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SI PARAIN)N lN A MIIRIN1:11,I1KI MIA VIRI/S 1'RI/TFIN KINASI: ACIIVI I Y 1 RUA1 I/ S I'I<+S•-PIN.YI'/(t111:1N St/NS1RA fL• AI'II•.R 1)NA (•F.I.I.UL(/11:('11R/)MAIIK7RAPIIY Tl+c nwnne kuAenNa viros IMu1.V1 as..ICiakJ pnMein f,inase ulivity lus re- «ntly h•en I.wnJ. /n Inr... hl pteJ.rwnaMly plr.yst.Ky1.Ne 11AS". a viris Iu.Mcin ple.ent in rcl.nvely .null an>,wnts tn parllaMy punheJ vlrw preparatiwws l uher virus pp.oelns. .u.h a% p111. Pt?7•- anJ Pra1Y-. ane als.s phuy+Mr71a1ed too 1•wu. Iw1 Iu a ksscr JcKrce /'unhcrnnue. when in.ndwe eare sulywtlcks wh/ch are cl hamed /n PMS•+ ale prep.rcJ h.wn vNNNIS hy Serhanlu 68 e.clusMm nlWnln.IN.unnl..Nraphy, alrwl SIY3 tA t1.c L/nase a.11vNy /a, assayed with Ihe euhcemw% sutMra»c pMuvNln) rcnu/n. asvoLIaKJ wnh the r/res ln Ilns paper. i1 is relurteJ thr /Ms c.re a.voa'uted w nvNy /s J/.l lnl I I rmn AAS" since N can he sep.rateJ Inwn PMM hy chnrl uNqrraphy .m dcnaweJ 1)NA cetluwne c.Jumms (ulbwed hy « nn/1uRatMw al the 02 nl N.('1• clutcJ I/r 1Non Umkc Ihese nrrlNll.n. A6Y' ts pclkteJ wh.k the hln.':e w nvNy. whNh can rM/+{Ilwv7lak hwh ewJ.le/Nws (MuLV PrAS" and pNll aa weli a. eure• /wws I/+IIanvN/nl suhslrMes• Kmams M the supnwatanl. Inlereuln6ly• when the am~w.N.i1 RAS" Is reduced. n In swh pmp.raliows. pit) then becunrs m:lre heavily ptw/splwor7laKd YusMnalta. Y. Shamcs. R swJ La{nR. R 1 Lwrnul.if G.nrrul VoulaRr 64 VS 1412. 1981 lhAcr raNwt: Nwl.uul ('anccr LstNwe and CavernrnclN af Japan IY Y 1. Fn+nl the 1)e1wln.rnt.J MarolwADgy trd ImnwrrlloNy. Univenily o/ SaNA Crnlina Sch.w.l n/ MeJN Inc. C..IumAla PARAVF.RTFBRAL MALIGNANT RIIA60OID TUMOR IN INFANCY: IN VITR(1 STUINIS (F A {•AMILIAL TUMOR Fur the audy preseMed hcre. Nledical and Rene1K evalttwiom was per(atllnt rrn a \inltn<d iN whnh twn klnak slblinp died widliw Ihree tnntMM d/er presenlNlN with pravene1wa/1w.N+n in the first yew uf lik. The prhuM+p d dle two wnwm was identical and characlerishc d a m./ipur eh.hdoid LaNlr. Thne were nu ider.lili.hk Iwrux p.uenls wNhin Ihe tNnhed which have bees associaled with any hereditary cancer IK pecrrcer synlnlrtl4s Flbroblasls were cullwed fnNN skis bilKnies ulNawled /nwn the setund patienl and both pareMs. Ass.ys d Rnwodl tinelics assuciated with .•eRYlar M.nshNnutnM reveakd IhM h11nibIWS fnmN the dkcled stblMA can be dlslm- guished (nNn IMne o/ Ihe parents and ate-/walched eodrols by increased in rinu occur.ence d letrapWidy Such evidence suggests I11M irNxaseJ in vina telraphlidy IKcwring tpodanerwsly 111 cYNured (lbnlbl"s 0 M eRpresSMM PI a cancer prune Aenc Increascd /n vitru lctrapllnJy has previlwsly been denuNlskMCd in uwlr Aimhe.ls with henuhk cuMn crNer synJrunles. anJ N may e stenJ wukntatnlmA.11 the Reneltc e1n.h/Ny of s.rne childinll.l cancers LnN A. ll T ir al ('un..• 52 2'N1 296.19111 (Nticr ruy..r N.Iwm.l (•.n.er Imuwle. 1).net MeJN'al Reser<h FunJ. ('arnell I/nmver.ny MeJaal 0dkKee anJ the ltmurray I uunJaNwl 1'I.en 11.c I )rpnrmem ol 1lcvenllve McJNlne and 1'ubhc Ileallh. ('rc1AM.Ml l lnlvenily I %IIMMJ.oI MeJoc/nl'. 11111.Iha: /IK I)Cpar111N911.4 Pe111a1rNS. 1)IVi\Mo11/01 IkmMtlhlpy• l'\hk..h~y, thr IAlunuta IA 1•:Nh.h~y :rIJ Ihe Ik~ntmenl ld SwFcry. Ibvi.Nrl /l/ 1JIauN Xw~ery. Ralnlr.w Ilahles and ( lllwken.llhrsfuld .1/ llmvenNy /M..plah u1 ('kvelaml. ('a.e Westcrn Resrrvc UnivcrsNy SaMwd 1o1 McJlcNte. CkvelanJ: and tllc (kpartmcnt.A MeJNlne. ('rKnell llmvcrsuy McJN'al ('.Ak6e. New Yurtt. A RI:VII:W t)F IIIiR1ihITARY MAI.IGNANT MI:LAN()MA IN('1.IIfNNG HI1)MARKI:RS IN FAMILIAI. ATYI'K'M. MtILTIPI.E M(11.E ML•LAN()MA SYNINt1)MI: MabKnant mclanoma. which is .aiJ h/ have beew Je.cribed br IlipfrN'rates w/r/ was thc hrsl n. cea•oKn1le Ns nssbRn.M p.Nentlal, has s/«Iwn an NlcreasinN incdence dw/nK thc pasl vvcral JecaJes lhcre are several vxieties d 00% anclenl Jisene. sr...JN• .% well a. Fene/w. and in the hereditary varlelies u( w1a11Ena1N melanu.na esl.essNrl nay J.Ikt s/lendicaMly. llN% irdep/h review pnwwks a esrnpehensive cuvcrlEe .d hereJNary nulhEnaM nalalwllna wNh entphasis opun Ms helenlRenetly as well as newly devehyled hiuwarAer invesuTatione. The rea•ently desertbcJ (rnili.l atypKal lauhipk nNde NlelalNUMa IFAMMM) sytWronrc is kaured. Partipdar aaen. /Nr1 ha% heen leiven /n KnJwqrs a( irk-tered hyperdiphndy dyerved as .n in LM u phealmemin in .wNured sf,tn IiMahla.ts (nwn hKth•ri.k and FAMMM•dkeled sllb- iesls. The FAMMM genlNype is canlplet tn that 01 PrelMyrses a patient ncN ludy lo tnel.rNNna /ewane.w. s.J NNralrttlar twlpewatN twelawluna/ ba aho 1o.Nhec Iw.wlM~ie vanclrcs 11( cancer. inchnhnE catn•er d the lutqt. pa•reas. atd haas(. Atlen/iwt b Eiven Nf cancer swvcidatNe anJ msnaRemeM pnograras (ur paluMs al tnc.eased mA tiw the several /t.als au( hereditary rw.liEnarN twelaNlNna T11is s111pr.wxA capil.liaes aJvanlaEnw+ly uport enlpA/ynlnN 1s( a Rnl.wkdAe o( Eensyicy and hereJNary cancet sym4.rne NktNiliCall{w. wMw p.rlicrlar anenlMw b IwrNlr assoCia1111ns. Ls.n A, N. T. ct ul. ( iww n G.nrrirs unJ CsNy(.w.rR's M:1?S.1SR- pr]. l1rAN itpp.rf: Nrilwl Cancer Irwilue rd Me NebraJa Uiviswn d the Fraurn.l ()rJn nl I:a6ks. Y FnNa the Iarpartmcnl u( Prevenlive MnMcine awJ P1lblic IkaMh. the tkp.nmeal d IkmnloMlEy and &qs Tlwrn InviltNe (.w CunMNMticalNlN IDis.Nden in (1wWlen, ('reiPhwnl UniversNy Schlr/l d Mcdic/ne: Uwvenily d NeMasla Medaal Cenlcr. ( Anaha; anJ the hLrau.y a/ ('ell Bw*Ipy. ('.NneR Umvenity Medical C's/1kEe. New Yurk. GLNLTI('S lC 1RANSPLA('hNTAI LY INI>UCF.1) TERAT(KiIiNK' ANI) ('AN('IN/K:1•NK' 1:11:I.(TS IN RAIIB(fS TREATI;1) WIT11 N-NIlR()11) N 1:T11YI.tIR1•.A • • In this Fenrlic stwly. pr.•ln.uN r.hhN. /d three parualy inMi•J strs/ns. Wl/ll. IIIVI l/ l, anJ X/ l, nuteJ lu a NINY IIIVI h I.M W N:1 /n.ks were (tlven Ip inicaiwws u1 (dl mF..l N nHnw. N ethylurc.IN1'U/ Jlss..IveJ in qwrlnwwn un J.y IN Id Fesulww. (.ene1N JIIICrencY% N11u11Mer WMYIMtINI11) Ir'twel'n slu/m Wlli) Iw.w 1unrm i/N'1- Jcm e s1u.w1 a/wl III Vl /l l Ih/Kh Iwlr1r /m IJrnce sha.n/ hasc hcen Jenwm%trrnl be LMe lN !! WIU1  111V1N11yMa1 p..la•n) wealaJ. 17 Jcw•LreJ fwln..ry nrnd lunrwsat.y>rruslnl.Nrlyllvcnw.Nhsul..Ke (N17111V1)/1 x WililhyM/Jpr..lteny Ih 1 17

wr:ww•J• IA ~kvel.ya .1 p nnx) trn.J lamow. al al.wl hNn numth...l aKe 1 N livc X r 1 x 111V11r) h)M.J t.n.r:ny wr.rs.•J. all JevcwyrJ pmury rrnal IunNrs at 7"11 S nrr+lh..d arc In aJJua-n. erK/N m.Ya.INN: nrplrr~AlasNwnas wtre r*"etvcJ. wnh the IunK heiNK the purury, .ola .d nwNa.rasls Ncan.lrhnMnas wetc uh.rtveJ in I' Per 12.12 prr 17. and tMcr prr hvr r.hMh. re.ywt nvrly, lnwnthe rari.m% hyMNl Itnwls. m•my.d whwh al.n h.J ncw~.kmnul rys1. In aJJrINM, rMe hcpaaMSS anJ lvwrlwm.n~N.ma. wcrr r.b.crscJ Alu., k r.a.yrnN: cllwh u( JrymS+.nti.mak unnialwttNN.n, nsA hN1- inK a klt nRM rrJu.tNm m car knph, wete ti.serred 1'T+NkrnNNJ cysls almr LwnrJ anJ then reKresrJ JunnF the Jcseh.cn+ewt rrf drest Mt.1cA ammals. /ln the hasi...l Ihrs study. iN ap.rars th.t suv epuMlay N$ the rMrureoic elfecls../ NF.I/ appcars Nt havt a JiMnnaN nNNk.4 .nhrnl.n.e, wheren the lctabAtwic cflecls.d NI:U are inllucmcJ greatly by the nutrrnal ItrtNyype. fns. R R . Mrrn, ll . HeJrltun. 11 (: anJ Crry. D. 1) J.w.rNd../ the NwuNwl ('um rr In.tuwr 6"11611411-1117, 19R2. (NArr rrPp.r/: Nati.nul ('ancer Instwat, NdwMal Scienece F.wtNlaliun and the U S. /1rMN' IkJhh 1crvHe Frunr The /s.Ms.M I~&Irwahsry. Nar l/arh.r, ME. IIISII)1.IK:1(' ('11ARA('TI-R17ATN)N t* RENAI. TIIM(NtS INI:1'11R()HI.ASI()MASt ININK F.1)TRANSh1.ACENtA1.1.Y IN IIIVOrt ANI) Wllil RAHHIIS BY NJ 111YI.NIIRUSOI/REA 1'PINiwmF RN.FnnNMI UI a Rene1N pYJlsp/sMNM 10 Knal etMhcal l•yfl I. fRnalNnl anJ 1n nnq+la.n~s .n. rrta~n t..na/ly .nMeJ suams rrf IalrwaNKy rahMl JevewT+eJ at Ihc )nLMM I.h.wN.try. r.hha.ul the IIIVU/1 and WIU) slrarns were whicateJ tolrans- Clxental .Jnnmwan..n.d N ethylnnns+wres IENU) Renal lrtmrs were tn•luceJ in thex .trarn% rr6nJkss r.1 whether the carcNNqten was aJnnmaereJ JunnE the Itesla- INM (serMd as a slnlCk hrlrh .ystem.< Juse, as nwluple M.w syslemic .Mrses. .w a% a c.NnlNnalNnl nf the preCWMn amN)e and nilnle by the IKaI nMNe Far the. auJy. the hrslohKtir fcatwes rr161 rcnallwrrNas induced in Ihese 39 rabhits were analyreJ. All IunMlh in the %etK% l•rMhlnnNl N1 ntp1M'11loIasNMM. p'nnt/1ing the C-,4ahhshnKM Vf Msh.hifN: slawlarJs frr 11n% nnSda.m in 1he rahbil as well as r.b.ctvslNMS .M IanNn pnKressNM 1•sseMUlly. nerhnada.t,wna Pnwed to be pcJ"miaaMly an epthehal /rmwr NkMtfyirtA with mNanc,oho jerac Wasken. which was peswneJ Ns he the tisrc n1.rsEm during tctal Jeveh.fMrcrM. Tht twlstaalieE katwes nmqriscrl chrskn rw .heels o1 wdrflcrenlialeJ Mavema-IiQe tast.e anJ JrlfereMiati.M ahMt the elwlhe- (1a1 pathway inh$ whular pmfiks and suwtaes s.Elresltvt n( punilive, M.nva.cYlx- treJ EhNnerah Mcu.lases.r•ewncJ.Mly in rala+ils r.( stram IIIV()/). whN:h haJ heea wh/n tcJ In a am6k Juse ..1 the crcxN'Fen• Rpe~eMM~ an nICMkM'e In Ih1~ sul~'nNlf/ rd !S'4 Nephn.Ala+NNrss rewhinR Imrn Maaydattnlal mJurlwM in IIIV/ )/) t.rhMls, partiralarly by sunRk. hrEh Jmcs 44 t.Nll. appcx M pnviJe a wttahk nNNkl lur the peJ.onNnanl hrs1..1..Arc Inrm n/ the Wrlms' hmN.r crMy+kR in ntan. /IatJ. (; C anJ F.is. R R IAlrirr. ll 1 Arnra. un 1.w.nu1.{ ParA.d..Xs• 111 /1 IN. WMI (ithrr rup/.rI Nas.-nal l'amcr InslutuK anJ the NstM'nal lnstituks rd Ileallh I n.nl Ihr I rI\ Kc...a h Insrawr. 1 ruy.k 1 lmvrr.uy S.)Mrd .A McJ'% onc. (9nt.wk) plu., auJ I Iw• 1..1•..n I ahwao.Ky• f/at ILrh"N. MI. ® SYNf111S1ti (N;l'AI(IILA(if MAIRIX NY MAMMALIAN ('IN)VI)N(K'YTIS IN VIINt) 1 1SIH.AIN)N,('11I.11/R1:('l1ARA(TI:RICTI('S, ANI) M(Ntl'/NM.tM;Y The yudrcs Ire.rnlcJ hete were JesiracJ hr inve.liltate whtlher is..latcJ INnrine p..lnatal artrcoolar chtuNhrocylcs can cHaMt.h a ttswe IAc matrirt in rin.., wNhsNA ahrralNrs. m thrir plwmyyfnr esprr..wM In thi. p41er, the taelMNh of wt1a1NM anJ the culture aharaxlcn.IN;s ol 1he.e choM N)nwyles we rNtlhneJ (ells werc Rnrwn m Ihr.r suNhe% wNkr a variety .4 .vMJNNMS, including a n.lkt-hrAlle sy.Inn frr mass c.hures. 7 he nNUrIN.1..RN: aMaranre.al 1hc.e cMNSJnKytcs ts Jescnbed JWaK thek i..AatNM and during Ihcw .rhayacnl c1alNnathM n/ a candaRe-like rnalrii in vinf.. Hrhwt cuhwa chorNkrK•ylcs wetc trced..1 wmwnJinR /eniMnial wnlria. Wilhwt tlre /ir.1 few day% r.l cahure /hey rceslahh.hcd a 1e.riMrial wwria. As Inne parigrrssed, chNNlraKytes symhrsveJ Mwh tenaurial anJ ealtarerriwrrisl wtatricn The wsrricts wroe tN h in a•..llapen hhrds and rwherwwn red rysilwe pwe..glycas. TAese ftalwes were nNw1 apsatrnl m nnss ndkr caharn in whirh aRltreRaks u/ ceNs awJ mrnt ap.earlJ a% hME yrcaAs anJ wrOrks. TMs nNUrlNrh.yy revealed aw d(taniruiua of cMNNk.ryks anJ /hen mauires smw/ar ht thal .d /he parenl a.licrlar caAilage in ri". Kawnnrr, K E., I'.wfi, K. U., GaB, G., Memuli, V. A., and SaheaA, R. K. TAr l..wrNd aJ ('rll Biul..Ri, 41:711-7 W. 19112. UrAer snp..L Na1NMal Invilules r.( Ikahh. Fn.nr the I)rf.xtmenls rrf Nwrhemiury. lMhupeJic Swltrry, anJ PathooIrKty. Rush Medical ('.Jkre. Ra.h 14eshyterian-SI. Lttle's Medical Center, C'hi:aEn. and Ik- panmrnl ../ Anat.any. l InwcrsMy .oI Ilerw. Itcta. SwilurlanJ. • i SYNTIII:SIS 1)1 CARTILA(if MATRIX 8Y MAMMALIAN ('IKNdIM(K'YTES IN VIIRI) 11 MAINTI:NAN('E lHF ('(x.1.A(:EN AND 1'Rl)TE(K:LYCAN I'111:N1)TYI't: Crrllaleen lype analysis wa% r.eJ in this rell eaMwr s1uJy Ms con/irm the hMA-lenw in t•irr..liarNwypir s1a1Nl«y.A clNMdnN;ytes. The results presenKd /nr cnllaEew wly- si% wrrc pertonneJ in nrlkt-h.wtk crhtres. TAe mai.n s>talris rwa.Ynnrrkx-rks, eulb- Een anJ p.Mc..rlyran. synlheuicJ by the cINMJnrcyles were eharacletireJ Jwiws Ihe nMr.e.d the culture prrNd The.e cells yMhesinr/ twanly Type 1) cdlaitett, which wa.IrMnJ peddMUrwwly M the ceH-ass.kiakJ malria. The nrtvhanMtaiaed a nsisnre ..1 Type 11 anJ Type 111 avdlapeas. Type I crrllaEtw was mM tleleclahle in tiNher tht roeJium.r the ceH-asuwialcJ malria llre p.wr.r~lyras rwrrunen GwnJ rw dte raJia anJ reM asvriateJ nulria had the sanrc hyJnNlywamir sires as tat~MNns syalhesixd by cartdaI!e slNr..r thosse eurw•1eJ InMr aJaN arlicdar car/ilalpe. Tht w..l.wty of prwayqelycans synthe.rrrJ hy the a eHs Mar LwnJ iw IwRh nNdea rlar werslr aFltreyeales whwh wra rraddy rccauvetrJ InNN the ntJa anJ were euracuhk Ir.rn a•cll aswa riatrd nuuu with M.w Nsir shtnph hrdlrrs lht rewhs JcnNMSlrale the hMK tnnt rs rwrn phcn.nylNr .IahilMy .d the h.wnsc ani.•rt.r rlNrNk.ryles. Alv, JrvuaseJ here were the aJvanlaKcs rd this in r rn.. sv.lem as s nNNkl frK .rwlyinE a vrreq .N trlws IhN xC cap.hk r./ rllrrlmlt a11erMNms in the syMhtsn. JeEraJali.M anJ tKEwN/atNM r./ carlilare nulns Kw•on.•r. A• I. MruN.lr, V A./'..Nh• H It . WnrMl. N C, Th.Mx. 1: 1 M AA and 1).nN•1. 1 l W

1 h.' l.'urn.rl..l (.lI N«41 )SI 757. HMl_s (/rA.r surpM: N./lnln.il lusnlulcs.d llcalth I rlwrn Ilw' IAM1utut'rws /-I IIMr'hcntNry. ()r1M1~'Jrc SutKcry, anJ Partw.k.Ky. Ru.h Ay.'JMA ('.d1.yc. Kush 1lcsh)ta'nae St I.uhc's M.Jaal ('crocr- l1n.vEo/, awl Ihc Ilnr.a'r•ny .11 11hm„s 1.h1n11 nl 1)kMnAry, (lIN'ag11 Cl1KK1 1. -N1 i()N1 011 WLI: .N ('1:1.t. SI+RFACI: PRl)TFAtiN A('l IVl l ILti ANI) AIINORt,MLII1FS/M (K'CLUIH:NS )UN(TK)NS IN RAf IILAI)IN R ('ARl'INOMA IN 17//(O I/hastrwlural ahcralNrm in tnnube rw'chrknles, whirh nc uh.crvcJ in many nu1/Knint tunwrs. hae h..rn egansineJ is t.rwsrJrrahle JNSd rn unnary hLrkkr cw- .uwwtus m hununs wwl lal.ratlry swimsls. In Mis aacmpt Mr 1cs1/hc hyprlwsts that Pa uc.ll ) tw cnr y na PIAy a rausatwe .nk in sMsrnulNres u/ irnwlae .w'.IuJcmes, the uhustrui/ure ol Ihrce raraunrnu rcll lines which were JctiveJ Inun N 1J 15 mltu 2- Iury11 2 thw+ir.lyll hnnumnk n./wad htnwrs r>< the tat witury Madlkr wcn crnn- Pand rn r m.r /)nr 411 these Irnes ha.l s Mrh ceK aurisce pnles.e acuvey: the ahcr Iwo hne, c.h.MtcJ rctAUVcI) luw a.tuvNres OaarNNalive ckcln/n nricnvs.'/IPy Jita te- ve.kd JJlcren.es /n ..nhKuratwln and Jnlnhwww rd nmula rwcludcns lntrant'm- hran. hMrls anrw+F thcsc scll hne., s% rnJa'areJ by means snd aandarJ Jcvraam. nl nrrulA IK.luwkn% wahhs snJ tnrmhrn al mltanrmManc bMds Ahhlwrh thc nAal knKlh /d the nwr.rnemlrrrrws litxds per aluwe nwcnrncar rd rwt Iwkns )uowtnln wes was r.a .utr.lw ally Jdlertnr in the tMee Inse.• junclNnss) nwrphrlrogy varaJ Itrea/ly. Thu.. c.ri mr.na cells with high swlare prwesse srtivMU's sre aMe w symhesve ncar- mralAl anMnaMs /d rnltanrcnArane hlwds Iwl sre unahk w nsemhk nwrmal trrwla ar.hr/cmc. lhrs rnJKAtes that aheMurrs in tunula rrclwkns nwurlr.k.Ey• whr.h have hcen rnJuceJ by t..lenrws Pnweulylw eatymes, art wkntiK.t w Ih.ne uhserveJ in a ccll bnc weh hrEh « II surln e Irulcs.e scuvrly Punh. M U snJ Wcm.tem. R S ('uw.c. Rctrur.A J~ 2•Sy.22•/7. lyll?. , (hAtt sr"o.rt: Naternal Imulults u( Ikahh and Ihe l)tlrt S A. Sprague Mcnwwial Insututc Fr.rm the 1)clurtnknl rrl Pathnkory• Ru.h Medical Crrlklte, Rush Preshy/trian-S1. l.ukes McJnvl ('enler, C'hNalta. 1'R(N)1/(TI/)N ()F BNK'11EMK•AI. MARKI:R SUBSTAN(-I:.S BY NR1/N('ll/Ki1:NIC CAR('INOMAS (iruwmtt rt.rl6nNwr+ Ih.1 ncvrlasln• aclls may have several inlputani kMures Ihal JIS11nF•u/sh IIM'nl It/Mll nnrtlNl a l'IIs Illkr\ an eRl1I/nF' In11NporcI Id IIMMI' %eMll/vt anJ lnyhly ytv lla tcsr% llw i art nMwlw - te.1% thal nnKM mdwatc nct lnc.rmr ..1 a n.m.r r 0 nn.r ..ht n'wrw.l ttr'ral+y wnuW./llcr a Krc.tcr MM+e /111 utc In tha' attwk Ir~ v M. J A.. .1 w a...w . rn.e~ rht Lw. !r~•nul tl (r..IIN 1% /ta IunK l'N. I/MNtU l cII% Me a.« +../ 1 1... .....«4 Lr« w•d d.. n1a1. rul rl v'm. J.Iwlw. Ihar pulnwwury r At I IIM41/~ .. II• /M..I... f a•1\'. n«I/I I.I sU1..1./n1l', Ilut Ill' MA lIMn11MN1Iy Nt.'LI11N'll In n.alual .1 II. ../ 11., /tUa. r A(Arl'c nuullx'r .It 11>,'.c havc tt'rn triluilcJ as plknlul mart.trs it lunuw Pre.em'c Thc.c Pnyrmm inc/wlr lutmw-aswKisled hrrr- nwrKS, rm,ulclal anuFCns, kla al rcywraNry Ira.i PnMeas, anJ /uowK-a..rt'i.lcd ssli- 6cn. AhlwwKh Pro-A(TII has been wrre.1eJ as a scnsilive tnJkahr rl/ lwrw r pes- enre• a n«wc rorcen rclrvt taWs s.n.re Judy nn 1k sensNivily seJ speeilicily ul Ihis PrplrJc ss a lung cancer tnatker. Kecenl researcA with anligenic sul.aances mAaled Ir1nn lung (ulnnr% rkrL% n/Itr VrIK h11Pe n( a lesl Illr Canl'er r/t1eclMnl. MnreOver, rkvekyunrm n/ anu.ers 1o su.h anlrgens rdkn the prn.uhilily o1 rsdMAshelinR such sntd.Nbes a. JraEnnshc anJ Iherapewrc h.rls Finally, it rs pwaihk Nw ahelMirwn in tespraary tract puwcins msy serve as sensilive esrly tnarlen u( 1he inh.laliun in- J i J we a rway cell in 1A1k I jurya Precnswtij cancer Mctnll, W. W. snJ B..rly. P. K./Rn'nnWr, H. Y 1 ('lini. s iw ('hrsr McJir iwr 7(21: M17-)2O, /y62. Fnun the Ik/urtmcnau( Medicine. Yak Ilniversity ScMwd ol Medicine, New /laven, Cf. anJ the ILlnrrnary SeclMm, Wesl llaven Veleraas AJmwusualiuw Il.rsplal, Wes1 Havc*, (T. 1 11. The Respiratory System ENIXX3EN(K1S PROTEIN PI4OSP/K)RYLATI()J BY RESTiNG ANb ACTIVATl:1) IIUMAN NEU1R()PIIILS Nwnenws lypes nf ceUs asrywtd wr ealerwd wiwwli by she.iwR Me levels e1 phn.pMwylalwa rd sekc/ed Pnrieiwu. I.Ihe ywlr Prese.led Aene, Me pwsihh enle o1 Pm1ri. Plnryrh,rplathM in the ulivalitw u( NAI)P1/ osiiase. sweetyrnt in Me plssrtrs tnemMane o/ thc human nrulrnJAil, w'as esnliaed i~ trtnnd snJ cAnrwir p.wrMwrsl• an dtseate 1(Y:1)/ nculnyrhils M tne..wttrlt 1he MCnrpMalMM u( "Pi iau Pnrkis. a delernwned by Kcl ek.yrayiwuevs Gtlhnred by arh.aJrrPrapAy. Resrhs s/w.wed tlw teslmE newnrllhih Irnre nrueul suhje.ls eslwhil st kssl 411 dis(iwrt Ph"y~h"P^~1eM A.e 4. The level rrf ptw+yiMrry4rNM td tArese hamis was e.at~titted altet the adAirioa nf plurlnA ntyristate acetre IPMAI. rlmuwted ty..w., dr=ilaewn. N-Lw,nyl- wn'thinnyl krryl Plrnylalanine IhMLP/. tr NaF. PMA and nps.unted tywasm in. cneasrJ thr PlrryllwrrylatNrw rr( r sel rr/ us Pnwein htMds. l)tpMrnie sad FMLP eaw.ist- emly cao.eJ the plw..Pl.rylalMU1 n/ hwr td Ihe.e Pnreis hawd., while NaF /aikd to bdrte nr•rea.eJ Ph..ylAlrplalMM rd sey (r.wcin hatd. AR awyivaarrs testcd. su.td Me delllrl.yaurylalww 411 nnc sPeci/ic Pralcin hanJ The (iwrc te/Miwrrs/wP AeNween the aJJNrrn rd a.livalrnl; arent. she allc:llaa.'c .d 1he P1rr.Ph,titnyeyt rhanRes anJ the on.et rrl NAIN'll .ntJase wluvNy, wa% dAineJ In atwMhcr eaPcrwnem, ((iI) ntu- Mr.llhds were a•unyurcJ wnh nrnul cclls hr thc.r abhly as PIr1.y11t.Mylae M,ytins tn rry.rn.e h.l'MA. and hnally. Prulcrn IIIr..ydnrytaltrw was delttmmcJ rn ntsllrnt.e ar NJ/', w11N'h nnhh'e% 4N1da%l' al'llvalMrl hW /MA de#!rAlWlalnrl In nfutrnphrls In sum- nwy. Ihe evrden.e .hl.ws rhat plwlyllurylatwln a/ p.rcros is a Pr.rmncnl Ic.rure uf ncWnrhduwlahlAr.m Ilw stnl.mK srnulxny rd /fi1.y11t..rylAtwln.h.nlecs rnduceJhy the vNMM/%M IIVAIIM% 1.'%LYI .uKyr.t. /hat Prah'rn PIw..PfnM)IatMr/ nuy Play A ruk rn vMll~a~yy1~11tna'u1L11.11/I.h1/v,NMW IL.wcscr.nl.cspknrcwASaMArncJrcKaJmRA hnt~ II~IwIYn IN.Nf1n Irh1hl11MMyIa1NM1 alkl J~//sa1Mn1.11 NAIN'l/ uswl~sc 1 ?11 1 ? I

AnJrew•.. t• C and 14,1.l.N. N M a6rur Ah 2- 111 1J11. IvN 1 OtAe- ruryort: to S IbM%: Ikahh Service. Fnyn she HLaxl Rtscx.h I.atxwahtry and the DepaAment rsf Medicine. Tuhs-New IrltlanJ McJocal ('cnrcr• H.nwn FATE (N: IIIIMAN Ni 1tiR(/P1111. EI.ASTASE F(UAWIN(i Rli(-IPII)R MI•1)IA1I 1)1:NINK'YTOSIS BY HUMAN AI.Vf.(1l.AR MA(•R(/MIA(;1•.S IMI1 K•ATKINS FOR C(k'INt{TIVE TISSUI: IN111RY AhMwEh alverAx nucrnphaltes IAMI re tnuww its be cqnble uf recclw.w• meJrakJ erxl.r yanrs od ncWm{Iut ela+ra.e M arrn, little has heen -arwn tKftue a11.w1 Ihelaledlhtenryrncalrcrendrya+.n llrrwevet,inlhiscellcuhwesluJynwaa.een that aUcr Mrel tsjArsurc Irr human kuRucyse IneMnyinl) elaslase 1111.E1 rn cun.. 111 citl rstracth 1(•Esl 44 .ulwreJ Iwman AM c.rMain dereetahk yuaMMrcs d neulnrMl elasta%e and claslaae axrrvny hu Jays: 121 etwkrcyAned weuln+pMl elwase is swrwly JcEraJeJ by the rnk ny+hare.:117 neMnTlwl elaslase and elasrne aclivily re s4rwly rtkascJ rnu~ rht s uhwe nw J~um nrrJdnrncd hy 1he n+acturhrees: N )elastase actrvNy reka.eJ into sc.nJnx.ncJ nrJoum 1CM 1 by the rnacn+phaftes has catalytic pny+emcs co( ncwnod cla.lase• and 1S) clnla.e rekaseJ into CM dunnR 6ve days in culwrc is InwlnMl rrtater than the rnural elasuw aruvMy of the CEs. su6t;eslinE that enrymMic aclivNy ul erx4wys,neJ cla.ra.e is nu%-eJ by an inlractllulx inhrhMlrw. In aJJaxmn, recem JMa wREc.t that hinJrnF rd NLF. by AM InRCen reka.t nl AM-JcrivcJ ahenxr• IACtrc (achn lur ncuu.rrhrls. whrch wrwlJ Irovwk a mctham%m for hual anMdtlk'alxm of tnAamrnatuny injury In wnw+urumR dus wrw-• n has been shuwn that ddxwlth sNrwly JcRrxkJ on r ur.r. 111.1: enJiw yarstJ by AM persnls rmrartllularly hr Jays anJ is pnogre..rvely rek•%tJ rnMU the eslrxellulr spat with hnte iTuest uh.ervarx.nv etwlJ help pnwiJe in.oFM mru the r,oxnpks n.le rr( rrrxx~nwkr pha94wy1e. in the nxxWlalMm 44 cunnntuvc Irswe rnlury in Jr>.Mden swh as puhnrxury eml+hy.cnw Canyd-tfl. t/. and W.W. M S The Jurrnul nf 1.u6ewat..n• and ('liwir at McJN Inr IOp4):S27-576. 14M). OrAn rryrarl: U.S. Public Ikahh Service. From The PukrMwury IAvisinn. hcpattmerN of Medicine. Washington Universily M The kwrsh 114P441al of SI. Luuis, SI Lewis. IIIIMAN NI:UTR(1PIIII. I:I.ASTASI: WITHIN IIIIMAN AI.VI:(H.AR MA(•R(/141AG1:5: IMPI.K•ATI(NdS FUR LUNG INJURY Irwereu in the invulvemcM n( humsn rrKwMwwckar pA+lhrcyles in the Ir-.dlic of ••neunrThrl•• elava.e 1111.1a in the lung kJ he this sruJy d the frrlluwinR Ix•haw the fare rd 111.1: ahcr Ixmhnlt its rnacnojoha`es and the inhrhHrr rA 1114. activity 14 unJ in nur nsPhaRe eurach In rhn wur-. nxrxdayrn rA human alverolar macnqh+pts were t ilxw J ru 'lI p K r rnl ..l lwrdx•J III 1' hr 111 nunule%anJ culwrcJ lut as hmF „•I J+y. lhc rllct r.d hVt-.rea ury.n she 1a1e id 111 1: HwnJ by nur nrluKts was rkrernnrx•J• arwl r%frii is ul A~...lif mh nq.hiKc, wrre runnncJ Itw dx•n ability In ughrfnt 11) 1•. Rc.uh..d thc.a• ~w.h. .%h..w t1sj1 111 dvc.dir mrn"aKt. stuwly dcKr.wk cmhx y- h.vd 1u.1::121 en.ym,NK any aclivc 1I1-1i can penw Irn Jay% wqhrn.uhureJ alve.4r ma.nrhaP. and 111 111.1: wNhin alvtrAar nwn~IraRes is larltrly tru.lcd by the preseme r4 an enJrqeerxws nwcu~haRt inhrlrMrK. hw artrvt entyme eae he rekased ar rrao. e41mially when The celh are injwid. Thus. n<xnrgAages seem to play a very cnwSrka rok in rnrxlulalin6lhe '•Iraltir" of the atulnromMl claslase. ('rwrqrhrl/. E. 1 and WaW. N. S. ('Nt:ST111S.S9S.64IS• 19111. (hAe-rtrppoorl; US Public IkahhService. Fnnn the puhrxrwary Ih.ease and Reywaary Care (Kvisiuw• Ileprtmnn of Medicine. WashmRhM llniversNy M The kwrsh IWnpilal of SI. lAwls• Sr lAwrs HYPUXIC INIURY TO HUMAN AI.VE(M.AR MACROPIIAGES AC'C'I:I.FRATES RI:LF.ASF. Of PREVIOUSLY BQUNp NEUTR(IPHIL fr1.ASTASE. IMPLICATIONS F(1R LUNG CONNECTIVE TISSUE INJURY IN(•LUINNG PIILM(1NARY EMIMIYSrvMA Farlicr sludies have shuwn that hrrman wculn>IIMil elaslast and nlher newnrplwl Rtanulsc cwmdrlaeMs we inrernabreJ by Iwmw aWarlar rnacnRAaEes to rino via n.t•ephn-meJraleJ enJncywnis. and inurwwrreanive IrwapMl elasuse is derecubk wilhrn alvcvrlar marr.y+Aaees 6esMy hxvesKJ Innn hwwM srrrt-ers. In this aNenlp to Eaar inuleM ina) crrwlrlirn. Mal miE1M aarhrlawe release of previwnly inrerwahred hunue newnN+hil elayaae by alvedn macnyiraltes. hypoaia was 11rJied as a aixrdrl of macnr~haltt injury Resrhs nl Mis slwly shrw Iha1:111 in a Ihret•M. imwbriun afser hrid eap.saue Nr weutrurhil elasla,e. curMnJ alvcndar rwn•n>rhaRes partially depaJed Irwml eniymc. Iwl they 061 nrkaseJ inbrl. esryaalicaRy active elaslase in snuN aamwas:1211ha1 teka.e of TCA-iwddde radiulahekd elaslase and elwase activity was enhanreJ IivehdJ anJ lwrdrdJ.wtr aywMrol. rtspecYively. by alvtalar rnacn~ injury JwinE a Ihree -hr. inruMlinw in haNwlrlied nwnrFen: l)I that enrymalic activity d IawnJ ncrrny+hil claNase was larprly aaasled br wrwaw nenlnr~hil elasuae•iaAibi- hwy activity nf nrarnrlrhaRe cell calcs•IS TheJala sultFes11111ha1 dle (a1c rd nculnrplul elhlaw IMwnJ as alvatidat nracnVhaFes may he nnrJrrlakrl by the Mr. al lissuc envrrun• menl: (') that artNw% atenl. nray cawe prolavdylie Iiswe injlrry, in the vicinity of alvedar nwtnrhalecs by enhanrinll release of IwwnJ newruphil etaslase: 111 that alvendx nurnoollure% nuy prticip:re is time ryrlnKtenesis u/ cnwrilulwlr Iwlmwnary emphy.cou by .ervtnK as a vn•ar her arwn+pMl elaNase, eves if elsNase arrwily is not Jc1n•IaMc in alve.rlar n»rnmphVie lysales. In swnmary, lherelint. Ihese results slxw that alvcpdx nrw alslultt mprry arrelrrares tekase new the ealracelWlr soare of ptevNrusly Ixwrx! 1wnm.rn ncutnod tla.ra.e. aJJinot ar the inrteasinEly crwSrlea hMly ni lrwwkJKt tcl:xJmR nncatl4wTt muJulalMrn al pnreinast activity in the caua- t•ellular y-wcs (:wyrhrll. f:. ! and Wa1J. M S Awrc-irawr /trri m r./ Rrqanuwv l1rsr4nr 1_7.611 A1{• (ylll. UrAcr rrypotf: U S 11rAlic 1k,hh lervwe Fnom rhe ILlnxmaty 1)o.ca.r arxl Rcyar:N.K) (•xc I hs•rsNm. l)rrartnw n1 rrl MeJicine. Wa.hmFhm Umvcr.ny ~I 'l lM )rwr.h Ih.yal~) rd SI (.rrirs. SI IAwrs 22

M1 l'11AN1SM /N- INIIIHITNIN /q Pl1R('INI: ELASTASI: HY 11l1MAN At /'l1A I AN11tRl'1•SIN Thc rntcraa-1w.n.d alt.ha I amrryl+sin la plasnu hlyavspraycin whir h InhihH•. nuny pnMC..ly1K entynrsl with pMalnc la.nanalic e1aVa.e was stuJaJ by rv.l.rinK and charaalcntlnK ncwa ccxlMwr pndw-1s Whe. native alpha I amrrylsrn arw! Is.wcrne ela.lase are c.wnhrncJ at rnhIM1.K cace.s. lwar mapr pu.duels rcwh lhrc .d /he pmaWrh r% a nN.Ndea ../ rhe entyme anJ inhihiMt wNh annm.-ICrnunal scr anJ val reskhrc.. wMa h rnJw•alcs rhal a pcpliJe laas hre. nevrweJ tr..n the amlms krm.wal cnJ ul Ihe Inhlhr.r T?w .e..u1J pn*hw1 is a ww./1KeJ (.rm ol alpha-I aMrrypan wnh a nus ra/wr t Mrl.d sl. tlRl, an annmr leenwnal Rla resishre anJ a earMrayl lrrnnnal llw- kr Jp.eplak U ha. m..nhrMhry a.uvey ytaiwsl ela.la.e The c.mnyr..err...l U.c ivdaleJ c.wr.l.ka a an he ydn al MFh p11 in Me presenae .d Jnw./w..l.yl nwM.~lw.. • phalc. whl. h resulls in a a Malylavlly wuaiive ew/yme wrh Ihe aame Mr and nnnr. krnunal resr.hre a% thc native entyme. anJ a IarEe (raRn.ent .rt dpha l anlnryls.n BaseJ nn the.e Jala. she f.4luwrnE hypiyhesls Is pupneJ hy the awMwa t.lasla.e a an ana.l alpha I anlrrryl+ssn 81 erher nl Iwo tna/rr sres If it atlaatts brst at Ihe cart..ay sKk ..f the Ilr k. Joryrptnle. hr'ateJ at dre earfrny-lernrnal pawliww ut 1he mtuMhK, Ihealpha ( arrrryl+srnrsckaveJrMUlwa.f.aEmcntawrhl~nsofinhrhilnryaauveyanJ d+senae../..wrM+ka LrnwMm It. h..wever. the elaslase fir.1 atlacks an a-.er h.mJ near Ihe amn.s trrm.nal end .d Ihc Inhdauw. thc elasts.e Ihew reails wrh alpha I anlnryp srn al 1he .anr ku rmwely N. Lnn a stahle curqdea with aumldele inlnMtwwr .d Ihe entyme James. 11 L anJ ('..Arn. A S l.wrnu/.1('hnn u/ lernr/e.m..w A! 1(N 1111, 1978 (hAee.ouN..l: U S Publia lkahh Servrce, NatNwwt Il..n. l.unS nW 81.d Inuilwe. anJ a PulnMwaary Riqtram Pnyeal. FraMn the Ilepanmenl n/ MeJk tne, Tempk Univeniay Health Sciences ('entcr, ITrta- delphia THF FFH:CTS IN VlV() ANI) IN VITRO OF OXIDATIVE DAMAGE T() PIIRIF11:11 a,-ANT11 RYPSIN AND TO T11E ENZYMF-1NH191TIN(: ACfIVITY ()f P1.ASMA ModrRcMitM uf s,-MlNrypain hy naiditinE 1ieMs can he rseJ Nf shdy the mecha- Msm n/ aa-IMM da,-aMArypsM aml Mr JevehoP M ammal rrwkl u( a,-aMrryP.m Aclicancy. Ir 1he saJy preseMCJ hcre• the hinelus ../ inlecactMM uf IwriheJ chhramme T-kealed a,-rMllrypsin wilh Puncine pMcreMlc elauase anJ Iryl..ut were eaamrneJ Oaidued s,-aMrrypsir Jd nul inaayivate ela.lase. lluwever. the uaNlveJ rrhJ»Nw c.wld wll shnvly inaclivsle /rypun. l1aiJ.lwor a% cartieJ rwl in lhcst uuJres ennveraJ melhM.ny1 resiJues io e,-aMrrypsln 1n mclhwrnyl wlfnaide. 1 hc data imin cate that uaMhteJ methM.nyl resiJoe was eMwe cnlical Mr elastase inMhaM.n Ihan hr vyps.n mhrMlN.n anJ aJJ /unher wcrRM Mr /he hyppllhesn that lrypsrt aml clasta.e MnJ 1u Iwn J.tlccrm .tIc. Al..r eaamrnrJ wcre the elastase rnh.ArrlR aauvnrcs.A ra1.f.N. ,Gqr .i.J nawLc v I.lasn.. I.w uv c(+.L.h/y lu 1na. uv.rw.n by . hAnanl/nc I I IK rahhn .nh.hN.nr w 1.vdv Ihal r% rrlaUvr/y mwu.Nrva 4.../v .r..mhlc, huwnan Ida.saa Inhavrn..us inlrsw.n r.( a larre J.nr nf chhKaminc T ilrn a Mcwmda oer wi.ks rmwti ey rau.eJ a Ja•crea.e In ela.lase-mhrMunR achvey pr rmnca.wahk valacs. with a aunanrnraM s1ipM urcrcase in immurwKCacuvc n,-aMilryPan. T11e Minul reverlcJ so tull elaslase inh/hiNay aalrvily within 1 7 Jays. Tuaic siJe elteais ad hee.rlylic anemia anJ melhe- nwrghsAinrmia wne mrnlmiteJ by Ihe adtrwnislralinw nf mnhyklae Wue. C.rhen. A. R. MrrrN un Rreiew cf Respi.aanr prseru 119:95)-9fi0, 1979. (hAn trM.rt: Naliunal lkart, l.unj and Bhrd (nslilMC, U.S. Public IkaNh Service• and a Pulnwrnary Pt.egram Pnyccl- Fnnn the larpwtmenls .r( Medicine MJ Physigrlny, Ternpk Urivrnily IkaMh Sci- enres ('clrec • 1'Adnklpha. ON T/11'R()Pt:RTIFS (W PORCINE ELASTASE RELEASED FROM ITS C()MI'LI:X WITII IIUMAN ALPIDA-I-ANTiTRYPSIN BY ALKALINE CLEAVAGE ' Ttn% slwly was carried uu11o invesliple the chewlkal slMe alf the aative sNe serMe n.ricly arl 1he en.ymc aller aMaline ckavage ul the purilied alpha-l-anlilrypsin-elas. 1a.e atrrltldea. The released elasla.e avlrrSrsMenl was iwlaKd and eowlgs.rrJ wilh dew native anJ Jti.arlln>ry111w.upMryiule II1FP1-ielwhilcd e/ltylm:. RewNs shrwM thr rr.n1 rrf Ihe elastau canrefIrrneM precipilaud aw Murwilaptbe pH 1u /rcaMtal . The elaslase avwryw.nrM anJ she nMlve entymc wlylalN In the.aaltt ea.Wi/iurs rf PN anJ lemper.- Irre rearlad In a/rllroaimalely Ihe,tame ea1eM wMh t.Jiu.clivety Iahekd t*T. Titese wene aMwr Iwan mnles of Jehydnaalani.e per lnnle rtetvywle ealher ila Ihe pesence a alwence.rf amydca frunrWlur. Tlwa. Me entymt b w/R e.phle af reaHing wMh OFP ar it is JcnalureJ anJ rruYivalea/ by panial arwvetsilw alf cysliwe residres lo dehy. at,awdanine. AnhyJra.elaslase is aQp.reMly aul hrwlsJ drri.SckavaRe.d 1he cowlPlea. lalnes.ll. L. anJ ('oArn. A. A. DNw'Mnw'rl wrf ANophs•sG d Reuwa'A Cc.rwrwwww~ws 901?1:317•331, 1979. Ortte alyr.rf: Nali.rwl llearl. Lwq anJ shrw11af1iNMed hn.r the IkPtitmenl ar( MeJicine. Tenq/e U.ivenily Health Sciences CeMn. Phil.. aklphn. - ISOLATK)N l1F S(ILl/R1.E. EI.ASTIN-I.AT111'RISM 1rMY f1lMlles amltJ at eaa111111/1F' fIaNM vIrwIrR aAll hMNyMheals na'aYssllak swllicieM anrnwlls r.l jwn/ieJ and aherwcally aharacleriteJ Irarlrl.cla.liw hr r.e as a slMJarJ. an e/NcrcM anJ relalwcly n.'apensave na•drd far uhlalnirrft lnyratlaarn rs ckarly Jcsrahk. Tln% rcp.n .k.cr/lrs Ihe Jcych.tinrn1 and we al eywtinaeMally imhw'eJ lalhynsm a% a waran. ul ..huranK Iny.rladiw In»r a vrrely ,.1 JrUrrrM eladic Irs.ues (.ysyl asawla.e i, the en.ynac rc.l..nsdik Nr a-ataly.rqt Ihe nuJal/se Jeanwnalrwl a/ lysyl reskMras. whah r. a lcy dcp an the wwduMbtalwna.d clasun via 111[ hlrnulMM UI a pti~ LnL.. .nt h a..1k•.nr..nr' anJ rvOJesnrsrle I.ysyl uaMla.t .-an hc r.hrhacJ hy rrnJ.rmK anunalv..yq~r .k/..k.n. srnae ly.yl aruJase ayunc.l u -A 1 ?S

ftw actiwty Sinrc IarhyrnFcns xc al-At krw+wn hr inhihit lysyl auotida.e. an altcmatrve w c4+{+Iw r.klw•w:n.-y r% the +Jnnnr.uatw.n A a IMhyrt+lcen dwa lly h.Ihc numul Jrc/ A an amnul. the nrthe.J.sl..ry Jr.anh.d in a sea'IMM uw the indu.lwen .f/ lathyn.m in CAKkC11f re1MCKrNs .1Iwlwm C.M1J.twvth f.4 11VhIIng Ir1opielastln INMB ChhL tl%%ue% IN thrs stuJy the shwl. lecacra/ly shuweJ delinNe symppnns .l( lathynsm /thr nwr.t nhvwws bring the maMhty No naive dr.q /he caltes/ wNhin 3-N days a/1ct inwia.wrr 44 the /athyr.Keen feeding Alvr, pigkts jrst wearsrd slww+ed srRns .rf lalhyrism dter 9 d.ys an thc lathyr.len Jw:t The IVrlilwnl of In1p1e1WM Is desCnhed In IhN Ifa1K7 fTHs pne edwe cmpwryeJ rw rhi. It anrtic ussre tewMs in a lurt.lene.ws pnacia orl -'(1•INN1 daNun., whwh aovrre.p.wls hr the MspalWra b spxies o1 .u/alde elaNin Several ahcr 1.o\ cJWes Jcv'rlhcd here are all designed for Ihe IsulatwM 1l( MnpKlasl/e b, the 741.411111 Jalt.on yiec.es Ta nfaarn any Insy.tsclaslie a, the 71.1NN/ dakun ya.•ies af soluhk ela.hn. 0Mhcr step% musl be 1a1ca alsu, since a siny+k prep.ralive prt eJ ue few purfyrnR s.Fmlicam anw.unls .d Ir.spalsslia a has aol yet heen devehSreJ Riah. C. 8.nd Lvurr. J A Afrrh.dr rn t'e:viw.d.Pjtr 22 66S 67). W{2. O/Arr st.yert: Nslwrnal In.luules o( Ikahh. Fn+m the (kpsrtment of Bw.hennstry. Univenily of Gerx6u, Athens. CIIARA('TI:RILATN)N OF TRACNEAL MAST CELL REACTIONS IN VIVO: INIIIIIITK)N BY A HI:TA AI)l1-N/.RGIC AGONIST The purpne of Ihc (vcsem study was to tes( Ihe suiwability of a new esperimenlal peparstwm. the iM4Med tracheal seRmerw. (ur esaminint Ihe relaMmshrp between etdoftawws bela-adrenerttc slmwlalwm by synlM/hHie nerves. a eal,Wmws aMr- IinerEa sunwltlwus by parasyrrMrathetic nerves. anJ the severrly of masl cell reartwms in the drways. Toddr thts, the ef/ects.os phrsnacuMsEK Ee(a-aJternertrc slmwlatwm un the seven(y d tracheal masl cell reactinws were lesled in 12 anesthnired daAs in rirrr. M c.rrwrol di.p.lracheal arlerial inkclNws u/ enrnpnrnd 4RlIN/ prsrlw eJ ancrinverMws ddktences ts Iwstamtne nwreasarM.n tKSnss the lrachea, btr( wM the Weg: thr% hrwhn6 sw"esKd selective de`rsrwlariwwt of (rarheal ntas/ celk. Tru heal ar(eriovemws ha(a- wune dd/crences conclated wrlh lracheal cswMraclrw% iahwed by crnnpounJ 4NrD(1 in Ihe.e anitnals. In .wher drqts, injccawn .sI ix+pnMeserwA helure cumpwnJ I11iNA1 prevetred the devehqwneM o( Iwnh tracheal ancrirwemw, differences and cutarar- 1Mrns. Since i1 was seen here that pharmac.*rAic Aeta-aJrenerFic slinwlali.m rnMfweJ dr6rnwlarMw nl tracheal mn1 celh, it ap,r~rr. thal the IesteJ prepxarwm is.unahk hK e.amnnnR the ellests a/ endulKmw. amwlr nw the sevenq.A masl cell teax twws in the eentrd airways nf anevhetrteJ Alps Bn.wn, l K, Le(f. A R.. Frey, M 1. ReeJ. 8 R., Iwarus. S C.. Shw:kls. R, anJ (:.dJ, W M Ainrnt un Rn rrw r.J R-prrnftwc Ihsra.r 126 N.12 11411- 14112. ()hAer trMsrt: U S Puhlw Ikahh ScrvKe I r#Mn ~he (•+rJn.vay ul-al Kr..vn. h 1-nutc a.wl thr Iltpxsmcnt nd MeJw onc. I Imver • sNy ul (-ahl.wrna. Srn I ramr.au HNK'IIhMK'Al. ANI) /MIY1I(N.(Kil('AL I:F!-ECTS OFC()NP(NINI) IN/NII ON CANINE 7KA(•III:A IN VIV() Thi. .1uJy wa, dcagneJ po e.amine IrMh the hinchemical and physM"ica1 tnn•hani.mm regulating the reka.e of hi.lamMe IfnNn tenl.vHs1 by c.wqrwnJ IKiSO iwacentralairway.A IrvrnEdd.As TuJutM.,ennqwwnJ4N/N11wa.in)ecled.ekciively wNu the tranceal cin•ulatMm snd 1he effecls tM hi.unwne nnucM in the 1ra.heal pnle- ri.r nrmhane anJ an ivNnelric (rarhed srrwwth nwsek /ensinw were earniwed. Rewhs dwnveJ that in flwr thop curtMrwnd ANiND cw.eJ at itcrease iw tracheal Icnswm I1 I± S(S1)1 R/cm/, while fcm.ral arlensl bMasd pe»wer rkcr¢a..ed nnly 14 211'N• Tr.•heal ti.wc hislanwne decreased 17 ± 6'A in live drrRs eeteiviaK imra- anerul c.wsqxw-r111{rlt(1 ('hhwphcnuarnsae. an N.-arMaAuwssl, selierlively inhihiled lracheslcunlraclwmarrwnpwnd4AiNOaaJhislamne.CimNdine.an/1: aw/apwsisl. Jw) now shcr the respon.e Nr iarrsnerisl Iwvunine. In 11 drKs. 1he drnes .rt bryh wwr.anenal hi.lammc and arelykMdwe reyrtwed so pudree a tMesMdd increase in tranceal tewsiun.d N Ercm were c.wnpared. TTueslwW dmcs fue ne/yklwAme varied N)-fu/J, cMtparcd with N N1-Io1J variatiww fat hislnnine asaortR Mese dt><s. Thcte was a siEmlicarM c.rrelatirn hctweca incrca.ed tracheal /ensiua puJuced by curepwwd It l t(/ and hidaminc. 8wed ow this dra. N was e.wcluded t1u1 eumpwd IM/1{0 causes a variable incrca.e in lracheal (ewsinn ioo ry..r hec•arse of rwatked variability in the 11,- r4cep.r re.pw.e rr( tracheal inwroth nwsck so hislarniae atd because nf variabilay in the rekase of inediarnr fmrn respiraNrry snasl cells by eowtparrd 1`/IM). 1eff. A. R.. Bnnwn, l. K., Frey. M.. Reed. B.. and Gold. W. U. J.wrnd uJA~IirJPArswd.yly: Rrspirar. Enrbow. Eserrise rAysfw.l. SI()):720-729, IYII1. Other styp.rt: Nati.wal Ikan.1 wK and Blood las(wtMe, CbicaKo Lwt~ Assocwion. and the CMcaEo Comnwniry Trrs/. Fnwe the C ardwwascttlar Research Ias(itMe and 1)eprtrwen( of Medicine. Univeni(y u(Calif.wtua. San Francisco. and the Prlmrrauy Secliun, Plileher Schoul uf Medicite. UwivetsNy ut Chica6o, Chicago. AIK:MENTATN)N OF o-AIMENERGIC CONiRACT10NS IN THE TRACIIEALIS MUSCI.E OF LIVING DOGS The majnr N.d of lhis slwly was kr lest Gr a.g merMdiat of.-adrenerEic rcspm- siveness hy M.(anwne rn the un hcslis awsck rr(.Wlts. To do Ihis. aw in siw peparaliuw wss u.ed Mr Iev the c/lea ts.r/ Mslarwine sed.aher aEenn aw.-afitnerlic sersprnes in Ihe /racheahs nwyk .ff N anelthNlfed d11Rs. unikr brdal l•/M11NNy1l, maswswtm a- ~ adreeetRir re.pm.cs were snall annM+awd with IMvse imlrced by a supanssima Isara.yrryuthmr sureulua. A/ter e.p-ure o/1he ew.a•k a histanrne. respwnivcncss inctea.eJ marl.crMy Mra -aJtcnnErc Nrnwli, whwfi rnclwkd Macheal arsenal mjn•taws o/ rrneparcrlwine anJ pheeykpMrne nr eks•kKal .unwlatinn d syrrtlrancirtir nerves- AuRmrnted o aJrencrRw• rryrm..vcness prrsiskJ hv 211 rninwes s/ter the enJ u/ crrtlractinn. wwhweJ by hiaamrne ScnMirwn and Mneg-aninE. bul aw sfwws a.'nnS. 0"Ilirerltic aKnwu•b. sl..r pacmua•J n atkcnerErr respMnsvencss Faun thesc .sb.er- vatiwm.. n wa.:.wwluJrJ tha e.p"rc fd the lrnccalrt srwvk M IianR d%s 1u a varsely ul c.wr.lrss:IMw .rmwle pncndy augmcntcJ qs u-aJrcncrKw; re.pwrveness 1h 1 27

Nr„wn. I K. Shw•IJ.. RR hMk•s. (' JnJ la-lJ. W At l.r~rn.d,~/A1q.hrdl'h,v,.l..ra Rrsl1r."e f narnn F1rr,rarPha.nd 5JIh11tSN 1566. 1'/N I (NArr Ir/Owt: Naln,nal Ilean. I unF. anJ BMwwl In.1i1u1e. Fn,m thr ('arJnsavular Re.eatah (nsutuk anJ Ikpartmenl 4 Madla•ine. llnlvcrsay rd ('allh.ma. San Ftxwlsaa.• anJ the Rcy+uaMKy Care Sn-1w,n. Ikl,utmrm,d McJI• a/nc. Vrtcr.un AJn11n/.Ira1MM MtJKaI Cenler. SaM Franrlx'u. 1RIA('YI.(:1 Y('I:R(N. IIYIN((N.YSIS IN T11E ISOI.ATIa). PI:RFUSI:1) RAT 1.11m; lhr mr.hanlsm,d hyJnaysis r,f cueulallnR YiacylElya•enJs was InvtsnFaNJ In the L.1IxeJ. pcrlu.eJ ral lwqt far IMs .twly. hyJn,Iysn ul enwlsllieJ tnl11 Md. ate ,r J,wMy IahekJ /'l I IElya cry 1. lnl •[' Fdeale wu measureJ by yuamMrulluw td I t/ falcaa ar rd J•t'bdcalc and 1'111RIyrrnJ reka+eJ irw, the pe*(usre. RewNs sMm Ihal o ucyl- IIyk er„Is rc hyJn,ly rrJ JwInK pcrluswn MrouEh Ihe is.,lateJ t.11unE. The rrh a.c „1 Irce lalty a, a!. was hnear a/ar an ImtullaE prtirn/• the knRlh.d whirh wn In.ersely pr.y.,rsn,nal M.Ihe ulw ylRlyacn,l a..nenlralnlw SluJrcs wdhdnrMy IahekJ /'11lp1y• acryl ull•<'Mdrale sh.,weJ Ihx. Jw,nR NracylRlycerul hydn,lysi.. the nn,lx ralnr.4 (ree lauy w nl t„ Flyacnd rekaseJ r% a M..e 1u 1. wEReslinE that aMrN.ntt thua ,d the (alty aa nl. hyJrolyieJ /s rtka.eJ nN,. the PuMnlwary aNCYlaln,n The tarlKt apprar- a,wc ad hrc laity n,J /han Rlyaen,l rn the ven,us elflutnt roJn'aks Ihal the hrsl.lcp in a,x ylElya ra,l hyJr,dys,. ,. a w. ar /he tmhnc~ha) wr(ae l/elwin wa. aJm/r1.IrrcJ M, rnvt•uK.re the r,de ,d Iq.Troar,n lyn.e ,n IM% pna-ess Ikpxln adrmmsa:rrJ NI m/nute. p,.+ tas pcrlusn,n kJ lu mx(eJ rekase .,1 hpquule/n Iqw.e Inun the IunKs anJ anmpktely aAnhshcJ the suhseyotM hyJrs,lysu a,/ cuaulataeE lnarylRl)cen,l. Pcrlusums aanuJ uul l,wr h,urs allrn ccPann aJlnNn%iralnMl sln,w ihat tn11,11KI1:1I Iq.Nu,Mem Irpase kvrls J„ mw relurn 1u rwrnlal within hwr Mwr. in the lanlt In summary, the Jau .M ow thal cnculaunE InacylElyeetul% art hydndyteJ hy cnJ,whellal llp>rnrcln Ill..u JurmR psssaEc IhnwEh the h/ng. (ial, S, Bassetl, 1) I P. I/wm,+A. M., .al Has.rsh. P. ei4r Mnu, a et eurlrau, u Aa w 711:222•229. 1982. (Other rn/l.rf: Natiunal Instuutcs u( lkalth. Fnnn the hepartments ul Physn,M,gy anJ Bn,physirs. .nd rd PeJialrics. Coearseluwn lJmvendy Medical ('erMer. WashrnRa'n. IK'. 11Y1)R(M.YSIS (>F` TRI(iLYC1.Kll)ItS IN TNE ISO1.ATIi1) PIiRFl1S1-I) RAT I.IINI: 1 hctary (any n,J. sre Iran.Ir,neJ in the Plasma a% larse si/e viFlycen,k. whw h caPm,l a ns% the en,4ahclul hartat until they we hyJndyieJ lUe s1uJy Irescn/cJ hrte wa% umkrsaken 1,. Jricmmivne the hyJnrlysr% .d Jdlerenl .alwateJ and unsalurACJ Inrlyarr,dr /Mry w ri. ,m.. the ussue hI,/Js „/ the Ln1MrJ perlu.eJ tx lung Kesulls .Iw.wr.i dha1 111111.41.1 u,klya. t.da•. wra• hyJ„dyicJ a/ .,Kn,haan/1y /ower ral.•s d.an unsatuu~.d unalwylin. uunynsun anJ uq.aluuun wrrr hy,hulyicJ at N I / I N, S J 1 1 S xwl 4 S / 1 N pnn,l Irtt lally wal./r ahy w1INM1 man, rey+aylwa ly. wlkrca. ua.k rn anJ u/bm,la m,.err hyJw/yicJ a1 !11 ! r 1 N a/nl M1 A r 11 1 poM,l /n•r Ial1y aa/Jsrp J/y wIrN11/ nim. rrslrallwly-. lTlr p,lyunsxwala•J IrlKlyaernks, trduw.kln anJ Urx:w6wlnron wrre hyJnJyitd at even htKhcr ralrs. l.Jk-k•J unsalwalrJ u/ylya•rrnks werr hn,len,wmn at slEn/lwanlly hirher raks than 1.1~kJsxwalrJur~lyarrrks AIw.,Nwas.rcnlhalrnrrqrralnan,dtri~lyacrnk-IMIy acMl ina, IunF hpal M a. pra/rr inlu rkuual lry,w/% lhan Inw Plnrph„Ii1+iJs In r,Mn lu sirrl • twar /aaars that apprar its allect hrng hl.,l,n,lr/n (ryuse aclivNy are c.uqrr.ilnnl arl circulM/nE Irlrlycerwk /atty acnh •rnW rnmzmratM,n r,l anculaunR IriytlyceriJes. UP- lal.t anJ IMlrlnMalnrl „1 laity w'nl. N1h11nWt I/(nth were .111rw11 /IMt Mt he T,ni1MN- li/mal nr Ihe rale a4 hyJrulysn r.l the panicular suhsuale N.eenn. therelrrc. that the i l 1r E ycernk •Ix1y w IJ. a•an hr useJ hy the IunE hr mctahaqn: neeJ.. ('unyyun, S K . llmwr.h, M arwl Ilannr.h, P. I p0hf. 17/ N11 MM 711!, IvN2 (hAtr suA.rf: Nat„nul In.Inules r4 IkaNh. Fnnn Ilrt 1)ePartmrnls a/ Physi,*,ry anJ Niwmfohysics, anJ ul PeJiatrics. (icarsea,wn Universny MrJa-al ('erMer, Washrlgarl. ()<. I A11 111/1 LARY-VI:NTRM. SIIRFA('1: (:ANA KI:CI:PT()/(S AFT•tCi RhSI'IRA 11)/lY ANl) ('AKI)NiVAJ('ULAR tI1NCf10N This stuJy Jrals w ilh the el/ec/ u( y-anxadwlyrie aeiJ /GABA 1. nw.am,l, anJ hla'ut ulllne tnl reyNfxlMrl, artrnal I+nnl hlr%%ule a/M/ hlart rale alltr JIreY't ilWN•a1MM Lr 11w venlral swlxe ad the naJulla In.rdn Mo hwdire the sile aal actiue. Peryra rinFs we/e P1aa eJ Juealy tnlh/ the Iranrslem swlacc ns-er ale a4 tMee area. JcslFruleJ as Sa-Mxl1t's. MN. h.ll's.r 1...rsrhrlc's. Arydlcalwrl a( nwv prn>t I(1. 25-2 6d pK 1 h. Sa•Mxlhe'% area M Nl a'ah re/1Y:eJ /nnMMC YtM/ixIMM (anr 1•/1 2 111 Mr !y1 i S! mU nnn hy reJw-nIK Inlal s.,lume Inrn II N z!.1 pr 17 A t 14 ml, wilhlwl aAiwlpinR R'4NfaNry ralt anll alwa/n1n 111 M4Nfa1111A /lylnnensinw anJ hraJya•XJIa M!R aLo ullserreJ APpln:ali,ul .A (7ANA 111/J-J Mh wW/ Pnrhw•ed sinwlat ellcrls .rl respua- N,ry aclivity anJ arlrr/al hwsd Passwt. No siRn/1iraM e1/ec/. Irtw.eJ when Iwrh drnes o( these a"s.ne aPP1ieJ w.lwr•vhc(e's anJ MitrAell's areas. ApE1lNalian r,1 hirucllllme 0,25 prl 1N/ SaMaellc's area hml ihe al/,lrlsile e/(ert nl nwsainnA anJ GANA rnl reyoirahry artivay anJ Motd Ireswre. anJ rcver.eJ the reylirawry .nJ carJnwasculx.k(reswN ellects.ul lnrh 4vnts l In tht hasis rd Mi..1uJy . Ihe awtwrs arwa hnkd Ihal (:ANA rn•rlr,v. are prescnl al ScMarRe's nrea ••arW that aclis:.lnrr ul lhc.t relY'Plar\ re.ulh /11 ra yNr,Alrs akPrCSnrl• h)lallleny1111• and MaJytatJla Mare- awrr.lhr.r re.uN..uKKe.r th.w liA IIA nuy he an InM.rtam inh/An.ry new.MransmNkr In /lw 1nw./ulxanl „1 rrspralay anJ aarSn,w..ulx a.rlud. YamaJj. K A, N,wn.an, W P . fldunu~b, P. anJ 1:/11is, R. A Aruin fl.• arurr A! 1N 71 /N, 19111 . (kAer ru//wt: Aow•rN an Ikart As..w/at«n/ a/wl the (.illy Rescxah I al.rx,rws, I:Ir LJly • In,m rlw• IA-p.nlnr•n1. .d 1'sfiuu,.w.d..,y. An.d-Mns. a1M1 h11s.M,h,l'y, (K,M~a'h,Mn llnncr.uy Sal«%Js.d MrJ,.lne a,wl lkal,slry• Wa.h/nKl.ul• IK' :11 I "/

(-IGARI TI F. SMl1K1 III IK'KS l'Kl /%% I INKINIi IN: 1 I.ASTIN IN Vll RO Thr Ihfrr J111K11,NMJI %nlKlufr ol r1a.11n f. MFhly .IaMhtcJ by a.vakfN . rus- llnl% hrrwccn allJ.cnl rla.un rrlwlJr .ham. Ik.nM..nw afwl /w.k.nMnlnr atr Ihr nwrN rfl.s ImI/nK mumw a.Nl.ln e1a.Irn and •arc.yrnhevtrJ hy alNrkn.alNm 1.1 thra'r te.IJuc. 1.1 u anumuJq», b.ennaWchyJe Ilyslnsl/ with /Nre ly.ine rc•Khrc In the 1tuJy rr11.KUJ hrrc• N 1. .hlwn Ihal waict•sl4uhk nNrKrNxms ul Ihe Ica. pha.e a1 /IhrrrJ a IKJtene ul«11•c inhibit Ihr Irrnulilrr.r( c.nraknt Jes/nnsine cnsss•hn\s Jutlng c.NlvenHln Id lallalJ.nn N/ tla.hn to ritn.. Thesc san+c cnnIll.Nrrnls a14r .uplNCS% ly.yl ocwlJ.c ralalytcJ..aN1alnlw.A Iysinee trwirMtEnNlpslnltNP"ela`unl/heahrnw• cal .tep prrcJlnE Llrnur..n a/.11 elsaw c•nns-lioollis. incluJ/nE JesnNSSmc / ln r Ju.e- Jrytefuknt IashMM lluwevrr. Ras phaae swulhe Jues mN hhN:h the nRwINMNI N( Jumn«II+.•ntawr by ly.yl uclJa.e. Thus. Ras phrrse cigarette smll\e may ry•.%r.. wh- sttaa Jue.1eJ Itancer Ihan rnryme Jfreckd) nth/hNary nlnl(IINatMs ca(uhk ..f uMer- (erlnR with etasl/n.r,nn hn1,InR to Iqrn. Lawenl. 1' , l./N..f}. A and Kagan. H M Anlrrn uN Rrlirr-.{ Rryar.n..rr /)/truse 127121.1R9 1V2, 1910. (MArr supli.rt: ll S Puhhc Ikahh Senrice. Ft.Nn the IkPaftnKnM 11/ ParhnlMSlty. St.a llnivenily o( New Y.N1, SIIMy Bnr.k, and the IkParlmenl IJ Hnw henuslry. H/spln l/nlvenity ScM.A ul Medicine. Hu.1.m 1111MAN MI TIIhININT Slll tOXII)C PF1T11)1: RF.I1lK'iASE, AN ENLYML• CAPAIII f. 1/h K/:Al"TIVAIIN(i I1X1111LI:U Al-PHA I PRIITEINASI: INIIIHI l(1R IN VII RI) Previwws sluJ/e% have alw/wn 1ha1 EwArrirAiu r./fi entNains ar entymc. methnmine .ul(uslJr (Mcullll peptide reJurtase. capable Nf calalynny. the tcJuclnNl of Mettll/ teesNbe. in PnNems atd il has .1w bete slutu'n th.1 this entyme can tearli• vate chemically uaNhteJ a1Ph.-1-pn+tiw»[ irahibtkat /u,Pl/ in ria.l lhe stuJy )xe• senuJ hete 11enN,n.Itales the prcsence fl( MeNll)•peplnk reJrctse artivN / in human lung INNnlltnate, and rn ly.ates tlt pulynnwlllnNNrku kukocyles IPMNI and a1ve.Aar type 11 c•ells. Frtyme aclivMy was tNN IktecteJ i. hbtnsn bnNlcln.alvelJat l avaye IIuiJ tw In Pulmnnary alvenllar macn+PhaEe lysous. The MeNI1/.Pry+tiJe teJuca+c JenveJ butn PMN Is eal+ahk Id teaa thvalinE n,Pl uaditeJ by lreatmeM wnh chhramfnc •T rx a myelMNrctu.idax uaNhtrftF .yslem Ilawevet. 1he PMN-JenveJ entynrc Jues nIM Racllva/e a,P1 MacuvMeJ by treMmenl /n 1•rlrlt with a11UN1um, yJu1NN11 /1I l•IgarC11e snudle Plus PetuaNk Al.u, aT1er rn.uHalilNr u/ n.iJueJ human u,P/ inhl IunFs t•t nl.mal w nnNre tnatcJ fats. M/ real'llt/aMl f•,PI cruW he (/NNUI fn Ihc Iw/nwNtxy IavaKe .If+uNxJ IrrNn lhese ammsls l ntdly, pNreM. wNh chranr uTr.hv. llvc Pa1NUr• nary J/.ea.e al4uar w have mNmal kvel% oi PMN Me1/1// Pe(IINk rcJurlax ('afp 11 . lan..// A . AINam.. W• Wriw/n/uwr. (:., Ilrew, R T.. Wc/shxh.ll . anJ Ila.. N A- - rr „,4 R, y..r.a.r. /// lro.r 121/1/ M/l Mlt, 1VK 1 Ilfb. Irp/wt 1 \ ,1.1. \rlvwc I L.III IIM 1 A 1'.11.1.1/11 .•1 /'J111..1.•/•Y .,fJ~C I1n/YC/\Ily .,1 NrW r.M(. \~••ny 111...~• rhr Rr.a ar. h Sca 1h1n,1 A•p,ntnK nl l.l Mrdl. lnc. Alhcrl ianskin McJN al ('cmrt .1'hdrk I Plna, Ihr MrJNallkrNlnrfN, H11.IthJSrn NarnNUl l•.lwNauwy, IIINI.n. NY. anJ the Rlrhr In.INUIr IJ M/lk.ulx IIN14.Fy, Nulky, NJ PR(1TI:ASI:S AND I.IIN(; IN111RY: A STATI: l*-TIIE•ART MINIRI:VILW Tln% murntrvirw Id unKuinp l.nuwkdEr ah,Ny the te1./nM.htlr hayweer, Ix.Aeaties aml h/nF fnlury i. INrsrmrJ In Ihr 1111MwvrltF ,iy1M,fL: IbsNNir.l Ptr.lara•lives: HiKh- hKM.ld Rccen/1kvrMqNnrnt.l) AMNwNtwkar PAaFllrylea: Rnle in flayax /MNneu s1a.r., !//.dallvr InxllvaluM 11/ I:Ia.1a.c•inhdNNN), and I Inwrwulchrmical As- yy% nl I:17UIn I/rI!raJa1MN1/• ('wrrnl Ma11N QYeyNNN: NIJ SfNne SuggeslnNlo, (rr Fwurc SIUJy In.uNNnary, N is wNkly.u(IltlneJ pN/ay Ihal the JesawaUve chanltes in 1ung! (Lra•n, hyma..4.Ialyd with IwlnnNVy clnPhy.ems are melhaled in larse part by unrrstranlrJ IN/wedybc r•tivny in IunR aNnrecuve 1us.ue. This c•.NrJNwnr ts IMIURIM 1n ari.e whenever elawdyln• IN.wea.es are reksrJ 1r.Nn hny cdls and.rt nre(lecuvely /bwnrrKdlalrJ by cnJlogrmNr. PnNeiru.e rehrhilNn M whc hlwtt rrspinln.y, pac1. MarFinalad newnlPhil.. re.ilkm alvcular mw•nNlhaEes..nJ Inwlte tecemly) Treshly recryneJ trMNNNwckar kutacyte. m ban.N helween WINd capiHwies ard.lve,llar y+are.Iuve 1+ren imp1/ca1eJ as lilely vN>tces.r/ lwqt-dam.EinE elsasses. lht the /whn , hafwl. alpha,-Pnllcma.e inh/AN,N //.,111 ha% heen nrlPliraleJ a% an itnprNtam teEulawr .401 newra(Ihrl atol! tmNNr•yIe elauaxs. 'I he hypMhe>s duN.n imhalance hnween Ihevt (arpN., lavlNrnp paNcase arlfvily. tv pall.rFenetic rw emphysenn tesla larleely tNl the siltrul IllhetvG/1MN11 nl IAureH and 1:t1L%MN1 wlnt te(ytpM7eJ that sekckJ cases u1 eafly .Nt.cllafmlul eoKlhy.ema wert as.,KiatcJ wilh herilahk a,-Pi Ik1i.-iency, and (:nrs% rr rA, wh11.1.IweJ that xnralwlnnlnary Ntyi11a1iM d elasadyue rnNea.es Pfo- JureJ anaNwlir JrranFcmcnh in eqarimental animals c'haracterivir .>f human em- Phyxma Rea•ent /+n/pe.% m 1Ms arer hys hcen e.rilwtlt aeJ has been Ihe wh/ect tlf Ji.rw.ilNt at vtveral marN synrlrsia fwee Ihe IaN JeraJe. Hlnwever. parlease-amrpnr• 1ea.e mrhalarN•e a% rhr mrchaniwr a/ alvealar el(acernenl in nNnt IrNms nf etrr(Ihysenu still renuins al he INUven. lwwlJy, A. rHf:Sr 811SI:S-IS-SNS. 19111. (MAtr tryr..I: TI S PuhIK Ikahh Service. FnNn the lkrattment rll Path/Mhty, Stak Univeni/y a( New YutA, Sluny Buull CK:ARI:TTt SMOKE BI.IK'KS ('R11SS LINKING OF EI•ASTIN IN VIrR() hN /he a..ay sy.Iem nryNteJ hrre• IwrilirJ InqNlelstin.nd lysyl NaNla.e wete incuhak•.I IIN '~ hrs p.laalNa/r 1nymlrly.UncaarrrvatnM nuJ Ihe.esrNanl Jrsnnr.ulc wa, nry.utrJ by a prrvMw.I) Jey'fthrJ /aJNNn111Wn1tfl~yy n~thl~. 1juee J/I/tYe1M kimh.d afKafrlle snr.l,r vllubnn wrrc N.Md m Ihf. s.ay sy.Iem Rewh..M Ihe five el(RtN11rIN% Jry'rlheJ hrrr %Ih.wrJ Iha/ nn Jl'NIMmIIIC Na% JrlecteJ unJre I+a.rhoe e.N>tMl.m. Ila..rvrr.u.fnpc/Nfl(Iklerntsnre-.uh.ualrnwstwr.anJmcub:Nmle1N (1' (' m 1114' aMcn. c.d %11M4r • Jl'%nM11Nn LNIIIa1MN~ wa~ Jrn111nMIrJIrJ hlNh W/lh hlNnNh/ rINf. cntynw' .uh.b.Nc /nlaurr. alwl ha•av..h.yaa. Nnawrr. / ln thr rNhrr hJnJ. fn rhe INl'V•nIC..1 Ja11pY.11\ %I1M4r 4.IINbNN, J.'~/IM.~IN.' \ynlhr\Il W^ mh/lNN•II fn J11 Ilve cahrlnlh'/N\ W/I~'n.1/111N1.'1\•IMIa'IN J~~Jy NM•/IM4I Wa~ YV'J. Jn InhIhN.Ny CIICII ../,'J\ NI 1 11

PIIJV ..FJn•Of .nM./.t a•n (h. ah.'InhJI r\a.tMM1 whNh lMCtt.k% and /% rryuucJ Ler .k%11Mn/nC L.r/1U1MM1 MJ, JI,eI,hHwn In thr.t tagwruneM.. ly.yl tnIJJ.w catJlytta) u.kIJavc .4•Jnon.ni.wt tul 1)sux• t aronM, paw.ln wJS n..nn.reJ fhe cllca 491 KJ. PAJ..• .nrd.e .•n rlJ.lrn a...l.ru.n ..JS ah..t-JclicnJrM. and /nh/Mtrin was teadlly 1k•It't Iahlf Ct'fn JI JIIu1NNn .4 ~nMAC M11utMM1 a\ hIF'h a\ I I\ll (UUJa1MM1 ..1 Iy%InC !• annm. Ka.q+s ryct.•.k. .)Mhc.rs .d all Lrntwn clJ.lin cw.ss l.nLs fhu.. t4e d.pa Ptev'me.t lKrr .uMrwt t1w ..m.ht.M.n Ihal crprellc srrw.lc l'an Inhlhll LMIIIJINMI ..l .whrr tla.rui cra..linA, he.wks aksnrnlnc. I aurenr. 1' , h.n.4/ A and KaEan. 11. M. ( 1081 N t, st A 1s A"s. W11 I (hAer rrh.rt: 1/ S Ibhlia• Ikahh Scrvict. I nrn thr Iklwtn><nl .d Pa1hnM.Fy. Surt Ilnivtnily../ New Ytult. Sa.ey Bn.i. anJ Ihc Ikpattnrrnl..1 Ha.henu.ay. Btnaen Univenily Sah...l..l Medictne. Busa.n I I VI.1 S(* LI.ASTASG ACTIVITY IN BR(1NC/10AI.Vf.ULAR LAVAGN 11.1111)S(W III:ALTIIY SM()KLRS ANI)N()rSM(NCtRS The /wrl...t.t/ lh1. sruJy waC a.nw.q%•nt elasuse kvels in lunlt wa.hes..( healthy vulunarcr .n«skcrm and rr.n•n..Atn anJ as prtly clurrlerite any cntymt./rw.J wrth re.Pec1 a, lheu ahrn+k a/ a IJSthcalrul anJ celNlat suwct/ s) wNhin /he lung In arJer a. Jn IAis. ela.la.e acavny was n.easweJ in caua'enMaleJ. cell Irce M.ukh.nlvn.lar lav.qee IBAI 1. u.mR the .ymheua' .uhstraae hulyl.nycarhiay) l.-alanyl 1.-alanyl (.- p.d)/ l.•valyl Jnuew. mcthyl..wm.nn Thr HAL QuNls aMJ/neJd /nwn y.wnK. asynM• awnata snMAer% wnh nowmal wine Jesrrrn.ne c.wenualw.e% tute Mwt aller ncey had .nwtled Iwo crptc/trs h.wcJ stFmhaalu urre..es In cla.u.t kvtls cuml.ateJ wnh tfwne rn mu+stmiA/nK aunrnd whKals Ncpcaltd BAI...ny+ks were .*+lanrJ ar la/cr lunes Itum .urc aivAet wish a high /nNUl tntyme value and laun aua mwssnrek.nR cunlrol suhlecl I la.use aatwny vaned nver anr. hut Inrh suh/nls c..nsl.temly rtmameJ within /hcrr teyeaave Rnwp tanKes. Inlnhrlam sarJas an pwakd NAIL laun snMoker. sMnvcd Ihal Ihe tlada.e rlivily pesent had Pny+rrlies ul h.wh senne atr! Inrlalhsentymrs. .uEResunE /hM ncMnrrhl6 a1J/.w rrrrMr'yles Isenne entymel a+ well s nwnyia.Fes Itneulhentymel auMrihwed at the .Ifaerved aclivily. l.wqt IavaRc cclh uhlalned tnun Iw.r rd 1he srnaiers and 1wu nl tAe nun.nalkers wrre slaincJ wdh IrNh a.hnwrr.ycnmc .aAtuare and by indireel inw+wadlw.e.a'ence hr 1Ar .eriee cntymc Tlae rewNs u/ lhne anJ.Mhcr .lodres slww wrne a.yanpawnalic s/m.lers have s1Em/K anrly nrwe clasta.e aaitvlly In 1hc» hnwrMrlwlnuwaty secrelam. ih.n ab nun- srraitts Ia% nrcasuteJ with a bw tmdtculr we1FM synlheue wb.lralel Al.o. 1he entymc wavNy .ecnvered in snrolers' BA1 aners In 1k derrveJ nuinly Inuu nen• Inrhd./setnre entyrnel and nucnoPhates IlnclalMantywcl. ralhcr than lrem uwrM.- cyles lun,4/. A. Ralu. I and Ika.nE. R Anu•r,,,.n Rrnr.. .4 RrtlrmnN.rt Ih,rwr 12715/ SMI SI•/. 141t1 llther tr"nrt I I \ 1'uhln Ileahh Servne 1 itu 14/...un. n~..1/'.Nlw.l..pt \ti/a• Ilmvt•r.ny.~1 Nrw Y.w1 ar Sl.uty Ita..•, aurl Ihr 1'ulnn.n..r~ I b r...r \.. t~nn. NJ..JU l.Mrnly Mtd.ul /•cna•r. I J.t Ma' wluw, NY 'flll: ROI I:IN• l)XIUA I IVI: PN(K'I:SSIiti IN I:MI'11YS1_MA N.Mh pni/ta.c% anJ a. avJ/cv) yaY it. u1 u.y Ken have heen mal.lia'aled a% mcdul..r. 4 Inww/w.M.ric IunK injury. and Ihc pe.eM repnl auenllM% hL hnf,lhcse Iwu lulhways nl avwukclrve a..uc Je.truclr.n I.r alslanaY. tla.la.e/rla.la.e tnMhiaK tnthalanct /w the lunr ha. hccn inMdK a1eJ In 1ht Parhe.rene.rs aA Iwlerawary etnphysema In hltlr../ rhi.. N nuy hc strmlican/ Ihal Ihc aairvay ar1 1wu rnaMw elaslase wrhiMav.. a/Pha 1• Iw.wcuu.c Inh.Mau Ia1Pha I an/Nryp.ur. u.P1/ anJ hnu><hial mwu. PnMeuw.e adwbi- ar. a'an he .kcteaTCd by uaalinnp aEetNs. The cllecl can he uAserved wilh otarr. suh.lJrwe. /uc.cnt in siFartllc sm.ohc. anJ nayEen nmctar.lxe% generaled by 1ung maaayohJKcs a% well a. Petuudalive sysletns rekaseJ by anher phapu: ylir cells. Thus. n,Pl ra•...vercJ InMn htnF wa.hinEs t4 a iltareNe .nuoken has unly ha/1 MC IwedkaW Irunul arlivuy Pcr arK mMMaw aml c'.uMaars f.nw ralks ai/ nlerAarnine wNuaak Luadved narhw.nint/ Per nrde d Inarave inhihNar Ily crwNrad. a,Pl Purifitd Ir.rn rMwVIMiLCr\ lunp wa.hinKs is fully ar/ive awJ cauMa/ns aruly nalire w1elANnwnt. Al lhe satne IInK. Iung wa.lk•s /nnn v»ne nwAers shnw .iEraMamly FreaAtr hydndylic ac1ivlly aRrnsl a spccdi. syMhayit elaNa.e wMaale Ihan du hms washes ur nueamA • en. In addwMm a. lhe prssrhk e/lecl ul ciEarc/le snr/hinE an bnE elaslasNel.Ma~e inh/hrair hdatwe. N.eerns.nrdnlp al... may inlerfere wNh elaslin repair rnechanisnn. SPecllirally. N has heen seen rh:M aa'idic waler-...luhk Eas Phase camtpntlenls a.l c/ra- nae snu.le Prrvcnl synthcsn tt/ desnwnine en.s•linls dunnlt elasuMveneNS ar rltr.l. %wu,//. A. rr d Awtrrepn RrIwN• aJRryriraam' piseaw 12712/:S11-S12. W1{). fhher.ry.tY: 11. S. Puhlir 1kaMh Scrvia'e F'rnMn the 1kTlannrtnl.o( Patlyd.hey`Stalc Univenily of New Yurt. Swny Bnrok. BNK'111:MICAL LINKS NETWEEN CIGARL:'TTf3 SMOKING AND 1'ULM(1NARY I:MINIYSLMA 1/ ts widely ht/irvcJ a./av Ihal Mt dC.trrrtive a*.rtEes a.wriated with enrrhy- .ema are nkvhaled in large P:In by wuewa/tcal pnMnllylir /esPccidly elasady/M•1 arlivily rn IunK a'awrkYllve //swe. N r% fwtkr arEued Atal lhis Ias1 etnalNMM rrsrNs fnun Ihe heiph/en.d rekase 4 clasadyli. Pralea.es by aYlls rn the Iurng. enupkal wilh an paYluMY/ tM ECnC1K' ak11a'It/a'y N1 Iht enlhwlalY! MMi1ql.lealCs re%pMSlhk /In reRrlalinR /hcse entynrs Fvrcn U.wgh dris hypqhesis s1iR reywrc% ritnKaws Pnutf, newer inl.warMrm is raPwRy drvel.ywnP Ihal lillls Ihe Ir.Mease•ParlrlPewnis nla.kl as an ens•inualr•Mal ri.l faa•aK a>..wialtd wilb dl.ea.e. n.nrely ciFarelle .nwiliu4t A MiaJ ad ahenncal and ccl/ular c/lta1. Pahhwed by ciraMle sn.ole has laren wyKesaJ a% a•.uMrd.utnlK h* allercJ t/J.an me1JIro11vn and eseMwl deveM.Ptaenl 411 enlPhy.enw in .nMolrt• fh.• PrC.rnl wth'k revkMS MwA .4 1he.e ulwervata/n.. .erls ar Place lhenr..Nhtn /he twctJll ItJnkM.wl..d Ihe /..ycav nwwkl anJ alkuyMs ar rav yucs. larn I.u Iwwc .lwly , ' lan../l. 4 Rr.larat fnu...n tu..tt. I'ht.nd }t/!1 ~MS.~y1, IVIt 1. IhArr sr//nK: NJIN.n.d 11.•atl. I nnK J.wl HL.*I In.aluN InMn /lM' (A•I..ullnr111 ..1 1'.dlr•MVy. 11.M.• Ibuv.•Ln) .d Nr.. Y.M\ .N 5t.M.) Ilnrd,. 11..a) 1/..r.1, Sj I 11

PROTT-ASI.S ANI) ANTIFMtI)Tf ASf.S IN TNIi 1.(IN(i ly.dea.e. .nJ +m9,n,te..e% tn she lun f have rectweJ tncreasinf M/ernwOn i" the PaN tS year% hecsu.e .4 RrawlnK evMkme Ihal an rnlhalance helween Pa"tndyllc cntyoa. and tht/t mh/MaKS may Flve r/.e /n ctAain Icalurc..i( cM.ww I"ru.nve WnR Jl,,ea.es 1('IN1)1 in msn he eurqde. unreslrarneJ ela.hdytK a.lrvlty in the lung ha% been wFRcsleJ ht he re.lw/n.J+k (.+ she slveular de(nrmalinn seen /n pllmn- c ar.es nary enolihystma • while se ver aI wtxker s ha.e rhrnnw that c1asN.ly1K MIKk alvS aheratn.ns in the c..wllup t/nE airways similar b Ih.we ms.rialcJ wNh chnwm. bnw.. hi- Iis. The tAn1 stctN.+.rf tMs Isal.Ct n devsreJ Mt purenn in rhe Irn61/w.rea.es ul the alvn.lar marnpha(te anJ../ lhe pulyrnnrpAlrwtkr weMr•'t>tiJ IPMN11 and to pwennal Ir(tcls u( marnrhaEe anJ PMN elasrases in hnR ealnecuve 1lsslre. FdM.wln; .ec- tMons cunsrder adlPrwtases in the Iwt~. ekvarww u/ bn~ pnAtases in snr.ken. Jepres- swn of lung aMrPnMeascs in smuken. inativrMw of r+uMoteaxs by o.idanh in N.baccu srrMokt. anJ Inacb.NMrt.1l aMlpnstases by ce11 generated u.iJrN. Summa- t.on.J 1hM% detailed review ahalMer shows /ha1 son.e of 1he elasNdyllc pruresses rn the IunR and s.me of she marw lung anlipnMtnts IAat regulate the aclivily od these enryrnes.redlscwsed the Invesh(tMnrsthenpnipnepdenlulmechanismsby whlch ciRarene sm.•klnE cuuW elevate the elaslase "bwden" of the lung r~ Je~~lt of IunF-s clasta.e /nh/Muw '•srreen " Finally. IAe proleax Pathn6 men at is Ktnellc /ael~ .n m~M e/luence he baltsnt~c btlw en PrlMCa~~ ~ea^t'Pru' ltaxs In the long lmwf. A and Carp. II In Newhall• 11 11 Itd / I/nwwnurAorw+a.JnLy "ftAw /a'nR• New Yurk.Marcel l)ek- ktr, lnc . 1VaI• pp 171 N1!< prAtr srp/.r1: Natnmal lkart. Lung and Blood InstiaNe. from she DtPartment of Pa1M*.gy. SIMe Univenily of New York, Stony Bnr.k. CRUSS CIRC(ILATI(/N STUDIES ON TIIE INFT.UENCE OF 11YPOXIA AND IIYPOXEMIA OF NIiUR(A:PITNELIAL BODIES IN Y(x1NG RABBITS Using young ra11l+Ns (nr lesling, the rcarliuns u( tltarocplhelul bndrcs /NE.BI hs /11 hypnata weh notmosemis in Ihe aAeria llnlmlrnslis nn the une haeJ• .nd 121 hypnscmia in she aruna pulmonalis with nlrtrKrsic serarial an the dher hanJ• wen: rnvesuRaled by nseansof eras.•eireslMmn ss RPers hutslw/sved that hypr. ~ y serNeJ mKwx~.K+/c and m'~Nnclnc ttchnnluc y.wnR rahhNS. which mt1"d mMmDseormor blMd in their sACna PulrrrMUlls InMn a Jonwn rabhil by means uf an arterMranend cnr..-cecelalNm wnh mutual eaahanEe Irsn•lu.wm. rcveakJ an tnerea.ed es.w yhna.l/ the Jcn.e'c'nc ve.Kk..4 their NItB. N.nrm..M ally aerarcJ young rahhn% whlah received hylos.aemic bM.al in an identical alit h oil ctwk N the Nlj IM Iy• en 1~ xt JlratlcxtW y a~ihe hylrnuhi.f the inh' kJ srrland ms1 Nt h)L... nua ..1 IM- p.u1bl.N.ary hl.aT By she rcltast u/ atdun,n and a Ldylwl'took .u1..1...I t1••1 n-V 1r../...c a 1•.al .a,.n..n.Irl.Inm /n hyry..n.lly xratd lung ar. a. . naM•nt an .nu at+.l••~+~•~ V or rula/w.n ..l she V.t) rala. I hs, 1% rrral.l.'J J. r~1 ~ ~al /.,.,r 4/.a4 d. NI il +1uk 1w.nK nr.lulalcJ by the I N\ In.4-ahly aut 14 irMralwlnrmary chcarneccpl.ns with hw•al secrelnry aclivilies, reacting h, the cumfr. snr.n u11he inhaled air. l.wr r.vns, ! M rr al. Crlf unJ Tlssrr Rnrurn li 19I:17)-1t16, 1971. Mer sryprl: NMiwrual Fnnds vwK WelenschaPpelijlt Owdeewck. 8el~iwn. Fmm Ihe (AMxahlry 1.( HislnpMhr>logy. KMholieke UnivenileN k LeYVea School of MeJk ine. (.ervcn, Btl`rom. INTERA('TK*4 ()f SE.RtYT(NdIN WIT11 VAGAL- AND ACh•INDUCED BR(Nr(1f(KY)NSTRICTNNN IN CANINE LUNGS 10 Ihis anempl u, derenrwne whether se.olwtiln acb at the level of qle airway tnnwh nwsc~c nwscanrnc recepw, a cumparispr was r.de of tAt e(fecl of serolonin ow hroarhnconstrKrwln caused by vasal s/inwlMion and by i.halaliam of acelykhnhne (ACh/ aerosals T.r Ju this. she broachonwalrkh,r response 1o ekctncal slinwlMiow e( - the penpheral ends of bwh cd cervical vqus nerves was plMeMia>M by seroAMwn aennols in N/ esperimerrs in sevels anesdKliaed dop. The bRmchocorwricwr rc- splMne to acelykhlrline aerusols wss nnchanRed afler secolowu. Specificaqy. /he Msur-hnamstric/inn carsed by ekcyrical sliwwlalinn of vqal nerves was siRwificalwly increased by pekeMrnnw wilh senlloain. but she respoose 1o inhakd ACh was tw- chan6ed. The pMerwiMrun of Ibe effect a( vaRal srirrwlMimr diA rim result fralm ahera• liun in base-hne airway caliber, because bne-hne R, was siol changed by serowo.in ae+vsds. Becawe uf Ihese tesohs, i1 war coacirded My Ihe sr~oolh nwsck nwscarinic recepNx is aM she sile where serolordtl irMerMys wilA the v.pl sanlor pathway /u airway senwNh nwsck. h seerrts. rs(her, IhM serowwin acls M 1he kvel of she parasym- psthnic 6anRlia ar Ihe pnu6aKliowic nerve lennied w paleatire the brunchocuaslric- 1or response w va6al s/inwlMiow. Shelkr.l. R.. Noktman. M. J.. Skuo6h, B-E.. and Na/rf, I. A. luwwuf af Aqr1wJ PArsinlnRr: Rrspira. Ewttiron. Earrriu PAnwrf. S2(11:946i-966. 1%2. Other a.pp.re: National lnstilwes of Health. Fmm the Cardiovasawlr Research Inslilwe anJ Depammeys ef Medicine and pAysiol- o1y, Uraivcrsily of Calikwnia, San Frarwisco. RliFl.l:X STIMULATI(1N (1F TRA(111:Al. M(1(-US GLAND SECRETK)N BY GASTRK' IRRITATN /N IN ('A fS , Tlris sludy had 1wa aims /1/ Mt Jelernline whether !hw frmm the ,rAnwiu..l 9land% af she rrx•hea is retkaly reFulaltJ hy senwny sunmb fn.m she sl.nna. h nt she cal. anJ 121 i1 sw-h a FaNr.Kwlnronary relkt tstws. Mhal sensary anJ nwN,r PMhs.ays nr inqrrl~ll Reyr.n.es te.led here im•hMkJ nn•:h.np al vtnwlati.m• bh~•ka,k.d rhe wwrehry rtyr.n.e wrJ .al.sislnt sullate inlwrrt L.IM.MeJ by ekrrrw•al stumularNUr ..f rhe awltal enJ.d enhrr v.Ku% nerve Rc.uh..tw...eJ /h.1 nle.hinwal +unwlnNon u1 th.' Ka.Irw nu...N.lm rt.vJ v.hmu,,...1 KLrM/.e. rrtw~n./r..m 7 4• 11 7 tu 1/ 4• 1 7 1S