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ANDREWS C. -FiCE PRODUCTS CAPITOL HEIGHTS, MD (K)

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I h/11Nl,q.m I I SI1/ /\ aulop.val t,l Iw.. .Nhunn• .t rnJ (t 1'fcvNlu\ly, wc navc o1.qq. tt IIk (\I I.. Fa /k• II. 1.NU1rn a h1.nIN....uk• h rlNl IINNI\l' tllf..nkrMNIK J In 1l61. \11N IV wi 11.11. I• M ./Iit l IIN II1/111.1/1 I . /k 1 . .1 l IntllIMt.,NIN.' I J1 11N 1)N W\l I i) I/ I \III( )l 111 ',i1N' Ilr I IIN'V• 11.11./ \11F't•a'\I 111..1 lhC I5i'IIIl F.a•IN' Ill'\ /11 a ltNl\l'rVr1/ 1u11,.11'r 1•I.Nqr Mt1h Ilk• I•t'Ik-. IIN rmyl,l\r 1 .11141 2, Ilrrvr Ftalwlh LNWr. •Nk IIN.' (N.N.NnN.•I'1yN- N1.1. N,/,/•.r • N I . . 1 •d \,4Ndte, (, // •rrh/ A/.-h, u/.n (., r/. n. 1 I 21 1/ 111) I I I I'•xh (Ifhrr lupl.rrrt' I1••w•INI III/FIN'. MrJ1a.J 111•I/nll. N.Ilnnl.d In.lnNli..a1 Il..dd. rlkl Ilk• hl.ulh Id IhNN•. 1 nnn dlr I h'1•.111nN•In ut ('rlhd.ll .nNI SInN 1111.11 Nnd.•F1 • I11: I l/nvr/vly Ilr.dlh \t N ntr l'rnlrl, %.111 Anlunlu ..) It'l.1\ 111i('1 l11 1.1IJKlX'Y11:/1('f1VA11ON(1N 1'111iIOKMA11ONOF I11 I 1.K//1 Y I'1(' I I/M/ )K ('I:1.1. A( i( iKt•.l ;A I FS IN Yll RU Wa11a•/ IunNN.cII.II x 11/'tcll.l/llllirkuhrlyda117"('ma\brrcJtuvcacwn111J1 1\'111/Nk'•II t',41NtJlt' al'll\ ('/ x I/h tcII\f111II w11h /lr W/I/NNIt 1IN .ynlhcla' IruAtN ylc a IN'lIM1 ,111/.N IJIn I M I 1' ( 2 x III 'M) a1/ h11.In1'I, ally N11/ Vl' t INN t'nlfJt/1N1\ nI IIk' II/JM11 l'1NII.Ft'INNh alk'11N1 .IIII.NIan1, ('Sa Ahhlcy!Jll.nl, IIkI1Nl'II by (IK lhl'/INrJ11/JtIJ/N\, wJ. Iklc.lcl( allrl 1 nun by a plrlckt JyKtcKtNltctcr a1N1 by \IlNlying cyltKcnu/lnt•c INl'1411a1NN1. I Ik' tl'\INIO\l' wa\ a/11I1I111CJ Ill llll' INl'?l'11l'C Ill l'yHKhala\m II I S/lgtI1/I/ I unNN acll% alNdal It Nkn111N•d in /lrc aKltreKalc\ hy Ihcir nNNpMdolty Iw hy auaNaJluK- IJldly allrr Ldr•Iluly wnh '/l t11yn1Nh/lr I11t11.Nlyh Iuf1NN.clle wrrc 11kINIwN;Nid ullu Ihi I lr .q•/•Ir/'•llt'.. IM'll' wa\ (N. JI•INl't /rlhlc cI1JnFc nl llx nun/lK r nl a/•Frcyalc. 1•.laN'd 1. Iw.. n INI.an . r11. 11N/o\t•lvr. I c.nk• Ill hunlrn hla•.1\I tunNN ccI1.1I + 11t I In) l/n In 1• 11 uun •I Inn•• .1. I.I.-1 witr N„ •ntrN.d• J Inln 11N1." Nr.l~ plrp.da'. w/llNn 1// 1 11un .d Itlllllll SII ll it1IN;1 Vl'MNII IaCl1/r IU ali/vall' cunlplruk'nl AylncFall..N ltNlr I:/IiII w1111 •I lia'tIC.IV• 111 a1111111Ia'lIN'llt INYIN/IytN atllVlly I( II.,1 I IIl' JI!1•/CI:JINNI Ir.N 111//1 wa\ 11401 l'y11A11\1l k111111NN tl'II. WIkYI l'valUallYl by I IY11:111 hlUl' t'l/ II/\1t111,/1 hy "( •1 la'h'.14' Wl' \INNIINle tI1aI hKal I\IIIkN t'a'II\ 4:a/1 hl' IIN/NINN:IIIYI /nh1 Jt!1•Ia•FJlI'\ IINIIKtI wha•n ku/..k'ylc\ ate .lbnlulalcal hy iI1v/1N/ alllaa/a1/1• Wr Ir/\lldrlc 111.11 nl I1.IVJN III•If :k11Va1NN1 t1I Ila'1/I1t111111I\ 11111'III JIIt'll II1C hk':1I1/a1nN1 a/I l//• 1•I.It1111! 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III/INN rl'II\ al'flt.\ Iha' v:IN'l1IJf WJII /\ J1111111NN1r111 \Ia't1 III IIM a'Va.111111N1 401 l':UN'a'r IIk'Ia\la\l• SIllll' II/IINN ll'II\:NI:N II INa'Ittl'1111aIIy I.t \IIIM'/l /11NIMII:/I nLNflq at .NC. 401 c1k111111c11aI 1n111ty alltl rv11aC11/N1 in 1-rlr1., we I1:1ve uv'd rn C.Irhh\IN'II in /'rl•.r 11NNIa'I 111 1111ltIN111ary a'/NhNI1l'11a1/1allql!l' 1/1l'RJ111nN' 1IN' l'lirah OI CIkM11IhIt:1I II/IUfy NI 1lfl' IIK'7I1/a1NN1 a/111/1k'lavla\h 461 t'/N'11Ia1U11; 11111NN Ca'It\ rr11l1vr ('S 1111. t6 mkr wcrc Flvcn a.myk i.v. 1111vc l/l hktillnyt'in (1211 nikiAgl t11 n/ultlplr l p inMcINN1.111/1oXrkK, Iwil•c weekly Inr 6 wlkt Fivc Jay% ahcr thc .u/glC /np't u,N11N J Jay. ahcr Ihr la.l 1 p iuKtlaNl, 2 X N/' 1'"1' MMIIKII'11;yufNhlle IJIK'Ia•II I/INO\Jta'U111:1 ccll% nr unlalrlcd rell% wcre injrcleJ i.v. Twll lo $ Iimc. •r\ ntany Irhrlcal cr II\ w.•ra• IINIn1I In IIK' luny. /11 hklNny.•in Itcaled anmul a, al/cr 2•t h. 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Analya. //l IwIwklNlalvcl/lar lavayc /IUill] /1CInINIVra1C11 S•/1/1lI i11t7Ca\Cot 1/( Iulal /IrlNC/0 cufllc/ll aMI leakage nl prcvNNl\Iy InlttilcJ'"I-IahckJ alhumin, IrNIk'a11n1,' nk•ta'a\C11 CnIh1/IN• IIaI I1Cflltl':Ihlh/y 1'.Ia'ltrlNl nnl't1/Vlllint' ella/t1/11:11MN1/1l lungv nl hIClNllyl/n /rl':/It1/ /IIICC Ih'IINNI\Ira/l'11 a'INIulhChal rtlfal•INMI w/lh CR(kMWC u1 Ihe uala'llyin/; bavnk•ul nk'nlhra/le I•JC['tfll/l /n/Cn1\t'llpy Id'Y10hy111k11nC Iahl'IIYl /unkM lrll., LKJICJ hy au1/Y.NIN11•fJl.hy, IlC11NNNIrJICII IIICH alla1h/11[M IIICtINNCaI ha]aI I./11111'a 1)JIJ lurol 11N'Y' Cll\'r///ll'111\ In 1 flvr WI.INNIIIIC hY1Nr111..1.Iha1 cnlhdlK•lirl dau1J1•r r,ul LN 1161.414, Ilk' /Ik'la\L1.1. U/ a IIl11IJ11n1, IUIINN ItII% Off.''. W , l't al ('.rn/cr Rrlrurlh 46:8Y1-R97, hchfuary 1986 Other support: Natamal ('alN•cr In.li/u1e ol ('anada 1'v/lln 111r Ikpannlcnl nf 1'J11kduKy, (lnivctvly ld ManN.A1J, Wln/lqr•g, M..nn..l.r. ('ana11J 27

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(il 11l 11KlINI1)A I IIIN INIIIIII l()K RI It11('1 S II11 INUU('llON /IY III•.N/11f+.I1'1KFNI:(11 A h11 KII l11)A1 I1)N I/Nl (111 IAI I'K(11I:IN ANI1 1)NA 111NI)1N/1 IN ('lW 1 Itlr ulhn•tllvr ++I llk• 1N1•vnt nklV w.l• /o rvrhlJlt• the L...th/lny +.I Irdutlnr c:ncuw-rrow Ily +d tr on+n h•yl+-1k• 1111•1 al 1.01, hy 11k• uv ul `.S 111 l l:wl'lyI I1 FIu- .aro 1.4 (l.( dd.kl+Nk• 11IA(;1)I.1 1111t INCV/nu..tlkly Ilt'/IwNmhatt•tI II1J1 I)A(iI1I.• a 111Pt urW w UI 1) I'IIk Jr++ 1.4 I•It tlwll .{.Iw.wn w+he a nJtnral 1nhlhdnf llt g1Ut U1.N/1+1J.C, tau.rlt a 71r< u•dlwli+m In dl. IIK1111'1wt'+1) IIIJII///Wry IUIIwM In.11N11+Mt 111 fall by 7.12 dlalrlhyllt o/~ 11 ~/nthl Ja r Ik IOM 11 A I l'u.whut/ll.tral/an ul 1)Al 71)1. alw tt•dut c+1 the ilwhw u1N1 411 a(1)11.d +wa+drlal Ilrlllein .Iwrwn 101r a.as'IatrJ wnh cart/nugelk •r. arwl 1nuwN Il:r/w••i., :awl ularlcdly rrdlw•cd huw/u1K a.l 11MNA In Ilrk:m 1)NA (n /lw• plrv n1 .ptJy we havi eu:lnntk•d Ihr rlletl ul hA( i1 )I. 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Nabunal In.tllulc• ul I Ir,d1h .nNl l]a• AnNrh.m I onp A..,tlatnwt I aml dk I k•p.nlnN•nn,d Mrlh. urc• 1'hy.i.drrKy anJ 1'.nvulmmental I lcallh• I Inlvrr.uy t,l ('lnt mn.rtU St IN..4 ..I McJn nrc. ('Int mnru. 1/11 K' INltlt( 11) AI II NAtU)NX IN AIRWAY MI1%('I.F. k1 SI't/NSIV1•.NI•`C 1(1 I I I t'1RIt'AI. 11111) SI tM1U.A III1N We mvt.UKatrJ Ir,..,hlr prr arwl L.a.yn.qrn cltct t. tul K' uKluttJ llcpd.uv:r lum.m It•ncl /tathral .m.r.th nlu.tlc II1M/ rc•IOa-mlvt•rk%% L.tIN.IlnctKn .luuula- tum lo a%%e%% t•kltronK•.h.nnn.l atlvey. lell nr•/uhranl• p•Ncutral (F._) anal Icnlnm 1 1_1 wrte %rmullarK•.,u.ly rct.n.kJ m Lulh'r t unt.nnu/r h• 12. In, lN 24 mM K' ht':urc anJalll•fl•Il'lltllal11rkk11111uIJIhN1/1'I 1I~NrluFrMNl~atl•Iy1.IM.tlrll•IA( hI InhueM K' ./._ wa. SR 1' 1 U nIV /urcan •SI'1 In 12 mM K' . t_ was JrpdanirJ Il. 52 1• 119 t11V, hatJl I_ 111J IpN tlNnge• anlt tMNh eRt Ilalury IIIntInNlal IMNt'rlllal• and t.Nr1r:N'flle te\h,MIK\ 1.. 1:1'S al .MNt .hmutu. Jutatnm wrrc Iarpa Ihan In fa lnM K' Nu.ut'h pdrnuau.m .N t urred al a h/l hrt K' , ahMNrl h rr.f 1oK F anJ'I _ mt rr.l.cd ptol;re.avrly aMtve 12 mM K' '1hc tt'n.ntvuy o/ Irne1 TSM hr exulecnnu. A(ll aM+carrJ una11cc1cJ by K'. ru tklcmrnr whrlher the hyperrear,m.iverlcv% in 12 mM 1( • was Jur• in Itart. Itu auKnlcnlcd A('h rrtcau Irtum Intiamural airway rkrvr., e.(r•nmenle wrrt J.Nrc u.InK TSM INCparalwm. InruhafeJ with I 'IIk)Mthnc N.Inramlrc /'11/A('h rclra.e al fe•t anJ dufinF I:hS AIIMwFh reslinK l'IIlA('h rrlcax ilw'rca.rJ INttytc.avely in highrr K' , release evld,cJ by GI•S was tnaanlal in 12 mM K' arul lkt hneJ m hlKher clNwrnualaNl.. We nNklulk that vrull ekvatwn% in the esuat'cllu- lar K' ctNn'en/ra1nN1 auKnKm re•Itnmivene..ld 1he anway.• by itwreaang Ilx rrlca.e 4.1 M'h MNh al tc•1 anJ JnlinR IiUS Irunl intr.nwral cMlhrKrKic nrrve lrrmi-lal. I:Ir/,q•r /IMft•am:% in K' ap(Kar hn ce rnhlh/aNy• pah.IMy due 1u vol1a11clktN•rtknl cllt•tl. thal...ur MNh (Nr anJ hi.LyniINltally Murl.rr• (' er al J,NUn.J n/ Arpll.d /'bclu'6rxv 614 11 61 67, 14N6 (Nher rrppnrt: Nata.n+I I(carf, l.ung and HhwNl lnctnulr• NatnN1a11n.lilulrl ul lkallh a1N11I11' A1/N'tNJn I.u111,• A%Nq'Ia1NN1 1 r.nu 11w 1 A'I.aHnN'nh ul A1r.htule, I'hw,.hq•V :lMl l'nvIn1n/1N'nIJ/11,'aIth• Il/ltv.•r%lly .d I int.nu./lU %. 1n...1 nl Al,dn uN•. (.n, ,nu,d,, f)II I A 1'.11i('1S//l MII(YISM.RI'.M(/VAI.ON(i111N1:At'1(; AIRWAYSMINIIII M1I1t'1 I Nl til'(/NSIVI:N1•\S I I1N• tnntU.lthlr rr.lNm%r lu hl.lalnnrr• att•Iy1t M.hrw /A('h/. K( l tut rlrt Int.d ht•IJ .thmul•.hnn /1.I \1 w•1, rKanunrJ in pa/rrJ trat•IKal rlnl!. IINN /d r:wh tt•u,y lk•na.kd by aiNCO.:J mbbinE 1. whlt h werr nNmmrJ lu mu.a k ch:wdr r. hllyd wld% a tuuhuu.Nr.ly .Nr.dcJ Idly.aduplt,J .:.It adouun at 17"(' :/tCtlnlYal UI 11N' /l'%I.n.11.11 y/IIUC.N31 IIN Il'a%l'J Illr 4Y1%IIIVIIy .-1 :Itl w•ly ulu.. Ir tu A('h. hl.t.umnr :mJ I I S. bul rN.l lu K('1 '11w hvl+t•r.rn.mvuy u1 .k•nu.lr.l r,ul. lu h1.lamuM• .md 1.1 S w:,% p,t•.nc•r dl.ln lu A('h Alr/qmlt rrdu. cJ Ilw hra llllllll hylk'1 N'/l ~l1wnV .~hv'IViJ 1 1'rrucatlnl! IIII.n 1 INl'I/.IG/IUN1~ with IIMhNIII'II1:1CIn :1111!Illrntl'tllhrl/ rN..1,. 1.1 S. In.l.unnN• ,NMI A('h •1 IINI,N111'tI1J,1/1 ru17nN•IIId11,N1..1 11NI.1/,II/N' allfl 1'.1'ti nwlutrJ rr.tN.n.r. w..I p,t•,nrr In INrparau.N.. wnh.,ut rINt1N•Iwm S Wr t,Nnlu.k 111.11 tlw• anway mutu.:l .u.ly ht• a.%..1.drJ wrlh a Ia.1.N 111.11 IcJutr% anw.ly \IInN1111111111t11' rr.pNrvrvrrw•t. 1.1 vluuul.u,N1 Afurlu.. (' ('llnn ul .C, rrru .• 70 571 575. 1'/N6 (lthir tufrynNf: Nab.m:J Iicarl, I.unE anll HkNnl lnaitutr, Nafi.mal lo.htulr. ot I1r.dd1 an11 Il/e Allk•IN'all Lu/ll; A\MK1:11uN/. I'rnnn tlk Ikp.utmrnlN ol McJirilk • I'hy.udttgy and liuvu/mmrntal I lr:dth • Unrvrraty ol ('/nt Innau Stlwrd u/ McJlctnc. ('tm'innatl. t)11 O. INI)(I('1'U('l1ANGli IN HK(1N('IIIAI. It1iA(TIVIl'Y lO MIiI'l1A('/lt)I.INh ANI) AIRWAY INI LAMMAII()N IN III1MANti lltr irKrea.e in airway rcvpun.iveneav inJureJ by (), estpNure in Jl.l;. i% a...N'1 aletl with airway elwlhrlial intlamnuNilm, aseviwknreJ hy an Imrra.e ru the mnnlnr.d tlrolnl111111\ IIM.Iy//NNI11Mmul'k:at k•ul.nl'ytest IlN/ntl in elNlhl•IIJII hn.IttK% a1M1 11t IM.Nt 1h11:Wetllat IJva)!l' Ituul We inve.tiRaleJ in K/ healthy human .uhleal. whrlhrr 0. intlured hylwrrcy>,m.ivcnr.% wao similarly a.akialeJ wNh airway In/lanmranun hy etanunmp chanEc% in Ihe lype% uf cells recnvcteJ in hnNU•IMralvcnlar laval.K• /llnd uhlannJ allrr caphure In air lw In 0. (/1 4 rw (/ A I.Ilml. We alv. IIN•avUll'd tht• nNKrnlralnmo,o/ t'yrhN..yrrna.r and hp/>tyKcnavc ntrlalNdncvu/ arxhnhmw• at at or lavuge 11uK1 We urca.arrJ auway reapm.rvenevv hl InhrkJ rnclhwiNdurr arn..u1 hettNe atNl iUl•t l•1N11 l•akIwNU1e an1l 11l•tl/Nnll91 MtNM'h/4IYeN1Itl Iaval!e I h(rtrr Wr laumi nwwe neuulMdul. In the IavaKr IIuNI brNU O, e.1llr.eJ sublrtl.• c.ls•.I:dly lu (hl1.C in wlMNll (U, cR/Mhl/lr pttN)w'cJ an tnctc..c in airway rcarmavrne.% We ahu hNInJ SI',nllh'anl IrK'rCa%es In the l•IN1lY11lralNN1oo tlf IttIN1yKlanJln\ I:,• I'.,r, and /IIr.NII Mr.anc H, in (avaKe Ilur) IuNn t)• eaplNeJ .ubjecl. 1 hrx re+uhs cM.w /hat In buman wbjed.l), InJu/eJ hylll'ne\INN1~IVCr1eN t/1 rllethll'hllhne /\ a~NIr1:111Y/ w/lh a///11tIU~ al nc 411410111% 111111 11N• altWayt a1NI WIIII l1UnKtt Ill lhe levek III NNIIr t yl hN.styFI'/IJw rnelalrrlue...l .rat hnwmn ., 941 111) 1 S t

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KItI',/nn.•tul.tnl,ulp•Itlt-nl,wtthlunr lh.c.l.r Wc1111mJUcdklt('hum IJ IF'JIII1y, •1Fa• J/aI I~a mkl u1.11a111•d at/!Jrt'll\• \IIM.Lt•f, 11111talnl•al nwur Ip • II INI I;lut•INlaroa• it, 1• 11 1 µMrE 111•h vrl.u. S 11 ' I) I yMly IIKhI:/11Jla1ala.r 121'/,S 11 • K 1117 u/al./F 11)•h vt•r.u, 222.617 • 7.IK11 unllay IIrh) than Jld kltl' Irunl Mn1,lIN.Lt'1• III a..n11.1,1. Kltl Ilmll . I~Jt1'lll' ,ItM.La'r\ JII/I /Mn/a11M.Lrr\ ttN11:11/N'II 1hl' %.InN• •hllvdlr,.'1 1•lu1•dlmalr Ir'aaalJ,a' 121 1' 1? Inln./y 111;h vrnua 2414 • S S u/ul•1F Il~hl kll/ In•m . y.n. n: .ul.'Lct. .d... p/.dct hJ Mrvulr pulnwrnJry attl•ry t•Ink-lll.•tlJl l a 11, In . nhtur Il~ ut h~dl../•.'n It I~u.k III l/) Ir'nrr Ip • I7 oS11h.u1 JIJ KIS( Iu.In nuu.nw Lrl.lt! (• t~ I'{ I•I. I~.It,nl vt't.u. 11 V• S 7'% Inulrttum/ 11n• rl•.ull..u)•1•.'•1111•It .d1a1•m.Ml, nl KIl( J//IN.an1.1111, IIIJy /l'Ih'lt l'alM.,ltrr J/I/llUt J/IIYI .u.vt•Iltlhth/v 1.1 na1J.m1 mJual•.I lnlwy I.ah, K M, Itrrgrl, I M, Ilrrhlt•1, (' I. JIH/ K.pIn.•. I! Ana'rh.ul K.•ln•u'.•/ Kry.u/m.n• fh.r.r.r 13•/r! :KI :K4. 1996 (It~lel rY~r1I/t: N:IIN.n.1) IIIa11I11I1•\ UI IIl•:Ilth, /Lllh'/1l'all L11111,' A\N1l'Ia1NM, Ihtwlu1 & l LJUlhlr, aoQ I :unhr:ulah, low I n/n1111r Ik•p•utnti•nlI uI Mrdlcinr JIIJ Pl•lhJlrll'a :1n111IK Wl•hh•W:Itlnl; I ung I11V11 tu1r, llnlvcr.Ny.,l ('uhlraJll llrallh Scirnl:c.(•cnler, Ilrnvrr, I'KlK'IiS%IN(; /)F /1N(;I()IIiNSIN ANI) O)IIIiR 1'IiPfll)IS ITY TNIi I.11N(:S 1lfxk t.tarnhnh Illr mlrr:R II/MI% 111 M/Iuhh• Ur t'Irl'ulah/llf l'IM1111NICn1] III low It•111n angnNrnan ty.lcnl Jle/ lhr kalhkrrtn klmmn .y.lrm with 1r111t1Jr clenlwmrnt. t. Inq>,Ir 1J111 14t'al/w IMNtt %y,lt•111a IuMINM• ill ICltal 111 \IN/N' IC~/•Ctl~, a% h1aN/ INNtINMM•a 11Uwrvcr, (•Vrn Ihl'tr .y.tcmlc al'lalrl. may Iqr.unR rnlitally uU1111rtJn1 rr:r1 flunm with t'rllulat l:nmlrlncnl% lhrt afr rna un/ltwndy JLlnhuteJ wlNlin urEatlm ur wlthln Ilarta'u lar trll lypl•.1.% a ylvcn lug:ln ut li..uc One unlttue Inturr.,l Ihc pulnNlnary liriula- t/un I. Ihr « neuLJhlc .clctllvNy n( N% ulclalyd/.m ul Ihr.e prpl/Jc. Ovrr tIK pa.t .rvrurJ yc•u, J.1.'t h.-1 the nw•IJh.dl.tn .I \tnmm and Jn~n.trn.nm I by Iwllnwlnary t•nd.allrlluut It,l.r 1.'rn 'k•hlyd Ilw• hwu. ..1 Ihr. lutlwn 11,1. Irrn .n Iwfi/1uuJry rn.l•d1H h.J •. 11. .h.. 1, .. 1•. 11.. Iv Iw.+. ,. J vIlr. n1 vJ.u.w tlvr ,uh.U/a r. CIUJu•. 11•Lr ,la•w n 11•.n ~ trl•NIh 1'•d .. 11..•i tl.. 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MI.-InHUI II' n(`IIV11'Y (11: 1'1II.MlINAKY I'.NIN)1'111.I.IlIM. 1 M111Hq.AII1INS()I' S7K11('111KIcANI)1'lIN("IIUN I'.1NkNIMI1.1I l'l•II, IIIJy a nu/llhrr OI al'llva• r1/Ir,I1My :/l l a% a hrnicr wldl hnnl.•.1 11Ctllll•Jhlhly; IIICy ht.ql•\a l'Iflltlall/lo: hIM111111M\ a/M11Nhrt hnl:lt'llva' /llala•ILII, WIII1 1,•rl•:111'Iha'It•IN'y J1111 N•h•thvlly; Ihl•y %hatl' 111r rr-q1111N11Hhty IUf hl•/INl,tdtll rr,ud,.n, with IrII\ :IrMI llnll(Mllll•111, 11I hkMlll, MII u1Nh•r IMNII/JI t't1/11I/1MM\ 1/11l•rJa 1 VIYy 111t11' wldl hkt.Ml lr1l% la hhrld htNnr t'h1111nK I:r.11K• Thc ruiyn/c%, t•niyllw• nllnltn.u., tCCClltln., arMl IrAna1h111 INUh•/11\ rl•-q11w\Ihk: IIU IIIC In/ll'INIK 11I //IICtJt'InUI.. /11 c//llu 1hrhJl l'CIIV w11I1 l'Irl'11IJ1/111; Ntwa/N'l•\ arC /II /IIAny l'aK% klNlwn tiaM/lr .1/ I)IC aK'Inc .uh.lalll•r% rclravJ hy r1lJlqhrhal rr/1e havc alw/ lurn JlwunrelNrrl, hul umkwdNCdly many rrntaur lu hr rh.m ovr rrJ lhc arlive an/1tlaunlhnKrnchy IN etwkNln•hum I.Ilr.d/a. bly dur in pan Iu rl•Ira.r 111 prlNlxyrhn, hu1 even whcn pnr.lx'ychn i. InhlhnrJ l•MIIItINhnlll tlltl'% /MN ht•l'l/lllr Ih11w/1h11I,•l•nll.•. In /:M'1, unly whrn r1lJllllll•hal lrlh nl v11r11 ate ItJll\h1rItIC1I tI1/1hl'y I1CtYN11C IhfIM11h11o•rnll•. IlnJrr Ihl'\c l'1111//11VIJ/Nl•% Ihr pl/l:lrlly u/ Ihe r1lJlrlw•liunl nlay hr kla arllllhe JLlillclnwt hrlwcrn Ihr I;lyl'ul'alyu un Ihl' IIIIIIIna) \ulI1KC a1N111M IM%C/lll•nl nICn/1lfa/ll• rIWIC/1:1b. IMI IIM al.luminal .InLnr Illay hl•l't1/11C l'1tn1uK1I 'IIIC lull ra11I,`C III /1r1111Cr1/r\ U/lll IUlll•INNN I/I 1hl• IN/r/11,1I ylyt'Ir'alys are tu11 ltwlwn, hu1 h i% rlcar Iha1 rnJ/Nhclium can play an ali/vc tulc lu 1114? cvr/N% k•adlng /u Im.ruvav'ular ul'c1u.Nln and Janlarr. lhr cmkNhrh:d .ur/:llr rvrr wh/CI1 hhMt11 INNIIIaIIy IIuwC un111111rrIC11 can hl•l'1u1M a Iucu% hw Ixut'uagulant anJ rlanpknlrnl-hnkrd rearlnm., and arl'h chankr. l/lay hr• alclwnpanlcJ hy a dl.artay 1.1 the glyrtr:dya 11 a IrIn/q1uK lo yltrulalr Ihal lhr FIyc/RJlyu 1% i/nlwat•ull m Ihr Il•t'1/I!Illlnl// llrlll'C.,V•, It•Iwrrll Cnik.llM•II:11 CCIk a/NI hhlllll Cla•Illrlll~ an11/1/.11 ./lh•/./14nh I/I IM•/IMN1Jl/l' NMI 11111t1111M.h1' K IMda•nllal JIC :NlIn1111J/Ul•II hy aI1C1a1nN1V I/t low t•/IIk1 1111:hal gIytu.Jlyu Rt•Irn, U S Annrrd Rrl•irn'..J/'hvtrnlnKl 4i.2h1-277, 19116. Other suOporT: NJtn.nal Ilrart, l.ung unJ 11kwIJ Inaululr I r/an Nlr (kpartuw•nl ul Mt•.ha ulr• (lllrvl•r,lty t.l MIJnu St IuM/l a/ Mrtht /la•, M/•nm• 11 S1 I S1

kl ('1 1•I(1N MI IIIA 11.1) I(INI)IN(7 OI' ('ly ON ('lI1.M(1NAKY I NIM)IIII I IAI // l l S N.NIIIJ) IIINLIIII.IF•1'1I INII/INlnuy cnJtNh.lr•d ccll% a/qh•Jr /u (w umuun/du~.a.Jly pnvlk•rl•J in thJl dN•y 16. IaN cit lNC.% re.clNtN. Ilse IlN• I t INN1aN1 nI II;(7INN ItN (' Ih II..wcvt•r. IIN'v IrtrlN..n hruwllc unma.lyd twl erN11NIN•IIJI .cll. InlurrJ h•/ vo.ll Inlr.tata.N r.la/.urc at whnc acll Iy.:NC. Wc IN/w, prc.clu cvak•ntr lu nalnJlc IkJI ('ly hNal. 1.1 Ih•l llN IclclNtN.lNllhc,InlaCC 44 /NNIIIJI hL'NIIIIy l'INIINhlILllll•I . IIk hlnJuly 1% du.c lklt•lak•nl, rcvcrahlc a/N) %alulahle I'unhl'nINNI' t/u1 llJla ,IN w IIIJI hualn/F 0.1 ( ' ly nt cnJ. •IIN'II:II t CII, 1, v1.11hC 111atJRCMIu\ 1\Ir11.N11/1 Ilse IIN.IrI Idc eaN vcl IIN 1 k11N11.1/ IN':NI ft').'I/Nl• I IIII, h1/Nhnl,' III ( h1 h/C1NkNhl•I/IIIII wINIkI 11Jv1• Ilse l'IICI I 11I cywt.m~ 1. It.clN.w. IhJI IIN/W thcn hirNl ln Ig(i ut citculJUny ulurwnc l.•nqtlc.c. Ih.u I t h'tcIN.N, ;NC /n 1x1 cula..cd L.hllwn by rlr.cne hN11W1aN1 WIIII JI hlqaly a...h Iwlctl ('ly. n.. hnahnF lh'runrJ u.ln~.l v n.IhirJ rrylhuN ylr. Wld/ I('Ir :CI% In.lhtln •uN/ lr•m.l.l J..ay. I)ur a•.ult• IININJIC that ( hl hlnlhnl,' IU CIa1.dIM'Iltllll Im..Nk ..1/1a Jn. LN I.n .dlv/oy UnrnulN clwlqdrae.lwl pulna.oJry vc,.cl. Jlal .uJy Ir• 1t111Mwt.1111 a/ IIN' U1114/taal Jlhl /Nt./YC..aNI r/ IIN• InOJmnlJltNy Ie.IMl/lv' /henl•. so l. X.Mllli. I) H JIN/ Rlan. fl •\ 18,11" un.l( '.!! 111411 11 IM• 1'/Mf. Illhrr lupp..tt It \ 1'uhht IlrJllh \.IVNc 1 1.•m 11N• 11ul.crvly ..1 Munrl C. h..d 1.1 Mc.tl. na:. I)t•prnna•n1 tu/ Mcda ulr. Ml.unl- RI'.A('111)N` A 1 1111 1'UI MONAlt1 I NIN)I I11 I IAI. ( 1 11. StIKI A('1'. Slnlc 1'MJ. it h./. It•tt•uN' cvld:nl ttul a wak• v.1r1c1y sit hnNhcnu..d (e.NU.N1. trttlr.ndlf.ullJtCt•I v.ntulJlCrN1.NIN'hufn Manynl111C.erCatllNl.•J(Illl'Jrt..IN.Ur l IN11/111NNt,ly Il' g ./IN'IJIM/IN' IN1tT%,InF t1I vaw1a.ilvc .uh.laN e.) whllc tNhcr% tN'l ur cplaNhcally IC F.l'IINC,VNwf 111 11nh'tla/,'ulJ/ll a'hvlllC] an111nleral•II/NN with t'INllllll•- nMnl) (*Crtem ut IaNh tyle% ul rcxlalnt arC IN.w u1NkrSaald in lair Jc1Jd a1Nl in 1CIn1. 411 UnNlu1C huAbtNl llNtClalntn.. Ilse (e\1 (hal Il/lktwc IIN:u]e. I) INI a1lNinwluc InterallaNlm td cnJtNhc11J1 wrtace (N•IMIJa.c en/yn.ei with h1/NNl lNNne uhpylclNak IN N 11M N1C%• anti Z) t M In1lul'IaN1111 INIh 11a~,'11I~111 .N'1/v11K, and l'INII(Ik11KM an1l II/It1111nC 11N111hNKni teICININ\ l't111Kt1UCnt 111 CINkNhI•hal InlUry. The e1NslN/ll' alhvlllc\ a(l/ll':/r rel:dcd in p:ut ht Jl.array u11/rc nlNmJlly highly INgani/cJ Klyl:ucalyt. 01 the canlinu- INI% x'llv/lle.• Ilse na" ckarly unikr.hNld •are the intcrx taNl% of erNkllheliunl with Iwo uh~ltltlNak.•thchlwnaNlchraJyklnlna/N11heINIlMwnalrleanKiMC/l.in) AnKiwwcnan I 1, t'INIVC/1el) III/I/ Ilse VNMIIIre1MN IawltaMK a/ll.'aHl'IINn II. and hradyAlnln• a vaaNk INl'\MN IMNIINNM, 1. In..Itva/eJ hy an~aNCn.m clNlveHmK enrytne Illc latrrr enryroc i.lh.IN1.cQ tln Ihc crNkNhelial .urlwc .uch Ihal /l hav vutually Iree .cces% a/1u hhNNl• Mwrle.uMllate. A%a l'INNeyuenCe• Cnl1lNhChulll lJlr1 he sa1/I lU re6ulale the MN/nINIJI t/nlqa/.ua.n td hhwNl nalving Iklwn.treanl In Ihe Ca,e (iI 11uIONlnary CrNkNhlhuill• tk.wn.lreau hkaul i. ,y.ICn/iC artetlil hkNw1 Hln.r II \.rht Rlin I W 1,. ..• 0.•l...l..l 1.....•h•.e.•! l...nl tll....l n• /.t.ur I r.n/'/nan. I1'eN5 I•I•, •I i (Itlerr cuppnrh NJllun•d I(cart• I.unl; anJ Flkwwl In.titulc arNl thr NJh..nJl In.lnulr, 4.1 I tr:111i1 I 1.•II/ Ilse I)l'll.//lllh'1N .II MlVI1l111C• Ilnlvl•1\Ily nl M/a11111tIN11.I OI Ml'1I1111N'. M1.11111• II IIII I NIN )111I 1 IAL SIIKI-M'1: ANI) RI'SI'1)N11.C ll) IN11tRY I•I/IIIMNLI/~ 1/11i1uV;INIII:/rCMkNhI'IIaICI•II,JrI•IJalwn111plclyanJ.I/vcr.dl-mIIN• cvcul. 1h•N k•.al lu v:IV11IJr JJnlay.e in Ilse nr11JU1n1.WNy rc.laNl.c IIN• cnd..dh•h.d ,II/I.N'l•. IaN111.11Iy 111.11111.a/h/F,ll';IIIy INlvlk'gCII :nNt VCry ;N'IIVCIy a/1111I1/11111IN.1!a'lla • t•NI rC.lrnal ln cC11J1n.lUUld/. FCIICrJlly inprraNl., by It•cunlUll!.trtNll!ly puN..JI•ulJal :IINIhyI'\INt'„//IF'IT:11hI(•lhll'Cl•ININ. Lll,l•III:NT111/11JL't',,.N'IIV:NI'tIl'/akNIN'ILIItI'II• t•1/1 I•I.SVNk' .1 1.N1111aN1 MNllll• ;nNI \UINII:Itll/ll ItN t'.N11I111N'II ht•IINh1.11h' :I1NI 1.N1111L' nN• I hnlyd 1c••N Ilnn. Sol h Icln.hNnlatuNlh t/t l•INItNIN'II•II 111•N'tINN1, n1./y nl...lv.• •1I11•1.11/1NN 111 Ilse t'/NhNI1a'I1.II )!Iyl'Ih'Alyk :/rNI• 10 :Nk111NN1• /•I;ly hl• 11111h111.1111 LN Ilse t•1111..1111h111 •N1NI t11,Iq.,.II ul 11161F!IN ytUKYI 11.111hul;lle• Whal /, CICar 1, 111.11 d 1, /aN •mq.lt .Iba-ult• a1 t'1a1.r1IN'111111I 111.11 I/J\ a Ih'all/ll! .NI 111. 1N11tIN1N[ ld tnlLnnal,N/wy ,11111/111 INII 111.11 ,n11N 1111.1I •/1NI II//IM'INN•;11 /l•\INnIN', III II11• l'INIINIII'I/.11 \1111:N l' Itt 1///1// y. If,ultln)• 111 •1Ih'1lYl Clhll'„NN/ nl Ih•/Ia1,IJlll' :nNI //1/111111a/IugIC IpNI'1111.1I• //1.1v I1.IVt• J/I unlrw6n11 It•Jlnll; uu Ilse Iulc 411 Ilse cnikNllChlun UI IhC rl'I;ulJtlun ul nu.1..v.1..lA.n IN'111N'JlnlNy Rlun. Il 1 t I yd.'noa.n I'r.n r.•.lulgt 45 11/1 111%• 19fSA (hh.r .uppp.rf: N•nNNIJI In,llluil'% III I Il•ahh. 1 ru/u Ilse 1 k•pannN•nl ul McJ/cirn • llnlvcl.ily ol Mlaun St hthd ol Mcdlrlnc• AhJnu. 11. I't11 M()NARY 1.NIx)II11•.I.IAL('1: .LI.KII I.ING HY IIIIMAN NIi1IIK1)1'1111.` PIriSIItI.I•. INV/)I VI.MI:N1 (11 IIYI)Rl)XYL RAUI('AI. Ilulaan hhNIJ ncuUnpllilz .tinwlalcJ by a varicly ul ayenl% wcrc .INrwu 1., h•Ivr cyhtlu.rc cllcclo uN MlvnK INIInaNlary artery enJl111N•hal rcll. I:Ilc.hvc ay.wn.l. t1NI1Nk11 1n•nnlnc cnnlpk•se.• Iql,amied ly1laN:n/ arNl IZ ('1ICIIaIk'CJIa/yI ItIW1IMII ;ccl.uc lln.imndalcd hunlan nculnqlhils anJ nculnlphd..tinwlalcJ wld/ N;twln) l IIN•IIINMIy) h•IKyI 111N'nylJlanillC cN with p1a1clc1ar1ivlNlnK Ial1tN /:Ilk•d al nalucC ]I);11/1na/N 1•IIIIIIIg l'vCn IMNII;h Xt'rehNy rCICa\L' OI IyMtNNUaI CB/y1111'] t4't'unl'tl 111 nanllarlnK Ihc cl/c. t. ul Ilse Jillercnl ag/N11.1.. e/ak/lhelial ccll Adling .Ih/wrJ a trucr rlNrc1:11NNIw1lhlhl•IN/NhN1 11111 111 1LO.II1a11w/1111hC1,•enCFa1aM111(1.• IUNkNhI'IIJIcI•II 1,1111r1f by .unlulJled human IN•uu.qlhik was inhihilcJ by raMla.e hul INN by .I/y1N•Jrl 1/yp.m I/lhlbnur IN.upcr.IRiJI• dl.nnaa.e Ki1hnK was rlsu u1h/1wICJ by 1wu w'av/•nrrr. IN• N d/nh111yllha,ua•a yral I/ nla/alihd1 ul hylh//.yl radN•al .IN/ by lk•Ic/u+JnlnN• IIN',yl./ll•. arl ItlNl tIN'IJIIN I//III%nlurUlCl/ lk.•ICr11f1n1111111• n1C\ylate wa\ NIrn11NJ111Iy Ic.% e/kluvc in IwtNCClullt the enJlAhrhal ccll. a}•a/m1 f<dlinp. Agcnt. Iha/ wrrc INtNCI llvc JKam.l cnJlNhclial ccl) Ad1inE dIJ IaN inlcrlcrc with Ihe Kc/lcralawl ul l 1' lu .unwlalcJ neulnqlhltc. These resull. suKEe.1 that kukacyle induceJ enJlNhchal cell it dlmF in rerrucan he in.hN'eJ hy slwne hu11aN all aKtNli.l. (.N Ileulnlph/1n ara1111J/ /la• kllhng 1% uaylCen Ikpcmknl and nuy tlc Jncrtly Juc Iu hyJru.yl raJN aI pu«h/. uun Va/Jlu• 1• 1•hk+el• 1 I' (; , I111• l; (1 , JntiRINn. (I .1 t5

II.h•o.ll.N1 INI'r\f.cull.'n 5.1/h1 AS(, /J.I, 1'/RS (I/IIPr aulr/N.rf: I bIN.Cl+ny .N MIl hll••NI uNI lhi I Imvrl.dV .d MlJtnll 1 uNn IIN• I Ial,du11N,11 ,.I M„h111N•. 1h,1.\'Ial) ,•1 M1.11nr1 \111,M1t „1 McJ1l luN•. M/.Nlll• 11 1)IKI ( l t 1 I 11 1\ 111 I f fr/ / 1 NIN)lt)XIN t)N SIKlll't11K1. ANI) I'I KMI VI!I 11 \ Ilt 1•!11 MI/NAKt I NIH/1III'.I.IAI MI1Ntq Al1:K\ ANI1 /llt I NIKfIIII t IAI ! A11 K 1/1 INIIMAI.I:XPLANI% I!M' \hl,'\ I+IIIIa 111/./I. 11N•1.1h11IN. :1/M! 1,11y+NthIFN• l'!Il't 1+1,1 / to IM'III 11Mt . 1'II •'llth, 1/1\1111N1 !nIV11M' IN1I11MN1.1/y \•IMkNIN'!/aI IIMNMI!.lyl't\ a1MI /M11!M' 1111.N I l'/NIIN!M'!1.1) I./y\'1 1111N'lnN• puhlNnl.n) a11flV Inhnl.drar!,t111, waYt'r.Jn11/N•d I 1NhNhr!IJ! IIM,/N,!.IVI'1\ 1•.Ih1.rd t// I..•II l'/NI 1!1 !u/I. It 111. It I, !(i• ,IIMI !I/ N(• llll!) !IN 24 IN1111+ IN IIN• ,Il.vIN r 1/1 1N,1 NN• Ir1.11 \.d1 .rlunl l l('S/ .IN.wrl) a Ik,.c .k Ih /Nkm Ir.l.m• r. :1% tk•nNN1.u.1N'J h% nlunlh'1 .•! IyI/NNN l.•II, afNl LN/.uc lkhyltfo)!r/>.Lr frkav t1t.d wa. rllh.nllyd hV •Nklitll,N .,1 1('` 1111.I:Nya!ul IH/NIua111N1 wa. uN'rravJ INlly In 111r INl'N'/Nl'.'I II'S I INIINnun.d.ucJU.ad,11111N1t':NrInIN'ft/MJh1hIy IlINkNIK!Lllaa'!I+ INI n/ulha•IhJ...a• Idll•r.I,IJIC/l /n a1N'uNN•ql.lll.lnlhrr. wldl fatlN.aa'live Italrr.ln 111r ulqh•1 wt•!1 J+q•I,d/.an1 ?t'{ 11h tl':Na' 1/1 f.Nr 111 l'1111/!1hIJ111N1 IIINIIII+ /n hlwrl wc11/IINUN• 1/1 uplh•t w.'IU 1d 11 wJla•1 J!Irt 2 .I/MI I INN/I• 11NI/hJINNI W/lh rINI.NU\111 1 1 INNIf+' l'INI,Nava 1/ %t) 1 11 (11 In I SI'. 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AnlrrM In J.'ul•NJ ..1 1'ulh.rl.rkv 122 1A!) IiI. I'IRh Il/flrr aYpptlrf: N:IIIINIJ! I Il•:It!. I.unl; :IINI I(hMhl In\IIIU1l• :IINI 11M KtIN: 1'INIIIlIa111M 1'1\Nn Ilx' 1k•p+ftntrn11t1 Mrd/.illr• (!nivrf.lly t,l Miawi SahlNd uC McJlritN'. Mlaml• 1t. ( il t l('1 K'()K 11( ()11/ MI 1h111.A I it IN 1/) I•K/ IS 1 A('Y('1 IN I•K(/1111(' I 11)N IN ('U1.I 1!K1'.1) I(()VIN1• PUt.M( )NAK Y h.NI x/111I•1.IA1. ('1 lh.• INr.rlnt +tINIy hJ% l'l<a1111111'lI IhC ahliny t.l Flua'/N'tMiruilb ul IINMhIy Illr ININIiN u1Nt Irl IHO.lacychn hy rnikNhrllal cr11. llrrivcl) lfltnl INrvinr IN/InNHUIy altrt N'. 1(uN1u1F' .hNhe. wllh / 11 ~lrranlrlhJ.INIC I/IJII alyd Iha! Iht•.r a'eltc pr..r..rJ hlyh- alhe,llv h/N.hny +dr• I,N ! IIN 1N ININ INd. lA' , a1qH.ltultalrty J nM) l hc trll. frla•a.rJ Iv.1.1.1... IN, nN•.L.n~.l .1'/l,h.!•N.dh J. n+ hVdt..h+l+ ININIINI fr Ilch/ hlu+ldl'!.uN!111 .t.,nut .N,! L. .. S 1.1111 INI ul.ntn.H tt,lh SIInM In.1.lyA/oa1, I It yM 1.11a1uN11nINq,hlnl A`11ft7.N I lo S µpoi1 :II:NIIIIkNIIa :NNI 11t•.J/nr/11J+nn\'. 11./ 21111t11• +I/IrIHI'+yII t1111+1.M )l llll fl'h'Jy I/l ll'+IhNly Itl hr:NlyAllllll .IINI NNhIpINnr In •1 Jl/+l• 16•IM'n1k'ul ul.l/nur/ IIN• .u1qNr.avr Itl!a1+ Irylalrll 21 1/1 1.01 11111 raplr..uln Maauu.d 1Nhdn1NN1 nl I]I.M/)I,uun nNlua'rd INILLN'y111n la•Ira.r wa. .Ilynovul.ll.l) hS'i .nM11hJ11.1 /1NN.IIIMN\' I/NIIIar,I N'k'a+C w•1\ uppt11tu11a1t•ly IS5{ IIN:d Nlhd.uN•H N'•1+ /MN /.IIM'/\l'.I IIt.I/.h.N1/NNN' :11 21/ nM IIIIIIIIIIa'tI !N:III)I.111111 II/Ihltl'.I tt't: a+l' .,I (NINI:M )t IIII IIV •II,IN.,\1111.11\'Iy •tS'4 INI! h:MI /NI a'!IlY! 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U J:IC/pCnla JIh1 th.NN11+IK. 1'J111tu1Jll' FuJnyIJIC tytlJM• J/IJ IIIC 1'1• rCa'CIN1N v.Iuhl- IVa'J by J:It'll;l'lll I:IJnKJ IIN'Ir Jhlhlla', lal INIhlult Cyl Ilt (iMl' JIMI huNl 11", /r.lrt: - Ilva•ly Ihlwr.a'r, %l IJJcJ u1 /a/1lJt. I+JrIwulJlC EurnylJl: aytlJ.r lo Iklall;rnl ra U,la h III a U1111.h1, FI/J/IylJli t yl IJV' It•,/,IJ11t Ill MIIUI11I1I.11NN1 rC1/1J11NV1 (u1k11U11J) J/Il) a1Nq.kJ lu Ilw 11 r:atlM,N ,nwa• a•tvynla• oallvJlluu hy 1'1 wJ. un,JlctlrJ hy vJINNI. l'a11.N1NN1 IN.Mt'Jltft', IIk• 141„1INIIly (11.11 else S1 flaalNlH J/NI (1JrIN1lLlli I;UJIIyLtI: a ya LIY' wCll' Illf ,JIIN' 111aiia 1/1e wJ, l•tld,N.J S'1 hnwhog rtNl t ya ha ( iMl' INUIu. u1N1 wa/r vp,nrta•J by .lihnlly aha/o1J1uflJld/y I/n (ill' JErruv 1ulolJ/ly. yamylJlc ayalJ.a• nufr:u.J r, J NR) IMMI JJINNI INlde/n, whlk Illc,l ICIa•1+111/ InIFrJtCJ .1. J /III,INN) J.IhINI p/1NrU11+n ~il IIIIIJl/1N1 .ININIIJtu~,rJllhy A1,1/, Iha+l t\Jluvf JI•.Ul, .1/a h,1.. y,t•IIIUIK' .IINI N a(IiyI/t1,1IC1111Nk' I/IIIIh/1ClI I;u 111yIJll' l yl IJaI' .M IIYJINIII hy 1 I, N 11I1/N/: Ila'a I 1+1l ll'a a'IN,N I11/Mt1111! //1 S*I I hl',l' JJIJ \Ul:l;l'\/ IIIJI FI/JIIyIJII' a y\ LIM' .IINI IIN• 1) li t rININ .ua• ulak•Iw'nikul p/ll/clo. a Iwpl..l hy cy/l/.ll'kIJI a u1t11N1/K111, /1111N'111 1N.1nC, /11 Itll: ,1111.J n1U. I,.J WJIJNnm. tiA , A/n/,/, I, KJnu.Jll, Y.l'hrog.l. Y,(iJll:py. 1.l)'llJnliy. I' . tiaIMM,I1111., l, , JIMI AIIII,LI F h1li, U.•n ,ln,f hnnNUlul 51111 1i// litr, 1'JN6 (1/At•r aupp..t: NJu,NIJ) In.tllut:, d IIrJIth Jnal 111c VrIrIJn. AJtInnl.tlJhun I t111111IK I)allJllllh'111„11 Mc.Ia uK, 191.lullra Id,ll•y, Jlpl Mla/+d+ud,/l!y, xIJlll,uJ IINI vrl.ny tiaMrd+ll McaltNllh', 11JIILNJ, ( A, JIIJ IIIc Varlrtro. AJnuuldtJluN1 Mr.btJl ('ulllrl, I'Jla Alla, l71 ('Yl l I(' l i11AN1)1IN1 MuN( )1'111/11'I IA 11' AS A MI:I )IA 1(1K O1 V ASl 11)11 •A I Il 1N AI1I11N/I;I1 tyl hl I;uJ/NNIt/N IINNN1111N1NIIIIJII' 1( IMI'/ w:1\ 1/r,t Jl'M'IIheJ 11111111I/11!1 CJI ,dltlllk', IINNI' IIIJn (wu Jta'Jlla% :1 fU, 11s t11IC In R/NIIC 11hy,nikl(;la'J) 111a11Y„C~ IIJ, /lnly haaNlla :IIIINICII) /1/ Illl' p.1.1 Icw yc:n. '1h1. tclJllvrIy vl.lw IkvcIlq)IIN•nl t. IN./IlJbly J1lrlhulahk lu else ktw lvNlacMrJlhNl% u/ /ht; nulkd/alr tn 11..uc., lhc t uo/plcR :Unl In,C/1.Il1Yl' nK1IMla1. Ja'711Jhk JurIlll; lhl: l'Jrl y f1uJIC).:ulJ the INJx% nwny mvr.ll• EJaNs h•nl rcF•r/Jmk 11. pll,ahk lunrlnNl. 'I hr IJttcr was u11JuuAlrJiy mliurlw'.J by else nlJny .uadrnllr% u/ else rylha' (iMl' ay.t/an with Ih:u u1 cy.hr AMP Jnd else :ntCntNM a ya'hl AMP hJ% rrlalvrJ Juring Ihl. pr/i1tJ Whlk anrk/rlr. r11J vlultiJnik. IKIwt~/11IK,. Iwa Cy~INnIN'k1111a1~ ~yal~lllf aMltRl,l, (hl' l'yl'ha (iMI'.yaclN p/a vnl• /IN/1l' a1N1111kR/lll', lJul' I,t (hl' CR/,ll'IkY nI 1fv\IJI 11111:///ynll'• Il',IMNl,lhli I.N 11• 1y111IN:,lI I1/, LlN/wn IIIJI /hl' a'INlvl'mIN1/11 I;uJfMt,/lll' I/tl/hlr,IlllJll' 1(iI I'1111 a ytht l iA11' 1. a JIJ1yn J hy JI IrJ.1 1wll Lltn/ynlr hwlos al KuruylJlr t•ya IJ.r I IN' A1 Ic11a , 11hy,/l'IKI1l'111h'.II, :n1al :It11/1Yllil' J11111tCfllfD ItI Ihl' lyllrw/ht' J/IJ 111cu1hlJ/ll' J..III Irll'J i,.Icnty/1K. Jll' quite J/llt'/l:nl IIK ICIJIIvt JIWIUIJIN'l' UI else .I/lubk JIIJ pJna Id,ur rn/yul. 1% vrnrhk lu Jlllrlrnl ll..ur. JIIJ ylr.lr. Whdc lalr,tul,d Iaulu.J JuJ ,a•unr la.,,a'„ INC.I.//IIInJIa•Iy IIM' IIJIINUIJIc /Nll:n/yllh rIMI 11IJli h'1, a 1NnJlll lhi N1I11h1a• 1,11 a'11/%11N', t1M1,1/1„,h', ,Ila 11 J, VJN IIIJI ,IINIINII IIIuN Ia' I/,IYa.• INN11/NMY1/y11M'\ I-I/IIIN I 111..1. 111, /.'1'11I•111.•/1,II,'•N11./IIIN'N'I,.la'll/y/1N',/\Il//llt'IIIIIilalll IIN'NIII/Llil'11/~IIN' .qq\al.uul.l,l. ultll,dlla,mlt•.p11aJ1fJt/y1,,N/laftlii LIJIa.J,.uaI+J\nn/1. ualak. JIUI IN,+11JhIy IIyJ111RyI Ifll r:hI1lJI J/NI V1111C I11NI1hyf114, ()11 fili INIIa•1 IIJIhI, IIK' I/J111a ul,lle 1,.4'nc y nla• t rn IIC Ja'l / vJll'J wllh il:a•IIL .IICh J. /: a. ll.•t It I/,U ,„b IIcJ1 .blbk l'/lll'11,1./\II/, Jllll+llilfll/l,, JINI hClllln (':1111111,, 11111/1,, 1111N'/ Il'l1,IR Jb'l'lll,, JINI Ja'll'/ gtul. JIw hrvc llaoq,l.R /:IIr1:1.INl lhc alnvlly ul I>1NI1 /v.lrniynlr. Alulu.l. F llnonal nl ( 71n1,,11IhnrVlAunun 78 I S, 1'1Sh (1t6rr supplrt: N,du+nJl Imululr..d IIcJl111 JIIJ dk: Vclcl,ul, AJnlNU,u:llluu IYU1111IN' I/a'11,N1111t•11t,./1 M:JIit11•' JMI IMIJIIIIJa7JU1!y, 11JIII.NJ IfIl/va'I,IIy 1a IUnl/ ,.1 Mrdallw•, SIJIIIaNJ, l'A, J/NI else VCIa'fJll\ AJ/IIIIII\IIJ111N1 Medical ( a'llla:f, I'JI+1 Ah.u, ('A ("IIAI(A('lI'KI/A 11(1N(11''llll• KI'l'1•1'tl)K 1'l/K III:Af 1'IAltl li 1'.NI I'KOIUXIN 1'Kt1M l.A('llf'Hll7ll.1 ('(!IJ IN KA1 INI1:111NE ( hr Irt a•IIIIN tlN else hl'JI ,IJhk r111c1,Nuuu 11 f) 11a/n1 1 t, ll,'l l, lml ,,,l/ w,l, M/IIIINhh'J wnl/ I 11h11/I I'X I1/N11/J1 11n1',IIII:I) INu\I/ IMNtk'1 /IK'111IN.11K', J111I a II,nJa (i //v.J Ihr IN/NII/I}' ltlKl/:, J/IJ aoak/X .Ilralllally ul t11c .Iduhdva•d ICCCINaN wr/r v11111JIIy /,k'1i11a.1I1aa1IN1,C nINJ11KJ WIIII IIk' /lll'111I1/J111' h.NnlJa:aa•IMu/ I'ut1IN'11/NNc, (IK fl' f UIJINN11/I IIh Ita'a'/N.K'%:/I h/llly by t'JI1/Ni, was :/1v11/1J1/11:11/NYI JI la•t ,./111h1I1/J /UNI, /INIIlJ11111! J l'IN1,l'IV,111/N111I IIh' 11/R1nI1/11J//1g %Ill':IIIC/ ICIIIIWJ) 1/1 1111' IaVa'/Nl/f I/aN1111,111~1/1IN:11K1'11Y11.Nlllh'/ll (ia'IIIIIr:11nN/:nlJ~ut'11/1,l'1k11,11yFIJJh'lll,l'JIIIN'IItJIN/II ml/aha, }Jve ./ tilllLl', f:rhu] III S. S 11111:1/N) J KJ/IIkIn:nNNl l'l1a'I/K'/l'li) IlI 1 111 hN else MJIIMIIII'J ICaa.'lNtN I he htlt'kY'IfN 11114111 01 IIK fCl'CIN1N WJ\ Jk-tl'111111KJ ,1, 1 S 11,1111! 1a'It11.Nk11 INl'ki111a Illau\IIII! ~ka1/11/11Mlll'~I~. III all l11 IIMM KIIJIJIhN/1itI/ /Uyllc.. Ihr S'I~ 1c. rlNul .IUlwral J.inl!k IIrJI UI Jt plvlly Ihrl wJ%a•ka/ ly .ayl,ualrJ hum 111J11u1 gu:InylJlc.ytlJ.e. WIICt1'•'1•S I w:/% a'tt/l.%-IIIILCJh/hru]h-IMNakf IIM/IIINJ/p'• w/tll Jlalaruuundyl .ul><rale, else alhnlly•Irhtkl) ra•a'rpH/t >uluhllvcJ wlth (I 1'{ I u- h1111-I'X CIWtJ UI L%IIIIIIJI INI,IIIINI :1% IIM /lillve IClYl11Ht IM 1,'CI IlhrilNln CI111NIIJ4Ir/J phy. Alwly.i% lal Ihr alhnny-IncckJ nyr11/1K by .IlJluln akllk~ayl \IIl1alc- pMJy,NIy Iamak Krl ekclrlq>fwlrra. In else prC.rllic aul fCJw'ing agC1a and by auaKrahula.qdly revc-rkJ I11u plrvllrea11 Ihlrr .Illta'tha'ally IrlwkJ LAyllalllak% wnh JIqlJlavn ue/ira u (:N wr/}hl' nl M1),INNI, 68 /NNI, r/1J MI,INNI. '111cat trwh" vuKgcN IhJI Ihr 11 rrlrlN../ L.uluh111vrJ by I•u1NOl .1'X In nn :Itpvc 1401111 w11I1 INCXf V:11NN1 UI u% rrgldru/+n by a'anlNl. Alvl, Ihr Y'f tccrplUf B Klll/ lhk IflNll IIpIN'ulJla' IUinylilC ay\IJM' /INIIIJ Inlg IIIJI lhr tl'l'l'ININ 1, l'1NlI/kJ la/ lhW :It1/VJINM111) 1',uJ/1yI://C a•ytlJ.a• I/y rll J\ yr1 UlMkll/ll'J IIINlI1Jn1,n1 I h/el' 1UI11111/1 Ill'I1111k-1 111Jy l'IN1%1/1UIl• :1 h/1NJ111g la'I;NNI UI Illl' Il'CCININ Ku1M/, I, IaJ1111,J/.1, Y, WJkI111,1/1, S A,( iJ11:11y, J, 1a INNNIII, ( i ,IINI AIULI.I. I /hr /,.N,n,d ../ HI„In,Se„d ('llr'uu.ba• 2Alt II 14711 1J7A, 19ti6 Uthtr luppai: NruouJl lu,/lulc, 111 Ilcrldl r1/J else Vclr/rm AJnuo/.11J1uN1 I'1/N/11IM' I)CI+J1111N'11t+ 411 MCtIn 11N', I'11./1t/1.N ULry•) , JrIJ Ma n1lNa/lup~ 11JNlo1,l 1 41n vt'1\/ly %t IMII/I I+I M,'1IIl llN', JINI IIM' Vt'ta.•/J/I, A.I//I/II/,IL//LN/ M..I/. JI • ('l'Ilti/, I'.Ik/ Ah,l• ( A 1 I`tl ~ I+I

('11M1'AKIJ(1N ( H- IIINI )IN(: ANI) ('Y('1.1(' GMI' A('('1JMI II.A771 IN nY Al K1A1. NA 1 KI(IKI:I K' 1'I:Yftl)l:s IN L•NIXy111V1.IA1. ('I:I.l.s Rat '") Ir1+.IcJ ruWl rWlnurctw' Irrt.w IANh (8-I 1/1 wa. u.rJ to nkuul) ANI• rruyNrx. aNr auhurcJ hr.vuk :wwtrc ctN>,wIN•IWI cella ti1N:rnct: buwhng ul "'I ANI• r/ 17"(' hratNdlucnt cnJutlklWl lcllt w.. sa/urrhk and ul high rlhnrty SrrtahrtJ ruJly- .r. nl low cyuddwwm hrnJrog Jrt. nxhulcJ thut enJaNhclral ccllk curuJrn a an1 L•.Ir.. r.t INrNhng +rlc. wrlh r A', ul 11 I! 4)(11 nM. Thi.1t (rarLrulJr chwre u1 crwANtk•It: 1.rll. hrJlfaNNl ~ /I/NIr.../NrN./kracll IlrclwrkrarfpMcn.ylaN.uuryklmgwuh''. ANI• huNlnr6 wr. hum.ur rtn.J rWlnutcu. Iw•plMk IhANP1= atrWl nJlrrurctn IJatrN (ANI• IR (111 Jn~.ptilNm II ruaqrlNm 111 .> .IriaK+elwin '11k wcrle.r aaml.uwr, rl/ N.Ih•INIn I, hrtl J A, ul 11 4S nM, whu h wr. unly A fulJ hrglkr uWn thc K, LN IrANI' JrNI ANI• Ix 11) ANI IN 11/ rnJ hANI' rn Ihe pre.en.c a•l ll S nrM rv~twrybrwthyl 1Jt11hll,l• /w.Mlual•J J IS ?II Io1J rn.tcr.c m t y.lwGMY l.Nncn/ a1 111 pM rrwl r NW.r 011.1114111 I11IJ t'4'NINNI ul l yl IN 1:M1' Jt K/ nM 71k awwcrurrrwwt. rryuuc.l lu a•Ira u r hrll rIWR/rrIJI Uh q•J.C rn. y.h. (:MI' low hANI', ANh IM 111, rUaqwlwm 1, rlruq+rp Uu 11 JrNI rrrnhti•LIm 111 wa•te 11 1t1, 11 IS, > S/M), 1// awl 5 1/ nM, rcar•ruvrly Ahhawgh ruNqirlNon I rrrrJ r. r prrlWl JK.NUa, il was unrbk low Jntrgumic dw a•Ilrat ul ANUIN IIIaNraylh. l:MP1.N11WINN1 lhe]CIInJInb`f Wggefllitrll'nJU1tKI1JIleII• hrvc urultupk .rN) Iun.INmJlly Ji.luwl ANF binding sites 1.rurWn, 1) C rrk) Murwl. F Hr.N hr.nu ut r fh. yIn rr. u A, ru NSS TI 79. 1'1NA (lthrr tNppurt NrruNrrl lu.nura..d II:Jhh rsr1 r1K Va'Iirrns AJnnor.IrrluNr 1 tunr IIw ( A(urlnr'm+ ul M. Jh urw rrNl 1 IWr.ura.dnyy. S1rn1.NJ I loivcr.ny Sa luw.l ul Ma'lIN IIR', 11JIII.NaI, ( A, JnJ low Va'll'LtlN AJrumr.,rrwNa Ma•Jr.rl ('crui r, I'rlu Altu, l'A ('O 1'llKll I('AIII/N OI- AN AIKIAI. NAIKIIIKI:II(' 1•A('IUK K1:(-I:1'IOK ANI) I'AK 11('(II.A I7: (:(/ANYI.AI l: ('Yl'LA1t:1 Kl)M KATLUN(i Arr r/llrl nJlrrUra•I/l' IJIIrN IANt•I rl'l'l•INaN IrlNll r:d lung W:I. ]Illuhlh/aJ with I u1NU) 1'X and IwrdicJ by xyucntWl a huwnJlaigt •rphrr .Irp% awr ( i Il' agcau.c. /)1: AI:• tie111411'cI, 111MI1y1 JI(JIUy, i1Mt wheat I,'l'llll JI;I;IUtinln-il;]rthl' 7'hc ANI• rr:rlw.w wa% cnn.hcJ 14,IMM1 IuW Ibc IwrdtcJ rraclwaN hr] a hlnJlrlb (/rUhk and INUIwrUl'] IIIJI l'rNil']IMNNI ht low rllunly :rrw) .pecrLarly IamnJ rn rncnJxrncS arNl t'rutk Jclcrycul e.lrx'1> PIt1yM'ryh/lllrlk 1,'ll 1kC11111fINNl'1U a/111h' 11UI1IICJ pl•(Nrit/1Nl in 1hl' INl'.CIKC ad s.N)ruru Jrrkayl wllrtc and JNhaNhrcihd .hUWCJ IhC INCKINY ttI IMrI' InJMN )NlwCin hJ/Ml w/lll J nMrklulrl Irlr\\ a/l 1-1) JNM) JJIIIMI\ Wlkll pIt1IN/I /Nal41r:a1rrNN Wa'ra nMUbJlcJwnh`1 ANI ,r)kn.un.Irnl,cJwilhJr.rwlrumrnlyl.uttrrtc,tlK 1'/11MN1 JrhaNtlwawemwr../r.th.JllyraJnJaltkJ 1M.hrghrllrnrlyhrnJarg .nclrw A.NI•a.a I+urdreJ with pJrtr.'ulJla gu.rnylde.yllJ.c. 1'Jtlnulrlc gu:nlylJle.yalJ.c wJ.lNnrla•cl hr J.(r'ldre..Uvny ut 19 puwd cy.lw C,MI' INa.lu.'cJ/nnnlmg o11NrNCUt uldrnng Mn (:I 1' r. wh.urlc 1 hr% trlwl•.cnlcJ a IS IMM/ Iu1J IwrdiaalNNr crMUprrrJ lu Ur ram.J lung nK•ndwak• Iar1+.uJuun with I utaul /'X (KI 1Mt/1N:aINN1 high htrlawnl]IKl' INIurJ lhuunJt..frr/dry Jrwl ) lµ.r.J .ku.ny grr.hrnl .cJrnN:nlrtN.n .tuahc. 01 low ~mrdr.J INCprrrruNr JL.— ri •ulra J Na ... nnl uu.nr •.1 .IRr di. ANI huNhng rnJ FI/JNyIJ1a' a y IIM V.N II\11/\ IhrllwNlh AN) INnJmp u1Jr a umldr  1'rr.wn r t Jbry ANf bunhng urrur. rl Ilk cslcrrWl nknrMrtk +utlJCC and a yl Ii. (:MI' Syudr.r. at low rnlernJl nrenrhrJrk sutlale ul /hr.Irrn.Nwortwark g1y..qwaNCw KuiNr, I' : ArNlrc.cn. I W, Karnl.;rla, Y, W;rlJuurr, S. A.('hJnl;. (. Y, Srlw•lr, 1. Ixmtnrn, 1) C . Nrlrrk. M,:aw) AfwuJ, F 1'hr Juu.n,J r/ Hruh.l;N rJ ('hrmurry 2N(13).SM17 511121, I')Nb OrAel support: NrINNIJI llhlllull•.111 NCiIIh JIMI the VClerrll. AJuunr.tuthun hr..nr tlk 1)a'prrurknl, ul McJn'nk• and !'1WnuxaJ.rEy, SLurhwJ Ilmvcrvty S.luhd u1 MrdM uK. %IrnlurJ, l'A, arwl the Vctcran. AJnnnr.uateNr Medical ('cotcr. I'alu AII.., ('A It1K1~t 11 IN. 1'11( /11'l11)/>I/'~I I:KASI': INIIIItII()K1, ANI) ('Y('I 1(' AMP ANAI (11:11NllltflI 1'K1)I.II'I:KAlIt1N lH• ('111:1'(1K1-.I) 1/()VINI: Al1K 114' I:NI 101 111 i1.1A1. ('1:1.1 S '11w ruk ul t y.•Irr AMP /NI l'INIINIICI/JI cell 11rUhlerrlNN1 WJ. Irlvl'.111(.ucJ, .or.c (I1i a l l'IIf l'Jrr hC l'4/w11CJ Itt hll;hflNlCl'111t:rINN1) a/I hlryaalllrl;ll'JI JIMI It1/r1111:N.rl.lgk.J agcnt.IhJ/ alter cyclic AMP nk1.INdtsur ('hNkJ huvuk awtrc crNhwlw•Irrl ..•Il, wrrc pIr1eJ a 25,1MM/ cclls/ lSnun Jt.h.nJ gruwn IaN S Jay. in Ilrt prc+rrw r aJ p1Nr.pluwhc. IcrJ.c /1'11fi/ inhrhqlK., hwaulm, rw cyi Irc AMI' awNrg. 'I fk 1'I )I: uJubrpw. dyqu JruMrk, 'LA 67 711, r.aawlylnkUrylaynihuk /IIIMX) anll /hmq>trylhnr inhrhrtc.l.cll 1,•LrW1I1 081 a lYNhl't11f:11NN1-Jl'(wniknl /II:ItMII'r. 1)IIIyrIJ://rNrk IN/MINieJ a U1'.(. and J SI/'A Inhrhruawr a SµM atw112 SµM, whrk hrl;her rlwwenttauaNt~ w.Ya'ryhAolr. AI il. IlrrrlruU. plr.ru.rrrNrrWrulaNrrnogc(SI/ 1/MIpMldrnyrlryllincrnhdNlcJ.c111NU1d ctrhat by IS 2b'.: , whik INMX and tlk highly .pccdre iyclrr AMP plNnlduNl/Ca- IcrJ.c Inluhuaw, 'LK 111711 rnhrMleJ gruwdt by (rll- 1K/'2..rN1 •11/ -SIN6•, rcyrrclrvcly. 1'aN.t,uhu (SpM) urcrcaxJ cyclic AMP kvcl.:urJ ryrht AMI'•AnW.c .:trvuy nuom by 2 S-Iu1J •rml 2.1u1J In the ah.ence u/ IM)1: inhrhrlaN. /:w%Aolor pnNlul•cJ a 21M%. gruwllh rnhrMuaNt at 1/ SµM ald a MM>,, irJNhnwNt at IIIpM. The IaN.6uhn Ju.e re yMN11e curve wa% nIN irllellY) by /IllYrplryllna, Iwl wJS.hr/tcJ Iu IIw Icll I/y yhNURI. nWlcly I/11aIJ wrlh JrpyrnlJnNrk anJ ZK 62 711 and S-IuW wnh IIIMX 1•aw.lulm ISpM/, hy ilxll Ixualu.•cJ a Ltt•hdJ mcreax rn cyclw• AMP In Ihe INC.ence u/ S/rM IhcaMAryllrnc. Jrpyrulauudr. INMX, wIJ %K 62 711, cytlu AMI' wa% wcrca..J hy 1rNShulw2//, 2,6, l.S,.rNlh h-hrW,rellA'CI/VCIy. M Itr1NINrl'yl'hl AMPJINII)1IN/rytyl cyclic AMI' Ix/NlurrJ a SS'1f% uw160'i• Mruwlh rnhlbnnrn.l KMIpM. 'I IN: ly.lrt liMl' aoaM.Ko were k.. eltcrlrvc inhiMawm uf gruwlh IIS !(M161 (Arr rc.uh. aknnru.nar that cyclK' AMP rrWlug% atal IrhJrnuclthrKra'al ypCnls dul ckvilr wbrrallulrr a ya la AMI' levcl% rnhrbd tell I;tarwlh and Wgt,`C.1 that cycbc AMI' rnwy IN: an rnnlNNlrul crNl.rl;caw% rc1;ul,xaN u/ crNMNIwIrJI cell puhlcrJlarn I4'/Irl/all, I) (' , 1•r..'u., K K Jrwl Alur.rJ, F J.wrnaJ r.J ('rffulur /'hvu#•l..gr 127:217-2i 1, 1'qu. Olha support: N.twnal fn+tntulc> o/ IkJhh and Ihc Velet.ns AJnuurv,trruun 1-11NI/ low I)a'IIJIt11K'/11. aI MCJllllll' :/INI IMIJn1/,KUhrl;y, titr111./1J I I/IIVa•thlly 1. h...1..1 McJw'u,<. 1(JrdurJ, ('A. JrN1 tiw: Vctcr,ura AJunorurrurrn McJaa l cntrr, I'rI,. Alw, l'A ' 1_'t 1_'_

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'I'1k cllcd+ nl IISV I a1Nl nkr.k% vlto% lNl ('1A ININIUC/lun wcfC mN /kpclnktN Iw allctalNN1t in dle IN.NIu.1NN1 ul ..- .N Yy nllc/lcr.rn by t11c n11CCICJ l'INIINIKIIaI l'eII\. 1111C1'INNI W/lll IISV-I 4111.1 /NN .IlnluIrtc cfNMNIwltal ccll. lu Iclca+c any lklcclabk mlcr/cflNl In l'/Nlitam, /1h ,ulwula/rn/..rl the nlca.lc% mlcclcJ.cll. clNltalncJ tnlly /i mlcrlCr.Nl• a linuwn iuhlhu.N .rt ('1•(' GA1 Ikvclupnknl •I1N:.c %IuJll'% %III;gCm Ih.lt ('1A INUl1UlINN1 by l'/NkNIN'IIa1 [CIIV L.h rcl Uy ahcrcJ hy u1lc.ual wuh HSV l a1Nl nlea.kv vlru. AII allCta1NN11111'1A IN.NIuI' tNN/ lu/ghl .unttllwtc lo changes /n myckqNNC.u Ihal Inyucnlly al.u/uprny vurl /NltatNNl In huUWnl 1 (icl..Nl, S 1. , I IlcJnlrlu• 1) M, and lin.•1, f/ fl hwnwl../ Clrrnn ul lrn-.•lnKunuu 76.1.1112 1 I 1'NI, I'/MS. O(h!r lYppu/f: Nat1o11a) (Ih111u1C) UI I kJ11I1 .IINI Ihl.• ,U)IN/ 1•lwlNlau.N1 1•run/ 11N• 111v1.1.N1 ..1 IIrf1lrN.tugy (hNUluEy. I/luvl•r.ply Ilu.pqrl. .d ( lr..lauJ. ('Il'vfIrINI• I/1I. .IINI (IK I)IVl\1M111\ UI IIItC\ IIINI\ I11N.IN \ r/1NI I ICIIIr111I•.I;y (/IN ul.yv . 14/.pArl..I IIN' 111N..yaly ..1 I'flli/\ylV,l//ir• I'111LN)CII1111a

AN111f1 N1Y ANI) IMMUNI: ('OMIN I.XI:S INUII('1: I ISS(11: I•Al'II/K 1'KUI)11("IIt1N IIY IIl1MAN 1:NIK)'1I111.IAL(1:1.IS 1'rtlrnl. wllh.yslcml. Iu1Nts rfydwuuwsus IS1.1:1 hrvc an u1crCJ.rJ nN ak•IN C ul JllrtulJllJvcauu.durmdwr..•s (11rnlc.h.ol~nlhywhhhlhnanhls~sJrvrlupwllN.c /1JU.nis 1. uul,INrwn W. IuJ (NrvNNl.ly I1h.etvcJ thJl Ihe srrJ ul pJllrnl. w/dl SI I: l IN11Jlt/ J1111IN-dN'\ J1NI /11 1 / 1111 111' l'IN111/Il'Rl•. Ihll l'71n 111111) III ClnkNhl'IIJI ll•II, I1ra Ju.r cIMLNIt•hrl a.•II. \rn .}rldN•,vC t1..uC IJ.Lrr, a p11CIN JCIlvJ1.N Ut aUJl;u1r1UN1, WC .tWINVI lIy V IIl'l 11rI Il;( . 1./1UI.ICRI'. JINI KIJ ItUn/ (1JIICM\ w11I1 SI I:1N11I11' IN.NIuI INNI ..1 llssu. Ix/.N by dK.C u•11. Iluwnrn wt1h11,ca) vClnMb l'MhNhCI1JI CCII) IINUh,11C.1 w11111wr1 a}:glryJlrJIF(i111A Ig(illtf $1u4Un1t) elablwJlrplmuJ1;ulJUlJ.uvnyul r.l.r.r IkI1rINkIn nlmuwr All IN1.uJEu1JrN xiivlly was /ou1N1 nl lht lutt/.ulrlr cal I1J11NNI, JWIINNN' WJ. YY'ICIC.I I/ILr 1hl' 111C1)1Ufn M711n1U111 Clllla'.11MN111111f.K...1FUIJnI •N IUvny /CyunCd 6 4r K hl, JW/ It.IN.N1wINNl wa. tINJI1y WIIIIqICJ hy dN: J.I./It1.Nl .rl i yl krll- sJ/nNll .N' ,M I//MNIIy. 111 I) I1K' t11C1CIkC .lI gCI /Ihl'/Cil IIIJII•k'1\ JU~nN'll/l'll IN.NIIMINNIIIIIN.M.1J/;UIJ/II.MIIYllyhyl'INItMIKI1JIll'II\)~IIIWIJiI•1I1/yIIA II:I. I IN!u 1IN'IIrI 11•II IN1N..rI;UIJ11) :hllvlly wJ./Nrl /nJ~1lvJll'll hy IIIIM/IIU1N..~N..I.yI111NN1.11J~1, ICw1/1Ca111K INCy1h C0.11 '.N f.N VII 1100 Ih C aI1rff.Nn1, and wJ.11Cu1/J11I1'.1 hy J,IM•.llll Jnn n.NK IJ.IrN J11l1INq)y I.INkNh\IIdI ICIL IIKuliJll'tI with KfJ ILN1/14 .rI Itl hrlll•111• wuh SI I puNlua rJ IlK 1. J.cd Jnww/d. ul Ilsu. IJ. LK /:.NIq1JreJ with 211Nwnul.rrJ Ip ,111125) Irr.lNNls.ll lw.r 1I I:.CfJ 1IN11JIn111F; ItNNMNIKfII II,'(I, I(~A, /N Ib'M, J1 wl'II J. ILNINNh HNtlJlllllll; I fl...N111.IC0C.. Cxh a1111UIJtC.1 C,N)1NIICIIJI CCIL IU IMU1hNC IINNC (I..UI' IJ.I+M IIun.111r1IJ/ II•hINN1./xtI1:WY1 INN11/w11 MNt1uI a•fJ IhrsC.IWl.cs .k•uNroslrrtr dIJ1 C/NIrNIN-IIJI .clls will IN.NIu.c IhC IN.N.urgulJnl 1lssut IxuN JUrr CRIN.W/CIUJnh C11.I.N111'11JI.CIIJ11111rrJ/C,.NI1'li..NNJWOII;NUOwllc.uloplc><.. -111c IN.NIINILNi..I (1,.W' I•NNN hy l'INI.NIM'IIJI lC1I, it .11C.1.I 1111t11u/M vJNuIJf 111)uly InJy Llry r lule m Illy drvl•Iryutr•lu ul Ih/ulut..vs /n IrJUrnls wdh St 1'. •1,tnlw•nhrum, ti 11 . I nllu, K. JnJ ( In. .. ll !t Ill. J..ulnul.•JlrnrnwlnlnCs 1l701I'V(_1 1S 1)• 1'/Kh Iphti suppul'f: NJlnrNrl hl.l/lulrs .4 Urrllh 1'IUU1 i11C IICIIUIuIuI!y (1/Nulul;y 1l'lllull, I)C1rJrLlll'ill 411 McJlrulc, Ilu.purl .ul dN: Ilnlvcr.ny uI IYun.ylvrnla, 1'h1l,NklphlJ AN1Il3I:N11• ANAI.YS11/N-III:MA1()I'1111:SIS V. ('l1AKA('1•I:KfLAIIuNO1- My III AN7IGI:N I:XPKI:SSII)N IfY NORMAL LYMI'IK)FII:MA•Illl'011i17(' I'K( Ki1:Ni 1t)I! 1bC My II) }IyCU1MINC111 N i01 IKIIIrh.INllClll Cl•II WIIJII' Jnlll!Cll l'R(Ml•.M'.I Iw.l /I.Jlly by u/N//11.rcunJlrJ 1111.1m) %:clls, alnslnuling 1'JI• 4'X• .,/ WNnul rJull f>,NN• tnrnuw ku\ury/rs Wl' Ua'll .CVCtiI //111111/1N.IIIr,/CYI and in v11f/1 tuI111rC 11KIINNL 441 Jluly/C II1C CaINC..NNI 11I II111 unIl111C :UIIII!\91 .NI J vJ/hly 411 Iynq11N111rnululNNrni IN.11!CUN.N .CII. (..LN,y LN1111111,' acl/. 1(l•(') lur l,'r:Inuhrly1C/1NNNNJy1C aukNUr. /l•It'liMIrlNlrryduu/J.u1.N11rs1111'lI I:Iwrl.IxrlMNntn.ndyMy 1/11N1sn/vC ('1{' wllll hil!IKI IN.d/lc•IJ11vc IMNC1nIJl wCrC UNNC .tl.Nll;ly My IO IN.,/nvC Ihrn (•1'( • wldl I,rwC/ INal11c1.N.v.IrN, nir.rl JINI IIN..a' lu/ nU\Cd bIN•JI;C rIN11.1.1.1.C11 c..LNla•. WCIC ... u rn.n. uu,l..rrr.l. K1. Ill I...r/r.c (. 11. In.rwulnu117 ('li • t iM nurn11.C/ .u .hwl 1. rw r.. ,..Ir.u• '1"• r 1/ r w. n L..md 1.. 111- Mt Ill L..Nmvc. •1. wCll• Iy/111rIN.NI INC.IU..N..k'I/IN'.I by (II:// 1 rN111'111 ul 1n11.n1W kv/ Iclnunrl J.'usynua IruUJyl /lrn. /.rJSr IN.Nr Nu1Wr C1ylI11U/1I IMIYuiNM\ 1(•1•U lil welc hac/uFa•Il.a.u. Iu/ Jnlll:rn CSINC\.NN1 JINI I11.1 My III JIIIIFlY11NUgyC.NVI•Iy, 1/111.II.IIICI Wllh .NI\.IIN7/11! u..Nw.l /IlN/rl .IJ fl' I 11l• My I11.11111F.Y1 IIC111111.1J11ipl llk•Illlhl JINNI .IINI INIr1/1l J11.N1 rr/ IM'/11J1r1 INrN•IN IN..1•!'IUUN IU111/Ct .IUJy .N INNa•lllt•d l(1Uk,d Jlllllh Jhrn1 I IN• . r,..lr (NVIJn.. rd 111. My Ill J1111gCn, 11NNCUVI'r, III:Iy hl• a INUIK LN dlllarlnlrlNrn h/drJ I.IlulJl rsrnls Sturu,.. I(' . K.rwl:y. S 1). l.r Ku.s.r. V 1•., 1hJ1A1., S I, SluJll, KK . ru.l ( 11•nl, t I li llti r lm. nhd Ilrm.u..L•~ 1 1J.K7K-KK(,, 1'IKh Other fu/1/Iall: N,IINNI•1I III,IIIUIC\ uI I Il'rhh JINI IIK A/IKtli Nn ('J/N CI S.K/a ly . I I..n/ 11w l% dhn. I l. q rk In, M.•JIC,J (•.•nlrt . I h v l slun. ul F'C.I1r11 N" ()IIrUL.I!y:u1J 1 s l K'r Inl. nlJl IlrnlrN.lu) y, luhns Ilryl(,/n, lln/vrfslly Sainw/l ul MrJIr111c, IIr11u1NN.. A11) 11AI.YI.AII•1)GI.Y(•OI.II'IU AN'11(iliNSl)N IIIIMAN I I:Uf:I:MI(' ('1:1.1. LIN1:.1' M.Illy FIJIIULK'yll• IINNI.C I/NNNIa'iN1aI J/IIIINNhI•\ Il'k..g/I/lC 111C I,IIIN.IIy tI1JIC .Cll1U••K'l' I Iu.u.yllJau.:wnwlc, (iJl/ll 411•t/.ul1)(i1rNA., whlah .N'cuf% ul .cII sufl,ne FIyCU111nd. rlNl /;IyClqlrarin. In gctntal, Ihcx :In111Nd1.. 1111141 1.. bL1.1 ICII. 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'lllc+r rr.uhs JKrrcJ, ul gaw•Irl, wuh (INNC LNIINI hy indirect IIII/IIu1NrdlWnl'XClll'C. 1l0.'y IIMI rCINC.C/111Iq• IIL1 .In.•.1 .k•lu IN111rJINN11111h1•]C DIJIyIJIC1II,'IyCn1/11nIslN11W1nJn k'YLClllh't:CIIs. ~11W\, 1// MNIK iVU • ilntcJ.rJ •rntlhllJy hulJlnti lu tautan11nn4.c-Irr.ICJ trlla aall 11e c.plJUWJ by IiN; I+n.rllre ul .uIyIJIcJ glyaufipiJ mlllgcn. ti1N1JI/11(,, S I. . SpnJlnik, P. F., ('twn, (' L, 111111. li I) . S.hwrut, I 1' . rlNl ( i1nNIN116, V h.l/M'nmrnm/ ll.nau.d..gl• 1•1 t.t 1 647. 19116 Other suppurt: Nru.NlJl In.lllulcs u/ IkJldl 1•IUn1111r NatNNUI ln.leulr ol Allhnns. Ihatw•tes. rlNl l)ly,auvc JIIJ K 1.hN•y Nrtlulu) lnsblulrs al l lrrllh • BcllN•.Jr, MI1, d1. ( hv/.NNI o/ I'cJlru N ( hN ol.ry•y , I IN• l hl.uky!y (•cmr1, kdu/S l lryrlln. l lulvrtsuy ti.IN.d ui Mc.IN nl% I/r111nuN.•. MI ), J1N1 111e IhIu/1aN-ul UI MC111a1111•, I),Ut11NN11I1 Ml•.IIIJI SIINN.I, IIJ/Nlv\-1, NII Wl It/,

IN l'lINtf kl l l'.ASI./lh Ir, A('Il/GI Yl'l)l'k1)II:IN kNA SI1)lll'N('I.S 11/11W1 I 11)1:1 I/ Y WI111 i l ll: Al'll I I I'11Ak%1'. K1:.11't)N11: IN Vll'() I IN.' 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I/axl' IN'Iil//l!t'ININI+IN.IyIA) 1(NA. J/N) kalaft .11 +1111k' IIA(II' \.YI/k'INl'+ Wa+I.hY'fviJ 11.1111 aINI/LII INl'/1JfJINNI• (h1/1++kN1//I At)' Il'+ulll'J 1111\',lII1.11aN1111 IIIJhna• LAIJ' IukNA I.I IIN' nuaku+ In alNllld.l Iu nA(iI' u1KNA, uan.INx1 IJ JI INIIIII/I 111kNA WJ+ Jl'l/a'J+aal I aX 1/1 Iu11R11I/l1f If\Jll'J INl'l/JIJhaN1\ IIk' IJII!t'+! LA(71' m111x1 wJ. 1ad IINnNI m kNA uJn.IrxlcJ h11/n trrJlcJ nualCl tlt .Illapla'Ic t1k•111un1 IIK 1 1 11 1 1111 IUUlJ1111111; I/J'IIk'111+ IcIIIJINCJ In IIIe nlxku+. 1Jtgay m ItiJy IA/ kNA Ilt a.Ifra.Nla.ll'IU wllhlrca• 1111fU11 1.NItcIIyh/1JIFa111N111I /111/1Nt+alhk'INl'• wJ. 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' , ~i INDEX OF 1 ItINCII A1. INVES'1'U:A'1'UIt S'UItS '/ ntt1.., K 11 . 94 nlrMol, (. G . xS. xh nJmo.. l) (1 , 1411 144 AJlrr, K It .41 Alhrra. 1 1 .117 An14Mn.Mk.. 11 N. 7. x A%Iljnl, I . xl, xx 11.rhMM, It M, xx. xv It1ng. K 1, t4l tr? Hu.h.a. 1) 1. , v. Io ('aiupft•11. 1; 1 .41 l'a.UO, A ,'!11 l'hca. Y I . 11 ('INvuwr, M .'MI (lnl1an, W M , h2 ('ur., 1) 11 , 1JS 146 ('ivur, (' I , 11, 1Jh 147 (l.wwwr, (i A . Vl), I4x ('kvmEcr, H , 1411 ('uhcn. H /1 , /h2 ('rMJwnu. K 1. . 41, 4.1 CranKt, 1: H . 141) ('rcutV, (' li .91 (•.,p.I,r. G .',2 vs Ihnnpmrv, 1 , 12.'ih Ihwaherg. 1' II . 12. 1% Uwwak, 11. I- , 97 I:rwur, V. H , tdl himlcm, A. K . 14 I•rnlay,l'. N , vM I•riJuvich. I., 4M-lo1 1•ricJhrrg, E. C , IS huae. K.. (t2l. 69 ' (iaub:ut. l. W.. 63. 102 (icc. l H. 1.., 44, JS (icralMm. M 1) . 70 (iiam. C. "!. . Ih (itil. (i N.. 17 (wMlnun,(D C ,ha, 1112•I176 GdJRrg, A 1. , 1117 GiWnwn. W I-: .46 IIJgIMf, N .71 1lcnry, (' 1 , Ilt Ilnthuan. K M, Ix ?l1, IUx I luprar{.r, 1. 11111. 104 Ilug.rnn. K I. . Itr1 K.rnl... •L v M 1 Jh I 1 K.ur. K W, 1w, 1511 K.ddcr. 11 . 151. 15' IJwrctwc, 1('.. 47, 1 S 1 Iovnrb,'L,>11 1 1% Acr, 1 , 21 I rN11,Y'nl'fll'(, (i 1. , 1t.1 I uL.a, K 1, 110-11 _'. I S I I wMlhrrp, l. M, 71 74 I y1Nh, 11 T. 21-25 M.nlham. K H, 154. 1S5 Mr Kechrn, W 1. , 111 11 S M.1 auyh6n, A C , 25 Mur..J, 1• , 115 1'4 Murlia, C li , JK 5 1 N.kk-/, / A , S 1 N.yhw. S 1. , 26 N.L.Mr. I/ 1, 125. 12h Ikr,P W ,.h?x ItnKcn, H , 29. ?Y 1'.iulo, H 1I , p1 1'c.ht, 1 , ISh I'1.\, 1•. , 1141 thiiu, S V, 127. 161 1'oy4oo. W A , 1?x KrhMMr, M ti, 11 14 K.fiAnunM+ll, K , IQ1 KrpnK.) L•,S? Kyan, lI S, 52.Sh, 1?x, 157 5i.uy, I1 V K., x11, eI, 129, 1 III Scrah.n, 11 , x2, 1iI s.rogytn, C. 11 , IJ, 15 lhrrhtcr, I , 1 111 Smeh. K. A.. 158 Soridr, J. S . 35-37 SIwrngcr, T A.. 158. 159 St.nhnJgc, t:. 1., Ix Sainherg. I)., 64 hh Jtrnacl, T P.. 39. 131. 132 T+yhn. I) 1... 1)1 135 Trivia, 1, 116 1 11S Varnw,, 11. G , 14 Wala./ck, %., 411, 41 WjI.h. P. N , hA Wch.. l H , 41 Wcl.h, M 1, 57 S4, I!9 Wcnnnmdm. A . 67 i I I I i M 65100 7786