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Council for Tobacco Research

1984 Report of the Council for Tobacco Research - U.S.A., Inc. [St]

Date: 1984
Length: 75 pages
CTRMN012459-CTRMN012533
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25 Sep 1995
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Ctrmn00010849-2859

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Hobbs, W.D., Ctr
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118
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ANNUAL REPORT
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006
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vvr30a00

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Page 21: vvr30a00
Otl/fr fMMor1: N:dNN1d) ( Jnt'CI Irl.hlulc 11.1110 11N• I)NI~LM .d Ilcnuhd..Ey lhNUk.ry• (lnl.lrt•n. Il..spn:d u/ I.n AnFrlv., Ik•L.ntnN•nl n1 MN rnhNJ..ry, ('.dk•Fl• .d MrJN ul.. I lnlvcfaly .o1 ('rhhNUl.l. IrvuN•. ,nNl1 )k 1..111nN-u1 .d PI'.II•I1rN %, IIIIIVc 1%Ily..t ti.niltkr,l ( JIIt.N111:1• St INw.I alI kl..Flt uN•. I ... A/yt Ir. 11. The Kespiralr)ry .Syslem NI(-11I1N1 I\ ('lll M(/1 A( •11(' 1( /K NI 1111t(11'f111 N ANI) I NIIAN('1 % NI 111141111111 /(I SIr )NVI Vl NUSS l t l( l I1 Ml ) fA( "I11 I•1 I'l ll>LN t/n dN- h•1.1. /d /h/% lA 1•rrrU %Iwly, /1 1% rClMx/,J th]I U/t-n/llh•• whN h 1% rf:Nhly :th..NtK•./ tt.nn IM. Il••prn.111Ny It.wl, ha. c11c11..N1(+I.Iy11NN1.INN111~ k af nl'ul/.4th1N tI1J1 rury IN- r: k..lnl la. lmll; tnllemnlalnM rrr rr/.. N/I.N/rIC Wd~ LNIINI I..IR' l IN IINd:N lit l.N IlUnl.ln tN•Ulr..ltlll. IN/1 /Mtl nNNN\ yll•.. with .1 1\v1. ,Nhv/ty .A 11 nuCr.N/N.l:tf In k.wt'f l. NN l'/11/.1111 M% I l. x1111Jf ahtl' Its lh..a• In .oN.kcr.' pLlan./ t• nw o11nc cnh.ux cJ Ilw Il•\I..N/%C .11 IN'111f1.11t111N 111 IW.1 .IN'ItN.1:1tIN IN'I•/NIC\ In l.Nn/a\t Ill /IN1%t ..IIN'/ l1K' 11N..1111.N1:1111% I.N Ih'u1111.1111%. III.wCvt'r, IIIt.N1111 did INM .II11'tI tk'1,•I:IIIUI:IINNI Ix %II' It•rutNk• pr.wlul INM Nn.dtnc thu% rrt.ly pnMNdc /n1IJ/11nGdNN1 ]nJ t'.N/K111N 111 (It11F ulllny /n .nN.ACr. . l.rln• N 111. M.('u.lcf. • K t•('./m//Mll, t. I.(:rdhn. (: I. • a1NI \.'11NN. K M .S, r.'/N 1• 221 IM) 171. 110144 (Mhtr sapOnrf: l l S IbM1la I Ic /11h tirrvicc UI.xn Iht• Nc.pu,N.wy :IINI l't/1N'JI ('ar.• hivi.ilM• IkprrlnN•nl td McJlcltk• )cwldl Il...p/lal ul SI I IML, Wa.hinghxl llnlvcr.ily MrJi.al ('cnlrr. XI. Isxn. NF.1/'I RAI.1'Rl)I L•INASI•1 1•ROM 1111MAN INII.AMMAT(N(Y l'LI.L1 A l'KIIN'AI. kl•.VII:W 1)1• 1'111:1R R//1.l: IN I•.XIRM'I:I.I.III.AR MAlRIX IWI:RAI)A I Il IN In MIIJnun7luxy It•at'1/1M., IxalcM.l.ca and a varicly ol .wtnr kuAtr-ydc pr.NkNi. :Ilc ICIt•:1N'J l/llll 111C t'.Ir:n:c11UI.N CnvlrlMlnCnl llll' IxU1CUtylit• Cn/ynlt'% tl'k':IwJ by mll.ulun.d.xy ICtI% mlllalc the Jllic.u1M ul INMvlahk I/..ur, lilx/n• a1Nl tk•nislurcJ Ix.Nf Im atl/l (M.dC..l;lyt :/n., a1N1 n/:1y at I/v:NC nll'Jiallx../1 in11:n1Ut1.11nM 1n 11N• n•vN•w INa.cnlr.llN rr. Ihlrc Ihlnp. arr nxl•Nk rcJ I ll lhe teli hNtk.y.y alN/ in vn.n :N nvlly ul tN•uual lx.wclna.eo tk•/ IveJ InMI huwan mlbnnllN/xy ce11.,12/ nx•chaln.m, by whN h llw.c Cnfynw•a nllgM /n1urC a'.Mllft'l/vt 1i..ut /n 1'llvr, and ((I (hC hNtllfl,'ltalalvlly /11 IN•IM/lk. 11'IC.1wJ IfINn t'INInCTt1Yc h..uc by /+rlllcina.c. 1't/ .uM/ua/vc Ihi% palx'r. hunlan inll.nnulahNy ccllt• Ilani.ulally rlruu.qthil.• reka.r rlculral (xalnna.c. that h.lvc Ihc' l ap.N ny In .k•rl:Nk ctlra trlhtl.n nlalr/. nNtlc. uk. Nculr/q.hil ela.la.c i% .•.IN'l 1•III/ INN.It1k' /MY A11M' 11 1'Ixl'N•111 1// L1/14• .//INNInI\ Jn/I hd\ Ihl' \:/1\:N Ity III Ik•KINh .L..IIn .IUJ 1n.1uv o1hc1 lunqNnN•n1., nNluduly haa•n1ru1 nN•tnhfuk tu1LlKcn IIyPr IV). pr.wc..Elycanm irNl Iitxuncctin. Allhnuph lhcrc i. /ntwh cirtunl.lanh.l t•vNk•mc .nFFc.IMK rn antxxlanl mlc I/w /N•uU.q.Inl tkrlvrJ In•utral pruk•Ma.et ll/ rzorrt cllulal 11411t111 hfl':1{,J..wn in II/It.l/lllllal/xy rl':Il-INx1\, JIfCII 1111a1111h1'JINM 1./ l'INIIN't llvl' 11,11k• p1.Nr.dv.1. 61y rll•utntllhd. in htnlwn Jl.ca.c Iw% rxd y.•1 hern p..ahk. I L./N• lk•.InN 111M ul a.V lYat11M wllh rN•UU.q11ul1.' in/illtiNllM i% alcarly a CUmpkvl /x.N.C.. Ih:u nlJy nlvUlvt' Ix1At•In:1.C%• 114141.1111%, IN.Nt'111aK 111I11hlllx-s, anll.wh.r .uh.la/Nl'% Ir..ln Itvl Ik•nl l't'II% a% wrll :1. /w•uUl.tlh/l Ix/xI1K1\ In 7Nk111nN1. ..M1parCJ w1U1 /N•U11..Id1J.. hulu.nl nt.NNMII• Irar phalvwylr. trlra.c vl•ry .m,Jl anNMUh u( tICIN/AI Ixult'1/1:IN' :Nhvlly alNl .Jw..yotlk.vc Ix.NI'/nw• inh/hlhx., .u Ihr f/.k ul Ihc.r .e1I. ul dlc Ix.druly./. UI U..uC. /. Cvrn nNxC llholurC Ihan tI1C /+.k UI Ill'uvU(thll.. %.•nnx, K M afxt (',rnq.lti•Il, I" J (7m1.. ul l.d.av.q.rrv Al.•Ju ul.• IIJ) b•15 (AA, 14K 1. (hhr..a/yr..ri: 11 S PIII.IN' IlCdhh &'rvq'C aMI IIIC AIIN'rN'an I.unl,' A%mN Idllnn al 1.:1.11•rll M1.MN/n I r1M111N• I kprrlnN•nl .d McJw Inc• Wavhml;hM Oluvcr>ily ScINNd 401 McJn uN• :Il I ht• kwl.b Ikr.p/lal.nl St I.IwI.. \I lawi.. 1'Al'll(K:1•NlalS ()1• llll: AIH)I:r RI:SPII(A"1(N(Y I)IS'rkl?tiC XYNI)N( IMI-. F , VII)I:N('I: ()1• l)X11)ANT MTIVI'1'Y IN I/R()N('1I()M.VI:()LAR I.AVA(:1• 1'1.1/11) llll• Ixrvnl .1uJy pntvitk. cvitkrne indicating Ihal osiJ:M1% arc p•urrrlCd in luny..d pllicnl, with IIM allult rc.pirahlry Ji.1tc...ynJr/Nrlc IANI)S1, lhI cvnk/wc wa. Jrt/vcJ IuM111h.ervalilM.lha1 u-1-M /al~ha-l-pnMCina.a iohilxlarl• rc.uvcrcJ lu IxIMrlNwlvrld:u IavaF.c IIMI.) IIuiJ. had hecn inaalivakd by a.iJalitln. pc.utn./hly IIIt111:NNM n1 the Ilnlhionyl tc.ithlc in the rca/:liwln .NC u( Iln' nN.krvk'. I hi% wav i1Nha•a1eJ by /IrlJlng. Ih:N at•livlly 44 the u•I-1'1 I:a11k1 hr ft:x(IxcJ hy cnpllwl.• tn 1hc rttlucinF a~l'/ll, JIIIInN1lrClhtl n11ht IxCtClllYnl nIC1I1NM1yI WIInRNIC 11C111NI1' Il'lluilJoC. lhe anwx//q ul adivily, rc.lufcJ wav pnlplnMlnal h/ lhc a/INN/1N u1 In:nlivc u I I'/ Ixt•.cnt at 52.11110 l). l).iJa1i1M ol the S2,1MM1-1).. (-(M wa. a1vl tcvcakJ hy Ihr hlNilnp Ih:ll /hc inacllvc nNlkyulc wa. whrcl M/ pnllctJylic ckavaKc In 17,INM 1) wlkn c.p11.rJ lo pxritlr pall. rcatic ela.(a.e. I/w•Iwalaln nf Ihc a-1 1'1 rn 1•nv, al.u rc.IJtcJ IrIM1 c/xlrydc><inK 1u an actlve cniylne, aw/wn prvillu.ly Io hc nrulrlM,hJ cla.ul.c. In trxNraa h.Ihae in 11AI. IIu1J., thr n-1 PI in l/laalw 111 pa1KMv wilh fcyxrahNy Jl.lri.. .ytwlnxla wa. hwlwllu Iw• •'MMIi. active in 14ul 22 ca.cls anJ S/) :Kilvc in R a a.rv Ih1% NII,'1•'l'tkYl that hx the /IMN1 I.afl, u1. IM wa.v inarlivwcd allcr Icav/ng Ule vc.vl% anll cntcnng Ihc lung '111c cirrulrUnK a-1 1'1 in palicnl% wilh /11c rr.piral.xy JINrc.c ]y/NhIMIC wai, /.x/MI ht hl• equally \uN'ClM/hk 11) n1111,M/vc /nal I/va1NM a% u I 1'1 I/..nl INNUWI /INIL'MIU:/L. It VCIn~ /1111MthJllk /herehx! IhN INII/C/N% tlcvl'kM. AKI)S 1c t•au.c /rI l.lblk n 11.1 mh/hn.x. ('ta hran.•. ('. (:.. SlxaKy. R. and Rcvalt, S 1). ~ l.wrn.d../(7iniad /nrr.nxorienf 71:751.7A1, 14111. lNArr srpperf: NrtilMal In.utulcc u/ lkahh anJ Ihc (Nlicc uf Naval Rc.rarth Fnxn Ihe Ik•r:MnrM Id InMwfxd..Ky, Srrip+v ('IMiI: a/Nl Rc.cuch Fuu1NIrINM, 1'm )ulla• ('A, uN/ the PUI/INx11f y I)/v/,NN1• I In/vCri,/ly UI ('11I/hNnla, $Jn 1)ICI,•u, I d IuIID 11t 1 19
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I'KOTI:ASI S ANt) UXIhANTS IN I:X%:KIMI.NI AI.1'l/1 MONARY INII.AMMA/(/RY IN1lIRY Thc uwvr.IrFanw% have etmincJ varirws hMUhcInN7I paramrlcn OI pulnMMary nrtlamrn.nnwr m rtpcrnnrmal anunal. IMrahnwK•hral in.UllJliam.,l rlunr.c oarJav- yhM ~ I( il //1 i1 ur rnwhave usnlanh rw hKmylalcJ rMwku kn phr (I N1.1') rw pMwl.d myn.tatc :KC1atr IPMAI a\ kultnl'ytK VwnuI1/nlluteJ KYCra• aa'OIC INrIrlNwtlry Inluly in Nrw Ifal:uul whnr rahMl. I'MA ah.e irw/uced in0anunauun whcn aJnnoi.tcrrJ auravcrMw•ly 1•.arh .unndus rnJuaeJ transuJalirn rr/1urArm tuwn Ihr va.. ul.u .paa•c rnlu thc Iwduawtary Ir..uc., anJ an inllua uf kukucyles Jutrnk Ihr J-t+h Ix•rnnl u/ Ihe c.p. nnw nl 1'atlM~hy.w~MqeK changes wert mrawtn) hy rrkma hKmati.wr I tran.uJa• tnm u1 •'Y Itiwinc .a•tum alhumtnl, anJ hislolrrgir es.mmviatnwt Nirt hcmical .maly.rs wa. Iw•rIrwnw•J by nr•a.mrnK crwktMralMrns d pdeMrally mlrnnwu% agcnt% m Mevm llwralvrr-IJr lav.rr 111q1.1 fluid Irkrra.ed aaiJ pr.Mcasc arwl myrl.•~rnarJrr kwcl% wctr 1.wrnJ m the IIAI. 11uM1 alter aJmmrVra"wt rd rnher r-1 thr .trmub Sahraad.tana•r• 1 tI • Rcvak. C 1) . anJ ('rti hrrrnr. f: (: f..urn.J.4 ('Inrn ol /mrurRdn..n 71 1175 (111J• (')/{J Othrr srppeA: Natw.nJl (n.thlulc...l IlrJlth am/ drr Ol/ae ul Naval Kc.rar. h Pmm dw• 1)\•p+rtnw•M od Immunrshly• G nM.. ('hnK arw/ Kr.car.h IfrwrnlJlrun• I a bdIJ. ('/1 1111K IIt•Ml('A1. I A('I()R\ IN Pill MONARY INI I.AMMAl(IRY hlSl•.4tili VJriuu% hNwlxuraal cvcnt% tJ\mk placr dnrruK pulnw.nary m1lJmnunrwr werc raanurwJ m t/w M.wlaIw611vlrrlJf IJYJ/ a' IHA1 ) Ilulll\ Ihw11/41tn•rN\ w/th aa tltr re\Iwra. tlwy Jl%t/r\\ %yn1I1/Nnr IARI)SI and /n cif\'llnla•IMJI anlnlal nwwh'I\ In p.da•nt. wHlr AKI )S. activr rr•rnuqrhd eta.ta.c wa. /rwnJ in the 1(Al. Ilord. In the.c IlurJ.. maa tt vabrw111I Ih( marw clamaw /nhlhNlw fl, prrwea.r inhrhnrw (r.. PII racuna•J I hr. was aau.rJ by nantalnm ol a mclhwwnne rc.rJuc at the aclivr atr nl thr u, t'1. and nl/rrcJ uwluerl rvwknaY r.l n.iJalnm aa'a•umng in the inllameJ pulmonary li..ur.. S1whrs wrth r.prturr•nlal aniuwls have been initiateJ l.u rain unJrr.lamtinK ut thr relative n.la•s ol pnwcavs. axklaMs. araaheMwule nKlalxrliles. l•rwn/rknll'M anll a'rwNal'1 .y.- Ir m crwo(rwr•mr. atNl rwhcr nrcdialrws in the pallwJcne.iI al pulnMmary inllammatnm. InnahnwKhial rn.IdlJlum ul Rlurr•.e naiJasr/Kluclsr Iu prrMlua•e n.iJanl% nr Irwmyla IrJ mwkwylkucylphcnylalaninr rw f+INUhrA rnynaate aartatr as kutrkytic stimuh uxhn-lyl .rvrre acute pulnMmary injury rn New Zealand whNe tahhil% awl rhr.u% nwwrlry. lhe rnruy was accrwryunn•d by kulucyur pnwca+e (aciJ.athepvrn.) te• ka.r in rahhn luny% anJ mtiJaM f.wnutiwwt. and awlJ he inhiMlrJ by ncutny+hrl akpkuww+ (/111JaH IownYNNM wa% tkrMwl-makJ by Ihr /nallttalMwl nI a'Jlalaw by V amuwr 1.2.4 krarrdr in Ihe (weaence rr/ a Jnrp in inlraccllular Xlulalhnwtc kvels. and rn dk rhr.u% mrw+ley by in•ictivalNrn /d a,.l'1. scAraul.taacr. 1. Rcvak. S D.. anJ ('.w hrunr. C. G. Frdrrurran PrrM•rrdrnK. , t 21q)7 • 2R10. 19114. OtAtr srp/orr: Natwwul In.litules nf Health and Ihe Uffice of Naval Kesearch I nwn thc Ikpartmcnt 4,1 ImmunuluRy• Rr.c.rah Inadutc af ticripps (Yinic. 1a 14,118. ('A (l KIII OIM.ASMIN. INl'RhASlib SF.KUM(Y)N('IiN71tATH1N ANI1 IMPAIKI•1) ANI IUXII)AN'f A('llvl'fY IN ('KiARlil'1"li tiMOKI.Kti, ANI) AHIIJ I Y'1( ) I'KI• Vt•.N 1 11/1'1'KI_1SI(MI (N- Ii1.AS"1'A\E INIIIUI 11)KY ('AI'A('llY (FAI./'ItA, 1'I(t)1hINASI's INHIHIT/p( IItINNM1,lIYl'r1IJt Illvaf'c fluid nt.nuncm anJ rwrn.oMrka•rv crwllJm. .rrruli..mt nwh'rnuatnwr. rrl arruhMd.r.mru • 11w m•ahu.rtum mhrM/rK ad hpid Irw.iJJhrwr, wrdr hrnnrJ wls tuauk Jr.nrolarr aclrvny 'liri. suKpc./eJ dral crrutrr~la.mur nray Iwrwu t Ilrr hrwa't /r]IqrJHlry Irall a)!JONI nRNlJntt\) in l/l,'arrlle NlwoLr arM/ air IMr11u1Hn1• Ie1 loll.rw up rwr t)n.• 1aw•.a• invr.bpahw..luJicJ (l) seruur ccruWoplasmm .vwacnlratnwr arKl anlnr.alJra aa•ttvny Ipa•r.rrnaKr mhrhNirur nl auhrardatnm ad arM-lwaln MwIMrF'r narrl un ce:dUry raalr ami lemak .nwrAer% anJ rwwtsnw>tcca, aml (21 thr capacily u1 armhy+lamnm ua fwrvrrn .ulqwr..inn arl Ihe cla.la.e inlnMhwy caprcrty r.1 allihJ, Iwrwr/11J4 1/1hlhn.w hy IIN' nitNt:wn ahhwanlnM I a/M1 by t'/l,`ara'tle %nMlke Mllulnwl MrJn arrulqrlJ.rnm c,wMrunatnwr was siKndi.antly hrgher m.orrlrr. Ihrn in rwwt %IIN-ka'1% a1NI 1/t /C/IGJr, Ihall 1/1 Ilqk\ whrlha9 rw MN Iha'y \IIMolerJ ti(Yll/n a1ltNrarlI:1I11 aairvny .Iw.wrJ srrmrh. Jru Imr.a cunclMwwr% with x•rum t'crul:Nda.nrm rn .nn.Acr. aml mwr.nrrl~.•rs ul Lqh .rRr. 'llu•a was a Irnraa rc1 rtMwr.hrp (alween rcrul.qda.nrm c.wnentratawt and 11% ahddy lu furvenl .rrpiwessinn arl Ilw rla.la.e inhrhrtrwy rap.N ny ul atph..• Iw.w.rnav mhrMt.w by ChhKamine T anti a9pafl•tte mnM*e mrI11tIHM (lM'N' IinJm~,'v rMha'a1c (// thJt crgart-/tC .nwolin~,' can causr Irartial maalivJiwm .rl Wnrnr 8nlnritplant :w lrvqy a.rmiMranp•d by imu//n•irnt cnwrMu•n.:uiwy increa.r in r rrut.qrl:r. mm awKrmratarn. arH1121 drat lrru4Y+la.rnrn nuy Ixawcat Ihr lung akJmm rmJ.mtl.l In a irarrnc snwdcc awl air ppolulaMs. At rt rd. Arnrrir.or Rrrrrn• u/ Rrrtrbmerrv /)r..rep• 124:258•261, 191(4. (hAtr srryrewl: The l.nurm anJ Ru.e Kwrsk Fund. Fr.wn tlk Ih•I+artment 4d MeJicrnr and the ('he.1 Servicr• Itrllrvue Ilr.yntal, aml lhr 1)rl+anuknt rd (:nvvrmuwnt•d MrJia•inr. New YruA Umvereily MrJu-al ('rulcr. New Yawk. ('1(iAKIillli SM(1K1: INI)IK'I;1) BK()V('H(X'I)NtiTRKTI()N IN 1)<X;S VA(iAl. ANI) I:Xl'KAVA(iAl. Mt:('IIANISMS 1he aulluws ul Ihra papar sluJied tht mnhanism ofv ciKarrllr .nwrkr uNluanl hnrnalMRrm.lrK9i.wt by rneltwd.IhM alhtweJ.eparalirwr rd a~a/ aflcrrrN arrl rt/rra•ul nruk. Tu evaloJlr ltr;.rvrrny of sn.rkc-im/uced IxawKMKrrn.lrwiiwm in arw•.tlK•tvrJ d.K.• Ihey nu•a.ureJ .uway Iwes.urc aml airMrw rr.r.lanrc (Kr., huccJ r.., d1Jta.n nr•thrwl) •Ihry slwhrJ the nwchanr.mn in nthrr JrrRs by uka.unnK anway Iwa•,urr. cemtal aaway .nrwwh mu.ck Nwt, in tra.hral seRmrnls rn snu• anJ reslwrahwyy rnter Jrrve by mwnlnrinR pAnnic nwwru ncrve rwqwl. inrluJmK the radr u/ val;al anJ e>atravaRa/ nrrvrs vs. ahe t+.k u/ hMwr) Mwne rnakrial. during inhahNinn u/ arRarcnr srrwJec. Rn incrraseJ mrxe than trwafolJ with amrke fr.wn une ciRanlle JehvercJ rn Iwn IiJal wrlutnrs. Ahaw1 hall lhe airway rcNtrm.e was Jue N. Mrcal et/ecl. rd srn,d,e in the IunRs. lhe remainder was due lo atimulatinn of the reyr'aalory a'emct, whnh activated vagal rrrrarw eflerents 1o Ihe airway snw.Nh mua•k. (N lhivi cemral .Imrula. la+n, atrwN hall was due 14, hhwr.l Mwne mNrrials anJ the rea lu vaRal pulnwmary af/ereMS Grmr thr IunR.. lhcse investrRauws awrclwk that inhal.lMwr t,l arRarette 41 411
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.nN.lr In J•.r. a•lu.e..cvtrr MINN INt Im.trn th/n whit h i% nN•JirlcJ ma/nly by r.Na %.q•.J nN•th,lnlan. 11•uhaLl. /, M,qh.. (' . Mltchill. K A• ShICIJ.. R 1. , a/N1 l:uld. W M l..urn.d•./.1lq.lhv/Yll..i•.InAa Rr.lNrnr I nrrr..n l lrrlr.r!'hr.ud 57/41 I?hl I_'7//, IvKt lbhrr tup/r..rf' N,Ihun•J Il.vn, luny atNl NkN.J h1.Ulutr I IMn IIN' ( dHh..vdN11Idr Ki.tarah Iu.lilulc, I)kluntlrenl.l/t MCIINI/R r111I I'l1y%NJ /.rv, I lnlvrraly Id (':J/l/lnnr, Srn I torl.iv'o I IK'nl I/A 11()N tll ('AI MO1)IU IN IN 1)I111•.RI NIInI1N(: 1'1lI.MtINAKY I YI'1 111 1'11111 1 IAL ('1'I I\ I'11I11hN\rry .ml,Nlanl, a.Ilnlph•ot nnalurc /d IIpiJ, Iw.Na•In, :ItN1 trrtrAlyJr•IIt• wlnl h INk'. ,Ilvr.d,u .u/tacc., i. •yu1M••vcJ by a1ve/Jar lyfV It InKUUN. ylc% a1Nl .1wrJ nl nN la.nNl% a•Jlcd IanN•Ilar LNhr. In 11•r prc.ctN .pNly 1h(• rr.raniN•t. h:lvc rmc•Iq••drJ t1/i ndr ul low t al.luul hltNhlll! IN.MC/n, 1a111NN111I111, nl rerl1I]IInF •ur1:N•. IJII/ N'l ll'11.N111/1hIIa•r/'/II/JIIIIF tJt Ir/•II IyIR' II fNN'1111Nq yN'\ I•a1/N'Ilat IwNIy %t'11i11/111 L.InuuLdrJ /n Jlt lrrrnllrlln/: lylx• 11. rl1. rn ..rt., by low t ak lual NNNIIIINwc. A211R7 AZ 11K ) IMlINItI 4YIf11.N1 1% hh.1,eJ by Ilr- pIN'1NMh1:1/Inr Jnlp• t11IIu111\r:1/lne rM1 t111.NIN.1111.1/IfN•, tlul 1. un.Jlr.N•d by low NI•NUvr rnal..)c., Ir/lhN.t+rra/tnc .ullutNk .NNI IIILNIN.•IILII/IN' •IIIIIItNh' III/IIIII/h.lI1NNt'NrINI' .IU.IN•% tln aulNucd Iylr 11 INN'1111NMylr..lN•w th.d low IK'tlcnlrl•i •d N.Nn.u.kl/kav inlrxt•IlNlar I:/atluk., whltlr 1rrN (MI~t1/v.Iy w/lll nlfh •dardulNl rnlJvooly, ul.rrr.r• wIN'n IIN• CCII• atc A 111111I.11\'II w 11I1 tIK 1.•Il 111111 N1/NyINN(' A21I/{ I%IIKr l(N'K NlN/cu.kl lk•nv rra/tuh•• ,uilw..u11ai1v.lr/rN•dhYldwnl4mN' IK,IIN•vrc.ulhnlJN•IN•1halnNrt•.rv'J:IIINNIIIINII 611111 1111NNt':Nllvr 1rI11NMI11I1/1 •Il.(a•.1f .MW\Ldt'J wnh IrnN-11r1 INNIy .ur1•Ni. wM•n thc arll. •Nr.t1lNrJata•J 1•N 4l'ra'111N/ Ir1.Nh11tN.N_ uhr.ntru. tu.J hN:Jv 11N.nld t: InurhJm INI aW /t,nl'1I I:I•1N'II:Ir hl Vlll % 11\Inr IN.NrIn A l IIIh•NI•II /!LhI IINht•atl'\ Ih•It t•II/INNIIIIIII /\ INrN'1,1 INI 11N•11 /N/It'r Nlrtrtl'\. I:Ikrn H•1'l'Itk'r• Ihl•1l' :I/NI IItIN't rl'%1111• 111111t11:/lt• aalnN.hJln In pa1lnN.n.uy .utlarlant .ccreb.Nl Ildl, I) 1• WnEM, 1('., )r., ArNhcw., M 1• , and Aurrr.nc.ly. M J I alurrurun• Irnrtn,q~.nil.e 5111) 297 MIG. 14R4. (kher auM.rt: NrINNIal C:rnicr In.litutc. 1•nNn Ihr 1)aparlnxM nl 1'a1MIMM y, 11:nvarJ McJical SrhINJ, 111/.1Nm GiI'K( )f( /NIN ANI) 'I IIIi /'lI1.Ml INAK Y('IK('l ll•A 111)N AIQNIuFh .rnMUnm Ii .hyJru.ylryplranne. 5-1111 ha% ht•en Jl..rc/lllcd as Ihc nN9I1.111N Iti hy1N.aNINIt11MNlary vaVq'111wrN'111N\, 11 f1N1/1n11C5 NI be C1NI%Itkn'J INIf nf low vrv.'INl.lttt Nny .uh.t.uN•c% a/Nl ha% hecn akrnlul.tratrd in Ihc IunRp ol all y+ciics Inva••UI•:Ill'J In~IIn1111ir///ng cdlhCt %tYJN•%.evNkrn'cha\I*en/1IICtlYIlhJIrYnNlvalnl S 111 1. Inluh/liJ by hylb•IIN'tllllr .n hypa•/ntla, i% rNN udlucnicJ by hYlNlaa, i-. Inhlhlh J 1.% ,NMw // r.'h/u h%IN.U/.I IN• l.M,hkn•J .cp.uatrly b/Nn Phy.h.lu'N IrytN. „•'1 ,,,,,) ., rl.•• •1 hy ....nNh' IIh.IN.111//1N'. IIII••/tM.Nllr/1111', r/NI .Nlrl.rol, q1/' ,.1tu .. l lq .. 1 uw 1•. •u1.1 udul.d.N 'I•14rq111N' t1/1Clt.l llll ,N llvr 1/.111\ pIM . Thc wurk rcpnteJ in Ihi%chapter rwiRinaks fr/Nn earlict audic. tul' Idclnnx IduKN I/NNt1IN•'a1NN7/11 11uI1nlNldry ar(Cr1aI Iun1:INM1 anJ IINNIIIMII/I~•y, A~ 1/ar( 1/1 Jtl Inve~tll,'a NINI ul thc cltccts ol vkucJ ~y\IenIK vaMMhlaNlrS tM1 111e IMIInNM:Iry c/rruLtNtNI, kclan.crin (K414(d11 anJ Jl p-ch1/1ratllllcnylalaninc (p•('1'A/ were tc.1cJ. A 1hnJ auJy wa. rntlialeJ tu calliml ur rcKt I Ihc rcwh% tl( thc earlwr ketan,crin study arNl a unNr./ 11% achvhy wnh amNhcr 5 1I'f. mhihiuN, cypn111cp1:Nhn. /Pcriaclu// In .urnwrly, Ihc.e .NNIN•..uplllrl llK prcvnlu.ly rclNNteJ .ugFeaNnl that 1he paNN.genetN Nw•U hr tn.m lel RV hyprrtrllpAy aal nleJlal thiatcnmK in chnNlN,• hypua/a tnry /NN IN' /IN' .anN• I unhrtnNNc..cneunin %ccm% tu c><hlhn INUh eta-ilaHwy and inh/fNhNy atl lvulr, rM In1I11NNlrry allctla'\ 1.( S/)1o I(M1/1M in )pe lhi. N(cla wa. ven hy cithct Ikpk•hn/~ 5 J 1'1 wilh p('pA IrcathlN•nt nr by Mlt king the S. 111% rct clNllt. willr kelanxnn 1 IN•v rR(ICrinN'nt. I/N-urrn anCnlnNl tNl new rYNN.YIN% and p/..IMlnir. hlr th.• l-INIUUl n/ IIN• /NrhlNmary t va ulalNNr anJ i. t INnpanhk w1Ul lht• hypnhc.i. thal rNlrnN/uc INJnN.n.u y va./1J11atNNt /% low acNvr Lha.c 401 Ihc pulnNlnary va+a•ulx rc.INlna NI hytN.ar Wdl. l A . Arnh, l M, Hucknet. (' K„(llacku, l., OLnn, l: It.. lr .:uNI Wru, l•. K In Hn'kcr, K 1• anll Ca/J:Ir• A. F (c.h.): 7hr f:nJ.r'rinr Lunk in /Iruhh A l/tlr.tlr, 1'Inlalklphia W 11 XaurNkr., 11/&/, pp, 117 1.14 1(hAer arppurf: ('olk fc nf Agricultural and (•11c 5eicm•c.. Air Farae, and /tN: NrNlNlal • InaNutc. nl 1lcahh. From the Ikparlmerll u1 Veterinary Sa•icnt•e, University nt W/MYNKIn, M:Nh.rm VAS('l/l•AK PR()TI:IN LI:AKAGIi IN VARI/KIS TISS111:S INI)11('1:1) IIY S(1HS I AN('1: 1', (•MtCAI('IN, BRApYKININ, SEKO'R)NIN. 11157 AMINf. ANI) IIY AN71(i1:N ('11A1-1•I:N(il: In (he wnrk ra'INN1eJ IMK•: (1) Plarnw etlrava%itNlll was /n11ulY•tl in r:1/%1N I!In/N•a piK. h/ inlrrw•rNNr% in)cctu.m. n/ I. wM11a•c 1' 15V/. 2 Ihc (' Icmnnal SI IN'ra1N•1wNk SI9(• I11, .1. .crahrlm IS•Iff). 4. hi.(arninc, 3. hraJykinln• 6 l':yl.aliln a/NI T hy anGFcn a•halknKe 12)1'la.ma eulrava.alilln iralua•eJ by CI', 1PtN 1//, by S 11T atN1 hy cap.aicinwa.,wNhlewesccptNlns,nh.ervcJin/heolanK/i..ue. 'Ihe ellart/11SI'wa. rull hAla kcJ hy 11, adl 11. hi.lanline ratyMrx anlaKuni.1.. '11K e11ec1 ul i v CSllhall 111 was ah.ent in cal'/.aicm tkxn.niirJ anrnwl.. 1'lawn.e caNav..:nilln nIMNI i v SI', SP(M1•I1/. S Iff and up.anin was Ktn in 1hc skin anJ m a11/wKam clNlt•/mmg nlw u% mrnllranc, e><cqM Ihe /nlc.linal rmKrw, aml l t/ l'la.una eR(rava.alNN1 by hl.lau.nK, IwaJykinin, and anhgcn challenge rd rlen.itvcJ Euinea piKa wav al.n Ilh.a•rvtvl ur low %Nwnax h anll inlc+litN7 I'I:I~It1a CtlraYiVMMM aMI hr/NN'hIqYM~ItN~INM hy anul;rn t hal lenge wnh 211 t.y/kK uvalhunnn war ctNrM+ktcly hMlikeJ by c,N,ANrN•J /1, .INI 11 hi.tanuna• ra•ca•INIr hI1N kalle Ih11h reyllrlvcs were reduced tn afrwl dN• h.Jl I,y..•u, In Jc.en.NtveJ Kulnca pIK.. thllugh the nvlua•Iam uf 1hc IrrnN•ahday rcqNlnv wa. .L/u% lically rNll .iRnifia•uu in all INgana. In clMclu\Nn/, several .uh.lana'e% low Iwlnik anaphyla.io inJuce pnllein kakaRe in many li.cue% with JdferinK.clcctrvc Jr.trJNduNn pallern. Anaphylaalia- hi.lamine release kada Ns prldcin kakax.• pattly via rrliv:lrhN1 rd .cn.ruy ncauln. til' i, a Idely mediaNlr /d ncunqtenN p.dcin krkagc In Nuny nrRrmc Sar/.. A, f unJlw.R. I M• Sku/i1.uh, (i , anJ I.em(letk, I• 41 1 41
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Nrrunvn Sr Ami.drbrrK's An Arvrs ..J /'Anrnwn rd.rRy 121 212 21111. WM I OtAtrsrppeort: Au.uian ScinNilic ke.carah Fund. Swedr.h Mcdreal Rr.carrh ('num cil. Swcdl.h fl+haan ('un,<+any. Wdhcrg. Giltclx, flam rth I.lu (1.Irrnun. 1111 tel.c• (iu.lav V I.nImIalhM, Sven.ka l.akarr.alI.kafrl. M./gnu. Itcrgvall. tillllrl.r. AuKu.ta and 1'etru. IlcdlunEa Slrlleke, and A.Ira houtnlaUrm 1'wmr dx I k panment .ll liaprrimenlal and Clinical 1'fiarma'aluFy• I Inivrr.ily uf ( 7rar • (7rar. Au.lru, an.l the Ik'fulnmcnl o( 1'Itan++atuk/~y. Kandm.ka Inallnlrl. Shlck- lathn• \werkn St1Hti'1 AN('1: P ANI) ('AI'SAI('IN INI)IK'1:f) (Y)N'I RA('1'111N (W III /MAN Nk/ )N('lIl In the lar.enl .tudy the elreata rrf .uhaanrc P(SP) and tap.alc'In Im huluan Iw.uw hlal arnrr-th nru.a k hmr werc mllnil.wed rn vitru. Re.ull..hllwcd Ihal SP mduc rd a dn.r Ikl+rnmknt ranlra.9ion ld hunan .cEmenlal Mnm hl in ritrrn with a Ihrr.huld dl..e ~.I ahuut NI M 1 he.r Preparalinn. wrre nMained lrum f+alienl. unikrKrhnK lung lunhw .urFery Ihe 1P-nhhll'rd l IM11raCIhMt were rr[Itlan) to nlrhytamhle and altll- Plne..uKKe.ImR a dlrerl elfecl nn the hnuh'bul.rrMwMh mu.ck ('aP.aicm (11/' M/ alv/ nhlw c•J a cL/wly drvchK+inR• .Irony atnqhne rrcl.tanl crmtrxlicrl n/ human hmnchi in rru.r A raPld lachyphylau% devckY+ed hK da rrspm+e la ralnaicin. HMh SI' and caP.ah in were k.. Pldenl than ax elylcMd/ne alhl M.lanune in induc/nK ronlrarlnwl% of human Mrwr hl I M. Irrnlmg may. Mrwever, he panly due tu the ealt•rhlknlal anrli- blm•• MHh X/' and cap.ahm were cluuparalrvcly much nhre pMenl in Kuuka pig preparaunma Tran.nuual heW .nmulalum ol the M//nch/al prrpatah.m% in nun re wlted in nonlrwn-.n. Ihal wrrr lalpcly .en.hwve lu arr.ynne lhr fxr•rm'r ul aap .alc•ln Induc'rd hnuxfilal c.wura.ta.n% h..wrvrr. In.b/alr. the cu.len.r ld a kwal mwKiwdlnerK/c au.n refleis cunhnl 1.1 hrun.hlal .nolwNh nnl.alr h.nr by SI' in man l.rndh.•rK. J M. ManhnR. C Knd Satia. A Ar tn I'Awi.dnKn u Sr.rnr6n.n'h a IIV 44 S 1, 1481 Other tr0/orf: Swcdi.h Medical Rc%carch Caunril, Swtdisoh Tuhaccn ('lhnpany. W/herK. titdlrl.r. Ilans rt'h Iar/ O.Irrnran. Suhel.r, Guaar V Iaurhlateln. Karo- hn.ka In.utulcl I:nhl.K, Nvrn.ka I Aato.:lli.kapcl, MaKnu. IictRvall. Suhrl.r, Au.- Inan ticicntdir Rc.carch tund,l4ym. and AuRu.1a I lcdlund. hnnd, and ANra Ivwnda- (hhl. fnwn the 1)el+anmen/ rtl 1'hannaruk/py, Kandin.ka In.1Au1e1, and IkpanmeM of Anr.the.u/k/yy. • K andm.ka I lu.pltal. Shn k hidm, Swedrn; and I kp•anmcru nl I•: rl+eri- mcnul and (limcat t'fiarnvlrc/trl~y, Onivcnily ut (7rat. (:rat, Auslria 1?I'Mi(TS ANI)1)ISTRIHUiION (N: VAGAL('APSAI('1N-SF.NSITIVI? St1I1S1 AN('li P NI•.IIRUNS Wffll SI'1:('IAL KhF1iR1iN('E TO TIIIi IkA( III-.A ANI) I I1N(i5 1hr rvrRln r.l cubdancr P/SI'1 mlmurhueaclrve ncunlna in Ihe lnwer re.pnahlry Irw 1, rvrhaKu. MMI hean.e/ RurMa pIR\ wa\ IkItMNI\Iratl11/n VNne I,/ lhr{C \hNln'\hy .urrp .1 h IwI.M..r. w I ap.ar on p.~ur.~lnrnl wtlh .uh.ryuent lkfennrntlNwl .d rhe 1-u,.t 1,.r1..•/ \1' 1.t r..,L.•/uu.......•r...~Y 1n.•Ihrr r.l.'nor•nt% Ihc r/lr.t..1 valta) Ilrl%f •Immla.••u ••n Il.r \I' 1r.. I. Itn 11% .C II%Wc+ wa% Nlnlit'd IIK l'll(lls 111 lall- %an ln-.rn.ilivc allerrn/% in Ihr rry+irahay Irac1 Auanca and hnrrchial .nha.th mu.c k• wa. al.u .hnhlndankrchyTIanalyre.rnl IhdllnyS/'h/ l:van. hlur arhl In.u111a1r.in >< a. nfJvalaa.cularirhlicalrrrrnlcaha p Prc'..urr a navvr. in thr ua.hra and IunF a/ arr allcrcnl aml ral+.ah In .rn.dlvc. Thr Irachra and .ICm hnmchr rrcrivr 11' aI lrrrm. nwmly Inuu the ril;hl vayuc nerve with crll hld/r. Mt-alyd in Irrlh the rhlJlr.c aml Iuyrdall;anKha lI1rS1'in/IrIvaNNml.lthrlung .rrnl.rlhavradualungin I Al/r/rnt. Inwrl IrNh vaFal nrrvr% wnh a cro..cd lyr ol nlnrrvalhm pattcrn; 2 A rhm vagal ..mr. r whhfi c.w1.i.1% rd alrwl MM>:.,1( tllr SI' nervr% in Ihr lung Thr.C ncrve. pulhahly IM/F`III:IIr Ir/M11IMM:N'h' ]IhIqI /,':IO)!IN lbr rl/rcl% rd rlhrr and iap.aicin r.n ul.rdlla IhN11Mr%%lllt' :I/h) Im7r:IV• in va%culN Ill'rmeah/hly were IkPI'ndrM Irl /hk' integrity ul ('a1Nah'/n V•nNIWI• alh'n'IN% nl IM11h val,'aI anal MNlva(}aI 1N11!In In IIK ku1/K':1 IHI(• .y.lrmlc caP.aic In Prrtn•abrK•nl lu alluh anmwA t,rrmrd tu tt.uh hr /ncvrlahlr I haurr% in l/h' rc.lutat.wy uacI. wlhk in Ihk' rat a%ul'Cr%Nvt' /etYWrry.ll thl Iulh IhM1aI rc.lwwl.r ol caP.ah ru wn.Nwr allrrrM. /r'culrrd f.malAwrr• J M,/tnwlm• 1: atd Salna, A. Ar i.r I'/n cr.d..~rr'a Sr endrnrrvir.r 11Y.211-252, 19111. Other trOprrl: SwrJi.h Mcdi.vl Rr.ran•h ('rwncil, tiwedi.h Tuh:hrrl ('unMany• ' WlhrrK. Stullcl.r, Itan.c n,h Lw/1Nrrnwn. Stdk'Ice, Guvlat V I'Irumlan.m• A%IIa • I-1N11hI:11hM, Magnua ItrtKvall. SlUhrl.r, Kanllm.ka 1nai1u1e1 hcw.knmg.l.mlk•r arrl S ven.k a I.ak arr.all.k aprl huwn the Ik•panmrnl .d Pharmanik.gy, Karulm.ka Inaitulet• SnKkfhdnl. Sweden Ii11 L(T (F ROI/TIi OF ATROPINE 1N:LIV/•:RY ON HRONCFIUSPAtiM FR()M (YN.I) AIR ANI) MIaIIACIKH.INI? llle authrw% unikrtcwlk a quJy hr drlt:nninr whrther the apparent dl.parity he Iwccn Ilk du,e cd inhakd Mnllriar rcyuirrd /n inhlhN hnwk•hncrrl..Uirlirm imluccd by inhaled ulclhachrdinc and the do.r nr(rred h/ mhrh11/he hrlln.hucun.trrc Ihm /nduceA by crcapr/ic hyprrlrrra wrlh ruld air is a fun.9ilm cll the nNllr crl adorinl.IralNwl ul alnlll/nc. ln.irt .ohKr•t% wilh a.llmn, /hry nxWrurlc'J dlnr m.yum.r curvrs hr inhakd nlcthx'MAirw and lu cucalmh hypctlrrca wNh cold air a/trr trralnwrN wl/h /nhak•d a/nrine (11 5tnK cklivrrrd) and inlravrmws ptacrlK/, with inhalyd Pl:K'rhu and inua vrrhnl% alnqnnr IIf S mle inM'c/cd). aad with inhaled and inlravrrrlu% ldal'ehll.. Aau pine by rithcr nKer .hifliy/ thr dlnc••rcynlme cwvc. N/ Mllh c•rdd air arhl hr nlrthx h.r line lu Ihr riFhl In every .uhfrr/, hlwrver, inhaled alnl(Ilne cau.rd a nlarkc.lly Fn-alcr n/;Mward ahllt rd Ihe inhaled nNlhal•hUhnr dlhr•/l%IMIIIw l'urvr than /INI InlravelhMN alntpllw • wlMreav Inhak•.1 and inlovemw% alnq+ine had vrmi/ar cl/eah rm Ihc rcd.l alr dll.r rr•Iwwl.r c-urve I1h•.r /I/rlinRs suggr.l that IhC apparent dNlwrNy hrlwrCr/ rtw dl„r..d Nnlnlne reyuurd lu inhihN rnrlharhldinc aml e.dd air-Induc'rd M.ln, h,K,MI .Iriclinn nuy R a lunc lilnl ld the nwle of ad/nim.lrali.m rd alalp/nr alr) thu• d.r% rww imPly a mwnrw+txinic ac7iun rd alnl(linr. lhrsr linding. vuparllhe view Ihatt uk1 au c.lu.c% hnu111hwcm.Iriclhm via mux'arinir Padhway.. Shc(1(lanl. 1) . Ep+lein• ), l/oltrmen, M l. Nalrl• I A, and Rrwshry. 11 A /.wrn.d ~~Afqdrr.l /'Aru..InKv R.qnn./ /•.nl•rrr.n F..rriv I'Arfad 5~1//1111 111, Ivx). IS aa
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Othrr .ulryHr.t: Nrnunal 11can. I.unl;• and NI/NKI In.litut. 1 fnM1 dx- ('.IIJN.va.. ulrr Rca•:Irt'h Inallule alkl Ih p lnnx nl.l.l MrdN i1K :.nJ 1'11y.1o1 "CV. 14uvrraty ul (:Itll/.m/a. San I rrnaivn. rnll t1K Mrdl. rl k•rvlcc. Srn I rrlx lvu ( a•n;l.d I(I..Inlrl. \.In I Irn.l.s o (•IIAKA("II KIYAlION Of tlllil AI)RI:N(K'IiP1OR SIIItI'Yl'1.` IN ('ANINI: AIRWAY \MIN) 111 MII\('l l. HY RAI)1OI.IGANU HINI/IN(: ANI) 1•I IYSK II 1 M;I('A1. KI'tiI't IN11 S I h\'w ta'4'.Ifl IK- hrvt mbl'%1/r:IIc1I Ir:ItIKaI \IIkNNII n111M'Il' 11( ttK 111.1; :1MI IIavC 114'll I 111111 IA ks a11NIy tIK ch:Ir:Nlt•r/.lwt nl IH•nl rrlcruH\ in /kHIM/•.nwtl.Id 1111. 11a,1k' 1-..1 t nlnllr11M.11 • 1IKy :II"1 %11kIKlI IH I ere.. /4 lle a1ln'1K1)!It' fl'lIMM4'\ In Ih; \.111K 11"N/l' Itmn)! IN/111;t1.'t'IH1U% IH'l.e NrIMI%It a1xl fh'\IfIt:1I %1/11NIIrINH1 .11 .yn1I..NIN'1N• 1k-Ih'• `Iq•.1111•Illy• IM'h1 alh.'Mkl'I.t.N N1h1y11(y I// 1:111/1K lfallk:.1 V/kMMh IIIUNIt' h.lv; hrcn IIlvc.turrt;J by raJN111yr1k1 hoxl/n{: anJ by phy.xdayltal rr.plHl.r% t..lwlu rylHn.t. rlkl .yrop.11/Klk rKtvc .umulatkHl en ren.r `It•cltic hllNbnk 1.f I•111 dlhy. JIU.JIHCrMd.d 11. u./alx•al .nNNNh mn.a k nKndHa/K% wa...I hlFh alllnny lK, - I U- 11 (I/t nM 1. a. UI (.l•rl(1tKrJI (unF' nlCmhralK. INMI IIK VIIK an/mrl.. hllt 11K c.Nk Cnlra- IHM..1 huHlmy alt•.1')S fr ! 4 7 1nMd/nly..l Iw.wt•Inl wa% lnuth ll.wcr in lunl!(5 12 ' 4K IHwd.d IN.N;InI ItlrxhnF wa% .lalru.ch'lhvc:llkl arIN11VttIN/11tIClI WIII111K ranll IH11;r..1 lrqcnl y 1..11N.dClrllu) Crlfk•/lh1uK •mHf11UKIltNUK, vgndym~ a(NCIMNxkr~ afx c Id l.. r,l _` It•.clw.H. I I,winK v kt uvi IYr11 anlat•IMI~I~. (IK rl'4'a1l IKN JCI~ r11111k'.I tIK 1,/1n..d IH r,l I ebrhe 2 fc.cpt.H. in trNllk•:d mINN.Ih 1n11V IC nK1111Ma1x'% In til 14 ( IKK• a1kl.Nhcr I;Ia1rJ rc.uhv .IIFI!;~I Ihat IINht IM'tU fCl l'tN1H\ In JLpIral IKrI \nxHNh nM4 Ir :ur .rl IIN• IN de 2.uMylt• nNl tlkdl.dC fl'./aMtC. 1.1 t nl Ida/Ulr catCt Ik.1am11K.. Mll IIN•rr 1% a.nt.d) l/MN1'l1Ir:MNN1 llI IN6I 1 fcc.IMIH. th:n uwJ/.nc tIK r~.tk.o.c tu IN•u1.111y rrkavJ mw;pnN•I.htnK Il:It/K%. I' I. N.edrl. ! A• S{,.u.Fh. I( h. and Rnhclt.. I M I br Jrmrn.d e./ l'hn.mu..durv.nn.l l Iprrnnrntnl I hrnryH•uril . 225421456 461. I'/!{ 1 Othrr tr.pporf: N:IU.N/al In.litulc. u1 Ilcalth I(INI\ tIK (:It/INWa41/Iar Kc.carl Il tn.litulc and I)t•parlnx•nlad MrJn'irK :Irkl 1'hy.i.d- uyy, Itmvcr•uy .d ('rhl.wnia• Srn FrarNi.an- SI; .I I('l IVI: (71'.NI•RATIUN 01: 1 1?UKO1 RIhNI: H. HY "IRM'lII?AI. I-.I'1 I 111 1 IAL ('I :1.1 S 1•R( IM 1 N x 3S I1111I11a1/1H1 by M'11Ir1y+hila ir a rrtnh.m/nanl hi.lulnFk' Icalurc nl at ulc Mllrnllna• kNy t;lINMti\ In IMIInkMrly anway. 1IK fftCnllh•/nlM.tl:/ll.Mthrt /k•ntrl.(.lal iu/llna /xM wr. IIkaIVI•.I IHCthN11/na/11Iy la IIK clNdKha1 (ay.'r .d IIK alrwry wall /n 16.E% hrrathulr nn1rK •Iq:ycvlcd 1ha1 crulcal inllamnlahlry nx•dcluu% wcre rcleav.11raHU Ihc cplllk•hal ccll. In 11K wnrk rrpHrlrJ hcre. Ihe ina'uhalxHl ol W,It'mkNl,, n1 r./mrK t/.NIN•.d cpt11N•tlal tc11% nf Krr:NCr Ihan 4Sel• purity with arathNMMir atkl 111 2111t prl mI/1.H h/) 1211 111M It'.ultC/l in (11t• ~,'l•nrtatM/f1 UI a maainlum nl 1/. 1 • 1/ I(.ocIMkrlca/l 1;H\.d/k•nt• 11.111? .;11.. Ic.. Ihrn 2 u pNlHlxdc, nr 1),. rlkl 1.•rhy ..11. .ual/lll/l • Ir,1 )hl • 1.411 rex11.'.I I/MIln.uoN.Ir.e111tcI1.u11S .11 .an11 • 6a.1,... .., ... d. /. . u•w .. .•I. n.l. 1. lnH "n •\I A( U /11 I IH' h11'lndy uI 1•..1..,..•. 11 ~, . ../.1.1. It..1...y,•.... ,t././, .,/r1•/..11..I1y•./r11H•• LIIt'.H11v1 ly will, nNrk/ q+r.y/ir anll pla.ma antl by thc Chl'/IxMJCIN :Kiivity 1.N rKUtr/.p11i1. 'Ihu.• IIK ryatlKllum Inay It an inlpnrlanl .nurcc Id arcJiallH. ul IIIILIIIIII1.11HM a/kI h)IN•rvnabvlty ul Iwdnxmary, airway.. II..Ivll/:lo. M). Avawa. 11 • Nu.lr/, l. A., and (:IIr1iI• 1: ) l/reH h.vnr. ul .okl Ifnqdn li..d I(rlr.nrrh ('eNmr/lnri. enx.n. 114( 1) 11171"K176, H/111 (Ilhrr lalpunf: N.Hi.Nwl lu.utute, ul Ilcalth arxl Ihc ('alihlrnia Air Rc..w/cc% liuafJ I'nM/1I1C (:IrdK.va%l'ULIf Rc.cart'h In.lilule• IluwarJ IIurIK. WJira1 In.litutr• afH1 IIK I~'I.,/r111N'111~1/1 McllN-IIK a1kl I'11y%N/h1gy• ( lnivcr>dy ul (':dAnrnia. San 1-r:uNla u IMI4 IKIAN('1,(11 AIRWAY INII.AMMAlN/NH)K 111'PTKKI %I'1)NNIVI"NI•S1 INI)(K'I:U IIY O/()Nli A..o/uloanird in thl. pa/wr. Ihc aullku. auJKJ wlx•lher ai.Hlc irkluccJ auway hyry•rrcywM.IvrrK...nnclalc, with Ilr /kvcllyklN•nt ul airway mllanntwtnM in Jug. I n a..r..:urway rc.IkMavcnc%%. 1hc m.cart•hcr,, drlcrmincJ Irkrrca.c% iu pulnkMary i/ca.lr/kc pf.klu.rJ by .IchvcrinK acclykhldinc :Kr/nld 140 thr alrway. fu aw.. alrway InllamnlatuM, they I/wqr.t/cJ Ihc airway nwlrlr.a and c'numeJ IIK uu/nl.rr nl IKIn/1.p1111. INe.cnl in IIK CpitIN•I/unm. Airway "kHl.ivrnr.% and mllanmla(NM wa•fl' a.v..rJ in a/K.11K.iicJ Ihl.l><hwa onHw cllplrult anl) 1 h and I wh :Illl'f 11/1NK (2 I IMMI. ? h/ Air way rcyxMVvcrN•.% inrrca.cJ marAati)ly al I h ahcr urluK and rclunxtil Io nMlrld kva. I wh later in curh /d' A Jllje.• t1u1 rl'NxM%lvl'/x'%s, J/11 /xM 111a11Fa r11cr ni/HN• in alxulx'r 4 JI.R. FurtlKnrxre• Je/g.1ha1 lercanlc hypcrrcyk/navc al.n.kvcl ul+ltil a/uaflcJ afkl rrvcr.ihk in.rea.w in llK nunllk'r au/ nrutt//llhlh in Ihc clHlhrhunl. wlKrca% dly. IInN JiJ Ik.1 hrclHtk hyptnarplln.ivc haJ /w/ changc in IIK /wnllKr ..I nc111rIK1h11. I`ur Ilk XrnHlp /d Jl.gs, lhr• kvcl lll' airway rryllln.ivcnc.i hchHc and rllrr ai.HK ctpr.urc t•arrclalarl ch/.cly with Ihc /wndKr 111 cpitlKhal /KutrlM,hll. "11N• rr.nlt..uyyca that ni/MC /nJlKtd aitway hylwnr.lklnavcnty. uuy .ktr•fkl Iln UK Ik•vc1/MMK/u Id an atwc inllanun:Nllry, n'yk+n.c in Ihe airway.. 11u11Vnun. M)., Fahhri• 1.. M•O'Kyntc, P. M. •(iuW• It. I). • Aiiawa• II . Waltcr.• 1:. I 1. • Allx•n • S 1 s.. alkl NuJrl. l. A. Amrrirnn Rrcirll• u/ Rr.piranrry I)i.truor 127:(>KA-MJII, I')lt1. (hhcr srppoA: NaliwNlal I lcarl. l.unp anJ Nhk.d In.litulc. ht.eM, t'tlr(xua/aM and thr ('ahhlrn/a Air KCWNRCCs IIn:InI. I'pN111h1' ('aNINWaV1IJr Kc%carl•h In51/1U1C aMI I)CpaflnKM t.I Ml'JKinl'• I In/vrr.lty 411 ('a111.Nnla. S:In 1•rafNivo. Al/I'1)RAI)KK7RAIM11(' 1.(X•A1.17.AT1ON OFAIITUNOMK' R/:(T1•Il /KS IN AIRWAY SM(K)l'll ll.ing eyr'rilnrntal I/NNIIIN-m Ihal pnlvtd lu hc IMllimal f/lr .ry•. il/c n•t rlw.H hindlnK. IIK.c ulvc.upruH% havc .ta1KJ Ihc JImu1MNNM uI aI111/a MIICIk9/•.N . Ik'Ir aJrenrrFNa/Hl mu%l.lren/t rclcln.H. in .nNN.lh nwvk n/ anway. I11N1/ ILNIN•A 11. Iclunnal M..IxhN.Ic. AHt.Naah..yr.qehk I/KIINHI\ wl9l' uN1I lOl1.'/C//nNK IIM .h.lnhu /l. 1 47
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nua al arn4rarmn rnrpars in airway snMrrlh mu.w Ir 4.1 Irrrrr Ir+Nn Ir:w'hca n, rrnnn,d Mnn.hnrk.; 1'II/ JihyJucJlxemrl.d. ('11) prarn„m. arwl /'l/) qmmmiclwlinyl la•nidatc were u.rd lo lalt•1 tr•ta wlrrncrrrc• allrlu aJrrnrrKir• arwl mu.carmic rr.rla.a., rr .pr. trvcly, uvny rapa•rurrcntal crwwldHms that Kavr rn•auirn.d .ry•rdia rrarlwar arMhnp M.rrkrd Jdlerrnars wrrr hIWN11n Ihr hMRUulhna) 1h\IrlhUnmM Ul l'aCh rrCcIN-U Jfnl In rI/%IrrIN/nqN/ u1 Ua• v:uums rrcrp/rw% in ranc calncit-r airway Na•tr rcrrpttK% wrrr lua•.rnt tn InMh rkn.uy thnrugMwt Ihr airways• wrth Ihr hrylM•.t rk•nsdy tn INUr« hiulrs Athh.r ra•.cpMy wrrc .I+ar.c in IrrKc airways hut nuuknro% in .nr:Jl bna«luuk•s, wlkrr.r% atwrhncrl h rracpNKS wrrr numenw% rn bnwkfira/ VIMrMI\ nW41r• •.IKU4 m Iw..umal hnMKMrdrs anJ alnw..( absent (nmrJiNal Mrwrahr.dr. 'fhr% n.•(hr" 1 may hr u.rlul in .hplyrnl; altcraturms ul wtrwwwmr tcccplur Ji.udwtnwr in .uwll :uwl laryr auw.ry. •altrr ca/x•runrnul manipul.nrm anJ in Jr.ca.r 11•urK•.. 1' 1• Ha.hauro• C N aml N.wlrl• ! A Anrrru un Rrwr.v r.J Rr.pnulnrr I)rvu.r 127 7t1{ 762, tVx 1 (hArr fulrpwt: NalMrnal In.btutcs rd llcahh I-n-on thc ('ardMrva..ular Resrarah Instnulr and the IkparUnrm% ul Anatnmy arwl Mrda rnr • llmvenny .4 1'ald.wnu• S.m 1 r.nar.cu ANTINISI'AMINI(' VI[RSIIS ANIICII(/1JNL•R(;IC L•Ffli(TS (/F ATRO1'INf. (1N ('ANINI•. I RA('111:A1.IS Ml1S('1 li 11he purlur.e 1.1 thn study was trr n-e.amrne the anhhi.tanunK and antn hrrlincryrc elfca•tl nl Nns+tnc rn csprnrncnt. drvRn.d In elumnate pr..iAk I+nrhkm. 1'n ak,cr• mrna• antihistanrmc vcr.us anlnhrrlurcrp. rllccls ul atrrqanr ut arrway .n„rMh mu.• a k, the rnvc.lrranw. u.rJ an rn r•rtrl. prrparatMNr.d camnr 1rx hralt. mu.ck .urp. arkl rktetrmncd atnpine's elle.a un annlrrauk rr.rym.rs rnJuceJ by hist.mmroe ur by electrical helJ slinwlatirm uf cMbhnerKrc nrrves In the hra .rnes rrf rapcnnrn/.• .53 .Irip% haJ initial resprmes to IieW stimulalnm aklrnnincJ anJ were then ranJrurdy a..iXneJ 1u a rnnlrad Emu(r or kf a Fr.Mrp Irrales/ with aln>f+ine bel.ue lickl .Irmulabon was repeated and hi.lamine waa Frvrn. A1rnopine in n+nceMralitms rd 111', tO', arwl N1' M Jerreasea) the re.pm.e 1o IirIJ alinwlalirm Ia 61.1, 1// S an,l IYX aul the initial reaxrnse, reyactively, hul had rMr e11ec1 am the tesprnse. lu hrstamine. In the .rcnrnrl %eriroo ral ei<rerinKnt., 24 alrpr" were trealcd with irwhunclhacin Hr prevrM hiaanune taafiyphyla.rs; the%C sirilh haa11111//aI R%ryMVCS Inh.Mh Iiekl \tlnWlatNUl aml hl.lamnle Ja•termincJ anJ were then aasiFneJ ar a cnuNn+i Emul+au lu a Rnwp lreateJ with alrrairrne Iw frne Iie1J sltmulalinn anJ hiaamine were rept:aled. In thr.e e.perirnents, a cnnaen- tra1MM n/ a1n11Nflc (1N1' M). whK•h aRain cnntpIelely hkr•trd Ihe resrywrv tu IicIJ stiuwlatn+n, sldl hnl mt ellect un hr.tamine•inJuceJ cnwNrarlinn. Thc rr.earrhrrs cuncluJe that atnK»nr in a c.mceMr,ainn that cvmtRktrly hhrcks the re.ryut.r ar aMr hncrKia nerve .Iruwlarinn has mr arwrhi.lamroic ef/ect. SkrerRh. H. E, NuJrl, J. A.. Fahkwi, L. M, Sheppard. 1)., and I-Inttvman• M). AnNrn'On RI\YeM• nJ Re.piratory I)isrose 1211.60)-6111t, 19111. Other saherl: Naliruu111ear1, l.unR ard Bk+od Inslilule and the Frsons ('rxluwatiun I ann the ('anlNwaKulaf Research Institute awt the 1)erartments arf Merlicine and 1'hy.wh•Ry• llmvenay ol Caldurma. San hrancrsco. "rlMl: . ('UIIRSI. t)I AIRWAY IIYI9:RRY•_SI'ONSIVIiN1:SS INUIH'1 1) NY (//ONI IN Ixx;1 In thr Ixc.rnl .haly, IIK :WIIMKs ClanllnlYl the /utlC rrNn.r .,1 unUrc /rMluarrl hyprrrc.l.wrsrvrrr•s in anr.lhclvrJ Jrrgs. fo.Mi Ihic, they a..esrJ auway rc.per srvrnrss Ithrrr nnwtr r.p.wrr anJ lhrtn at I h. I Jay, aml I wA allcr av.ur r~ryr.urc '1'u a.x•.% rr.ryMr.ivrtK.., the rr.rar.hrrm aa•ahrtvrd tha• aMj% and aAM:urw•d rb.r rr.rywr.: .urvr% o/ uw',ra.iny aYnhY'nUa1Mom UI aCrtylClMrllnC aM hNlanmC :K9uW~I• Jrlrvrrrd t., t1K• anway% vs Iwdmrutary rr.islanrc Owwrr caryrsurrs were a arrnd vut wuh tIN• rh-gs awal,r and at re.r m an rxryr.ure chauhcr law 2 h Mrathinr rrthrr thrrwq•Ir thr mr.r aNl owouth at A level ul 2.21qrm aK tMawKh a arachrustrwny at a Irvrl id / II Iqwn 1 ra h.t1h aactylal>.rhnr arwl hr.taminr aml l.w hrwh nMprs .d uirurr drlrvcry, auway rrsl.ar.wa'rt s. uw rra.cd rmrN marArJly al I h ahrr umnr. inrrea.rd 1u a 1.•.x•r rk4rra• 1 clay la/rr arwI rctunrd to CuMnd ItvrlN by I wL. lhr rrwlls arc >nndar la drr authrws' IwcvHwr. sruJN•. m human. thal .hnwcd Ihal uiamr inJurrJ hylrnr.ry.n.rrr IK,,% 1hi Ur% \hIM11y aher eRryhurr anll ls rapidly revrhrhk anll sn'(,Kl'11 Ih:N IIn' u/, NN• rllc.l rs kn\eJ ru an aculr mllanunatory trspwr.c in the arrways. Ilutrvnrm• M I• 1•ahMi, L. M, SLr.rgh, Il.+_.., O'Hryne, 1'. M., Wakcr.• li 11 , Avawa, 11 , anJ Nrwlrl, 1 A `lrw.rwrl rrf AlqdrrJ /'Ar.~a~/uXr Rr.pirul. F.nrin.n. l:'.ert irr I'hraud. SS/.11 1212 /21h, t9)! {. (h6rr supPwf: NatinnallkaA, LWIR a1M1 RknM1lrlSlltule aMl lhl' 1'INNI] ('INIhMatnM I•nMl the ('ara/NWa%cular Resrarth Inslilwe and the Ihlwlmcros ol MeJia•inc and I'hysudrryty, UnMVenlty ('alllorma, San Franc/.rn. NI:UR AI. C'I )NTR(/l- OF AIR W AY SUHMUCY)SAI. C;LANI) SI:('RI?TIUN Mapu aJvance% have ata•urnvd rea•en11y in the uruler.lanJinR arf the pnK-r..es uf airway .r, rrtiun, due in large part 1o the aptdiraliwm arf nutkrn trehmyues rr1 anaaeny. • cell baakrry, physHdoRy, birKhemislry, anJ pharmnvrhrgy lbis rrl.ut mwr% that airway.ubrnwo.al Rlaruls nttwpy a subxlanlial vrdume of Ihe large curuluclrng airways and are regulated by vaXal mu.carinir nerves. alrtu- anJ hela•adrrncrRir ncrves• aml mNlatktnerRK MMK'hnlirlerRll' rlefve%. Vagal nerYet IIMMkrIWC varirws rrfk.cs that inr:rra.r K/anJ secreNors by stimulating teka.e af Rranuks Iraun nwcawa and srnw. celas. StimulaleJ.ecretiwn are unaltered fnmr hasehne in hiwKhemiral anJ vr.rrw las- tic pnrlrrrties. Ilela aJrencrRrc winwlalNrn reka". rwcreliars avuNamrnK rrlaiva•ly little IIuiJ, high c.mcenlratiun.s nl pnNein anJ wllur. Mrw cruKrnlralNm. rrl lysniyme arul hiKh.v vi.crrsily anJ f,rwer elaslici/y, nd seln•tively akrkle% rmrcnus cell.. Allrha- aJrenrrKic .Innulalirrn causes high OuiJ /krws with hwr /udein and .ullur a•rwkrnua /inn., hirh lywiymc c.rmrrNratinns and krw apparent vi.nhity, and scla•.lrvrly rk (+kle. Rrnwks Imm srnws cella IVrurarkenerKic muwlurlinerKi. nrrve. alvr arnw/.tr mua•in .rrrclum, pnrAably by reksrnK vasn.ctive rntr.Unal prptiale NeMGI, 1. A. E.'wrrlrCUnlrwrwul nJRe.yrirodrrr Uixmse64(supp112111:).2•126, 19N]. ptArr sr/Rerl: l/. S. Public Ikallh Service. Vkk IAvi.iaM Rescarch. Im ., am/ the Fisoe. C.upwa/i«ur. Fran /he Canlirrvasa•ular Resean h Inslitule anJ (kpartn,<rMs uf Medicine and ITysnd ogy. Univer.ity rd Cahlemra. San francixu 49 •8
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NI IIK(11'1 1'11hL 1 YROSINI:INI'Y1 A NI WI.Y I)IS(•OV1=.K1:1) I'I;I'I II)1: IS 1'RI'.11 N1 IN 1111: MAMMAI.IAN KI:SI'IKAI()RY IKA('I N\•un.frplilk lym.nk• INI'Y1. a nrwly JivIwcrctt Iw•INhlr AIN.wn ht nNNhJ.Nc hlurl vc..a•1 J1.1nIClc1 nNl %nNMNh 11111,tk IINIC, ha\ 111Y'll I.NJ/NI in /llally n1:111111L11/J11 INF.In. Ih JLtnl.uh.Nl l. anldat k11h:N .d .ynlpalhctia lN rvc hlKt. anJ NI'Y nolnulwl h•.N Ilvlty 11.111pY'11 I.NIIhI 1/1 n1N:NIfCnI'r/,'k /,'anFINNI aY'II\ III a%IWIy r.I IIN' rl'\)nr:/1.Ny tt.a 14.1 I.Nn rlcmhnallrn yalk•. -- nun. a al. pu/rlta ply. anJ lat - - NI'Y /nuna/MNC:K hvNy han hl•rn h.allird h.IKrvc Itlk•r.. NI'Y nIMN/n/NC:N I/VC IICrvC tlhl'1% Nl•1l' LN1MI In dk• :Nlvrlthh•I .d hH N N) vc.x•1% and /n Ihc airway .nN.Nh 1/luvic II\ JI\IftLu NNI wa, .t1/Auq•Iy \IIIIII:11 1.. Illal al/ %y1111R111k•1/\' Ilerve tlhcr] a% 1k/1MNl~tf:lllYl by Ih.(.:h1111K It Ibvdr.nyl,l.a• anhh..bc. 111r nMan (SI)) a.•1NIl'CMra1NN1% u1 NI'Y in 111c )•uun:1 p/)! Ic.pu.ll.Ny IIJa1, a, Ih'h'fnlln\•J by raMINN/1N//1nN41%Vy III 11\\NC l'xtraCtl, wl••f: 111.ih'r ILhIN•:1 I I tt) 71. Inw\'t trallh':1 211 II) Sl, ,I/NI In:It1N M.NkM1\ 1 S II I) 111111.I11!, Ihuln)- dk•vcl.qlnk•nla/ .lu.la.ln man, NI'Y InlnwdN\a.hvc mrve hfw•r..vr/.• hr.l 1.11N'/vt'1l.11 ?I'wl'\'la\ )'t•,IJINNt/ItIIICItatlk'A,:IrIlII/N.r\)'I,hI1l.lllyl'atCIMkJJ.w11/111.1 dw ulu.ynllnNN/rry a.rw,ly% altrt hltlh NI'Y 1n1tINIMNI'.Nll-w IN'tvC Idkt• h.1vc a II/~I//h11h.N1 d/NI111'V\'LhNIw•nl:d p.Nlcnl.uoJ.n luthal ot %yulp.lthl'llc nctvc tlhrl%Iu Ihr h•.pnrhwy h,N 1 I lk• hlwlmpnl NI'Y numurwNcactpvlly in /klvc hlkr. in IIIC nlrlnma II,u1 rc.pa..t.Ny tt•It t,wl.lI lu dk' rn.wlng nnnlFt•r nl Itplkk% havinl: LNCnt hlol.y'k J1 :N I/INI% LNI/NI //1 tll/% IN 1•,1/1. an1l %I11.w, Ih•N (IN' Iung INI~µ•~K\ a tll"h Ill•INIII\•rF kly,h•/11 Ill.ll llldy /IIIIIN'IkC IM11/1MMIJty /IIIh11NNl tiho'IM'rIJ, M N,/'nlu4. I M, A11.•n. I M anJ HLwml, S R //t. N.11 1') 1211 1111 1')Kd 1•n.u1Ok• I A're1mN hn ul 1 h.l.. 1>.,nl.u y.Ind Mcda nr . Kuy.11 1'n.1E r.Nlu.dr Mr~h\ .11 S1IN11.I, IL/IIIIIM't~11111I1 IL..pn.J. I n.M1~Nr, I N,rl.hwl I W( ) 1'Kt 111 INASI: INI111111/)KS Ati\()('IA1 I•I ) W 1111 I'1:K1 I uN1:Al M A( •KI )1'11 Al ;L.S Ill lhlv %ItNIV. t)k' I/lva•vlgatnrv A" vnKnl :InJ \harallcrvc /wu flr.NClnav ndnhi- llNc awt /aliJ wllh F wllra pIK pa•fi1NN1Ca1 nrk nqlha~c.. KcwN. rhuw Ih•N InluhuaN/ i. ah..c Ikln•nJc/N, lu.l IN1 hCat1111C 7UN) Jl'1lY"IIYI in IIK fNCMn\C /1/ C111'C%% :Ilhullllll ( ht In\U11:NNN1 Id nl:lauq4s:lyc eullute nkvliuln wnh ''I e1a.la.c, twn canuplc.c% ol M 711.111111 and rd1 InMI are Rcl/rra1CJ whiah arc .1ahk lu IIca11ng in v.hunl dkk.'yl \Illlal\'. I/NIh.Nlllg 1.1va119N a%VqY•IINN1 '"I rryfhl/l hN111\ lwn t'IN1111k1Cs III wlltlar I1klklul:U wC1F'M, a1NI af11N%-InI11ININNI cst)M't1//N•nl% ah'IIMNlllfall•J Ihat l'I:I%la4' :I/NI hypan /n/cr:Nt wdll llk .wIM Iw1- nl•1\'rl.llh•Il!C udnhihN. 1'IN CINIIIIatINNI, CI:Nta.a• 111I1th1/1Nl in Kl/lln•:1 INI,' Illa,llla anJ t'eII (h'C fkY/1/Nhi1) II11/1I wCrl• alvla'1a1/11M•J In .u/nmaly, tIK InhdnhN wh/.h LNnI. 11k' M hA /MM1 clNnpkst w11h "I cl./.lr.c 11.1% hrcn Icat.Nivcly na111cJ Ml'I (Inal hy111aLV' IN.N\'111dw 111I11h11.N1 MIM \' 111 ht IIIN /InCJ Ircc .•o u,1'1 hy \ IJln/lnp nucn/pha~c. f/N 1 h u,l'1 1% rclra.cJ Intu 1hc nw•J/u.n thlnng thc 1.1 Il III .ultllte a/1J 111crCahcr 1% rN1 hN1I,'cr Jetcllahk INI Int:Ili nlatn.I.haF'c.. in whvvpk•IN a Nlhlrc n/cJla aN in \•cil iyvtc. l hc.c hmhn~. vuKyc.t thal pl•Lma a,l'1 1. IIrcV nl in 111'1/11NIC:1/ lll/lll in htl,'II l.Nll'cnlrall/M% a/Nt /% ahMNhCJ INNII IN /INII nt:N In Iduyc. MI'1. I.n Iha• INhcr hanJ. al+l+l•ar. tu hc a ma./.qduKc p/N/wl. .Inrc it 1. v, n'1cJ by In•N hyAlare..tlef 1.N 1) h In \ IJrluc aIwl 1. (Na•vnl In Iy.:NC\ ul n1:N h1 ph.q•1 . INa•. NhorcJ /.•r I rN 17 h N.•n1.dJ (1'I)r.nnrll, I•F and Itwatklrtl.kt. K. 1 hr• l.Nnn.J .rf Ifinl..Cn ul ('Irr.nrlrrv 25R(5)- 1?51 - 1257, 14111. (PIbcr trppnrt: NatNlnrl ('ukcr In.tilulc. I LNn thr ('clncr IIN ISlrwnl Kc.car.h and Ihr Ih•pallnKnl UI Hhlllr)[1CJI (•hl'11/1%Iry. II.IIV,IrJ MClI1CJI SllNM/I, ItU"ItN/ NI.tI1Kt)I'llll.ti ANI)'lIll: AINtLT RI:.SI'IKAT(/KY 1)Itil'KIiSS tiYNI)K()M1. (In. p:qx•r rcvlcw% thc IwNcnllal nIk ut rlrNlraq111d% a1N1 their INI~Itn1. Irl du I.:I/IN.Fa'rk'~h Id llk :kutC Iwlr /npny Char:k•ICr/.tk• /N :Nhdt IC.I+ir:n.Ny JLIJC.. .vn Jh.nh /AK11S/ NI uu1q111d. a:/n a'I /INNa1C O. JCIIVCJ (Ir/k11ky~, ININII.Iy1N' anwtllw•. :NNI .N•M I1hhN/,111• INIMIIN 1\. Ilk'V• N1MIanCC\ havl' Jr:N11:NN' a'IIl\'t\ /NI C11fIC1111N'111.1I hln)• INC).Jr./111N/% I IK uhK•/vpIhNllllat 1kY/t11M11t/I% al'a11/1N/I.NC In llk hln)'. ut AKI /S 11,11/l9N\ y1.•Ilil ah':1/, 11111 IIII\ /Inah//l,' /\ 1,hvNN1\Iy INN 1mltk' IIN (N JIJr/N.UhInt AKI1` 'I hl•N•IINC, all•%INIC (hC ENl'K/k'C 1/I I11111•MIaIIy Ilqtk' Ila•ulraqllul% ln Ilk• lurlyl ul (IN'V' 14NK111%, Ill\• 4IlY'Itla' r11k, II :/ny, ul tk•ulnM>tuh In cl/nlc•al ARI)\ Icluaio. NI lr• /knrm.h.NrJ Whllr h:1.N; IIIKYva1NN1w, nw%1 CIN111/n/C 1/t be: t11:Nh• in a'etI49111NnL1i i nNhkl.. an a•yN:d CII/N1 1\ Ik'l'JIYI In t/l'tCrnl/fN.' i/ rnik•a/ulcnlal oKa /1:1u/.u1% ul Inult injury h:wc :my rr1alNln.hip hr Ihr I+aUNhlhy.Nlhlry ad cnuc.Jty dl ARI IS palirnt. ( hdy whcn Ih/. IinA i% cnnvina•in'ly n>+Ile a'an INk h•gm lu Iran.lalc cslN'rulkvN•d 111hhn1'\ Inhl t IInN'aI tIKtINNI\ IIN Ihal,'d1\/\ and tlkYary. It 1\ a'/NK'a'Iv:Ihtl' th•N .u1uM 111:11111N1Ia1NN1 1/1 na•ultnllhll hl'IUN'NN 1YN111I IavlNahly aIIC\'( IIK II:IIh11/111y%N1I1Ty hI ARI)S 11111 h1YaUlC IIIII:IIIN11711NMI I~M/ IMt/l/all•Iy InW11YlYI l/l lhl' /MN111:I) (M/t-l'~~l•~hI IN..t rklcnv alNl 1i..uc In)Ury a1Nf h'11a1r• Ihl•rall\•t1/N' I/llcrva'ntNN1l Ih,N allccl Ilk• In11.InN1/:NrNy cav':Nk l'IN1W hL' JIIUhk•CJ~'lYl ~WINII~ aMl \INNIIJ tN1Iy hC \IINlk•II //1 tlk' /IIINI l'arl•II/I Ia%hhtll ( iivcn the trcyllcm'y snJ klhalNy ul AR11S. the cn.10/ c/NNhN I- iny .ut h atklK. .ccnl. Iu.tdicJ. Talc, K M alNl Rr/rim•, /. E. Arnr.n aa R.•rerN• ~r/ Na .pirnra.l v I)r.ru.r 12N: tt? tS4, 14N 1. Utber srpplwt: NateNlal In.utuk. uf Hcalth, AIIMtIt'an IIC:111 A\Mk'1:11h1n III Wyll nnng, and 11k• Kuk'• tldl, tiwan, anJ Kkha•rg I•IN/INI:NNM\ I'1/N11 tha' 111vIVIN1 lUt I'UII1NNIary Sala'IK\•% a/NI tha• I)a'(I:,fl/lk'nl ut (/lla•r11aI M\'JI\ I/k', IIN/vcr.lly 111 ('au4NaJu Ilcallh tia'iclk'c.(•cntcr, Iknvct. MA(•K(/1'l1A(:I:I:Ili•.('f()K IlIN('11(1N IN PIII.Ml1NARY ()XYG/.N 1OXK•//Y. IIYI'I K(/X1A hAMAl:1i\ AN1) ti11M111.KI1:S Al VI:tN AK MA('KI/I'IIA(il:S I(1 MAKI•. ANI1 KI•1.I:ASIt (•IIIiMI)I AXINS 1014 P1/1.YM(1K1'IIIINU(•LIiAK I.1:11K()(•Ylla Macr/11111ayc..yn/ha•.iie nwny .ccrr(rwy INrNhw•1% in vin.r INN Ihc.t111wl1 t/N tIN'u fNakltk'INMI JIkI thl'Ir 11:nIM/11hy~N1111~N' \IRnlhl'.YIK'C nI lYN/ a1C Iaf~'t'Iy U//t1/N/Wn 1n t1N• prr.cnl invcairalilln, lhc authlN. flwnJ Ihal hypcnl~la tlalnaRcJ /ahhit alvcuLn /n:h h. phagcc IAMI fn 1•irrr, a% nlandc.la•J by akcrca.eJ rel) nulnhcr., Irnfra.a•A I.Lt,uc .khyJnlpena.c rekav, a1M) Ihe rkvchqNllenl u/ ullra.IrucUual ahmNlnahl/c. Ihat rc xlNhkJ dhr.c acn in AM /n rm.N lav.K.•J Ih1/n luni! Id rahhnd c1lpr.cJ h, hyL*r.../.1 sl, 1 51
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i r./ rrr1. Ilylt•n/ua alwr .IlmulalrJ ruluacd rahhn AM tu rrka.r ahrnaMJUn% hK Irdyn«.ry,l«m~a ka. kuk/N•ylr. 1/'MN1 1hJ1 wrrr aundar In na/kaular wrlkhl lu a hr- naqA.m. r".unrd Iron1 luny /avalr% nf rahhN calavd 1et hyttruaia /n rnv.. 'Ihc.c rr.ull..uF1 r.l /hat Jlvc.rlar mx'rry4ugr.rarcUNy turrhN 1% may play a Phy.adul;iaauy rrlrv.rnl r.dr m rra•rullnleM /// 1'MN NI Ihr luny. in plda«mJry o.yKrn Ioaa:ny I IJr.ala. K N• Vatler. A t: and Rrl.iner, ! f'. /.nnrnul.4 I.rufa r1r lfiol.rKv 1S:J71-18t, 1994. Othrr au00nr(: AnN•riran Itr:rt A.viaialinn, Anll•II(all I.IIn(,' A1Nq1a1aN1, NatNNIJI In.ldulr. ul I Irahh, anll thr Krnr, Ilill, Swan Jral Kklnly Fnund•J1Nrn. I'r.Nntla• Wchh WarinKl.unKlnVilulearafthrPuln«maryhrvi.amullhrllulver.ilyul ('/d.Na.M/ IlrJlth Sc/cnar. ('rnler, /knvcr IN1A("r 1111MAN UKYTItR/K'Yl1.S 1'KI:VI;NT t1Yl)R(X:I:N 1'1 K(1XIl)1 MI.t)IAI1:1)1)AMA(:I:l//1S()LAfH) 1'I:RI•lIS1:11RA1 1.IIN(:S ANt) ('111.11IR111 N(IVINIi PIt1.M1)NARY ARII'RY IiNIX)Il11iI./AL ('1•1.I.S Alu1r rlknlaNNr. 1unK uqury. .uah a• Iha/ vrn in Ihr aJull rr.(NraNNy d1.lrrc. .ymhemir 1ARI)ti/. 1% an urq.wlaM lIm1.JI rrrd+km whlnr palhl.fdly.a4.9y 1. pawty .6•1nw-.1 Ihqwrvrr, rr.crN r•«knar .uKKa•.1. Ihal tuua .I,yrrn mcla(wdnc. /Ilay alN1- trdwlr tu:n.w.dhl IrJI lrll +nlwy aal xutr rrk•uul,no.lunK injury In Ihl..lucly, alhh- lwn ul unlrralrJ lw ylutarJl.l.-hydr tharJ huuun erylhnwyte% lk.rcJVd hyJa.Mrn la'/nu~A 1114 1 / nN•dha1rJ at utr rJrrual.ou• injury rn ivJalc•J ral IunP.• 110 nNlwrd J.un.q•r 1ts .IdlurcJ t..vrnr Iwlrl«roary Jrtcry c/ahNIN•IIJI 1r11., and 111), drtw•mkM uard..IBmulrrJINrdtylrahrlane('urlrrru KN('.aJvcnFmyol11/1,aly.eJreJWhr Ik•It'r«k•nl rrr /IIIIhrlllltar gtu1JIMwra• J/RIr11r aJIJIa.e altlvllN'\ the rr.u11% auyg.•.1 d1AI Inlal crylhaRy/r% can vJVrnKr 11,11, aral. a% a/c.utl. Paqral Ihe lung and lun.rhly rNIN•/ b..ur. (nMl IIa/11AKa' 'Irwh, K M.('IclhNd. U P.. IkrFcr• 1: M, Whne. C. W.. arNl R.•pinr. / F. Jhwrn.d r4 ( 7rna al lnrr.r(rR.nurn 74 292 295. 1VN4 (PIhrr su/port: Nalimal Inaitule. u1 Ikalth, Anlrrican Ilean Awu-ialeln• Amrriran 1 ung A.wKi:NNNI• anll Ihe Swan. 11111, KlchrrK, and K. 1 Rry/Nrld. FnundalNmr. 1•nNn thr I)rpanmeMa n( MrJicine and t'rdialria., anJ the Wchh Waring LunK Inui- tulr. t)n/vrraty lll Cllhxadll Medical Cenlel, 1)enver. I1XY(iFN MI-.TAH(N.ITI:S STIMt/1.AT1:T11R()MIK)XANI: PR()1)ll(TI(1N ANI) VAS(K'//NS'IRI('1IUN IN IS(K.AIY.I) SAI.INI: IM:KI USI•.1) KAISt11(' 1.l/N(iS (icrKralNlr111f Raehve llltygen rne/ahnhle.%. 1hr/NnlMlRarlc Increafe% a/111 vaM1a'lNl- arNlw/n havc hcen inlPlicoled m the ps1hwigene.ie /4 aa•ule elknuNu.lunK injury. suah a. that vtcn in Pahenlr with the Adult Re.PirauNy, 1)i.lre.. SynJaunc /AKI)S/. hu1 drclr /ntrlJ.la.n, arc unknnwn 7llc mve.tiRahN% hyprlhe.iied that real uve (1. PnNI- w t% wordd .I.rnutMe .ra tN.Gma r a1 mrtatwdr.nl in IunR% and that vaWoartave pr/«) a, 1. ..1 err h..l.wul. aa h a. Ihr IrwYa) vJ.4w em%lnclrw /hnnnh.vSarK A,. might then , /IIr/I/Jle () . I11etJIMlhla'-InduaY'd (NIIIINNIary vaflKlMl%irN'INM1. Illty hNIMI IhJI (), nktaluDlnrc Kcnrralcd by injcatilNl n( IN/rinr p/ua sanlhinc urtida.e cau.cd /rlr/ra.ck m nr an PolnaNlary anrry perluciwNllwea..un:127! 41Nm11K) in i.wdatcd Pcr/u.cJ lunl;. In a,h/namn rylnnr plu% tanlhine oada.e al.ncall.ed MI luld uN•rea.c. m Prrlu.alr Irvel. u( IhuN111alRanr 11.I/he aahle n1aMalNAile ui 1hnlnlbusane A,11:INn(urcd with /Ndy Iwu luhl lm rra.r% in A krlo-l'(iF, Ithe Nabk rnelabulile 11( /aa!uarylin). MlNrovcr. INNN arkhti.m t d calalJ.r nlhiMled INah vawKOnarw'IwNI arNl the Ihnnalrl.anc It. Irn.dlN IaN1 xrn nl Iw.tJlyd hlny. Iulh/winK mjttyaNlbf INnine Plus saMhlne uaNla.r. SNndarly. I1rCtrralullrnt wlth ay.11NIRyrcnaae inhlMan\, aMhlr a.l+irm nr IINhNrlrlhxnl. JINr arNnplrlrly hh«krJ IhreNalN/tane RerN!ra1Nm anJ m.rkrdly attenuated Ixc.WN rr .tuNlv% u.uJlly a•n a11rr (N/line Plu% taMhine u.illa.e- FurlhcrnNlrc• imldarnlc. a IhnNnha> anc.yMlklJ.e inhllNhr,atwakrrea.enl(); urclalNllile i/NHN'ed Iht/NnMraJOe /.'l'nrlalaNl alld vJN4'1NNIrN'INM. lheve reN/Ih Wgge%lyd 111a11hrIN1/IrllalN: 1,'cnl'IJINNI m/l'IN L.Nlil rpalr /N (). -NLYatN4Mr-inJuard vaMIlYN1.Iria/1n/1. 11/Iwcvrr, .IrNY a.rKnl lit an1 aNtrlalaNllrHwrcn IhnNnMlstane kvel% arNl Ihe dr6ree l1( vs.aK'/N1.IrialaNl l/1uW md hr lkna/n.Ir.qrd. and.i/Ne add'llinn 11(.uprn/itNk dl.nwla.e rrlhN'rd IhlrNal«.a ask l' hul dNI nId aILvY the /Men%Ny nt vaMKrNl.InrtNN1, it it, pls.ihk Ihal lhrulolw~aanr 1% mN Ihr /N11y vJ.rv.N-/ive rlk•JiaaN in Ihis nN«kl lbe te.earahrr% alNNiak Ihu raju r.ml• lung.ln (). nw IalNdne. resull.ln thnNnlNlaanr Rencralaln anJ that Ihnanhw, arlr N a/IIarN a1rdlJlnl /ll n1lN1aM-IMhll'e11 va%4KIN1.irK'/NNI Talr. K M . Mnni.• ff. (i., Sa'hneeder, W. R. and Rrpinr, ! li. lr•nrnul /q (•hnrrnl lnrtlnKuri.N174 AIN4-AI1, 1994. (Other supprn: Anlrriran licart AsMrialiun ld WyominR, Nalnrnal In.lululr. ut 1lrahh• alNl the Swan. Hltl, KkherR, Rnche, ThnNnMand% anJ I'rootNN and (ia/nbk I'INIMIa1NN1\. 1•nNO Webb Waring Lung Inz/NUk, anJ I)ep+rt/neM% u( Mr/licinc and Pcd/atra., l/nlvcr.ay al ('nhxaJu Ilealth 5tience Cenler, I)cnvrr. HR(1N('111AI. I AVAGf: IMt()TIi1NS AS C(NtR1:LAT1•:S (* 111S'fIN'ATtN)I.(x;K' AIRWAY (l1AN(aiti IN IIIiA1.T/1Y SM()KI:KS ANI) 1'Al'II:NTS WIl'11 P111.M()NARY CAR(1NUMA ('Igarrne .nadeinK i% known hr be an inlpnlanl elinhlKic laa•Irw in .rvcr-.d lung di.ca.e.: IN/wcver. the numher a/ snNrken whn akvehq (he.c dl.ea.e% rrprrvM% a .alall .cKmcM u( the .IrNrkins pM+utaliun. 11 is prssihle that evidrnre ld rnhalalaal. indlN•aYl inlury In INrNkhial ePNhelial cell% o( snN*en will be rellrcle.l in /hr prwrins- ce/w.1+nNhN /x uf Ihe.e aYlls, lhereby wktiwifyinle a hiRh-(i.k w1+KnNp+ 1 he invr.llKa- INNI. have 1r.IrJ /hi% hyfaMhe%i% by analy.is nl 2 pnNrlnc, free .crrehrcy r.NnpNKnl /1•S('/ a/N11hr krralm., in lavage IIYNIS rr111a//led IflM1 4 RnN11N UI fuhlea'1.. t111aN111J) INNLIIaIka'rS. IS a\y/111N1N11a1K .1rrNlkCrt, 22 \yln(It/Nna1N' \/INlker\ a1Nt 4/1 l'arl nNn11J (1:1111'n1• AIINNII,` \ynl(MINIIailIC ]nN/kerY, I-SC relallve 111 Aolal jrr/Ma•In (11C/ 11'1 wJ% deprr..nl nN1111.red with that il Mln.nwken and asym(NlNlwlN' snNrkera ( hc krrat/n. were drteclrJ /N1ty in aynllNrNnatic cnNd,cn and cnrrelaled wilh r:w k/yrar. al .nark ing h1.NN'y IP = 11017). ('an:inrNna p:Mien1t had defNeaed F1(Y Il• aral d.N•aahk kerann 1114 lK pJlieMa .ludiedl. LunR .ea'1iwN1. (nNn ca/a•iaNna pallrMa .IwIN-d imrnunuhi.Nn•hcmically revealed an a11(Lrrnl inverse retalinnahrp hclwrcn Il..ur I S(' anllkerNm, lL/.mver.e/rlali+Nl.hipwasA.rnelNNhyanalysi.n/lhc.rpr. Neln.lNlhe I
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11 Lrv,lEr IIIOJ al r.lrkrr palicnl. It =-111• p = 110d/ Ihu.• in calNCr pallrnt.• unnnm.duvtthrnl/aal cvNknae Id airway inlury r1.nrLnr% wllh MlNlchl.d lavaKr Icv a•/I t.I mut t..al rpnlw•H,d u•II prl./cin. U 1. (Nl.ahk Ihal.rtNd rr. wdh IhrrcJ kvrl. ol 11N•.c Iwlaa•/n. Inay tr• the /NIC.:N /nrrca.eJ n.k /11 %nwdln} am.Naala•lI HI/tE dl.tav. Mrnlll. W W• IIirwNk. K W.• MaJri• 1• Slnlhtt• W• Mallhay. R A.O1 .IN.w.kd. 1. N.N•yrl. l: . a1N1 Rrlrr.dJ., ll. Y. .lnrrlrn url R.'IrrN ../ R.•.yur.trarv I)t.rav IMMS/:y1/S W)4• I')IW Othrr \Yppdr1: Na1NN1aI IIa•arl• tAnl,' aRIJ tllralNl IlNt/lull' anJ Illr AuKraau (•a1Nrr %tla ra•ty I r.Nrl tlx• Pulnwm.ny tic. rnNl. Ik•p.N1nN•n( /d MrJK•irlc. Vclrran. AJunui.n.lu.Nl McJ N al Ct•Inrr. Wr.l I l.lvt'n. Iha• I'u1rINNl./ry %a't tMN1.1)epunnN•1a td MrJla•uM• a1Nl I kp.ln oN•nt nl 1•.IflNdnpy, Y.IIa' Ilnlva•raly \aIMNd ut M.d/.uK. Ncw Ili vcn• 1•1, a1Nl Illr I IInN.J (nmunadtq ySr.tNNl. NrINN1.J Ca/l<'rr (n.l/lulr. Itr11wa1:1• MI) I I/1\IIN /Mt(ll)11('th)N IIY ('lIL1`11KI 1)(•AI 1• P111.M/)NARY AR f1 RY I:NIN)IIII I IAI. (•1 1 1N lllr qhrlaut.n 1o1 rlNhwlN•huwln hl rl.l.ut hts•r. in Lul'r :trll'llce ami nl Ihc F.1% ruh:InFc rryNm. t.l t)x• IunF .uE'r.t. 111.11 .'INhqhrhrl tt•II. havr UN• t.q..Nlly h/ .yntlw•.vr rla.tlN, lhc IrNrl:r.ll 1 tN11(t.NKnl /•I IIN' 1'I.I%l/t blrl lll lh/% IrINN1. 111a• a/11INN• .IN/w 111.11 rakwlNrhal..•IL L.ddlClt IhNll t.1111N/I/1NNLIfy d/It'ly \y1/IhC\I/r I1111N.a'Id\I111 u1Nk 1.qMNtMxI /lr t Idnur uNIJdi/N1. I IIN wp~ Ik'IINNI\Ih1IC.I l.y I,NtN.alunun..r..ay l/N M1lhh/a'r/.l\I111• by 111111111614 .pn•111NIdIhN1t.1 .I /n1% N'I.1,11/1 hka' ININIuII I/tNllll'II a'llhl/la' nlt•Ja/nl. arNl hy IomnNNlfllnNrarnl nlNl..vtM.y ut111nnF :Inl/a'l.l.un 1r1: Hr.ult% lahcalr Ih.n rnJtAht•H.J rrll IwqNlclr.hn .IN/w% uuny .aoulrrUlr% with InqNr•la.lrll .ymhr.vrJ by o11N:r INWIna' l•rI1 lyrt'%• InIIUMhnl' l'tN111F•ra1nN1 tNln SI)ti I'AGIi wtt11 InyNt la.tln HtNn tdwllhla.l.• cMNrlnlhla.l.• arNl.nwNNh mu.ck arllc a. a•InKk a•haln /NlNrin wnh an alirarrnl nNllcrul:a wriKhl .11 all(Irnnin.alrly 711,(NM/ In athlltN/n. the cn/.. rcaaiivny tll IrnqNacla.lin. tnNn cn111Nhclial rcll., %11uNNh mu.rk .'cII% arNl car aMNNHnhla•1. with auliacrurn lu IaganlrM cla.lin i1lJlralcv rHrvc hlNtNlh/yy lwlwcrn (KIn61ry rla-4/n rcrlr ININHM'1\ ir11/1e vafMNla ela\Iln-]CYfelinll fl'II (Y11eS. 1IN'%l• fl•NIII\ hrlrvuk rlNllpcllm~ evitktxc that a'ulluta•J Mrvi/le arMa cnttiwtN•hal acll% prlNhlrc r la. Un whcn aullunv/ in nlcJium rlNnl/uNNIrJ by .nhNllh nrov'k rrll.• awl .uyKr.l a IN/.ahla• rt/k ttN .nNNah /llurak ar11. /n IIk rcKulalNN1 nl cle•I/n pnN1u.INm hy r/Nk. IIN•h.J ar11. 0% tr Mraharn. K 1' . Matlara.. 1.. M.1)tlnaW. I A• and Rwrn• 1) r t9 lauwnul.{ ('rllNtnr I•lhvvlll..xv IlA 2R2-2111(• 14113. t9 h II 11 hli lhh Ilr S P ()thlr aY/1p/Ur' AlnrrN.In IICJA A\V\IatNNI. I :rlc. MI\MN/rl A . : u c J an (J t1't*Nt' .NNIItN' A1/N/NI111IcJn A\VNI.IINN1 Il..m d W.•hml•LN/ I/nlvrr.Ny %.INNd u/ MrJNUr• .1 Illr /~ u.•1. 11•••1••1 •1 ..1 \I 1..n• •u•I /IN I A I•.NInN nl •d MidN nN'. I/n/vclVly .A h161/11/. Ml.nu. 11 1'NIX )1111 I.IAL (•I:I.1S ANI) INFLAMMATION lln% rcvirw nl cntLllhclul arll% anti intl;nnnlalian hN:u.c. Ilrinlanly nn rr.cart h Ii1NItnF. anar 1979. hby whlfh IInIC a'l11Y/] nI Int1a11U11a1NN1/N11Iq' INIIIINNI:ny v:1%a ul:llhlrr wrrr rrca/rni/cal .1. rt Nlttihulml! (tu IIIC H/rn1a1/1N1 rll a I+nNCin- arNl fr 11 1/) h INrIn1Un,lry a•Jrma iluNl ( hl IIN• haa% ul nNNr ra•1'rM aalic., nlvc.lip7NtY\ arl' rNlw in a phlUtNl tu t1N1Vtk'r Ih:11 wha/ h:1111k•M lO (11l• rlNk11t1a'11u/11 a\ i11N\II•' ItN' IU rINhN1MHLl l•rll\ IINYIIN I Vl'%I th'ry'/Nl% III Iflrl /N/ active ra':Il INNI 11r /r1111ry .•I•11\ rr%plNl\r t1/ l•nlh Nhe Inlnl 1.. Inluly vrry Hkrly atl'a'1lYalr% vaN'utdr Iloxtu%NN1 in (ha• %INUI 1l•r/n tNll Ill:/y pruvuk a La.1% llw rrpair :InJ rr.111u1itN1 0l vaxular Janla(.•r Ilt the tiMt. Icnll. III a V CINNI /NI Ilh•JI:AIN\ t1I Illr rr1/1:U11n1a111ry hrllea•<%• alla.•/NNNI la 1.9va'n IKrr (u: 411 CU/11- I/k'Irlt•//I t INIpNNN'l1I\/;M:/Ithyl:lltlRln~; (2) rINhNIK hlln/ a/NI /IIaa11va1NN1 rll Iha' an:11111y- l./lo.m..l II ta11N/aytxyN1.4/v N pl r'MMNIMIaJI Cl'II~: I~/ Iu~N tlay/,•cn ININhNI~: IS) I.Illa'r nN•d/.N. N.. :nNl l l.l nN.ka al.rr :IINI MIt1a'rII11Iar tr%)NNI1f\ IrI l'INIu11Nf I1111/1 048 1111111 y Ilu/l.lulr .N/ lln% 111.nr1/.ll. J IIY/NMtn•%N /% INCyY11rJ wI1N•h Jral\ wllh IIN' ]t•t11N.•IKt' 461 rva'l/l\ M•1 1/t /IN./NNI wlN'll a V'n%lh/a•J a/1//11aI ra•a•a•Wl•% IlNravrINN1\ .I/N1rCn W1u1r nYl/:nk:ahlr IN'll)•ra•N ha% ha'a•n Il/a1k 1/1 WMkr\IanJlng 1/l aYllUlar• \lrlh'a•Ilalt:If a/Nl nN.lty Ia1:U nla'fl/anl\/Il4 tl) cnllullla'lial tnjury a1U1 rr./NNIM•\ /tl /Iltury, it aNN•iu% a l•/l:nn • uvrwll. that aa'ulr Inllanml:ItNN1 w1II /hN 11l' 1MIICf%lU1NI /n irn/h llI a\Inl!It• a1N'atlallN • a111rr1eJiahN. I.1kru t1/ffitll'/, tN I+lalcll'1.. nCUlnlhlld.• U1:n•nlllha(!r.. /N t9Nh.r1N•t/:d .rli% takrn aHNN• K:alw•r• ulywuvrJ ualcr.la/Nllr11; wJl Irka•ly c.N/lr I//lnl .Ir:url Ila•I/IIIINNN tlt IN/w pII IIKK l'INIIprNIa•nl\ arNl CrIINIar l'h•/lll'IM% ilNrraat w/lh dN• IINII/nl! .Inoull/. •nNI Ihrn wnh rarh INhcr Rtmt. I) S arNl Nyan. I W. (•Irnl. a rn l alrNtu.rr t )Wr.lu tra• 1(11:577 • Syq, 141(1. ()thrr.upwrrl: II- S PuhIN; Ileallh ticrvia•c. 1'r/Nn 11n Ikpartulla•nl 1/( Ma•Jw-trlr• llnivcr.ity Ilf Miami. Miami• I1.. (•III:I1/NIiO1- 1'll/ MONARY I:NIX)1IIIi1.lAI.CI:I.IS ON MI(•k(X•AKk11:N IN:AI)S 11n..halNa•r nvicw. IIN• Irahniyua•% availalrk liw Ihr i.,d:u/.ln a1N1 .nhurr n1 p11nNNl:uy clNMllllclial crll% arul 1hc navJ anJ nlcans lilr oNNlilrlrulg Illa• yuality 411 dN• crll. IhtlN/gh .ura'e.avc pa..age.. (•uhure na•IhINI% ran hr Jivalyd Inlu 11NLa• uang eniynlr% arNl llNr.r whith awNJ eltpll.wc of a'r11c tu cnrytnes at Mwh the i.IdalNNl arp atNl JurmE .ult-ullurr. lllr IlNOll:r are hy anJ large rlN/linc, wh/la• the laurr arc .lill at Illc rk va•AIINtw•nt .lagr FNN INC.rrN ncw vi.1a. Nr Ilc csphNeJ •Illc rniyn/alla' rlla•IlNNI% illaiuk : 11) LtJ•I/NN\ //1 a•INIINIk'IIaI a•r1I\ InN111N1I/MNWry :Irlery by a'l/I1:1prnaY' IIIFy\- IuNI. I:/ l..datnNl n/ IN/luwNl./ry u/ianlvavulx cntLN/nliunl by alnlfr,nk Ir•/lrlawl w11h rnll.ll'l'l1aV•: J/NI I lI (•1111ut1• aMl V/ha"UIIWr III IIuINNNlary a'/NIta1M'I/dI r rll% 11%111(j Irylr.in/1.1)tA hN h.L.aE1nK (M1/1N• IMhet halld• the rt1e11NIJ% av.nJ/ng rap/.un• In pnNa•IllylK cnry1.K% ina-Imk. l ll Ma•a'Mnil:al lurvca ul (N/tnNNlary artrry c/Nhalirluuo. 1211a/1a1itN1 t/l rnJlNhchunl/nNll lhc cnall veoow•la r/l Wc IunK% by IrCr/u.nN1 wnh ar1i.1 .ahrlc anJ ulia•rlrarrirn ccwJ.: antl ()) Mrcncarricr rrlhurr.: (.INIK knn• IuFr .aaA• a•uhurc nl INdnNNlary erNMNha•liunl avuiJinR eapraurc hl rn/ynlc. Jur/nK p...aK/ny 1lcvllwa n1e11uNh hN auhurc nl INIInNNUry enJtNhehal cell% have yK•ttk•J an alwn d.rlce /rl I/xlul tl.sla. paluk ul.rly in hcllllrq(/11 rtNdirn/ the rlde ul the c/N11N1N•l/ur/u In 11k INrhINNl.ry pt.N'e.a1rlF o1 vawaelrvr +uMlarNr• Now• in a11JnNN. tu tlr n IA.vN.u. atlvan/agex, (lar~c nomtN•r u( arll.• cctNNNny ul mcdia and ut per.INlncl), Ina nla an/rr -1t 14
Page 30: vvr30a00
Ix•:at culturc. m.y alb/w rexatchcr% to .IuJy Pnq+erties which Jn raa .urvive hing IrrilKh ul culturc aml w!t•uhure mvulvlnl; c.ryre ure lo PnMculylw' cniynK.• and tn .tuJy .uMlc p11y\a1h1g1c naldulataal\ Uf IIIIel,'ral nlemhrane CUn1lMalrnt\ anJ \Il)hlttlt- lurc..u.h a% cavrulx Rwrn. U S In lallc. 1: A tcJ ) 8ir.brRv rtf the I:roGrncrliul ('cll, '111c Nctherland.. Martino. NI)h.dl• 111114. thap 4. pp l4-SO Other sr/Iprrrt: Nanuaal Inaitutes n( Neallh fnan Ihc Ik•partnrnt ut MeJicirle, llnivcr.ity of Mlami S\Iwad of Mcdl:lnc. Mwmi. I•1. 1RY1'SIN INI)li('1 1) A(:(:RF(;A11(1N (1F NOV1NF. 1't11.M(INARY ARI1.RY I NI tt) I 11I.1.1/11. ('UI.Tt/R1;U ()N MIC'RUCARKII:RS 1he aullwa% o( thi% paper Sludied aJhcrcnce between "luminal" .urface% nt Iwl- nralary ancry cnJlnhchal cells by •IandarJ .KgreR/anrlry tcchniyucs widely uvJ hN Ira•a.urlnF aKgrcRataln 1d Plalekth and grarwhK'ylc• l1.inR suapen.inn% u/ Iww/ne Ixllnamxy artcry cnJlllhchal cell% cuhureJ -In Illk nK amer IKaJ., in an ayKrcFiwncler. they llroral Ihrl Iryl+an cau.eJ erxllNhehal aFRrcKaliras The a"re(.':NNM rC.111MM rx•.urseJ at rryPan Ilraemraliun% a. M/w ..II IMIt'7i• The degree 14 uypan tndured aXFregala/n nah..neJ by the magnitude /d thc t hange in light lrammi..ilul thn/ugh the enJlnhrhal .uyrcn.aat% wa% relalcd Iu the Irylnln cnncenbalaln, rcaahing a nw.inwm level nl uyp.m clua cnlratnms u111 111'F Thr inve•tlRaha% a+ncluJr the myp.in. even in vt•ry hlw c/arccnrrataal.. cau.c• adlxrcme between "lunnnal" .urfares ul pdnal nary eral%i1he11al tellk prahahly Iw'tau.e the en.yme Jc.tn,y, cell surlace Prdemm which ate necc•.ary tn pevcnl rntercellular adhcrern'e. 1hc mclhld Jc.cnhcd here may he u.elul l.w .IUJy1nK cell cell mtcra.tumc n( cndlahclwm BriKham• K. 1. . Mcyrick, H. anJ Rwrn. 11 S 7'usuc d Cell IN2) 1h7-172, 1Y1(-1 (ArAtr au//ort• Natirxul Instilulc. uf Health. IIuRh 1. Mlay.an Fund fnr Cardinhlgy• The Jnhn W('Iwlke. Jr , and lAura W. ('ulke Fund /lw LunK Rescarch, anJ the t /pPuhn ('nrnpany Fnxn the Pulrnnnary ('irculalilm Center. Ikl+artmcnt% ol Medicine and Pathuh+lty. Vanderbilt tlnlvcraty ScMud ot McJaine. Nashville. TN, and the 1lcpartmcru nt MeJlcinc. Univcr>Ity ut Miami Stlaud ul McJicine, Miami. Ft.. IN V!V(1 AIIT(1RA1)I(XiRAP11I(' INiMONSTRA'1'N)N OF (VA1)RI'NaR(il(' ItINI)IN(3 SI II:S IN AI)UI:r RA r TYI'I: 11 ALVF.(N.AR I:PITNI:I.tAI. ('1•.1.1 t In Ihi% study. aduh nwk rath were injected inlravemlu.ly with the olu.carinic hrnJinR Prahe 'll qulnutliJlnyl hcnrilale IVNH) ur the (1-adrenerRlc Ixtllr 'II J/hy- Jn.alprrmlt.d 11111A) Other rat% were pre treated wuh an Intraperillarcst m)eatamld a NM) 1./b1 r..c.. -•t I wK.r.Mearn.l pran bl the 1111A I IMhI rnirrn.rly+a' auluraJan ..t tl I y... .f.l-• ..t 1...1/ ILMn ItK QNlt r/.NIII Ik11MM\Ilal.'II very llnk r I.fA It1,. A/IMH.//1• ,.r...Y11 t// I/M 1M411• •IIM.NII /1.I/V I( /n1111 tIKSe an1111aI. Clallalln'd .uh.lantial (abelinE. AuNwaJil~raplls of lung Inml ral% in jccleJ wnh 111IA /k nam.lralcJ IalrhnK wbich was well wwahnd uvcr alvc.dar .rpt.e anal caan•rntratcJ uvcr the cyt/lhlr.nl n( type 11 cells. (juaeti/Nive analya. nl Ialr•Io/K in t1K• 1111A yr1a1P% irwln atcJ a.IEnilia•am redurtinn n! lah ImR m aninlah trealcd with 1. L/IPnwrr.'ad Pran 1u I1I IA. in huth the atvavllar p:wtinchyma in Pcncral aral uvcr lylt• 11 ct•Il. 11n rc.ultI ul thi. alK1y /x1/v/Jc nalqlhll),Igk. cvkletwc fur tlk uP(akc •rml yt•rUir b/nlhng ol 11 aJrem•ry/c antaylalist% by the adult lunr rn rn•..• while ladinti In d•naal.tratc .nndar hnlJmP nl a nluaarmic Pnlhc.ln alkhtNal. /hc re.uhs rk nam.tr alc' ylct rGc (t allrrtw•ryq' recrlNllr.lal lylx 11 in cnvr anJ .uh.tant/atc the virw u/ a Ju.•.1 cll.•ct ol (I :ahcrlcrgic aE.au.t. la1 alvclliar lypc 11 ccll.. Sanrh. 1) M. a/1J Salhu. N K. l lJ.' .G rcn..•1 t41A) St9 527, 19114 . I-nlnl lhl' 1)rpannk•M Id Nadaga al Sticnres, Welk.ky ('rdleke. Wclh•.k•y, MA 11OW IMIA(;(K'Yll(' LEIIK(K'YTFti MOVE A% thl. p.lller raltes. a rcFulaled. clrKJinated nawemcnl /d the cytlllll.r.nl 1% cWntia/ hlr Ihe /unclaul ld Phapryles. In thc.c .elb, a% in nw.ck ccl/.. the plwer uuu (.Ir nawcnwnl clln.ia% ul thc cnrllracluk Pnncitls, sx•11n and mylaol, w11ah arc .'raK cmra/cd iu the reKawl ul Ihe cell nlnet. In the peripheral cyulpla.m• :a nn hhcr. nuy hc in a Itnal.lale Ir Ilky nuy (nrln a~d nelwurk by s.vlcialiwul wlth a laalanll- nKYw , at'11n hualing PnMCin 111e rcvty.ihk Irans(rxmalNln uf thc cyt.IPla.m /nwn gc/ tn wq i> nlrllratcd by a rcKulahuy pm(ein called Rel.nlin which• when xllvated by /r11tNa1a11M C1ah'l'nlra1/1M~i nl ('a/', causes shnrtcninp uf actin Uhen, leading tn,h.rntcgratiwwl yd the Kcl nctwlak lllis 0 aelwnrk rc(ornrs it the C'a" cn>nt•enuati.al lalh h•knw the Ihre•IhdJ value fur the aaYwa1i11etA Kelallin. ('a", acting via rclalhn. 1% a x•c/rsll c/ulll\Ian•n1 in Ihi. syacrn: i1 nNllnlls the /mkr a(evcnls Ihal slart Iln the pla.ma memhrane u/ thc Phagl.•y1e in rcynm.e NI a vtinMllus, nu11ha1 sre then nn,maulcd by an alrllnlllriate rca.Yiurl ul Iht' naMractik nnil. h is ta be ealltt•kd that the ehrclJ.wNal yd the nalkcular nlt•chani.m% that rekare anJ rrKulate the nulvcmerw o( cyhll+la.nl in thc tYll will ryrmil an urakr.lanJmR rd fachws that inler(err with kukla:ylc luntti/wl /IartwiK,) II . Yin. 11. 1., am/ Jms..el, T. P. l.nrrrrrd nf Clinirul ('brni.\nv un/l (Yinkal 8i..r Avnu.rey 21(9):S 13-541, 14N 1. (kAer tuppwt: U. S. Public llcallh Service anJ the Edwin S. Wehsler ha/ralatiun. 1-nun the 1lcnlaudlq:y t lnrlrhogy t tnit,llaxvarJ Medical Schwll, l)cPassmrnt 1/( MeJi cine. Ma..al'hu.etl. (:encral 1luautal, (1n.hln. IS(N.ATIt1N ANI/ SOMli STR11('TURAL ANI) FI/N(TIONAL 1'ROIMiRi71-.S ( )F MA('Rt HM IA(:N '1 Rt )P( )MY( )SIN Tn/lllanyrhin purified fnnn rabbit lung m.cnlPhaFes ir very similar in.tnu'turc to IMher MMIrIWH'k IYIl Ir11IMa11y/Nmt. Reduced and derlaWrell, Ihe Pruldcin h.r% twn PI/IypelNiJen which m/gra1e during ckdn111111we.is in vdlum Jlaktyl .ullatc un pllyarylamide Kclk with aliKhtly different mnhilltics cnrre.lanalinR h/ aM,anrnl M,'. ot aMaN W11MM1 1•rdMrwinR tru.. IrnkmR by air IL/JMam in the preserKC nt ('u('I,• cktlr.qlMaeus uakr MI/Ire/IuclnK naabwals rcveal% a sinKk p1/yPeMak ut M. u, I c v

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