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ANDREWS OPFICE PRODUCTS CAPITOL HEIGHTS, MD (K) s

Gn'1'ItA CUI'Y RMRT

Ns3 R EPORT al THE COUNCII. FOR TOBACCO RESEARCII-U.S.A., /ec. r Il S ~~ Tllt: l'/NoNI'll t11R TIMAI'l't1 RFtifARl'N - A Iwc .. .tt: ....

SCIENTIFIC ADVISORY BOARD ro The ('awrcil (t. T~vharco Research-U S.A.. Inc. as to1 December 31. 1'Ir_3 LEON 0 IACOBSOrl. M O.('Auirww Jrn.rA Regnurnn Prt~rssw of Swiry(hn/ Scinres (rnwrirrs( Prsfissew aJ rAr lkprrteww oJMeirisr (rs.rriws) llnrversNy oI ('hica`o ('hiraRo. (11inws RK'HARD I BINO. M.D. nirKaw .f Esiverinwwof Cordiobrr.w/ Sckwi/k' Dnuhyw.rw IIwMN+61an Mcdicd Research IssurMe. Pssdera.. Cahfornia VesninR AsuK taw Csldania lnsrNure of ltchwolop. Pasadew. Pnfnsow oJ Mrdicinr (rnwriaul I Im.ersily o( Snwherw CaldoTSia School o1 Medicine I.os Angeks. C,lirtrma ROSWEI.L K. BOUTWELL. PN D. Professor of Omti1loRr McArdk Laberakvy far Cancer Resesrch l/errersNy nf Wixrnsin MaJoum. Wrsc4mm . DRUMMOND II Bt1WDF.N. M D I PETI:R M IK)WI.EY. M.D. l.abiw«my tof ParM*iry Na1Mru1 Cancer In.tilule Bethesda. Maryland HENRY T LYNCH. M.D. Pn*ssiM and CAuirwan Ikparrmenl u( Prevemive Medicine and Prblic Health PruJissar af Mrdiriwr . Presid.ns. lkredilary Cancer InmipMe Crei6Man llniversiry Sclkwl at Medicine (hnaha. Nebrss4s O. BARRY PIERCE. M.D. An.ericun Cancer Snrkr. Ciwrnnl.l RtrumcA ProJissw • University of Colorado //eaNh Sciences Cewrer Denver. Colorado GORDON H. SATO. P11.D. rnr.cha V11. Ahun Jones Cell Science Cenier Lake Placid. New Yort SHELDON C. SOMMERS. M.D. Scinui/ic Director. The Cowicil for Tubseco Research - U.S.A.. Ine. Cliwicol Prdfissnr afRutidogy Colkge of Phpiciaan A SrrSears of colwnbia Univessily New Y~xt. New York ProJissar and Heod Ikpsrlmenl of Parhnk,9 r Universiry d Manixuba Ikalrh Sciences Cenrer Wrnnipeg. Canads ck.Uh slafr.r 111111, c..sdl MICIIAEL 1. BRENNAN. M.D. Prtsidrw and Mediraf Direrar SHELDON C. SOMMERS. M.D. Michigan Cancer Fandarion Sci4nri/k Dirtctur Dermil. Michigan DONALD H. FORD. PH.D. HARMON C. McCALLISTER. )rt.. PN.D. Ass.xiurr ResrorcA /)irntw Assorwnt RtsrorcM Dirrrwr 10SEPH D FELDMAN. M.D. Menrtwr (enariws). Research Insurwe d Scripps Clinic VIN('I:NT F. I.ISANTI. D.M 1). IAAVID STONE. Pa.D. Scrpps (.linic and Research Foundstion Aer.r-inrr Rcr.orrA Dnn hK Ass..riutr RrsrurcA Dirrcaw La l~~lla. California EdNo«•. 1ow nal u/ Inununcilogr m ('alifurnia San I)ie`o in . ~ m WIt.IJAM U GARIN1rR. PRr D m i rrrl rri4.rrsn tof Anoh.nr kwwr J Y.k I Imvef.Uy S. lu«A .4 MtJK ine A Ncw Itavcn. ('.winct tbt ul W OD III

. 1MnwluclMm 5 Ahslrarl. 44 Rr as 7 p ('amer Rclalcd SluJrcs . ........... . ... . 7 Thc Re.pirata.y sy.lcm ............... . ......... . . '1 Iknl and Corculalw+n .................. . NrunMdurmacuk+ry and Physiufty......... . . ............. SO 1'harma.ovk+lty and Rwc-hcmi.lry ................. . ......... 116 Immurwlkory and AJalNive Mcchanismt ... .......... . ... . . 1/11 1-piJcmiik~~ Acuvt Itivlccls Curq+kleJ 1'nqecl. (:()NTF:NI;ti .. .. .. ....................... II11 Im1ea u( Ptimipa InvcailC.aws. . . . ............ . Ill 1I1 144 Irrkx n( Scrwkx AWhmus ........ ................ .............. . . 146 Introcluctoon In 1957. Ilree yerrs dltr il% furmal~m. lAe C.wwcil f.rr Tah.cco Re.errch priacJ and JistrdwkJ nce lir.1 d whN hccame amwa relwn% ho c..raiw .fruracrs uf p.per. MN hrJ Accn IwAh.hrd in vrNws vierNdic medw wilh actrwnwkdEemcwr a( Cwecd slVrrvl lbcrt wcrt unly 16 ah.lrwls in du1 kwK•.pr.kwwoerM h haJ. wwkrsrawd- ahly. laLes lime f.w .w`anitalwrr. revrew and aQpr.wal of panl aMrcalums by dw C.wncil's Scienli/ic AJvixwy W.arJ. rescarch he be compleKd. anJ rerw.rrrpls w. Ae pepareJ. arMniucJ and accepled..w prhlirarwti. By miJ-WA7, die Mrlal.wnher o( scinNilic Iwhliraiuws acLmwkJEira` C.wncd slyy.r/ wa. 616. and Ita years (rer dw Mlelrre haJ tisen hs 1.307. Iw the 1953 awrw.l reprt. 1116 acierNrlic fwMicaliun are.MuwleJ.lhe (arFesl ewnher iw any am yea.. Thn bture Arrqes wv r kat 2.354 the mal nwnhee d scrcrMilic pagars achmwvleJEirg C.wncilsrpprllwMishedsiw.elheCowwilUeFatasqpulinEn:+earchh2 nwkpeakrN screMish ieW snaAiwg .rd heahh. TI1He IM/hlKall.Mls are an MYahlr/lsk a.MIRY Of M(nrrRalMM1 anll n:krtn[t (A rescanhers everywhere and.ll.eref.ue. relre.erN a w.jrw ZuMrilwliM to 1he .cieMilic /iuratwe They also cor be c..niJerarl a synrArrl ul a research pn+Rram rAir has hecurlre Me aww eaun.ivt clfmt ol iNs LinJ in Me wwwhl. hN year. the Gwacil McrtaseJ dw atarwd h*Jo (.K its re.eanh prugrarw and rnainl.wrJ the increa.e Gr Ihis yer. This arlwM is irbcalive.r/ the C awad's Jedic.• 1kM Mr dw lrnrrarn. - As d 1he enJ .4 WM1, dw C.wecd's 1q•yer pn.(uam has pnhi0eOl rreo SII].OIKI,dM/1u 497 wrse.li/Caars kr NAS .rrpwwl fw.yc.ls in 279 mevbcal xMrrls. Mnprlals and research rwslNWMiws.

: I Abstracts of Reports FulwswinK src aM1rx1.. alrr.wcd by 1hc aMhar.. a/ rcpnt% on urw rc.r•rah altrwv/cdr.a.K wni.wt Inae 7hc ('.rarki) rhsr hawe appcrcd tn.crcnldk jawrnals sincc puh/u arart ~q rhe 14112 RaT..1. lltc name u(1he Eranr recMieM i% to iNali.-.. hte ah.tra.i% uc Rnwpcd w./et 1hc.c hrahnR. (('.ncct Relared Slwwhcc.. 11. The Rcywr.Hry Sy.lcm, III Ikarl.nJ ('ir.alww-w, IV Pkwrh+hxm.cr~M~y wwl Phy%NAsry, V. PIwntw1sM.Ry atr11lMwhYna.My. VI. Inataawdtogy wal Ad.Mwe Mechanl.ms, VII hpwkTashopy. 1. Coneer-Re/ottd Studies I t hV(N.I/TN/N (N: A("f1VATN)N-/k:T()XIhICATN)N ENZYME PATTtRNS U11R1?fi PNI:('AR('IN(X:I:NI:SIS IN SYNL'R(NSM: )-M1:111Y1.('ll()L/1NT11RI:NE ANl) DIMETIIYLNITR(KAMINE The wmdinE hylrahesis rtf Ihis srwly i% dtM Iwlnrwry syncarcinWeesis be- tween polycyncc hydracrirwts atal wilt.sarniae. is dre Nt rAe tecil.acal elkcts nf drc .KeMs to IheN Inve and aw tach Iwher's melalwshc palhways To ksllhis, the e/fecls d ) merhykiwdarwlrene IlMCI and dinrnhylnrnnamise /UMN). trMrwti.rered singly .w in nunAinalMm r ChroMIC cyPCMMwMI- dlhef, atl Ihe evalwMan td uytvi/y p.oertn iawAved in the meulrtlisrn to( DMN and pnlycyehc hydntcarlrt>tts were stadred in de livet aal hnyt nl S"ae Dawky tars.eJ Swiss twict:. The dala accunwlaud iw rhe rar sradics wRSe.11ha1 in the Krsl suEe uf 1he pnress. a17 weeks. rhne uccw% a decrcased aerivarart snd ittcrea.ed delo.ifiFalius u/ 1MC: this i% firlMwred anwwnd IS weehs Ay a EreN increa.e to( aclivaliuw canrtanilaal with decrtasial; deNfailicaliue. The we1 rcwM r>t Ihe.e aLlivily chartEes may he a hirh e.rsocewlraunw 40( artiivared inrrntedisles .l( .1MC iahe hwyt. Alv., lhe twrkrau: e.haMatsenM al aniviry mwed wirh DMN-d i. dt hnyt a1 rals ladnwnidered INNN ut INNN • 1MC1 w.wld swralarly kad 1o iwcreaw in the reactive wteubuliuisl af DMN. This and alher d.u strltEesl rh.1 the previiw+Jy uMetred pularaury syacan waWnesis Anweea 3MC rd DMN in rars is prtdwbly dac at Mrreast al Rarlive twelal+ulNes a/ h.uA 1MC.rtd DMN. h rhe erw.e h.et..w the alher hand. a cawthiwalNw rof wa/i.l irr reae n( qrNtik hydrase and UI W-EhtcwnayI kartsferase artivity al 5 weeks. M"her wah dec.ease of AHII artivNy ar N/ weels, wae.1s a dccreax td a.tivarcd hydntcartaM wtnasolNCS available fa SindinR /o as•xnawtkcak. The rwerall dab (reynred hne.ne cuwsis/erw with luevio.s.dwerra- /pen.lhar aclivatted nrclaAdNes.rnleiawinlt (r..w liver are wdihely 1u be eatlobaMUS ia DMN r 3MC Iwlmottxy syecareitwqteee.is. Ijoi,1). Y., llryanl. (i M. , Myers, S C., War., Y. T., Arps, M F., sd Ar..ar,l. f. liwrnaf uJ('arw n Rrwaro Auw.l ('bnanf (hw'.dagt' NI3:!!7-2411. WNl. Unnn thr 1)cl+artmen lef Medicine. Tdane 1leivenily Medral Cenler. New (hleatn. (YIMPARATIVI: P(II.MI)NARY T1/M11RNa.N1:SIS IN /)8Ai!/ andCS78116J MN'1: HY AI)MINISTRAfN1N (W 1 MI:IlII'l ('INN.ANIIIRENE ANI) 1)IMI:I IIYI.NI I R(/SAMINI. SIN(:I.Y ANI) ('I/MHINIa) In the% puln«.nary wuwwor.•nr- •tudy. ('S7HIiAl uarc .vhwh rc awhwrhk hr Nwh Iw rytK' .nd Iwlnrmar y n yl hydaw..h..n hydi.r.yla.c 1 AI11/1. +nd I)H A/!1 nare. ti

I 1 I I wlush arr n.mn.lu.rhl.' l.w hepalK AIIII hu1 nrakr+lrly inJurihle hK rvrduwmary Allll. rc.crscJ Jrnwlh)Inru..vmme IItA1N/ 1 p. rK nxlhy61r4anlhrcwe IMl'AI .wally..K j a'.Mnlwnjrw.n.d h,wh .K. n1.,1.M N1 wcel.. lhe anmul. wcte ahv rveJ 1.w an arWnwrlJl :b wccl• The lung k.M.ns inJwad here were alvel~l..~lnK Iu111MM% and a.kmwnal...r. Alv.•..1.jenN'/wlMw% wa'rcInJIKCJmanNhIIIXrernu/nhl't14 IUHAt21 mwe Ihan m('S1HIrA1 mwe IL Ir.wevaY.lhr sumrd alvr.~l..~eeuc lunww. ard xkrwn mal.w% rr%luk. r....n.NkrcJ anJ is c.pesseJ p'r lung k.nm hearrnlt rmw.c. then Ihe.e ra1MN are /Iw Ihc.Iwar1A• MCA. DMN anJ M('A + DMN Enwp. 2".1 t, 15. anJ S J rn the 1)HA/') nn.e ard 111. 1.1, 2.7, araJ t A in the ('S7HI/A1 m.:e. te.prc- uscly Ihn .uRKe.l% a relauvely Rrea1R wmrpd+rlay.+l lhe ('S7H1M1 .Irarn r/ Ihe NIMht arr l'rN1114reJ lu Ihe re~aY Uve f.MNMI YalYt~ Thi. Kteaar w.cclydahty ..1 Ihe ('`6)H1rA1 r% hcsl .cen by c.wulwrng Ihe prrrent warease.d The tarw.l.w Ile Ml'A / 1)MN yu.q.., the ne1 rmrese rs NKY4 f.w 1>BAr2/ and 2M1')i l.w l'31HIrA) ArRu.. M F. 11.. h LrRem. (' rr.) Arr nr. J('. Nr.~/.l.rrwrt `WSI 521 SIJ, IVIl2 h.wn Sramen's Mrn«wul Revrarch l.ah.vratiwy. 11 S PuMK Ikahh Servw e 11.nptal. New lkkan.I anJ ehe I><•p.ntmenl d MeJKrne. Tdane Urovenny McJ.cd ('crwer, New Ikkans IN('RI AS!•U 11 VL1 01 P1t/N AC11N (iFNI: SI:QUp.NCFS IN BR/)M(N)1-OXY11R11)1NF TRI ATkUGIt('I-1.1.S The Ihym.Jlne anal.orue. S hnwr..h.nywdrne IBrJIIrJI. has he:n f.wnJ w mAw'rqe Kvrlal JI/Ieren/l/IeJ IWYIMWM M vArNWn eullaryrAK lYlls harlKr s1uJ1e% h.ve .Mswn th.r HrdlkrJ mc..{•rales rnhr cell DNA replacing /hymdKrc. anJ Ihal urhw,wm .d p.dwlrn 11'RI./ synthesrs by 1Ae JruE .eems Nr he JeptnJenl an DNA synllrsr% nd sw h bavt wh.lNUrwuls (n Ike rew/1s repneJ here. q was saen " The S bnwmaho.ywdrne-tnrslarwlHrdllrJ)Jenv.lrvelF,BG1/,2C,l.dpdaa'unmwr~nr- ducmg IPRI. I ral p1u11ary Iwrrr cell albcMme GII,2C,. syrllhesrtn ('RI. in the pre.rnce r.f the drug Analysn rA wckar RNA isulaMeJ fnwn Brdl/rJ 1reaKJ cells Jenanslraled sevecal hrgA emkcular weiEhl R NA,,, seyuenres, sin+i- lar ar IM..e ulnerveJ It• The nrckar RNA /rattinm rrf PR1. pndwinR (1'RL ) ( i11, cells. No surh RNA,,, scyrence% c'urW be delecleJ in Iwckar RNA Iractrm n/ wnreakJ I•,B01,2C, cells PRL seqoences in The jewonrc u( (iN, (PR1.' ). (:11,2C, IPR1. I and (:,B( i11,2C, IPR1. . HrdllrJ', (:11 celis a.wW be iJeMilieJ hy hkA analysus in 4N-S.21ib Ita6med rrl resuirtnwt erdi.w.ka+t. IImJ 111 Ji1K.NCJ I)dA. B&wh M(L' anJ 1'RI. cells seem hr have appnnimaaly the same level rrt PR1. gene seyuences in awal cell DNA 1lowcver. Nrnd 111 JrKeslcJ UNA d HrJI/rJ treated F,BG11,2(', cdlk rcveakJ the pe.ence u( sr6mficarMly hrEher kveh ra PR1. Itcne seywnres. in c.wr4anv.n 1hr Ihat nb.ervrJ m Mwal DNA ..( untreated cells. The increa.eJ kvcl ..1 1'RI. Rene seyucm es was Jclamknt rwr the pcrwd.4 Jrup trealnKnt anJ a parakl mc rea.e rn Ihe a y1NNda.mw RNA,,, seyrence% was al.u r4+%erveJ. Mr.wos. /) K anJ llanes, SO Nut fru A. uh R..rur. A 11M111 1WS 1111M1• 141{2 fNArr rur"r NNM.ni) ( .NKer Iw,111u/e I o.wn rtr I af.w.r.rr ,d I'Aaiona,.J.,ICy. ILrvarJ \.h..d ee1 Iknlal McJarnr. anJlhc Ikp.1rlrnwn1..1IlauvirJ M.Jnsl Sah..d, H41NLul 12 I (i1-NI.TK' ANI)1:XTI:RNA1. RI:(;I1LAT1(M! (M- NATURAI. KILI.I:R ('1.t.L ('Y 1(!I()XI('11 Y IN MI('1: Nawral kdkr INK LYII., which avw.INwe uwe ra the nalwal inlntwr• me.iuwwvm pntula/cJ lu rlay a rl./a' /n r/a'1eMt al'aNIN nlYr111a%11C J[veMlpn[1M ard nK'la%la%h. aR trFuLNCJ by a num(ar d Eerla's aN11n.IhnR jky rwly NK a•ell rwrnher bw ah..lherr lylk ability In urany .Irarns of miae.lhe mrmal level ro/ NK aatrvily Junimshe. wrth aFe In Ihrs papcr. vudres.w 11 inbred and recrwnlwnaM rnhreJ Vraiws rd awce, anJ wMne u( Ihen hyMds. rc Ire.emrJ. 'fhey JenMmdralc 1ha1 the Ftadnal Mss rd mrrnal NK a.uvny with aging n al.n aaa•rnn/.anrcJ by a IMSS in 1he ability to respwd to inkrknrn inJua•tw.n wuh aupw nkJ NK aclivNy hwthn. evrJenre is puvideJ thal JiUerences in Kcnnlype can 17r..k1aY Jranlal/a' J/IferealY% in NK aaYivily in mice chnsnKally e,p..eJ t+s a vnus in a a'nntaminaaJ www.e c..l..ny Fuully, a Eeneti: analy.is../ the cllrrl u/ an .mc..renic aEnr, Iwnlane, ue NK activity is prexnteJ Pri.rane. which inJu.e. (da.n.ar yauns rn ..wle Vraws u/ nwe. swA as the BA1.B1c. suppes.es nrA un/y 49 ccll anJ H cell respw„es IMA alw NK .crivily h is wuw shuww Ihd Ihere are srRmlk am arain Ji/leteeaes in 1he el(ect rrf pri.tane rwl NK aclrvity, a% well as JA1cr- enres m ren.very Inwn thal Jrpres.iuw Panicrlarly. sruJies of hybriJs reveal thal dre Fc'neuc mcchanmsnn re.prnsibk l.n Ihe prnlaae-im/u~eJ krss .r1 NK activity in the BA1.H/c nd in Ihc ('57HL srram% are 011 The .ame. Ml.ur. P. 8 rt ul. /x ('nywn. R. (7. /eJ1: C.ww'rr frwd..,tjs' wr/t rrnrwri..n. New Yort: tlsevier Science 1'uMrJwnlt Cu.. IrK.. WN). pP. W1-1411. (MAer sr/pr1: Naliunal Catrer In.lilule, America. Cancer SrKiNy awJ rcsearcA /urd, ad the llniveniry o( Clikrtwa. Fnrn dte 1)clwtmertt nf Mirndwikrry aMl ImnrwtrrMVy. anJ the Caecen ReseanA La1.naAUy. Umvenily 41111 Calil.wwia. Berleler. .. INIIIBIT(Nt CI:LLS IN SPLEENS (lF M/CE WITH IAW NATURAL Kl1.Ll?R Al'11VITY 1. swvey. rl(varwws irthrcJ .traiws rt( wtice fiK wattlral (.iNer INKI ceN activily, s/ri~inl variatM~ws ar rMrn+al re.prwveaess have Aren wrweJ. !:r eaarrvsle. BPS wrialt n.rnwlly havc very w.w y4cca cell NK activity. 11,nvever, lheir NK arlivity cr be sipuhcantly aulenrerNeJ with the Ine al art wlerierun iwdlwtier. which srEEesls IhM dris basw h.w rearuvily is rrN a rcwN r.l w.w twrnlhns al Prem-ws.r cells .r Je(e.h iw /we 1)IN me.ham.m. WerepulthalHPSyrkenscynMwvirl.essarells.asevwkrnedby the aMlay ul NPS y+kca ccRs wr wrhihrr in rar.. lAe NK nli.ity o1 shkea ceds (nun high reyrunkr .trams uf mice ('e1h respM.rhle f.K Me sApplessMm are hra MeJ in thr .knv /ra.lMmalkr.cl.araMi.sninFw'.oH IlypqueanJarcnyMiww.Md- adhrcrenl KinerK .IwINs wdN:we IhaN Iht me.hanr.rrrd mMhnnM ts MN rnerely cunr/rtNM.n flr /arrer. MnJmK snc. ANlw~ul!h 1he.c .ryrrc.MK arlh c.n srl uw nsalwe NK ellea•Mw%tw rru... theo aiuv/y .w r.r.t rnav he nMwe a•.wnpka. swrce nutwt BPS NK AInMKS are ai1 rcvcakJ whrn The wpue.vrs arc rcnrwrJ MGrn. /' M. Sla.lawwi. 161 1/ anJ Sam. I S J.wrmd.{ rAY.• N,ua4hrl ('rrwk rr lwtwrut.' 71111 }11 i71, 1YN 1 1hArr rw//w.t: N,dww.al ('..mrr In.INUtr. Amern.n Cmwet Su.w1y anJ rc.eraA IWMIN 1/1 IIK (InNI'1%11) .d ('ald.wmi y

I r.wn Ih.• IA•Pxtnw•iw ..1 MMr..hN.k.Fs anJ (nwnum.h.Ty. .nJ the Can.•cr Rcvar.h 1.1vw.l.wa . I lm..•r..la ul l.hhwn... Ikrlcla•y MIU 11111. IMMIINl111R NTK'AI. H11tMS IM- PIII:Nl1NAR81TA1. INI)lX'I:I) RA I I 1%'I.R ('Y f(K-IIR1)Mt:S P JStI ARI: (:NC(Hlfa) NY t)11-N:RI:N1 ruRNAS lhe w.wt rel.wtcJ hcre arrv..IveJ iw .-itnr tnwslarine NuJies wsinK t.w+r t:vans anJ 1 k.himaw rar. In dn. vuJy..wre cuhiwy u/ l awR F.vans rals e.hrblcJ.wdy rylu- chmnsr. P-1NN,. anJ P .1Mlr anww>P Mese iwwrwmN elated ewtymt.; wherca.. .wrc ...kwty..//k.hrnunr.hwa.aharactenteJhycyhMhnwnesP IMN.,,anJP IM4 A/kr Phcmdwfwr.l tre.rnw•M. hcfurM p.ly IA/' •w.RNA was r..J.kJ Ir.wn lhese 6nwP...1 ul. snJ u.n.lareJ rw . ma the "S IahekJ pns.Ma1s were InMwrwws..IMeJ •wNh anli• Ir,ly tn. ya~hnwne P 1SIIA„ anJ analyteJ hy Iwr-J~men.w.nal Fel ekauNPlwwc.r.. lAe rcwlr% ww/w attJ rhat the twahwls syn/hesiteJ iw vim, cuttespwW esactly hr the twu P.nh uln hwms .4 Ihe entynsr that ch.ratetite liver micwxmrs (nwn each uf Ihr.e RnwI+..A rals h rs c.wwlwkJ 1ha1 ddlelerM .uwrlwal t!enes ennM)e Ihese rm- nwmvcl.ICJ Lnn..d cyhshnwwe P JS// and 1ha1 viRnilicaM prst lranslatwwsal PnK- cs.rnK nl thcw P'lyl cMkle PnMbas d.rcs rwl1 uc.w rn .•nw Waltj G,)r , Vlawh. G P.• (lmrccimki, C 1. B.rsniuk, f, Tlwwns• P(: , Ryan. 1) 1: . and Lrvrn• W TAr hwrnrl../M..d..Ri.al (•Ar.wrstn 23711140234026. 1002. Other rtrh.r*: Na1Nw+.l In.lnulea of Ikahh anJ the Nati.wal Science F.wnJalwwl Fnwnllx• tkPsrtment.d (lrcmi.lry. Kewt Stare Univer.ity. Kenl• (NI• the IkP.rtmrM r.l 8wahcrm.try. 1lnrvtr.rty rd Vemrww SaMw.) u/ MeJrcme. tiwhnlrarn. and the (kP.nnrcrN../ Hwiahemrslry aal l)rug Metafw.lnrn, N.J/nunn•1a R.Nhe, Inc . Nw- ky. NJ 81NI11N(: (N- NI:N!(naIPYR1:NE AND INTRA('FLI.ULAR TRANSPORT OF A pl NINI) I LU(1 R(1PIIILK' BI-.N'L(l/aIPYR1:Nt: MI:TAB()LITE BY LIP(N'Itl)Tt:INS In Ihr% hwnhcmical .1udy. rwww•uvaknl upute rrt l '11 lhewno/a IPytene was yuanh- ta1eJ Lw Iralrum culkcleJ (nan the cl0uenl u/ a Iwpd a hnwnaN.llraphw• scparaaw of hurnae .errre anJ wa. Gwnd hr Juea'lly nwtclate with she IqwrnMCin crwwenlrNwiw. Aw ek.tnsgrhdit: hcntu/n/Pyrene wKtalwdNe. 11lMrrar. 7.1{ JrhydnwtN.l 9•It1 epray• henn4n/Pyrewe. rwon cnvakmly asvocialeJ with knr densiNy liryruwclns was uan.- IeneJ hn human Iynq+Mscyte% rw r m.. and IrwnJ acw) precM+ilahk nw krc aa wls..l the lyuy+lwocytes a% a lum Iwm.d ume Ikni.4uMytcne mctaM.lilc IwnJingh, lynrlrlww y1e I)NA wa% drnww..u.NeJ by mc.n% u/ ('.(1 Jcnsrly Eradrcnl analysi. N.wrmn..Ken- .bn.ul.a•J IynqdN. ylr• e.Ir..rJ 1.y very h.w a.wr cMratNsns.d csrn rnuKen in the /wcs- cn,.-..1 I..w Jrn..1y hlrSw.rcrn.k nr.n.lr.k J ~'l I1thyrnNl.nc rn..wpwalN.n. wnh.wl the ...w.rNd.M wLhoN...a 4.w .k•w.My bl.qn.ycm rIM k.w ..akcnlrMN.e..d . aa uNq'cn dN1.r.r •I...... ... ( I1ph~wN/.IK IrrarlwrMN.1 1lvcull, Ilw•JNalwcvMrJIh-.r• wl.nh NNIN .d. d.,..fw . IhI w n. s ul . aa .n../•. N h.nJ.n/• L...M Iwp /a1NM W wh, I11rya.N.•N.. r• .klh .Nl.Nl ..Nlq..l•..•..m....N.nn~n..u •ia.uE'.•.1.v.•.d..irmh..iUn.la IawI/l.hwo Iru~. m Ow• . r16.Lu m~...a ~N.N ..I lqr.l.hdn . aa tm.l•cn. wnh humrn .cll. I NwJr•r. I) f. rt rd ( br. rnuKrnr.r. NI111 11117-1112. 1'IK! (hArr.w//srf: American ('rncer S,wicly anJ a N.wth Tesas Slale Universily FacwNy Rc.caah l'.ran1 fnmr the (ienclirs ('emcr. I)cPartmcnt ..f bwrk.Eical Saiences, N,wtA Tea.. Stak Unrvcrsny. Iknlue. I:NIIAN(T.t) VIRAt. TRANSH/RMATNNd ()f SKIN FIBRUBLASTS FROM NL•URUI IHROMATInIS PATII:NTS ('uhwed .\rn /ihn.Ala.l. /Shl lnwn pNiewls wNh certaiw .wNSwwnal J.wwwawl Iwrcarweaw. uale. e.MMt wwrea.eJ .emawNy w.w>,..Teac vevs uansl.wsnrw.w. The JMa (wesenteJ slww the .rcwtence d enhanced viral uaml.Kmaliuw ul cwhwes u/ St evahb.heJ Inwn Patrcms with newur/rht.wnaktsis INF) Iw 1Ms sludy, crltwes of sAin hlw.rhla.h /r.wn pcts.nu wNh and wN/wwl elilwcal NF M(anrhes in which she di..wJer had 6eew drsgwrneJ were eaanriwed hw Itaw.GKrwdwlwy by Kwuen nwriwe saraYwna vIN%. The vNall trMshKnlilwMs feswlls wefe erwepweJ wah the"e nMnwed wish SF cuhwcs irwuakJ Inww c.wwnds in lanwlres wi1Mw11wswwy.ri aey druwJcr wMh an heredNary c.wrqwwrnw. ar caecer The rewhs awwr du161 Perceal.uf cuNwes /nwn Iwuents wnh chmcal Nt wen ttawshwwrcJ. c.wqweJ wlth seven percenl cd awrnd cuhwes. ('uhwes n/ Awr AMuhlasls fnwn peros.wls willwwl she classical/eaNwes wf Nt. Iwt in fawnlic% in which dAe diwuJrr had heew tec•nrgwiteJ, alsas eahrMted a relrively hiTh Iran.hwrnalw~w ra1e, siwc[ 75 Perc•ewl wtre lranaf.wmeJ. This sww\ indicates Ihd wew.r//1w.wruNhls can he aw W.kJ aww.wE aNhet hNed{larr dlNwdets in whMh ew- h.ww•cd aam/.wouM/qy uf ewhwes r.l SF h) an nwc..FenK vrns may he Jenwwlslralcd. ®wkw-laqut. P. and Fr.orRrt. J. W. Annwlt..f ('tinw•dnnJl,d.w.uurrS.•irrw•r IM1/27-)2. WN1. Odtr.r/P.rt: U S. Public Ikahh Service. trnwn the Tanllra Hranch LsMwahwy. (kPawtmew/ a>t Ifealth anJ Rehahililalive Setv- ic, s. Tany.a. !-L. 1)IKT• I:X(K'RINE• ANI1 t:Nfy()CRINk: COMPONENTS ()F C1/1.TURt1) 1-1:TM. Ml)1151: PAN('REAS SwKe wwerccllulr interartwws nuy be rnrlwwuM in caniwrrPewe.is ad the P+n- crca.. tht Kruwth .d at ka.l tlwc. lrnd. .d efwlhehal cells. r r. • Ju.1. MCrwa. anJ ccMnwrnr rn the .aww ruhwe .duW h• inq.wunl. The Pwrpr.e .d the p.Per pe- vn1eJ hert was ho char:wlcrvc P.wwrca..clh rwhurcJ un a PilCslnr .uhslrae anJ 1o .kvnhe she ..Ptrmal c uhwc .rww/nMws I.w dw..luJv. a h.1.1.d '1/ Hr !! Jay% pw- nwlwn nww.c Iclal jsawrca•.wK:ar hN. wcrc.uhweJ an the Jctnul wr/are.d ina.h- y1Cll/w1,'s\Iwasa~u1N11at~ Ih~nNJlulnuvJkwkw~1~n11aul1welYwlslNfJ..llafks Mrmnwm Vs.rnbal Ma•Jwm wwh /ht ..klnw.n .d hl•4 h.wure serum. 1/110 ll.wd insuhn. tt _'*- yl''nJ /•Iu. AF.m. 1 na M f rm1 hyJr.a'.wtr...nt. hMs ypwJ ..ryfaan rry. P.rnrnlNhn.w.Mh1'M./r.qanc WlrndrwkJwmla.\.JnyP..nu.MlM.w.warn~wnc IMn a.w1lJInlYI1IM' Ihrl'.• IMMnNwICs. Iht' INr,AIn WIjMw11h-1.'dn h1 t1t- J[%/raqaJ J11fr ! t.r 4 11

taI,mrul+u+c Ilwrcalkr•Il+c.ulwrcJccll.cuulJmwFn+wandwrvivc.+olheJsKt.tcJ h+r.t,rn M+h.n 111 • M atuT.+ne wa. aJ,kJ h+ the meJiwn, amyla.c secrclMm lunn culturcJ «ll, anJ Jr.lnwtnm..l ple.l+n werc rnh+MleJ..mM+ktcly IrN I++n.rca% acll% c.wlJ n.w Kr..w .w .urv+ve In c..Nra.l. NMI pprml .nyhean IryP.m mh+Mnr.M 111 ' M ah.ol++nc pcmmoieJ .cll Kta..th anJ amyli.e xcreliun Inwn the cuhurcJ ar+n.r ccll., anl PrcvcnrcJ Ihc Jc.uu.ln~n n11.+K.(m llakt Ihese crmJdN+ns, luncrcas.clls mrlCra• teJ xw/r.K Krcw Ir.n thc rM y.n hx..nMU Ihe swfare r><Ihc p~.\m dermrs rK7.rKam+n1 ayKrclt+lMan. LrcnwJ IlyJaw,wtw~ne wa. netvlnl h+ p'rnnl 6ruwlh Lr awwe than 2 wL (ilum aF.m anJ m.uhn had rJJwive t/fMs.1.iEM anJ ckalmm nacnst•+ry+n rfi+er- vatMon% nwln•atcJ the tulwa d at ka.l llve hiaJs o( cells. i t., drd. r•mar. ccn• N..x•mar. cr.h. nnc . anJ mesenchymd Tht majnrNy ol cahwed ecRs were Ju.-l ccM. rr/ .+nxa ell.k thr.e wtn lew mesenchynu/ eelh M.nse prMen ce11s wea awhweJ l.w at k..t 1Q wl by tMs natlud lina/a, K.(1ka, T r+d Itacwrw, A.E. In t'u.o IMIV1 71W 749. 19111! (AAer r.pp..t: N.IMrul Cancer In.trwu awt 1he Anrerican Cancer S..cicty. ir1.m the ( tnKr 1ur Neun*.Rrc Strdy. Srr brcNo. CA. P()PIILATN)N hICTRIMIITK)N UF P1.ACENTAL BEN7.0(a)PYRENE M1:fAM/)LISM IN SM(lKI:RS Iluman placMal mirnwMnes /snlMed fn+m Ienn Placentas der/ved Inun mm- sm.iAmR wumcn onJ w.Mntn .m~ dmR nne w 1(1 c+Krenes a Jay were anilyieJ Lur the mctalh.t+•m.d hcnr.~lo q+yrtnc 1 MPI n.ca•weJ as vrMws metatr~l+KS hy hiKh Pre..we l+yunl.4nun.heCr.q+hy /f11') C/ anJhr a. ryl hyJrucaA.m hyJra.yl..c / AI1111 arluv- Ny Re.uhs str+w thal AI111 wl.vuy wa% x.eral t+nsts ln6her +n sm.Aers than in rnmsnMAcr. ReEressr+n .ndys+. un 11 ddlerenl Pla.ent.l a..ucs /nnn w.wncn .nwA- inE (nnn rme M ~tl. +Nreth s derrr~nslrrcJ a MRh ameelNww+hctwetn At ll l.. Uvny l.w Ihe /twmatMon ul 11P phemAs rc.n/ved by IIP) ('1 vcrsus the LumMMm ../ the p.r ar- cttM+Eenw MP 7.6 J.a Suh.equcM vuJres un (dwenlas dcrtveJ Inwn 67 wunan whn smroked N1 h+1(1.+Earc/1e• per day dem+wsM.tcd a Je6wac Jarse•re.pm.e rclatMm.Mp between AIIH avvNy anJ the wamber uf cigarelles srm,tedtd.y. The J.+.e•te.pm.e cwve was.i`n«ndal ia .hqrc. Mwtver. whtw drc dNa werc ph+MeJ r.n a.ctm hst; .eak Ihe t•wve asswneJ a Iwear.hapr. KrhwK saltralnM of A/III IrreIwlN+n belween 2(110 2S ciErelles/day VYAik mean AHH activity was dep:wJenl upm the rMnnAer tu1 crEreNes wtmokediday, n+nsnkrsbk imee>rtdividwl.ariaMlily in AIIH Irangirye nwne th.n I,IM1U fuld m snme caxs/ wa. nh.crvcd armrK iwJtviJuak with c.»ty+xahk smiolimR hislwks In fwthen sludre.. pypulalMM dr.tnhulnM sNW.teJ cWskrmE o( the populaunn in the bw-Allll wUvNy rtrnin wlwk curd•Mhd IhN.yunalt analycis anJ tw+n sludres suRges/ed that Kenelk fwhw% cntMr+lwted w a maMK Iwwtn+n r+l the rnter rndradual vanabley m Allll ulivMy ubsetred annmN smnker. crrn.+• If 1. cr of InrirnwuMwd luurnol u/f•wwrr 3111) 2Y )7. 19111 (Nr,tr wppowI: NatMw+al In.tnules ul Ikahh and the Mnencan ('anccr S." rcly 1t.wn oM 11` I.atitiwni .d 1.h.mr•m.l lbcrapr•u1N. rnJ (:rxe ('.me+ I)ruK (-enlcr. N......II 1'.,i1 Ml u..t+.l In.Intdc. hulid.., aal the 1)ry.aAmenl.d PtJodrw.. 1/ntvcr .~~y..l / ..Lr.n6, \.h.,.l..l M.Ju.nr• Iknvcr 1 I t 111f.1M(1:PARAf11)N (M VS) IN/M(K'YSTEINI:TIIKN.ACfONF. I RI:E (N• 1I1N 1NIN1: A rw+scl. .m>rk anJ la.l PnKeJwc liw tetrwerutE mrlhMminr-Irrc (' :C~ h~+rruKys- kmc Ihn+lacawc t..Ih+wrnK M..ynthesi. is ekscrilaJ in Ihi% tneth++Ja+hqey pal+er. As. rcp.rteJ hcte. alar I "S/methM+t+tne wa..ynlhc.iied, the Pu.arcl wa% iv+laleJ fn+m mcthwm+nc by la4m(e the nu.lwe up in !1N/ pl .+t alndule mnhaaA and placing the rrwhmr wAwMn+ +n a.dwnn curMaminN I ml r+l M.('.B. dry chnmutr+NraPluc alumina. The evdunw+ was ehMed wNh methamA, wtd the parily n/ the pn+th.c1 wa. Ihen dc/cnnmeJ by rnnwt acw) an.lysis. Thm laycr tiw.Mnah+Nraphr was r.ed a. a.ccand mrlhr.l ha rkyernunc rl the syrNhe.iicd /r+ttmwysleine was welhnr+urc-Iree Re,uNs sMwr Ihw the yield r+l tht alunwna cr+Mrntw prnficd 1"Spwwrncyskrne i. S-N1'i bw, itnprt.rwly. N p.wwks a melhrd hw the t•nnVlele sepraainw.A /'.SPIInmwy.lerne IMnlarh.nc /a.m unreacKd 1':C/wN/wuniwe. TAe tnel/wiwine is held sln+nEly by Ihc alununa thnwleh Ms carM..yl RnwP rd ik n+y ehweJ by wrelhwrA. IMnmaysuine IAndw %ant, I..h+nR a crl.+.yi RnwP. is c/wer very rywRr. Tiws r.Pid and tasy prnMaw+n rd Ihc 1M.+IacM.re. lice el sahs, twahcs * rtry cunirnnet>t ennhud /.w the peparatn+n .%1 mclhnwdne-free label tiir use tn lioloEical .y.lems This radio.dive crrt+P.ami suwW be rii mtpxlattl we as a trave in swdyrne the impntam teaciwra uf hnnMwysteine with nu .mbhgrily dre 1o tYUtlamwwrinR melhwnine. Surw. P. 11 Mecham, 1 0. .nd Na//nwn. R M. l.wrwd aJ Riuc 1lrrnirul .wrf Rwydls sir u/ MHArtils 7:e 1.>W1. 1962. lhAer uyprt: Naliaul lwilwes of Ikahh and 1he Uniled Crter Council. Inc. Pr.nn the (kPartmetr r+f Pediauics. Univenily t+f Calif.+nwa-San Diego. la lolla. Tiil: PK(N'I:RTIIS OF THF. NI:I/TRAI. PROTEINASE RELEASED BY PRIMARY CH1)NINt(K'YTl: ('1/1.TURES ANI) ITS ACTI(Nd ON PRQ I E(X iLYCAN AG(:RMA;ATE The mechanism uf pare.+plycan calabalisw a.d its reEulMiaw is af panicda irMeres/. since it ha, beea Prol...ed /hal iw•rtased ewiynrrlic beaWown of pmkvgly- cam may he inv.Aved in uutr.xthrilis. The /+alrr PreseMed heoe describes the popet- lics af the L.ye.+Nlyran .kltradiaE eluynrs neleased Wo Me e.w.ceNrl.r mipeu by cMwtdnw ya cahwes that Pn.hwt eandaEt•speTilie lype /1 esrMaRew t1M an delecuek type I cnollaKcs Srncc nce PII.A Ihe e.ltacelblar trttlriM is anwrW t.ewahq. aenriok hss betw Lw•used a+n truymts arlivcsal neuhal PH. Biule/ P•AO ehnrnah+Paphy d nmctMraltJ cuhwe medium sh.wed a mapw prat af eruywte activity on p.weaNlycaa nr.r++unn emrappeJ in p+lyw•rylamNle head% aa well as nw.alive proleaElycaw aRRre- Kates. The tn.yme yalds a sPrcrht Irnw1 dqte.tM+n peNide fnnn IAe aEtreEtle .a1 .~nllmutciy St,IrM/Jaihms, The pawedytK tn/ynte is Irenl bw cM he acllvred by nnwm~hrnylmercw.r ardaK.r vyl+.iw ll+e aravr/y is aa1 iniwANCJ by phenyhnetAyl• wM.u+yl BWNak .M peP.talm IMN r. c.w+l+kkly inMhiAed by n phenamhn./me: the w Nvny i% awacd by /n. w('.. M+n, m the Iwr.erke ol cakium a•hlnwae The rckse af su.h mclalMrnwcma.c by cMrwh.w yks +nhe the esu:eilular nnNrcu, its anivwy at 11 12

phy.r.1..KN 41 pl) +nJ rth ability th1 dcFraJr nalivt PnMnT1y.•an. art cunv.lenl wuh a a.k .d Iht eniymr rn p.wc.•fly.an ns.ub.do.m M.wak.. T I anJ A r.•/nw•r. K f Rrr.. Auna u er Rr.yA..r... A. dr 705 V!-K11. 19112. OtAer srRP.rt: N.INrul Arllwilis Furndatiun and the Nalianal lnstilules u( Ikallh. Fnwn Iht Ikrynmcn/s ul lktlrreJir Sw6ery a.d 8iuchemislry, Rush Medical Col- ktte. (lorcaR.r T11t: RI: ' SISTAN('1:1)F f:PIT11E1.1A TO VASCUl.AR1"IATI()N. PR(yT1:INASI: ANt) I:NIX)111t:1.IA1. CI•1.1. (iRUWT/l INIIIBIT()RY A(?1VITIhS IN t/RINARY BLAI)IN:R EPITIIFLIUM The ava.cular nature n1 uss.es htl betw studred ealenslvtlr in a mndel ll-we, hyahnt candaEe 1 mdn.ts ianccale dW 1he mted avascularily of epuhelia may he farMx a11nMAed In Ihe (ntstnce nl a/1 e>rMaclaMt, hsw-nr.kcu/ar.we*tM (scbr Thir cnntarnm puenl rehrMuw..rf pnre..lyuc ewtyntts as well as a tn.wth ieh"kry activity directed aEarnsl cnJ.whelul cells rn rnro The fn•Nw a eatrarteJ 6.Mn Ihe eplhclwm of bwrne ursnary Mnhlcn by I M NaCI The ealracl is ahrdiheted IhnwRh an Am,.-al XM • 540 memhrane. then a.ncewlrated rd dialyzed i/Mo a U 9'R N.CI suhwrun usins a l/M 2 memMane Tbos Idlndihrale. called the UM-2 releaane IIIM-1R/, cnetaits approarnutcly 6 M6 pn.lcin pet Rnnt of tissue. The UM-2R has a bw cnntenl uf w.usic nid and is praclKally Jevurdof hydroaypruiiae. SDS-PM:I- reveals Ifiat the UM-2R nmsnls d u. marr prulc/ns Thc UM-2R coMairas a Tn.ylul-lAc ptioclwa.e inhihiNK that e.pesses strun6 Irypsm inMbkry activity. Crunpris,un between bladder and strvm UM-2Rs and ekclroqolr.nelrc aoblily assats indKale that lhis prule/nase mAihi- wry acllvMy is derived (awn the Maddee eplkliww rd nrA flae drc serum. The l/M- 2R n cyuwoaic w crahured endulhelial eelk. Cuhwes uf alher ceR types Inormal and ntaplaMKl we MM d(ea•ted. h seenn. lherefae. thal the bladder-derived pmteilase and endwhehal cell gnswlh inhibtory activities may prdect epithelia (nwn vascular invasion. Waakr. B.. Kwnwtr, K. E. and Podi. A. U. Tissw d CeA 11657-667, 19d2. (hAer sY/a*: Nalional instilrtcs of Ikaldl. From the (hpwtmenls of Patlwsl..gy. BiocAernistry and (klbopedic Surgery. Rush- Preshytena.-St. l.u•e's Med/cal Center. Clwcago. 16 TI11: . RF(i1/1.AT1()N (>f INVASION BY A CARTII.AGI:-DFRIVIa) ANI I INVASR)N 1 A(T(Nt Thr% in Jcph d..cu..w.n.d Ihe reRldalN+n uf in-iun by a carUlaRt-.knved •+nli- rnv..H.n (a t.r is ./o.NII'.I tM.. ~tvtNl T/rM MYIMMN 1nlluJ/nR RtmN/NMt 1.1 IMMmal 4 anJ.rc 1.. .n......n %w rta.h.ldy .d e.ur ttJ ..r1d.Kr u- rnv..nM.. .n•/ l'.nJ.Kt .krn..•1 YNs .n•&•.•. In r.• A/.so..IusMM1s KIIN.n l.MH1/n\ 111e L.IL.w1/ K..h-t•IYd { I I tirm...n Ihe espenmcntill %eric% which have pnwi.kd evidence 1ha11hc re.ivance a( carldaKt h.lunwu rnva.M.n may Mc Jut pr an coiIraclaMt, h.w-mnlKtrlar-weiRhl (acMU, (unclMwully JrhntJ a. anu inva.irur /rwK /Alt1. Thi. facNU c.rNaun the f.dhwing anlrmvasive arlrvna;.: /1/ pnnemw-e /cn11a6eane/ ildMbary aclivNy;/2/ arMi-proh- kralive anJ anli-uuKraauy aclivrlie% directed aRain~t eahnhdiaicells 1.rMi-an6N.Resic ulrvqyl: anJ I II Iwrwr Enwrdl inhiMMVy activity. These acuvNies nccw in the l.nr- nwAecular-werEM /1.II111/>MW<M/,IMM// PnMCira franww af a/ M N.CI eslracl of hyaline c.rld.Re.u, a..l.wvn rmly rcrenlly. M duradnrryle crhtan:s eslaMrJred Gont bwine anu-ulx cartitagc. They nuy well aat as hrcal reRlrlalon fur suane o/1hb major wechaniai.- pw/hways by whK•h twlar cell% re IIrwgM w isvade Iwna uswes and meta.usite to dalanl siles. namely by mwna JtltradinR enrymes and increased h.co- nrAMw Al.u. they may inhibit tenau nK.waxularitalios and ewNnil lucid lunuw gn.wlh. Pw/i, 8 lt and Karnosr., K. E. In: Lireu• L. A. and Ilan, 1. R/eds l: Twww/wraiitrn.wdMcLUwis, TAe Nague: Mannws Nqlrrff PuMrshers, 1982, pp. 267-Nl//. Oder ssyP.rf: Naliunal Instilutes uf lkahh. ~ Fran the Deparlment of Biochemis/ry, Rrsh-Presbyteriaw-SI. Lrke's Medical Ce+rer, Chicapr. . VASCULARITY OF CARTILAGE This bw~k chaPler is a review.d /he lileratwe ow 1he spxial anyMnicd cpdilimn of the tanilaEe hhMwl sVoy and dle nsct-halislas 11w pnMecl.dull cartilaRe wntrya 6ulw p`netralNnt by vascular elrhOehwtt. Tlle pericArwrlrial Mad srpply, canilage cmals.lhe 6ru+qh Plau and artic.tar canilaEe we all surveyed in this section of the chapler, wlak mechanisnn u( the resisla.ee nf crtilaRe rnatrices to vascuhr ilwasiot and @rc lesistancc ..f canilaEe N. Nwlwr ceN iwrasirrt we discwssed fully in ndler secliwun. In sw/wnary, Nre cunk hniaws drawn a11he end of this plpn indicale IIW Me residance of cartilalte ut vasc dar and twtuor inva.inw may be due Ms an eaMaclaMe bw- makcldar-weiltN (actnr (unrtinnaNy defined as allli-invasirm fa.yue 1 A1F/. This bc/uc can he eakarled (nMn ancakitied hyalille canilaEe ne (nMn ctihures of bovine aniculr clawwlr.r•ples hy nuW sah sululinns. The hinh.picd activities of the saM e.trnet, s.ch as putelnase anMbrtMUM and ca.hMhehal CeR Enwah rhlblMlw, a/e Pn:seM ilt a PnreM frn•tNm Ihal has a mukculr wciRhl rrl hetweelt 1.11110 aw/ 30.(101). These w liviucs may a.1 as ht•al rcEulauuN trr v.nw u/ Mt nuxw mechaaislic p.dlways by which ealnttie- lial ccll. anJ lunwr cell. invade 1004 bswle., by mal.ia-deltrading enrymes anJ by im•teaseJ p..Idcra/Nwl anJ nupalw.n. Krcnncc, K. F.. anJ Porh, R. (l. In.llall. B. K. led 1: ('.wrduTc, Ntw Yrr\: Acadtmic Pte»• 19112. wd 1. pp 'N1-t12. (IrfAer taOpp..t: Nnn.n.l In.lilwt% of Ikahh Fnwn/tw Ikpxtnrra..d Hu~hrnu.tryanJP.11w.I~.fy.Ru.h Rt.hylerun S1 / ufe's MeJirat ('tnltr, l ha.Ka 14 1 IS