: Secriow. A!- bert Ei.Yer. Iiledicd CeMr, PWr~ dciphie. T1tOMAS C. WFSTPALL, rw D_ rn/i.r io. o/ rArw.rolory. Uwi.ettity d Vir- Rid. Sclool of Meiaiei.ti C1r1am. .rk. OP;OROH rVOI.F. l1St_ D. !•tac. r.oJer .or of rAp.blorird CAewdsny. Deprt• .+ewr of Nwritwn eed Food Scuece. M.necIsr-eu. IwrNwe of Tecl.oloaf. Caabnda.. Mau. PROJ[CT Tiill Tb eded of ciA.rette .awke oa luy .euboli.n deaelic AiQeranop i.1kr !w vitro srw.bo- (irw of cbneiu) careieoAeea bY Mum.s ar/ noaw Uwa L..y protel.aw: erripoaeiaa.e bel..oe .rA IAe efect of ciaarau ee.oke ow this 1.wr.aio. Adfon of doWi.e o0 peripker.l and oe.- uel .ewoer in e.i..le cAro.icallF e.- *oreA b Ytatir TM elea a[ vilri. A om elycoprolein eyrbreir i. ror.al ." Freca.ocrow re.arNory qitt.clwe• 72 I Connpleted Projects FoUowiag ia a Wt of the principal iavestisators, or inatitutiar, o( projeda that have been completed prior to the period covered io this Report. Several of the individuals named are deceased. The titks and 1AUia- tbot listed are thwe ia eAect at the time the work wr completed. CLARENCE 1`I. AORESS. M.D., A.ao- cwe Cliwicd rro/ecsor of M.Ik/we. Uavenity of Cd'dor.i. Medical Ce.- ur. Los Ayelee. ANTHONY A. ALRANPSP, Pr D. D/- recror o/ l.Da.rrAu. l•s bwke Re- AebiNlYiow Ce.w. Wt+iM Plai.m~ N.Y. ANIIIONY P. AMAROtSE. Pr.D. Iw- .nrno., D.prrmewr of ObrN.ici owI GyrwcoloR). Tie Albany Medied Cal- lep ol Uro. Un.a.ily. Mb..y, N.Y. 6. T. ANOEI.AKOS, M.D. Pr.D. ho- les.ar of rAsa/otoRF. RoMaa U.irereity Sclool of Medici.wk t1a1... . D. MURRAY ANOlViNQ MD.. Ud- ~ r o1 Wbco.ri. School .1 Mesi- STEHILMN M. AYRES. M.D. DAtirrer. Cer/ioPdw.owrr L.ilor.ro.t. S.i.l Vi.oer'e Ho.pitA Now Yerk. OSCAR I. t1ALCHUM. N/ D.. N.r/me rro/eawr of Me/kMr. Udvenit7 of Sew\er. Califorda Sc`ool e/ M.N- eLi.. Lo. A.{eka FREDI?RIK It. l1ANO. M.D. ea.or .wI CAdrw.e.. Dery.1nwuer ./ .rAa Scsoal of Hriier ..a Pt~We HaMR tldti.or+. A. CUFFORD RAROER, M.D., Roilerl Nrw.r rJ#i/er rro/es.r of rAyrbt- os1. Her.erd Meiical Sct+ool. !<o.10.. •RODA A. RARNPS. M D. PM D_ ho- jeuav (A/IIIMe) of rAlrblatl. CdO- redo Suu U.IvenMF. PeA CeYiwa PREDt'RICK W. BARNES. h. MD.. A+.oclere rroleau. of AIeIkMe. Tw lob.e Ilo.kiw. U.Lu.Mr Sclool of Mediciwe, mehie.or.. T. C. tlARNP R.sercA Sc4w- tler. Pbii.del~p ~i. p~ ~i. 1)3c. Siate Hoyit.l, PWIe- "phis' R. FREDERICK BECKER. h.D_ Auo- ci.re rroJe..or o/ A+.erowry and Direr ro.. L.1a..lary of rer4.erd Sciewce. D.ke Uwivereitl Medicd C4a1er. Drr- M.tiN.C. RALPH S. !1L'CKBR, PtD.. rr.}er d CAew.irry. Ua.er.4F al Howoq IioU••o• S R8U.1*T, M D. ~~~ AMP1. rlUa.v.l HoqM.L _ e~ RARU/ RlNACERRAP, M.D. l.irw. r.o%rar. and CANrww o/ rrA.Mw. Har.ard Melical Sdo.l, Dew. JOHN A. BEVAN. M.D_ rr./ia..r o/ • rArw..~s1o~ U.i.ereY, d GY/ar- .ia Scbol o( IN.dici... Lee Arplr. l1UDHD8V RIIAOAT. Pr.D_ rn.l..w of rAl+iolopq. Sc. Le+i. Uai...MF ScAoot ol Medciwr. S1. l.erll CESARE tiIANCIPIORI, MD, D/d.Y. of Cancer Rerr..cA, Ud..nMF e! Pamyi., t'e.>.ow IWy. HYLAN A. RICKeRMAN, MD. AaMM .M h%aw. of M.IkMr. crd AL. VAN L. BARACH. M D. G.u.i../ in MeJkM.. Collegs af PAFitl+w A S.rytor of Colir.bi. U.Iw.Mr.' Oo1L wwer M.mwid Hoyitd. New Y.A. 81O-RESlARCH CONSULTANTl. INC. C.wticiye. M.r. l110•RPSP-ARCH INST1TiJin QIC., Ce.nbciCp. M.r. PRlD O. ROf:K. Pw D. Aawdr. C.+ cn Ri.ercA sc/ewdd, ll/ot.sk+d fe& riow. Ro.weM Pe.k Me..ocW L.tM.* SteiepiNe, N. Y. HERMAN V. tkOEN10. PrD. BwA CAew/ur) and I/ocAewd.ny De~.rw wwru. Sliadelq Ree.arc! CeMr. Ls iyto.. Kr- IAMP.S P. R(NiNER• Pfr t). M/eawor o •Aoloe,. C.ufar.ie IerMrw et ech.oto.r. P...ea.e. 73

FENESTRATED ENDOTNEI.IUM OF THE ADRENAL GLAND: FREEZE-FRACIURE STUI)IFS Although there appear to be but two morphologic b.rrien, the basement membrane and the endothelium, little is known about the mechanisms by which adrenal medullary and cortical honuoees pau from the interstitial to the vascu- lar space. Using the Ireer.e-/racturiog techoique, the authors have begun to elamiee the adrenal eodothelium r a barrier to horrnooe passalie, and several structural characteristics have earrped. Two major leaturea of both cortical and medullary endothelnwn seem b be /eaeqratiooa and caveolac. While the latler may play a pan in bormo.a tra..port, there is so evidence on this poiet, aod tbe /eeestrae would appear b ton. lar {ess of a barrier so diAmion. Ths more numerous wsedullary uveolas, bwever, may have a function in the pro- cesing of horrwones and related n+b.ta.ees. For «ampk. ATP, speciik pro- Itins and epinephriee are rekaaed /roat tba cbroma/Bn edM durinQ eaocytow. Epinepbriee enten the vascular sQaea but ATP does .at. It may be that tb. ATPase eszymes, wbich are a cowr..o. /eature of other e.dothclial caveolae, occur r. the adrenal eedotbelMue as wer. Tha Rlobular particks and piu seen on the te.estrae aed o. the (radure taoaa of the plwna membraoe, moreover, wuest. It the concept of side.doas in membranes also applies to teoestrae, tha possibility that subataoces leaving the vascular apaee may be processed diQer- eotly from those wbelasas eaeri.R it_ Ry.n, U. S. er r. TUrwi Cell7(1):Ii1-190, 1973. O1A.r esspp.rtr lobs A. HarUord Fou.datioa and the Natiooal Institutes of Health. Frorn the Papaoicolaou Cancer Reaearcb Institute and the Departmrnt of Medi- eine. University of Miami School of Mediciee, Mumi, Fla. ADRENAL MEDULLARY STORAOE VESICLES OF THE SPONTANEOUSLY HYPERTENSIVE RAT The adrenal medullary veakks of .orsoteoaive Wi.ur rau (NWR) and spootaoeously byperxmive rats (SHR) wen eaamined is order lo determine whether increa/od sympatho-adnea/ activity plays a role in the ekvation of blood presaun !n the SIIR. Whib a11•metaruniooi uptake was the same, iaoo- latod SIIR vakks displayed a greater d6sily /or epiecphrine than their NWR couolerpart., u evidenced by a higher uptake of r'C<pinephrine/100 pg of eodoAenous catecholamines. Tlris dilleresce in uptake was due to a lower Km in SIIR epinephrine. Storage of amina wr the same in SIIR and NWR, as demonstrated by measurements of eateeholamine:A/P ratios in purified vesicks, and c111uscs of cndogerw+us and eewlyincorporated amines from the vesicles. 1 he higher talu. u1 taorcMd.minr. ro dopamtoe /i hydruylase (1)1111, a matker tur a.tr.p veorksl f.runJ u. 1i1R r due to. (1) (ewer ve.kks per gland; I (2) kss DBH per vesick, as indicated by an increased precursor:product ratio; and (3) a higher calecholamine content per vesick, as shown by an increase in the ratio of hesvy:liiht vesicks on discontinuous sucroee density gradients. Insulin administration caused greater catecbolarnine depklion in SHR than in NWR adrenals but induced lyroeine hydrosylase and dopamine A-hydroayl..c activity in both strdns. These resulls are not eomistenl with the view that sympatho-adrenal hyperactivity occurs in the SIIR, but the data suggest that bypoactivity occurs perhaps secondarily to the hypertension. StorA/w, T. A. and Oras, H. O. siocAemk.i rArrnarotory 21:17I-1!(l, 1975. OtA.r arpprtr American Heart Association. Walker P. Inman Fund and the Duke University Research Council. From the Department of Physiology and Pharmacology, Ilrrke University Medi- ul Ceater, Durbarn, N. C. SECRETION AND RECOVERY OF CATECHOLAMINES BY THE ADRENAL MEDULLA 11 is generally aeoepted that ueeretioe troru the adrenal medulla occurs by the process of e:ocytosis. While a few of the eaperiments which helped eluci• dale this complicaled, two-slep phenomenow are presented here, the maior body of this paper deals with the quaalal aspects of secretion and the evenls wbicb occur during recovery of the eatecholamine stores. Investigations conducted by the authors and various other investipton, ootably Viveros er at. and Krone- berg and Schumann, are discussed here. From these studiee and otben not described here the authors can reconstrucl the events which nast probably rccur during physiological secretion from the adrenal modulla. Stimula/ion of the splanchnic nerve causes rekase of acetykholine which, in the preseew of Ca+ f, resuhs in the quanlal, eaocytotic release of the contents of the oecre- tory vesicks. Immediately after secretion the vesick membra.es are detached from the plasma membrane and retained by the cell. ()uring recovery, new vesicks are formed which contain the normal complements o/ soluble proteias but are deficient in ATP and catecholamines. Subsequendy, these vesick, re• gain their normal content of ATP and ealechnlamines. As a(urther eonnse• fauence of neural Mimulation, tyrosine hydno.yl.ae activity increasess. which mosl likely accekrates the rate of recovery of the utecholamine store.. Kinhner. N. and SlorA/n, T. A. , In: Usdin, E. and Snyder. S. (eds.): Fronrlers iw Catecho/atnlnr ResearcA, Oalord, EoAland:Pergamoa Prea, 1973. pp. 447-452. OtAer support: U. S. Public Health Service. From the (kpattrncnt of Biochemulry and Ikparlmenl of Physiology a.d Pharmacology. Duke llniver.uy Medical Ceoter, Durham. N. C. J tn 70 51 f.

( COMPARATIVE STUDIES OF THE PRODUCTION OF ANIIB()UIL'S TO ANGIOTENSIN I While ankiotensin I antibodies have been wsotesafully produced by im- muntrin6 animals, little is ktsows about either the formation of antihodies in d'Jferent species or their persistence over substantial imervds of time after immunization. Such informalioo, bowever, in siSnificasA In the productioe of antibodies for radaimmunoswrs of sa6iolessie I sod reds activitl•. In this report, the author describa Ihe us. of rabbits aed Vosts in iromu.iz.lion pro- pam. Iastins up to one year. A.Ilbodka ts ae6iotemis I-BSA were produced in the two diRerent .pecies so compare Adr apecilkity. binding cap.cities. tiwer., aed cods. The antibody respo..e was apt/id ever wbNaMial ieMervsl/ of time following cornparabb imnm.izatios in diRutM anbas6- TUs pau iproduoed large quantities of antircrww bul dtis bd to be furtha purided In order to oblaia adequate titer aed sRieity. The rabbieti on tbe other baed, produced soti- bodies of high tiler, high sAimitp s" adequata .pscifcity, but ths vohane-yietd of aslirera was coasiderably, kless Uaa W/ o( p9b, it eetkdy sde<pate for most purposea. The e.pensa of raid.y aalarra In rists and rabbits were corn- p.rable. Although the initial ooU of pab ww Y6her thsn that of ralaits, this was o/ae1 by the far smaller qu.aities of a.6io/ensi. I required. Thz rabbits received about 50 tirna as nmcb aatipes r did the psta. Carrro. A. RrzercA Cowuwrwkarbws b CAewdcd ParAofory and pMrwcobp 11(3): 199-302. 1975. Otker.rpp.rlr Florda Juvenile Disbete. Research Fouodatbo. Frorn the Ikpartments of Medicier and Patholo6y. University of Miami School of Medicioe, Miami. Fla. NICOTINE ANTIBODY PRODUC(ION: COMPARISON OF TWO NICOTINE CONJUGATES IN DIFFERENT ANIMAL SPECIES Tnin report deaY with the peep.rstion of two .icotine protein eonjuple., the specific characterization of ttae of tbese conjugates and the production of antibodies is psta ssd rabbits. The low aNiMe.kity, lack of s functional group and the need for pre.ervation of the sntyeuie pyrrolidise riog rnoiety in eko- Uas require the introduction of a functioaa) {roap a.d a(airly long rigid linkage so the macromolecular carrier. Tb. preparation and charscterization of N-succinyl-6 amioo-tx.-.kotiue-BSA ssd 6-(.-smwrocapramido) •tw--nicoline- BSA ane described. The nw/ecular ratio of .iootiee to BSA is each conjugate was 10:1 sad 11:1. respectively. (losu inoculated with the 6-(.-aminocapta- mido/-or-amino nicotine conjugate produud aatibodies with a higher titer and better sAieity and •peci/icity. Also di.cuued are comparative studies of setibody productiue. purJkatao, .old phase a.wys in contrdkd pore klw, titratioo, and specificity. I Carrro, A. and Prieto,l. QiocAemka/ ond alopAyrkd Reterch Cotnnrrnk.riotu 67(2):St)-SS9, 1973. OtAer aupporls Florida Juvenile Diabetes Research Foundatios. From the Departmeots of Pathology aod Medicioe. University of Miami School of Medicioe, Miwli, Fia. RADIOIMMUNOASSAY OP PLASMA NICOTINE IN FUBINTUATED AND NAIVE SMOKERS A new rsdioimmueoeusr for .icoliee is deacribed which roquiraw o.ly crude /nethykne chloride aatractiom of plaama sampks lo reduoe bi6b bis.t valua. It is .uAkieetly .easilive and tipcciec to permit estimation of aicotioe is human plasma in the presence of its principjl metabolile, eotieine. Plasma sroo- tine concentratiom determined after iohalatios or 10 puQs of cigarette saroke were hilther at each of seven poiNs in time for habituated thas for saive smokers, individuab who had .ot .moked for the previou. 10 years. Mes..ico- tine conc.entratioas in sia habituNed and sia naive snaker., one miwute after oasatioa of snwki.l, were 20.63t1.1 aed 7.6t2.9 na/ml, respecUvrl7. Studies on buccal abwrption of .ieolire ie volunteers who smoked 10 puRe. holding each in the mouth for 10 seconds without inhalation of unoke, revealed similar plasma nicotine concentratiora, one minute after emoking, of 1.1s0.1 and 1.2 f 0.2 a6/ ml for habituated and wive smoken, respectively. 1s e.ch wbjecl, blank valua for aicotite were obtained prior 1o smoking and rub- trscted trom subsequenl plasma nicotine eoacealratioaa. Mcss of blank values for .iootiae I. fasted wsive and habituated smokers who refrained from smoking at least eight bours prior to the eaperimew weru I.St 1.) and 7.ti0.7 ng/sul, respectively. Nairw, C. F., Ir., Mahais., D., MiljkoviG D., Milikovie; M., sed Yezeil, E. S. C/4dc.f pArtnoroJop ort TAeraprwkz 16(6):1067-10a9, 1974. FFrom the Departments of Plunnacolo6r. Obstetrics and Gynecology. ..d Bio- ebemiury, Tbe Pennsylvania State University College of Medicine. Hershey. ACi'IVATION OF RAT MAST CEI.LS BY LOW MOLECULAR WEIGHT STIMUIJ Tttis paper reports oo part of a seriea of atudies esamiaind the iorerscdon of low rnokcular weight, eonimmundullie activators with efloctor cells. /. /hir i.vestiptioa, two radiulabekd mast cell acttvaton, compound •ti/k0 a.d a eatioac protein from neulrophib, were shown to bind almost eacluuvely 10 37 56