Jump to:

Lorillard

Report of the Council for Tobacco Research - Usa Inc. 850000

Date: 19850000/P
Length: 40 pages
85702232-85702271
Jump To Images
spider_lor 85702232_2271

Fields

Type
PSCI, SCIENTIFIC PUBLICATION
ABST, ABSTRACT
BIBL, BIBLIOGRAPHY
Site
N14
Master ID
85702113/2332

Related Documents:
Characteristic
OVER, OVER SIZE DOCUMENT
PARE, PARENT
Litigation
Feda/Produced
Request
R1-037
Named Person
Abood, L.G.
Adams, D.O.
Albert, A.
Ali, H.
Andrews, L.P.
Aune, T.M.
Basbaum, C.B.
Beanue, P.
Becton, D.L.
Beyer, W.F., J.R.
Blair, P.B.
Blech, D.M.
Blumenfeld, O.O.
Borders, C.L., J.R.
Bourne, H.R.
Bowman, E.R.
Bradford
Brett, J.G.
Brown, J.K.
Buccigross, J.
Buehler, J.
Castle, L.
Chang, L.Y.
Chesrown, S.E.
Church, D.F.
Ciabottoni, G.
Civin, C.I.
Clark, R.K.
Cohen, E.
Colley, D.G.
Coltoffschiller, B.
Conover, W.B.
Conrad, J.
Cornell, K.
Creutz, C.E.
Cronan, T.
Czapski, G.
Darr, D.
Degregoria, M.W.
Dooley, M.M.
Dotan, I.
Dowling, L.
Draznin, M.B.
Eddy, B.
Engerson, T.D.
Erwin, V.G.
Faison, E.P.
Fischer, J.A.
Fiscus, R.R.
Forssmann, W.G.
Franson, R.C.
Fraser, C.M.
Freedman, G.L., J.R.
Frey, M.J.
Fridovich, I.
Gepner, J.I.
Gielen, J.
Godman, G.C.
Goldstein, S.
Granstein, R.D.
Greene, M.I.
Greenspon, L.W.
Grisham, M.W.
Hall, L.M.
Hamilton, T.A.
Hammer, R.E.
Harrow, I.D.
Henriksson, T.
Hue, B.
Jacobs, G.P.
Johns, T.
Jones, H.P.
Kang, C.Y.
Key, T.C.
Kohler, H.
Kremers, P.
Kyger, E.
Langendorff
Lemestregornet, R.
Letawegoujon, R.
Lewicki, J.A.
Longenecker, G.L.
Lowy, A.
Lundberg, J.M.
Macher, B.A.
Marty, M.A.
Mcauliffe, D.J.
Mccord, J.M.
Mcnamara, M.K.
Michener, M.L.
Mitphell, J.A.
Monji, M.
Murad, F.
Nelson, D.
Norris, K.J.
Odonnell, C.
Parrish, J.A.
Peach, M.J.
Pelhate, M.
Petersen, D.R.
Pryor, W.A.
Qwan, E.
Rapoport, R.M.
Reed, B.R.
Reinecke, M.
Resnik, R.
Richmond, V.L.
Roitelman, J.
Samuni, A.
Sando, J.J.
Sattelle, D.B.
Saunders, J.E.
Schnaper, H.W.
Schwartz, K.
Shechter, I.
Shields, R.L.
Sinacore, M.S.
Sparkman, T.B.
Spitalnik, S.L.
Stdenis, R.
Summers, T.A.
Tannenbaum, J.
Thompson, J.A.
Towell, J.F. III
Tshopp, F.A.
Vanvunakis, H.
Venter, J.C.
Villarpalasi, C.
Waldman, S.A.
Waltenbaugh, C.
Ward, R.E.
Warren, L.T.
Wennmalm, A.
Whipple, J.H.
Wiesenfeldhallin, Z.
Williams, M.B.
Winquist, R.J.
Wyss
Zaks, W.J.
Zgombick, J.M.
Date Loaded
18 Dec 2001
Named Organization
Alcoholism Clinical + Experimental Res
Amer, American Tobacco
American Journal of Obstetrics
Anglo French Exchange Bursary
Arc
Arthur O + Gullan M Wellman Foundation
Beitrage Zur Tabakforschung Intl
Biochemical Archives
Biochemistry + Physics
Biochimica Et Biophysica Acta
Brandeis Univ
British Journal of Pharmacology
Cambridge Univ
Chemical Biological Interactions
Ciba Goundation
Circulation Research
Clark Univ
College of Wooster Ohio
David Opochinsky Henry Segal Memorial
Drug Metabolism + Deposition
Endocrinology
Experimental Cell Research
Faculte De Medicine Institute of Healt
Folksam Insurance
Gesellschaft Fur Strahlen Forschung
Glenn Foundation
Hebrew Univ of Jerusalem
Huddinge Hospital
Immunology Letters
Inorganic Chemistry
Inserm
Intl Journal of Immunopharmacology
Intl Journal of Radiation Biology
Jewish Hospital of St Louis
Journal of Cardiovascular Pharmacology
Journal of Cellualr Physiology
Journal of Chromatography
Journal of Cyclic Nucleotide + Protein
Journal of Histochemistry + Cytochemis
Journal of Immunological Methods
Journal of Reproduction + Fertility
Journal of the American Chemical Socie
Kroc Foundation
La State Univ
Ma General Hospital
Medical College of Va
Merck Inst for Therapeutic Research
Micro, Microbiological Associates
Monsanto
Mutation Research
Natl Eye Inst
Natl Foundation for Cancer Research
Natl Inst of Arthritis Metabolism Dige
Natl Inst on Aging
Natl Research Service Award
Northwestern Univ
Ny State Dept of Health Aids Inst
Oak Ridge Natl Lab
Pacific Northwest Research Foundation
Petroleum Research Fund
Pharmacology Biochemistry + Behavior
Preparative Biochemistry
Process + Instruments
Research Communications in Substances
Research Society of Sigma Xi
Roswell Park Memorial Inst
San Diego State Univ
Science Foundation
Science Press Beijeng China
Stanford Univ
Strobel Medical Research Fund
Univ of Heidelberg
Univ of Va
Universite Dangers France
Universite De Liege Belgium
US Army Research Office
US Dept of Energy
US Public Health Service Pulmonary Spe
Vanderbilt Univ
Vascular Smooth Muscle Program Project
Blumenfeld Family Memorial Fund
Area
LEGAL DEPT FILE ROOM
UCSF Legacy ID
eta98c00

Document Images

Text Control

Highlight Text:

OCR Text Alignment:

Image Control

Image Rotation:

Image Size:

Page 1: eta98c00
V. Pharmac®loyy an4 Bioche©ia:ry. SPECIFR; BINDING AND META9OLISM-CiF (-)- AND (.)- ['Ht-NICv^TI_NE eN -- i$OLATED RAT HEPATOCY-T ES AND HEPATOCYTEvIGM9h.ANES - ` Tre spern ec-hir.t}ing of')- anc (.) -.+H -nicotme, as well as their relati:e aates of metabolism, were iuvz;tigated i- :sdlated rat hepatocytes and-hepatocyte membraae=.. A Scatchard plot of both tritiaied er,antiomen-revealed two compodents, wi:Fh the higher -, affinitysi.tehavin-3Kasaluesofixi0-"n rid3x!0-9-hiard Em. va;ues of 3 x 10-t"- snd 4 x_ i0's motes/mg protein for the (-)- a.:d (.;_eaantEcmers, respec8vely. The - io.rer affinitysite fo: bcth enaaticmers had.K-a of-4 x IO'4 M and Bmu of - Sx i0-tt mole,/mg protein. The pH optimum of bir.dirig was in the higher pll rangc,-in contrlct to brain-membranes where [he optimum was 65 involving the ps.:toneated form of ._eicotine. A-gooes-correlation _~+as_observed between the pharmacologic_ potency of a _group of nieotine analcgues and their ability to bind lo intact aad hepa;ocyte membranes. The r.,ie of co.:+ersion of- nicbiine to setinirse in heDacocy+.es is-reiated tc -the degree of binding and accumulation. The results are discussed ;n-terms of- the possible relationshiii of;ha nicotine biuding and rranslocatio: to its-mpm-bol sr:r. - wDood. L.G. et a7. Archires iaiee-.etionctes de Pna.macody^^-mie et-de Thercpie 273(2):6`c-',3, '985. - - Other m.yuor:: DA00464. _From the Center for Brain Research and-Department of Biochentistry, Univzrsity o: Rochester Med:ca! Center, Rochester, NY. -- EFFEL7S OF CHRCsNICALLY-ADMINtSTERED NIC3TINE AND SALINE -- rJN MOTJR ACTlYiTi' :.^! R.aTS - - This study investigated the differentis= effects-of chronically administered nicotine and sa?ine_on motor activity on th=Fat. Nicotine was administered via a slbcutaneousty implanted osmotic minipunp to effect an-8 hour off, 16 hour on flow. Subjects were 48 male and 48 female albino rats, each ai:out 165 days old. Activity was monitored every hour for-1_42 consecutivc Sours, Results indicated that the femate -animals were-more active than the males and thatanimals receiving nicotine were significantly more active - on the first two day3of drug administration thzn control anima3; however, by the fourth _ Cay there were no significant differences between the.-actfvity levels af animafs-that :€caivzd nicotine and those of cantrol animals. Cronan, T., Conrad, 3.,.and Brysaa_!Z. - P6armucclogy Biocfie:vistry a Behanior 1'.(5C897-899, 1985. From the Departmenr of Psychology, SasrDtegn S+ate !rniversit„ San-Diego, CA. 0 a
Page 2: eta98c00
- reasons.-they cannc.-Yxpect th5t the effectt of-Q_H` <-cavengers in biologitai-Sys_tems will= . - ba propor: or.al hte4fraie cnsta:- ; - Goidstein, 3ar.d rizar3ki. G. - fnr<rnatmnt.l journ i c? Rnd at an Biolog+ cb(o) 7Z5-729 -t48$. - - -- - Other-supporri US.'fxpartment of Energy,andGesel'sdtaft-fur Strahlen Forschnng - NEUherbe:g, West Ger:aany, - - - - - - - - From the- Departintn_t'-of- Physi al Chemistrg; f,eSrew' Unive-•'sty cf- .Jerusalem,- - Jerusalem, Israet - - - - - - - - - - - KINETICa _OF-OXIDA'fI6N- 4F--CLrPRC7i7$ -CUtrP'tcALES(7F SIiB$iiTIJTEb - PHENANTF+ROLiNE-AND°2?'-BIFYRIDYi. BV MOLECULAR flX+GEN AND BY HYDROGEN PEROXiCE IN AQUEOUS SOLUTIVN- - - _- Ttie- kinctics -afA the -reactlon -mecSSnism= cr --soDp_er(1) complexe -of = 5-metiiyl-1,t0-phensr.throline,_ 3-chiur:.r-I,lv^-pf~snanthiolir.e, 5-nitro-I,f0-9he,-:an- throline, -2 ~-0ime[hyf. !,.0-pher.ar.:hr3iEnz, anG 2 ,2'_-bipyridri- with _ ozyygen `-ae.d- _ hidrogen perex:dc-ha:x been inres€igated in aqueous solution, rith use of Ihz-puue radto!ysis iecFinipue.=-The - z"datiou by 0, is sect;nd _oeder in the sepper(l) complex,-- - v.hile tAe-oxidatWdt;-y-firUr u fiat orde in th_Gopper(Dtmnple:.-Bnth reactions are - --first order_inrxidants. Tie kinetic resuls of Om uxidaticn-t cooper(1) co,:!p'.eze5 by - orygtn srFnterp-ete'd ay_a meclrenism thaC-proceeds vsa a.ss:sEroxide snt=rmcdia:e. - - Goidstein, S. and Czay",ki. G. - - Jnorg,:nic Chemivr,v-29(S)a0fr7-1092, 1985. -_.?:he• suppo'e: C.xs,^tis±.F.za_i0r Strah!en Fcrchang NeuherDerg a„d the US. L~pertment_ of Energy. -_ From tnC Dep2rt2en: -o_r f'_nysica_7 Lhemutry, Ftehrew--University.- of J_erusa!em, Je u, ~er.:. Is:aaL -TIiE CCrNT12IBUTION i>F"ENDOCiENOUS AND EXOGENOUS EF_FEC-T.; TO -_ RADIATLCN-INDUCfD DAMAGE IN THE BACTERIAL SPORE - - Radicat scavengers such as polyethyler.e_glycol 400 and 4000 ani= bovine albumin - have been used to define the contri,yutioe o: exogeTous and endogenons effects to _the gamma-radiation-induced cramage in aqueous buffered susper.sions of Bacillus pumilus s(nxes_ -The- resuttg -in0i:ate chat -this -damaae_ in the - haeterial snore ;3 pre- - dominantly endogenoA Doth in the p"-s.nce-ot I atmospheX ef oxygen and in a.wnia. -- Jacobs, G. P., $amuni,-A., and Cz¢arkr; L%. , - - - - - - Jn(ernoliono! jour-nal oTRadinrion Biology 47(5):621-527, 1985. O:her suppcrt:3J. S, Department of Energy. From the Depart.ment-of Fharmacy, School of Fharmacy,-Department of Molecular ~ - BiNogy: School of Medicine, and Department of Physical Chercissry, f+ehrew University of Jerusalem, Jerusa!em, Israel. -~- G7 121 ~ G:
Page 3: eta98c00
A --'xANpD.iTE RNHAF=CEtii7FNTt;: THE=v,'f1f3Afl'Jt> CF.F?.DH RY Gj :EFF'c•: TS PHrhPHsTE,etdDC,:1ATf:?t:f.GE3ris. - Vanadat -ta-z;dl-y r raates the c irati:oii. h **Rt3'3 by-i.--- - Poth -phos{fr:?te -- -and--Trds ace .nhihitqt;,:but phosphate a•cfnishes_the g ezte; infii v-rdiy xf(er 6f Tris_ -- acd thus _ gt-es- the-,a,ppearance of_ sttmulattng _ w5en_add>d to rris-butTered- reacflior. - mrxturts: Chelating agents moderately,increased the txfdation of2•1ADH but ehminated . the mwzh greate_ catalytic effect-of-var.adate-__ Desferaf was the ri:xa effective of ihe -_ chelatiag agents, and cuuh be ased to titrate vxnadate speetropnotoinetri.:ally or in temts - of- tne- domrnution_-gf -its catai tic actavtty.. T~ ' y ha_ permitted the demunstra[:oc that .. metavanadate or srthoea+adate -could form 1:1 complezei s~ith_desferel -and- that- ~ orthovanFc3•.-te-was the-catziyucsil; active sgeciei: - fYarr, D. and_ Fridoelch f. - - -~~ -. - - ~ >lrchevea of RrocP rniary-and Btoyhy=+-s c43(1):2i0-227. 19g5. - Other sup-v'orr [ rr Statg; A.my. Rese_rcn O_t P:ee, P au s s,l Sci - Foundation,~anC-N3.•icnai:nstitutesofa,a[th. r'r3m the-Depa *me%t•nf 4tochemist€y, Jyc e liniver r y-4f=dical e ccu^datio-, i.lean 1er, Durham, NC. - eSS 7TidLt"'-0t='f3fE trv't-SiTEevPCrpN!t3Er-2f's:DvtF.FVRTiiE'iORM.aL - CkTAiY3IC A:7irfTY-c9F,,u,in SUPEROXIDE D[SML'TASE- - - - ChemicaF modi: icatien -of- bovine ar:d yeast-=Cu.Za anp^roxrde -d:aauta.e - +•i ; -- pPenylgiyoxaf mtrin Srs the catalytic e.trv t es by >_ 98% and treatment of ahese nzymes with butanedione p u borat 1 ads to > 95'i6 inact vation. = The acttvety loss is - i -= accompatied by t e-rxad;f c tton-of less than two arginm residues per xc ynit with no --- concom.taht=ross m c:u a_ Zn. Th._phenvlglycxal-mod rred epzy~se2 requtre reast a -_ 3_p-(c(d greater toneeutrat;on-ef cyanide for 50% inhihiKan then co the correspending - , ita:r+e- eneymes. - Folyacrylamide-gel . e(ectrcnherecs sad vuis-it_y_ staining_ cf -trte r pitenyl;iyor5l-faaetirarR.d c rnes dcr•oisriaie that the-resldual-_.trvlir -!-_-large:Y-_ - - asso9iafed witY s:xii:ie2 fcrnss tiat bear lowe[-net pMitive ehargc than _thb n.ative - superozide distspta9ey_ . - - . _- - :~- ._ - - _ - Fprders, C.L r, Saunders :£., 61eCh, D. M. ar.d-Frtovich,i d - - B1a.:hemittrylmurnal_'z30'.7 1 7Tp, Nd5 . - -~- ~~ . Other supporrr _-.Pe:rcleum R€search Fund,-U S. dirrriy_ ResearchOffice, the Natioral- _ -Scie-r,ce Fqundav-oa-andt',e G•"a. Fo:.ndatien.= From the Department -of Chemistry, College of Wocster, Worster, -OH, and the Department of Biochemi<.ry;.Duke=Universiiy Medical Center. Durham. NC. --
Page 4: eta98c00
-PSEUDJ'?'ATAL.+-.S'v FRbhS ZA!=T°J@A€;.r.L€/S.°e'.,t.Ni.AR:IS+:-EY3DLI~CE-FOR A .. - HOMOPENTAMERIC sTitlJt.'Lt/RE CONTAINING TWO - TO[dS OF M.4NGA*:ESF __ PER SUBUNIT .An idxGrpved vro.edure !or tn . satat:on of the psetrdecatalasa or--Lacrehb: [lrs pluntarwm has been devised, and.tSe_sluaternary-structure-and-oie~aaesecan>-ent of_trtis_---_ _ enzyme have been reexa+„ined. Sed:mentation equilibrium u: the-native eniy;a severl salt coneentrationa ga+e s moletlar w ign! uf. 172,000. -Thesuhunit we .tt,.. obtained by sedimentation Equilibrium _in 6.4rv1 guanidini,tn•.-cnloride; with ur withaut- pricr redu_cror, and csbexymeinglation, waz 34 kiloda!tcp? The amino -acid comp,-,;.tior: .- indicated I50-R.rg .-Lys. and aftex exhaustive trypric d:gestion, 32 peC:ides kerc - rso!ved. -.SSess dat uggei• thyr the-P=S-dret,a!+se-s a h-..oDe:tan:er. Cross-l:nkiag -- with dimethyl suberimiate, faliowed oy Cot,acrylamide gel eie'_trophoresi= in tne Cresenee of sodium drrdec+: suifate,- yieided five ma ur hands, another indication of - pe,ntar rtcstructure The m3r.gane e rntert was found f be i g-2.4 C scvu-iit. - was found to bei.6S and J/to-._ ?, ugge ting a gloL?utarst-u ture of Stoke>-radius 44~A:v - Beyer, W. F.,-Jr. and Frcoeislr. L - - - - Bioche>nistrY 24(23):6460-646i,13g5.-_ Other snppo.t. Natinnal Lstitutes ofHealth, U_ S- Auny Rescara:^,_ Office, and the 7iational-Fience-.'-oundation. - - From the OePartrnent of Bi:xhemin.ry, Duke Ztni.ersity?.",dica' Center; Gurham, NC. - THE SALMONELLA/MAMMALiAN MICROSOME MUT CFNICITY IES.t. - _COMPARISON aF_IIUMiaN ANU Rt?T-LIVERS eS`ACTiVA7INC JYST.EMS _ - The --mutagenictty of several. test compounds peunds was - ver:fted -bythe 3al.~noneiia/micsesomemutsgenicity teit (Arr..s test), using t•athh humas-livgr and- rat liver- :. ... funtrzated-or pre[reatcd witi.Atcciur i.^54j S5 un_der-iden[ieai=xperimentaE conditimh5. .- -_?Sla?oxin.Bt, ',-_me[h hnlanthrene, and cigare n. -scnc.e c- nd €sa?e t+er-. ;a-matageii-- . in the.oresence oChuman-t~er Sa .nap in thc 1`:esence.of rai •iver SY (uart'a_cularlr aiter-- - treatmetlt with-A:a^.lur L'•54j. The ep1.+o5ite was obserrved with ~-amir;aanthraceac and-tc a iesse: degree wie: 2 aminofluocene; coirclation studies indicate -that the two -_ compounds were activated_`uy the same or by very-similar <nzymes, prebably cytochrome - P-450s. These results clearly indicate that human-liver S?, as an activating system, - behaves differently than r_t-!iver S9; therefore, it may constitute a usef ul, additional _tool - for the study of mutagenicity and, probably, carcinogenicity in man. -- -- _- Ltege, Belgium. - Beanue, P.; r_-eme;tre --Gornet, R., Xremers. P., Albert, A., ,and 6re!-^_+. ;: - - ,Hutafinn Research 156:134-14ti, W$5. - Other suppart: INSEP.M (Franoe'sNaroqal Institute of Health and Medical Research}.-_ - - From the Laboraioir2 de Chimie Medicale, Institut de Pathologie,-Universite de Liege, I
Page 5: eta98c00
CrrL4RACTERIZATION OFANTiEODIES TONICOTi.h'E--. The researche , stud:-d the specificity nf-antibodies -preduced against four - different hapten-carder conjugates: (D,L)-6-(p-aminobanzamido) nico_tine-boane serum albumin (BSA),-(D,L)-b-(c-amioocaparamidoi nicodne-BSA. {D,L)-b (p-amieabenvmido) oicot;ne-SSA and (D,LI-6=anriror.icotine BSA. •;It of the produced- antibodies showed ab<mt e4ual specificity for both D- and-L-isomers of nicot;ne. The _ - carbon length of the tpacir~_ mp!ecule bztween the hapfen anT carrier molecule did not givea substanfiai inftuence to-the sye^ificity for the=pyrolidine-por!=on of-the nicotine motecu3e.=Tne specificity.:.[ DYridine pertion-w•as ia.creused as the iena_th of ihe spacing- mofecule increaseQ. AIl of the produced antibodies did not_cpss=react significantly (less. -- Yhat 0 1%) with cotinine;.N-,tiuethy;iyridieL:,m-con:pounds oR(L;-N'r.itrosoaordiyc:i:z... - Studies an nicotine levels in.[he-biolo"aical fru!ds-cf man and rabbits indica:ed that the rxdieimmano_assay tesF.niqne.developod in theD';>ent stpdies could detecias low a•, 2-i 8iochemicu!.4rckives t(4)173-Ig3,1Sg5. - _ Castro. A.. Monli, N., Aii, H<. 9owman, E: i2., ead Mc4er:nis, H. _ College of Virginia, P.ichcn;d. School of Medicine, Miami, FL and the Division of Biochemical Fharmacoicgy, Medicat From the Departnfeat of Fathology, Hcrmone. Research Labora8ery, University of Mi:.mi ScMi-RIGID' AND'FLEX§5LE' LINKAGES IN Ah F15ODY-PRODUCT.ON FOR DETERM{N.4TIpN OF#J ICOTINE - conc!uded that 2- and-•`,-amironicotine were not suitable f'anctionalized nicotine hapteps - for various re:sons.- Ipn the-.present study of the nse--of racemie an:inonicctine-as a -€unctionati±ed-hspten, nicsu:ri,, antibodies suimble f'or use in nicotine creterm:nationa - have been produced from antigens in which bcth'flexibfe' and `ssmi-rigid' chains serve As-increasing interest=ir. Vreci:e methods fo: determination of -niceTine 7evela_in . body fluids-has Itd tcdecslopmer.tet numernus procedures, all of-,rhich have some disa3vantages. However, radioirnmunoausays and relasd F.oc•_du?es havvproven to have certain unique advantages with smai: samples and low-aicetine_concentrations. In the - first published_study of-a uldioimmsc,assap for determination _f nicotr;.e.-it= was - to couple racemic-b-aminonicotine.to-bovine seruna alimmir. - -Costro, S:..M.cKenni;, H.,:r:: M.on;'r, N., and Bcw:r.an, E. R. Biochemical Aicnires I(5):205-21A, ISg`•. U(her %upport-'- The Americar. Tobacco Compday: -: School cf Medicine, Miami,-FL, and the Dirtsion of Biochemical Pharmacology, Medical- College of Virginia, R:nhmonz;. : - - -- - - Froni fh.e_Dcoartment of Pa nolog"y: Hormone [iescacch'aboratorv,=:Tniversity of Miami PHOSPHORYLATION OFt CHROMAFFiN GRAIVULE-BINDINv PROTEIN - BY PROTEIN KINAS'c C -- - Protein kinase C svas detecte# in a group of Car'-dependent .hromaffin granule - membrane-binding proteins (chromobindir.s) on the basis of Caa'-, phosphatidyiser.ne-,
Page 6: eta98c00
MON0.,LONAL ANT[BnDiES AGAiNSTH"siNJAt4 L74ER CYTOCiiROht£ P-450 Mbnoclonal hybridomas which produce antibo-5ies agair,st Jiu:mn liver microso::ral cytochrome P-450 were developed. Three similar hybridomas produced antibodiea which- recognived an epitop- specific to a family of human P-450 isyzymes (P-430s). This epitope was-also present on c,tochrome-P-450-PC_N-E (pregnenoions-lfxz-carbonLrite - induced) from m( livef microsomes,_burthis isozeme differed from-the humas P-450, by in molecular weigh.t.--These antibodies eaabled t,`.e-authers to quintify cytochrome P-4501 i^ human i':ver micrc;omes and to demonstrate af, important quantitative _ poiymorpham-in the human liver usonooxygena=e syssern: - - Beaune, P., Kremers, P.,-Letawe-GCujon; R., and Gielen. !. E.- From the INSERM. Fasuliz de Medicine Necker, Paris, France. Other supywr: INSERM (France s Natior.al Institute of Heahh and Medical Research). &iochemical-PtrarMaco7ogy 34(19):3547-3552; 1985. - --EVIDENCE FOR REGULaTION O_F AC:iN SY:NTHESES_ 7N CY-i'OCHALAS_IN D-- -- TREATED HF~--2 CELiS -- - -- -- - -- - - - In. HFp-2 cells treated w,th 0,2cr-2.0 yte, cytochalas;a -, (CD), the relative rat- of suppressed by actinomycin D (AD). When CD was washed from cells which had_ been- treatedfor 20 h, the eievated rate of actin synthesis deciined_to the control value within Ca 4 h, aa Iheactin-co.=aaining cytoskeleial components rearranged-by CC recoe•ered thei€ normal morpholoBy. Subsequently, acttn synthesis was depressed below control va!uzs for a prolonged perrod; during recovery from 2 h trealment with CD, this depress!on_ wae __ of much-shortes duraiioa. Re-addition of M to-cells after s;h recovery pariod-again induced the cytoskele'-alterations characteristir: af CJ treatme::t but did not rever:,e the- -prior decline in-_the rate of actin syn?hesis: ts HEp-2 cells ?reated with tyc(oAeximide during exposurE to-C'7 for 20k, the relative-rate of-actir•._synthesis measured after removal of- cyctoheximide wad twofold higher-tha+`with CD atone-and- such cetlc exhibiteda twofold slower decline-in the rate of actin synthesis during recover,v-Yron. CD - in the continued presence of cycloheximide. The3e effects of xycioheximide; which _resembie ob-,,er.attonson-',uper-inducti2r.' suggestZhatactin synthesis in CD-treated _~d reovering HEp-2-„ells may be regulated by a repressor protein. -The possibility that _ the proposed repressor protein is actin and that actin may thus be-a feedback inhibitor-of- its own synthesisis discussed. -- _ actin synthesis increased for about t2h and then rtacheS a p'- -- ;-4his increa=e wa: -Otier support: MuscuYar-Dyserophy`Association-snd NeYiona€ tnsiitutes o" Health.-- Tannenbaum, J., Brett; J. GG and IIodrnan,-G, C. . Fxperimanta{ _r.q1 Re.t,?rirn160:4?5-448, 198i.- - From tAc National Sciencf -F.iundatiaa-aud- rhe Devanmzst of Fatho!ugy, College of Physicians & Surgeons of Cclumbia-Univenity, New York. _ t
Page 7: eta98c00
From the=DBpartm€nt-of-Ph2rmacdiogy-:-University°of yirgicia,Charlcttesvil:e, and Departsnent of Bieche:niits;-, Medical-CoE:ege_of VirBirtia,.?cichmond. -- _ - .- DIFECf EEFEC"tS OF ADR~-NOCORIICGTROPIC-NQFiM. N£ ON BOViN"c . - - - ADRENOIS?EpULLARY CELLS ADENt)Si;JE 3'.5'-MG•NCPI',OSPiiAT€-_ _- DEPENDENT-PHOSPiiOR`tsLATiON-OF T{ROSINE_HY-DRL'X4-vASE -_ - Rel,we.of a.aena] cateehoiamiae by +a:Lacho! has bxp shown to-cnincide with in increase i:r-idtraeeliular-cAMP-levets_.-BOVir,e adrenal mcdcliary 1^AMj._ celk were _ prepared aid maintam d-incuRure=and used-ts ermine the role of cAMP~ itt'-- stimulu -secreticn ccueting:--llieaddition-of AX'Tb:-to thesEcells caused a:D- to ,54-fo!d -_ -- - increase in-celfulat-cAMP dvithout-an effect-oo'ca:echaa.:ne-secretion, su€gestng -eorticai celt.contaL,ination' Percoll density sepantion of ho'ttt BAM _celia and ydee:;al cortical cells }evealed fnat=-the-greatest cAMP resp[>[=ses .e-AC':H torresponded to_ the " catecholamine-con:aining celi-fracicns and net-m those density lai•ers where- cr.:;ical _ YeBs sedimented. _- > - - - BAM C€ilss LAl21eu on PerSotl d:d not nl3t4bCliZe (liCir-i.o:e:terC: tC 3terotdc ai wocld be-expected we;e the ACTN-stimu;xted-vAMP a: umulations due to-cdrtic.al •_elC _ contamination of- the cu:tures-- ACTli- st7mulated _pretein pho=-phphoryiation in 3sP-labeled BAM cells ie-s inasner ineistinguishable_ from t[sat-.induceat by caruachol_ - ar.tl forskolin.- The msjor-soluble pliotphoprotein to be.affected by these -agents had a xiative mot wt dP 55-59 kda!tons on sa3iim-dodecyi sulfate-gds an.; carresp,nded ic tyrosine hydrocylase, which ',s-a speciiic marker cnaFme i± ihe_.drenai f~, chrc_ntaffin cell_s. We propose that bevine adre;:a_I-chreattafiin cells-erTress-?_TY. r_ei'cptors which ars eaunled-tn adenylate cyclase-- it'hiie no acute effect of ACT}I was fourc on- _ - catechota-mine secretio:,, A."'e H may play a direct rLleiu the reguiatio.^n of -eatechoiami5e syn+hesis }y= stimulating - the- p'nosphaEylation of - tyrosjne -hydrozyia?e by - cAMP-dependent prDtein=kiaase.. - -- M:cheneq M. L.; Peach, M, i., and Cretdz;C E. "- End<ttr:nnlagp il7(2). .0 7g7~ I9f.5 - - - - ~_ . . . . - _ - . li:F,er supporf: Natio>tal-IUSt:Yefes of E[calth, and the.National Sc;ence-Foundatioo-with _ additional assiTtar<re fram-the--LSnive•sity oC-Ylrgtaia-Diabetes_Resear<S a.d-:raiw:e_-;. - MANNI:OL• AS AN QH--SCP.VENGER Y=:-AQUEOU3 SOLU-TtONSL AND IN BIOLOi,1CAL SXSSEMS ~ _-- -- - '>- - -. _-.. _ -- - By using the technia,uc of pulse rs4ioly Is togenera e O`.} radicals the eutbors have determir.ed through certlpetition vrith-SC`:".i- and i•e(CNiy _ the reaction eate cen-- atane of mannitol w•ith OF[rsdical at pi-P - 7_ to be (1.8 : 0.4; a:0° M-t s t: This - value - -;ustifies the d,e of manni.ofai aF_9}: scavenger. However, in biological systems there is some uncertainty wncerning the releHant.concertration-of_th.is-scaver.ger. -?T.e , -concentration inside the celf`mar-1ti very different frLm that-in the solution 3ecause of -active transport on the one hand or thmugh _metaba:ism on the other. Even if -the _ authors ean detercine the concenteaton of mannitot inside the cell. they are n?t able to determine the concenvatior, oof the targets where the damage occurs. For all these- 120 - - I- r.,,r.. -d v~~r:Jnr Cmnrv3 S1,icrb. Prnwam Frniac"r_ - . - L . - From the Departmer[ of P:arrnaco -gy, Universttyof Yi.ginia,CharLotteseil'=e. _.
Page 8: eta98c00
1,2-dio!cin-, and phorboPmyristate_acetate-stimulated_-histor.e kinase activily. When the- -chro>E!ob"sndins sxtr:-ineubatedwilh j~;-'sPJATP, czl.uni, ant- phosphaeidylserine,.sxP was incorpor-_-ted predQminant!y into a protein of nass 37-•_ I-kiLdaltons-(c€!romob:nd:n _-S, oz.CB9). -phoslrgrorylatii=., of-this-protein was-aso st:mul„ted by G%otein'°aid phorbc; _; myristate 2cetate, :F,dieating that ii is a-SUbstrate-for tKL Drotein-kin2se C y^tivily=piesent in-the chrotrobindins, Maxinum phosphate ibcorr_,oration-into C64:n~Cae Cr_esence of -°1mM ealcium,•'5-7fg/mi-of bhospha;idylsarin*~ 2:5-Fg;m1-oPdioEeio; arsf2.5 pg/mt of - ~ dithiothreito!- wasr0-.53 2ot/,:ol of CB9 itr 5 stin: EigFt rrP-tubeled -phospRopeptides - were resolved in--twe-dimenssbnal e!ee;iophoretic -ma'vs of tryp,in- dige,ts of CB9. - Psosphoamina acid•ana.ysis revealed that- pnosphory!atioa was exelusivelyos: serir.e (9d%) andihreoaine (6%)-residdes:' Ihcubatioa-oi 1hz-cht-oTtobindins with-cSromaffin .-granule memCranes#n (he presence of [ry-rPjATP iesulted in-the incorroration of '-rP into additional eight pro€>ins may regu!ata e•,ruts und°r!ying exoey"tosis in the c:*omafSin cell. - --eentrifugation -iz-- the -presen_e€' of eLh.yPen= :gtyccl'- Eis!be;a-aminSecAv!ether)- = N,N3>!',N'-;e;eaacst r sci,!. - Wesuggest that'phosDhciylatitn of _ CB9 or these --sight addit-:onai_prnteins besideS-CR" that ceuld be sepa:ated-irorst-the-ri!embranea by From the Deparsment of PM1armacology, Uni=er;i:y of VErginia,-Char:oitesvij(e. - of Frirginia Diabetes-.Reseau'h anSTraining Cent?r.- ' ~ ~ -~ _ --- --° _ Othe(.support:.Natiouatins'nu€es ~x Heafth, National Sdence Fodndation and University Summen, T. ,_5. €r3,Cieutz. C. E. --TAe Journal oJ-ai,/egicul inemisby 260(q)2k37-24c3. 19£5. _ - PHOSPF:RTID`TLi:4-~)SITOL-SP);'_'iFiCPHO$PY.OLIPLSi C ACTIVIT]` -- OF CHRCrM.4FFIN.r-eRRN:JLE-BIV51iVG PR'JTEINS: ' .- Chem. g5F,-16c5A'qf,74).. Thra:tivity uwasmaxima: at neutral pH and_represented an ` Dowling, CG., Sando; 3d.;-S 7EarPalasL, £., Wnipple, F.f1-, and'Zakr=; EP'.-: (i9g3) !. &icl. - -ehromaffin grar,ule-membranes.in'ths presence of Car-'('cnromObindint,"Cieutz, C.E-, activity war-detecteccl ina group of bovine adrenaP^.t2dullary-proteir•s tF.atbind to Using-1[7-"CJp6osphatidyiinositol-assebstrate, Ca='-dependent-p?osphrrlipase C - Creur.-. C. E.. ibwliny, L. Kyger, E., and Franzon,R C. - - vrcenity of the clsro maffm-granule-uiembrane during the processof exe; ytosis.- - . activity may be regulated -by [,.as'j at 1 uM bn addrtmnal ac svatton at h gher eon rr[ ation of a cium is seen in vrtro as a result of C s depend nt b ndira-o the - actr e enryme-t6- ubsrrate contatning membran-s This en yme Tay gen rate - aracylglycero and p4osphoryla- d-Inos,io: so act as mtrace11u1a mes a_gers n-the presence of 2 mM Caz* but was released at 4p pM, suggesting that intrinsic enzyme presen:_ in i,ye absence oP calcium, -2594 activation occurred_at : pM -Cas'.. and full activation>EtS-mM-Cazw: Tkeenzyrue bound m chromaffin granule membranes in the .._ measured at pH-7.3:--Tim sttmulation oCaetivity by Cas' was complex; na activity was - 80- to290-fold ereic-hmeat of adrenal--medullary- cytosol pAtrspholipase C- activity- . Other set;porr: National-ISstitutes of Health and National Science Foundation. The I_munnl oJ-Biologica; Chemisr:y 250i12):7171-?173, 19g5.
Page 9: eta98c00
EFF"cL'ISOF ETHANOL AND-TEMYERr]TURE ON GLUCOSE UTtI=IZATION--' IN THE IN VIYO.iND hGLATED PEP,fUSEDIrOUSE BRAIN braens are treated wetn equivalent concentrahona;.a ethano. along witn a d'u-c.tasi3u of the apparent discrepancies observed wheg in .4vo and perfused - utiiiza_ion rates inn the iscia.ed perfused mouse-brain r:.r.28`C and 3i'C--are-'vresented the twa lines. lnterp:etations of ithanoi's differential effects on eerebrai glucose- di7ferences:in bssat-metabo:cm or-.folEowing a d-gjcg-dose of efhaaol ex:sted between selectively bred -for -differencey - in -etha3oi=inducecaleep"-tiru~ - isdicated- t5at-=an- pedused brains,.-!n rieo:.ratesof-cerebra3:-eh:cose utiii:at;3c in two Iiness aT rei4s; .- produced an increase in giu~ase utiliiatic• n ia the medu':la-;xons and in the cerebe!ium of in decreaee= in :he glucnt uti!iraYion rate. at. 3% but i,ot at 28'C. At 28'v. ethonob -Perfu.ion of the mouse bra:n wi:_hh a fluid contining 87 mM eth.anoi (40C mg;"dll resulted - with a medium cuntain:ag ethanol, which u-known-to increase membrane fiuidity. - temperature-dcpena,nt-membrane phase :ransitionx-_ brain perfasions were performed' between - 28'C and 32'C. - To investigate the possible ievolveeoent - of - sugges's that a change-in-tha_rate-limiting futp ot cerebral giucese metabnlis:Y oecurred - temperature dependenccot the,gEucose utiliration.rate--ia the-peefusedmouse--tiram : - mouse brain. Gl:cose ci:.lizatian ratcs in ii:°rzgioa.: of the i,sci>aed perfused mouse vrain at 3T^- were <-imila3 to !Iie rates ea compa rablt iegions of the in eivo rucuse brain. The - and tem;~erature_ variafion on the rate of giucose ufilizv;ion in the i;olated perfuse-d --A [rtij?-deoxy-n-g:uvse technique was csed to invesiigate the effects of ethanoi Teweli, I. F., 111, a:d 6rwm:-V. G. :: From the Alcohol Reszar-,h Ccnter,Schoci d f harmac:, Uni:brsiey o7 Coiorado, Bouider. - O:he°supgori. U. S. Publie ff_alth`ervice. AtcoRoliem: i;iinical and Eseerirnento( Reaecen 4iI):110-ti6; 1982_ - reductioa of input veltage, a.biCbut%ic response of rapid-dcsye.chronizaticn toilowed _"r_y -'- IPMB was monitorEd: .Nicotiue--indoced charaeter:stic- ECoO chan.ges including a- - _ s=cr-etior, of -- MSH anC-A-eddorphin. Etectroccrti,;ograpiic.•('eCot3) activity -of the _- superfused p!tuitaries.- Tbe;data suggest nicotine acts :n the.brain to -stirvuiate. pitvitary the secretiorn of B-endorph=n, e MSH, or ACTH iramunnreactivides frem the isolated - and 12.2 pM aicotir.ecresgectively,- Howevzr, hicotioe(a3-yM) -had_.eo direct effect: oe of a MSH immunoreactiriL-.was elimltt=2d.2ppreximatel5-,wy--and sii:fold by 6.1 pR5 s^perfvzd pituiir,ries of C',hf mice. Nicotine (6:: I.Mt stimulaled secretioa of B-andorphin immuaoreactivity from C3If ITMB approxima:ely?wofcld. Secretion -EFFECTS OF NICOTINE ^N P,-EN-[20RP13IN- e-MS4L AND ACTH_SECItETIO`d BY--- ISOLwTED PFRFUSED Icft7USE BRAINS AND PITUITARY Of.ANDS, IN VITRO -- - - The eff ects o'-nico:iue_oa sccretion o_r the pituitary peptides-g-endorDhin,_ a M$H =_ and ACTH were:-st;;ied usinff the iso:ated perfused mouse brain (=PMe) ao: i€v0.ed _ prot~.,ngect 5lnchre~irztion>aad seiznre at-oigi. arses (12.3yMj------ -- ---- --- ---_c-= Ir(arfy, M. A., Erwin, V..G., Cornell, K., anlZgombick, i. M. -Phcrnnco:o8y. liixhemis:ryi Behawior 21 317.-32~ 1985. Other .tstypori: U. S. Public Health.Service. -.- From the CenterSor-Alcohol Researci.: ScroOl of Pharmacy,-University of Coiorado, _ Boulder.
Page 10: eta98c00
equipmer,t were.designeatg_provide the inice with ezposare corQitions xhere (I) ;aie :ung= _ _wae_the maJor targetprgac ~fbr s't,asm,,s ;(2) £3rge quactitiesbf fresh; whe!e cigarette smokHtAuld_begerlefntedF(?)-targ+.^•umJ2re of SGimals cou',•d fe ext}Jted ar o9e limc, (4) routlne, daily CS~oOS4res ^Ji!d be-gi`.en over a mijC: pertioh of ttlC lifetime of ?he - animsF,- (-S) monitoriug da;:-ao<umentation-ot'-the qtiantity ci smoke £rresented :o~ the - -animals was prhvided during each exposure session, (b) safety systems were provided that _ ass.reGexyssure of the ani: als~to smoke 3hly under pre-set expo>ure conditioue, and (7) - cigarette smoke wasg€aereted under conditions wher factors, sach as-cig_arette eype, smoke aeros,l coa^..entaat:ou and smoke particie-size, were-:.oatrell€d. _ - Henry, C. J. r, a!. ilt;icrabiDlogicui :4ssocictesJ - - 8eitra-3, aur-?0..t'ekfors-A :rir Intcrnatior.ud i3(7}.J7-5i, 1SgS= From :he Anaeytical Chemistry Divuioe, Oak kidge .Natio:•al Lab^rator„ Oak Stidge. TN; Divis:ca of Toxicoiogy ar,d Molecular Biology. Microbiological -Associates, Eethesda, - MD; and Proc_-:.c and instruments Corporatiot?, Brooklyn. NY. in respowisG tG actlvatinn $J-phNrb.t myrSrl -tf:etats. F1i011y, neutrophi! zAD YiRa9e - These data are interpretect-as-imphcating-.-.elmodulin in NAD tinsse-reoulation.- The- tota! cnace~?tra;ion of NADF a-Nf.Dnti in-tas hulnau-aeutraph:; used in=reased 2.2-:`o!.; - stimulation -is inhibi[ed 'cy- the addition of 20 -`M trifiuoperazine to the incui+ation. - appro:imately?,41,Vf, In`c2ildarextaacts,caicium•3ependeaHacliratio:eof _NAD k'3ase increases the maximunr-ie!ocityo the reacca fro-m 2--lo S c dwhiie no.-affecting-, F- vatuz; for NAD and A:P- -The- activitT of the partiall;--pure.`nd NA.D-kinase s- stimu:ated 3.5-fold by the:'a+lditian-of ca3moduiia-ie the gresence of-ealcium: Tnis - - _ ATP. respectively._-. -NAD-kinas4- acttv;ty-s- extre_me!, stnsiti•e ~ rc~ -frye =rsiur[t eoncen:ration, _with ha4-coaxim..7•act:vir;•-taEserved at fres 'aicimr~c cen:atiors of - appitc;Lon oE -nced ,.Agaro3e,: ron-exrAange; aniget-fatratroncnromarography. 37ie -_ en_me has=a broad pff •r]ristu.•-, 3.0-93, is siriet!i• depecdent-upon -the presence of - and i,E tae_s8se~ ~-c-:est.m ex3s K values of.05 add G; snA-for NAD aad - F1AD-kJnase frozn.humaa-n ctrophils has been-parua°;r=purifi d 5y seq!-•entiaT-- - CALMCDULSN-DEFEN7£hi NAD KINASE O-HUIvfAN NEUTIROPH:S.s -- - Tias a Mr, based upon gel fittration, of 149,000. R'illiams, M. 8. and Jones 1'. P-. Biuchemi.rtry and Biopfiyslcs'237(i ):g - - .7ther yqpnrl-' K[oc Foundat:oa. -87,IS83. - From the-Departmeo£ n;.-HianemisEr~'-Eol.ege--af A"ubama Mohilt- - _. - - . -- ~ .. . - . S7edicine, Unive%Sit-Y-: A Caf.:PARitTiVE_$TUD-': OF NEt1TRQPHIL PU&:FIi'A!1C-iti' AND FUNC7 tfiN - utilizing-discontinuous der.sity gradientd ~upled with dextran sedimentation and in some - cases hypotonic lysa.-Sothe investigators refrain-frbm using certain purifKat%oa-sthemes because certain steps or-reagents used-ia a particulai-met7fodmig!aadverseiy affect the - - Several difierent methods are curren:!y_ used by numerous taboratories for the - isolation-of_humar--r.eutropl;ll=_ ~-Thesemethod, inc!u_de-0*rtsai purificationbj dextran sedimentation_ fo!lowed b7--sr"ater lysis, andinore _omP!'tc purificatioa procedures 129 -
Page 11: eta98c00
-_ EFFECTSOFNICOTINEilNO3`fe7UCALB3;OOD FiO!V`AN__^--EMyRYO-= -- pEFELOPMENT FIs THT-RAT-- - - . - _ - --- - - -- -' -Nicotine_(5.0 mg/kg_1 waiir.g.c:ed (s.c.) twice daily da Dar'i or-Dass 1-4 or S-3 oi-- proliferation.-_The embEyo-is thereforee srrceptib/e to-the2ffectsof nicotinc before- P< 0: `05. Tbe results in3ica_te that, in the rat, even a- brief exp_sure :co nicoti:.e, the chief al&a!oid or tobacco.reduces oviducal blood i':ow-and the rate of embrvo ce!1 blood Ilow (pretrealnent ax 9!J mia after nicntine: ti.ct .0.0c-es. 0.31 s_ o/lo nil/min.g `; - reduced cel.l number (yaiine-vs. nicetine: 42.5 g i.T vr.-30.5 ±a.9, at i2:00 h day on Day 5; - P<C.OI ). Nicotine ir..ectisr alse-res :tcd in a marked and pr ionged reducticn in o+tduct '2:00 h on T3ay 5; P s-Os?5.- However, treatment for even I day (Day 1` sigaificxn9y - -reaucxd embryo cell'nurbE.r [salme rs, nmcotise: 42-5 y 1.7 s 2?.! ~ 1.9 nuciu/emb:go, at pregnancy. Cumulative doses ot ccotine re~arded-erub:yo cellcleavage and scbstar•tially - .Hnchrl?, I. A. and Hammer, R. E. lournal c! Repra4aci:ort e Fert:(ay na:7i=74, 1985. Other suypor.: 7Le. ResearG;:=Sqaely-nf Signsa Xi- - From-the IlepanmenFaf Anatorr.;, l4ame Statsilnivers SPECIFICCi.AS°aOFFOP$M'Rs.N: ._---- -~_ ~~ --~ -- SELEL-T-19E- A_^f7:,ATlON -.OF-PARTN'CJt=ATE- L:UANr .47s--CW'L A$E` 1§Y' A _-the interaction of porphyrins with particulate gpan9fatecycl2se is r_ompkz-iii r•ature_ and- ' be activated to the sarwc extent-ac-enzyatr in native membraoes. These d,ta sugg ;t-that= - - presence of detergents ?uch as Eubtol-?X, xndhighly purified particulate enzyme could - to-activats guany!atc cyclase. The stimulatory effects of hemir,- were observed-in the the iron-nucleys of porphyrans, such as cyanide,},ad little effett on the ability of hemin - - - form of the porphyrin-m:tat chelate for activacion. However, agents which interact with -__ abolishad hentin-de`pendent activation.- These data suggest a requiremenLfor_ the ferric -- particulate guanylate- cycl°.s: activity ar,dd sodimr: bnrohydride almost -comp!etely - in5ibimrs iailed.to alteret;mulation by hernin. Protophcrohy:ir.9X-ha:t l:Ctlesffect an - toncentratio@s. Activation was not-decondary to proteoly;ir3ince a variety of ptitea,< _:nhsbrted the solublr form of gyanylate cyclase -r-0 [o 9t,>% over-a wtds range-of - activity-reftected:eiei,tveastivaYcnaf.tn>Farticulat€formofgaacydate cyyclase; himin - Mg '-GTf- but--nat avhea :vfn-`=r:TT was -uxec_ as the substrat,e. ---Increase7- eazytne._ - hemin wtth higher concec*rat;o.ns- being inh-betory.-- Y+cttv.,tcon v;S observed when-- - -- B103 rat_r.ecrobiacRoma cefls.Maztmum acttvation was observ-?d-with-56 to 7C0 pM -- manaes-in membranes T•repared _from komo$endte? aYr67 X-ng;-Cs iat giidma cElls,-_6r ---- - --Guanyiate cyclase was-acGvated-3~ . to-l0-fold by iiemin in-a= doss=de:.andeht ---Cifferent fr6nt [ rat with the sotubie enzyme. Wsldman, S. A., Qinacore, M. S.;iewicki, 1. A., Char.g, L. Y. and Murnd, F. The Journal of Biological Chemistry 259(7):403g-3042, 1984. - 132
Page 12: eta98c00
seperuxide productiolt induced..t;, . opscnized--zyatosacz p?rerbol- my=i=tic scetate- or= system in activated neuironhils-.a- haa been 3uggesfedbyi35ers.--_ -'- .inteTreteZ-_s<_ e :d.r:ce tkat-zantnioe= mtidase -n -unt _=q-.:msior-'supeatxide-genetatirg- -superax:de-mediatc._ca=rageena:-indueed foot edeaa--ie tho-rat. These-:Fa.',ies ars-- -formyl-m4:F.i2nylleucylpherrylafxnine. =-Furti.ermore, neiiher <hemotaxn-nor degranu--=-'- _ --lation-evaa affected by atlopurin2i; rA!lepurinol was-also {onnd inefL€cti,e in bl6cking_ -_-° JWr[r, Y- Y. Ef ai. and rJte American HeartRSswiatien. - Other sapporr: National IteSrit~tt of Arthritc, .M.etabOlism, DigestiVe aAd adney Disease 3iorhewdra! Pharmacologv a4(20):3573-7675, i9g5. From the.nepartntens_ oS.-Bic:;h-mst.v, iollege-of-Medicir,e,---LJniversity ai-~South A!abama, MoiSile. INCREASED BETA-THI'i9's+13'sOtr'3.OBULIN IN THE SEI2LtM-OF SMOKERS O_ IfcFiS - OCCt7ftS B€CAUSEOF INGAEAC_ED PLATELEf COUNTS. - in ;he two-groups.- Aa-invetse-r_efationship between release=and glateiat numbcr was=tiss- __ -p:atelerconFent of e-;G,-siii,^e_the roucentraFOn o..r-0-7;'s trer, n:ate!et-is ,tarly identi:.al--- - likeiy due tn.observec irrca?ass.4 p'ate!et-nenbers i~ smakers,-raibeer-=ihan to i: =ta.ed -_ - found iu be sigrZicantlY bigper ipsmokersah?nianonsm_ker;-."Phisir.crease-ia r.ds-t-,= released inthe serur. ~f-.~irkers$;~ thro_t»bin-for:ned-duting w3te:ie-btooei-c!ettiog-+ss--- The amoun, of d-th;omboglobul!n (t?-TG), a platelet aipha- Franute-_protein,_ ~-_ - Lange.~erker, G.L: et al.- __ ' 4_ - Research Commaniealinns.:x 3upstance, of Atrr.trS(2):!37-152, 1984. the hypertensive effect of-ezpsaicin.(30_gM) and reduced tR.e-response to-nicotir.e- -- = applicatica to about 25% of.cnn:rol-(g < 0.001)_-Local capsaicin-nretreatment_ of i:w___ -F-ye the Departmert of Phan-a logy: Cn!ege of-Me•.jlcit.e, --ncacama, muwtc. M_ ECHAP3IS!vtS FO&kir^LEXIV€-H`_`-PES2TENSiON It`v`DL'CED BY :.CK'.AL- -- PLICAT)ON OF CAPSAIC€Id AND NICOTINE TO THE NAS. L MUCiJSA - - The cardiovascul_ar effscts of :ocal;y applied nicotinaand capsaicin to the na..al mncosa--were-studie9 in anaesthetized gun:ea=pigs. Local -applicatio+ of capsaicin (03-30 yRt) ar nicotine (0.7-3i1 mivi; ir.Guced dose-6epead€nt increa:es in ar ierial- blood Eresura,_ nsinlY due-to11n'iuxreas= in periphees!-vascutai resistaace:-'ftie-csp:aiciij- and- -nicctine.e:pos!.:e; _uxre abcshed_after:leca7 snaesthesi< and marked;y reduced (to about 20% of control) by _ronrN.ined prer.-e :ment- with phento:arnine and p=v-prar,olai, suggesting re:aexogerdrsYrs9athBtit actioation.- System capsaicin_p:etre.,aient abolished-~ laasal mucosa.one week-eaiierai3a.si8nificantly.revuced ahe-capsaitin_respcnse-(p < - 0.05), whila the- nico3ine-i3duced-iqrea;e_ in- blo0d- pressulewas not-significant!v -- changed,.-Thepresent (indings suggest the.presence.of two-afferent mechanisms inthe - -nasal mucosa which -nduce . hibeaeasicn- ttpoa cltemi.-_at irritaticn. ... The _capsaicin- -. response is dependent upon tigpsaicin-sensitive afferents.= Tfienicetine response iavr„'ves -
Page 13: eta98c00
mainly capsai.in=sta'iitive_ cetir^=?i:-ar,d, ir-adQi;ioii; -a--minor domazonenc which- is , resrs:ant t4 cao aicir'pr>-• a:men?.- T_hus, the_hypene:ui•.•e etiecr of _cicntine- applied-- _ i.".^al!y tU the na5if-r[luCA+sa eL.R! -to be .na ..:y-me4iated v!a sePSory -mCChaMsnrs oSber -_ 'han thESneez g re t~nu=e s+R s: 3 not 3aqender::en cagsaicia ser.sitive ;teraes.--_ - ..ond"aad.' Fua.-X:-Y.. aaG Zta:dSerc I. t3 Aria Phyaiofogicc-8e=vrdisnriec 121:?'7-2E2,19g4. - _ - GlAer=saOC+%rt: Swedish--Ricdica: Resear:h Councii,_S.dedisi Tobacco Corrpany,- Astra . Foundation, anc`the 1<arotinxka institute. - - - - - erot.m the=lse,b mect of-:'Ga:ma_c!ng -a in:Fa ]nst:tu.e; and the Ixparimrnt of 45ro-Rhinr-Zar:ngciogy, KxrolEnska dStspiial, S,GCkho:m, S~-den. _- - EFFFC':5 OF Nli~s T1_Nii Of: 6LAST+YST DEVELOPMENT PR{CR TCi - - =1hS1Tr,4NTpT[ON=!>TH€ RA7_ ~ - -- ` --- _ -` ' -~ - The foilowing: study was undertaken_to determine the effe_[s of nicotine treatmer.t on conceptru deva!izjnten?-during the initial 5dav- of r egna :r;: !n_ addb'n- titters _- were n:onitore7 fo lae3-teEm yo3 pa ss~ effet~-rf n,c_t~ a msy~suz_c^_- q ev?th as.i = -- stxUal 013Inr8rinn'1`J IOV~>Figa[e pds^-I ~JC°.: of %i,C-0FlAe'aCtiCR, plaSm?_ p,•dgsiterGne _ -]evels }aer: de err••taed ia treateA (Ni-v contrc; (L') -rats-durieg ihe-irti!ial 5-=dxys of _ pregn ne1.-ard :h~C f. t9 ftFe a1kaT Z-s nt ri+E'i.7TOd fltI '2'Id Tn ra112er-rle Ax gc r~ = ten ton were rn a-u ed in a eud paegna r rs - r er,er s ze--and bt -h -wzigfit were determined ir 1' vs T rats nd hou growth absequentt pECt€et'. he onset of ub - r• - in femate waz r*a c~ by ncr the da o' ^.agina epeniny xe ults show -Fat -- twtce-daLy-sP.O),.c44.^y of wcoOnS'furing the L•L„ $ day5 3f pretinar,Cy _iUflrds .en-en,n -- grcwth a.s_indicatsd by the reduc;.d-numSer.oF ce11s y-ar blastocys€. The- same treatnte2t had oo_elfeco on li[te$size- brz'h weigFd or Lrody grawih. liowever, the-day of t•_aginal- opening-was de;ay_ed._Nicotine IreatmenegeneraEiy rnppressed plasma pro+kes'erone !eveis _ = during the ini::a't 5 days of Prrgnancy~- FurtFerm?re:-a sinele injectiors of the ai>aloid =indlced'=. rap'ri_an3 sustaire,3 reductioa ia-ute:ine biood-fEow_anQ z concomitant _ decrea<e lrt intrauiecine ixxa_en. Rs ir.d'uaud by -th;s- -we .-;- nisotinc ir:ay- T•cAi(y _-- =--canc^ptus-leveiopmsnt-by e!tering-reprodu~live nact r-naiai.- -i•'icetne-inriviced changes iri serum pragestero.^.e 1€ve!saed uterin,- blooF_Slow probasly_>-su!4 prrnarily= - Trom the-alkaEoid's-diveise and eoTptexac:icns on the necvcus sys•e.F= -The presea5_ . resuits confGrr and eicend=nteviousinves.igatinns=reportiog-effers-af pre-imp!anta;ion - nicotine esposure oeconceptus develoCn;ent and progesteree secretion. In- add;tion,-the present study aemon;trates thad ecen? -elative!y firiefexposure-to ntcotine,--i:e.- during . Lhe-initial-__days of Dr.ebnancy-=r s_?fieienr_to rnodifq-ehe-timing of pyberty_in thz fat. - The delay in onset ai -pubet:: suggests long-term 6icotini' ia.'oced modifica:an_ - of CNS -- . nLiichefl. f_ s.-aniPlatime~ R=~E=-:`- - u1 Ca 3agii, F Tt obiaii-E:, a<nd Paelet,i n(edi.1: De elopmentai - Newistience_: Physfalogi~ai,-Pharrnocofagia!`~nd_Ctinicaf-Einei'rs. New York' `r:3se+ier - - Science Pubishers B.7., i984. F'xom-the Departrner.=of=Anatoroy, Wayye State linive-a ts~,ch,wl h edicine; Detr:iL __- i
Page 14: eta98c00
MACROVACi1OLATION 7PIDUCED BY CYTOCHAI.ASiN•. FTS R-ELATIOP7 TO- - OBSERVATIONS. . - THECYTOS[tEL-ETON;i!:ORP3IOLOf:iCAL AND-Cf'7TY.C-iEt.aICA`u-- `-_ a'ncht by other means causes no vacuo!iza:ioc- Nacroaacuotatioa, like the other changes - membrane is thus formed xithin the celDCr,der the inftueece of :.D• Rottr.ding brought enveloping__actin-fitannenL ivregats--are sursounded-by arrays of v:mea:in-based intermediate filaments. A new mes.braeous compartment with sharac(eristics of -plasma fodrin- and vincu6en ara localized- at the vacuole boundaries. Vacuoles arc their cetl anface. yacuole membrane is always in tnttma=e re!atton to the actm-based microfitament aggregatet=.batr,trround the vacucles,_anG actin-nen:brar.e lirik<r-preteins marars associated with _eirdomerstbrnne systems (e.g.-AcPace; TPPa,e, IDPase} asd are not lys..^somaL Va:uu:es represeet i,tercaiized plesma membranet they apparently resuit from-retention in the-esd+;plasm; andof rihccytotic vesic7ta or:ginating at the junctional specializations a, those £ound at the_cel! surface; they latk ;he nembrane Vacuole membranes have the same dimension (85 A), surface marker Snucleotidase, and 80% atli-hr), related tc.sotai dose{coneeatration-x time! and';n coogener (CD > r°_B).---- which aggrega¢e in the endopEasm. V"acuolaiion is progressive'(eg. 12% ceL -at 6'hr; : rounding; and develop big-cystic vasusles.3'!:e4e-varuoles are always cl6seiy investad`by -- 9icrofilamentous-onasses.-thef.D-indoce& derisati.:vs of-the-actin-based eytcskelemn, - fibroblastoid-tine, _HmF<s snderge -exrreme-retractioa-, 2rbo;izatior:. and--subsequenr - - - _.:A:-hiyher Eoses--of_ cys,chatasin=le.g: 3- /egjml-fcr.3-Y0- hr3r-cetl, of-the-rzi .-_ _ causen d by CD, is completely reversibte on res•.aratae of cells to normal niedium. -- - -----_ ~ ~ --._ _ - . ,-_-. llrett,d:t'i.=nd.^m2man €tF_C:- ?is,ue & Celt 16i3).3a-32a, 998i. - Or'r,er supyo,t:- National-Institutes of Health. -_- -_ -.- :-. -From the-Department of-Pathology,follege bB Physicune - Gniversity, New York. -. . WITH H cy ADRENERGIC-REi:EYTORS - - - 9RAIry_ANDCETECI-.POSSIBLESTRUt-li1RAL-HC:MOL-'JGY ~-.- !:'HOLiNE1:vIC RECEPTOR STRLaC: U&.-E FROM DP.i3SOFNiLA TO fIUMAN: - MJNOC:ANAL-:.FJTiBOD1E> PETECf Tt;E-CONSERVAT!ONOFM?JSCARINIC -Muscarinic cho!inerg3c receptors_isolated--from-Prosod'ni!aheads:rat-nne human - liver c_adrenergic receptors. Furthermme, two out of five monocional antibodies raised - muscanauc :ecept.^r mGnouonal antwoases also immunoprenpnated rat -receptors are highly conserved-over aconsiderabf= evLlutienary perio^_. One of the six human and 6rosopnila-brains; with equa!-efficacy.- These dar: indicata that muscarinir immuneprecipitated muscarinic receptors from ary tissues and species te;ted, ineluding _ -rat brain htusca.it•.Sc:receptivs as the antigen. -Th'x six different monactcnil aetibodies - monoclona; anttbodtes spect?:c tor muvearattc receptors+ve-re deve!ope•- by ust:.g pur:.:cu - an i_soetectric point of-5.9-- The 5ame proteins all atigrateti-with a. apparent molecular - nia.ts of g^u,060-da:rons_on•sodium dodeoy_l-sulfate gels. $ix _h-ybrdomas secreting - - sub;ected to-isoclectric `ucl~sy. Muscarinicleceptcr; from each s;rcies focused a.•.h _ Muscarinic receptors were affinity labeled w;th {se jpropylbenzi:ylcholine mustard and srmlarities/crfferer.ces- -,cy utilizing _tur?ectr;c - dxusiqe --- sodtunfdodecy" sulfate/polyacrylamide-gelceiectrophoresis,-and menoctonal antibody crossreactivity- brain,_-doB -heart;--and- mockey siliary--muscle were--examinedfor-.structhtal -° -
Page 15: eta98c00
I ATRr."1PEFTIL. I-Er E5,4TES CYC IC GMP; AC'iYvAT'•:S i".Z'LtC -_- -- __ £MP-D PENu..i-ff PR3 E N YrNAot AND CAL S RFLAYA ION IN RAT PdvRAC'Ir ' A'Ir' A A Syntltr,tt arsizpep I an t t I rn.nee na-to with F tent sso la rv Ifecr , _ was stud .i sc'ated t-ips of rat trorac ae t+-to a t nine ts ac,-or., on - coaGact rty cyNic nuc ottde sonce tr i-as €nd- endogenous- ac v s of -_ -yche -- _ n,.clco .d apend.n, pro2e.,.-kinases. n.rrepept rl w_ fou d,c re1 ao ,.c st rps -precontracted with D.3.gtM ndrepiaepnrino- whether-or--not the endothele! iayet was- - preseat. - Relazati;rn= So=,strioqeptib. ilwas -ciosely -ee related -in a 'i9me--_and .- co[tcerlaiion-si.e'yend a[-;n?nnG£r w;eT-ine:reases i.i cyclic r__,ytP-C]nCentratiOns and_ activaeioy of cyclic G:iP-aependent protein kir.a#e (cyciic GM?-kinaae). The threshold - concentration for ail three effects was 1 nM. Atrio"ptin II-(lO nM for l0 _m;nj, produced - - an-30% rrelazati:m; ar- .-'utd increase in-cyclit G'ryiP son_cen rar;ons and a 2-fo,d increase - - in c5clic Gr.4P kina..e-GC;ivit,.ranPS. iAtriope5i:u H'd~3 rC+ =ignific ru a tdr e;•clic -- - AMP 'onceruation o cyclic A.!P-depenaent 7 o.ein- rmas a t_ivit} '-ie e data .uggest tFa cyc;ic GNP .¢nda e}cnc-GMP-kinaxe may inedt r~ vas u!9 elaz--jon- to a new class of vayo.chve-sgentt,-the atriai r.ainuretic factor5-. Sumi-ar e.'`:ecL--ha,e be,a - obsar°- d wrt-`i;:ihen.trvvasod7iatur soaium~n:r.-witiKSiBe, and ttseendetheliutn-dependent- vasodilator,.acet}lcho7i^e. T*etefore,:-:ornmon-biochemiealm2chsnism`of actionlhaf include,_cyclic- GMP accumulation and activatwn-aY-cvciie:rMP-4:in-ase mayhe-ineolved = in vascular-re:axxticn tor.itmvasadit3tars, endcthefsm_-dependent vaodilatovs and a-triai _ natriuretic factors- - Fiscus R-R, Rapgno P RT3., waldman, S. A and iiiirad T--- Biucdimir e, Biapkya ca Aca gJ51 ^ 184, 1985. _ _ -_ _ - - . -_ _ - c?th:, suppeort: -National :astitutesvf Heaith and Veterans Administration. - Froin the_Dtpartments ofMedicine-and Pharmacc4gyr Sta.^.furd-Jniversity, Stanford, _ CA; and `Jeterans-Ad.ainistratic.Tigedi.al Cente.r,-Palo .4_ lto, C-A.- --A Tk'O_-STEP PROCcDUi2E FOR (iBTAINING HIGHLY PURIFIED -- PARTICULATT GUt.NYiATE CYCLASE FROM RAT LUNG - _ Guanylate-cyc)ase (CiIP pyro7hosphate ]yase (rycYizing), fC th-e er.z-ytre _ cataly>_ing--[he -forrtation of f cyclic GhiP fnm GTP, exists in_-both soluble-- and -memhrane-b9und forms. These=e+zymes-hs_ve Ceenimp:icated a'e- key regulatory- - components-in a-varieiy of triologicai events_=such as secretion and smooth-rnuscre-. r4 axatiom lTnderstanding the rolethese enzymes_play ia cellular regulation i> predicated - -- upon obtaining Duri6ed yreparations of guariylate cyclase. -$evera: procedures for pur; fying the solehle-enzym_ to apcarent nomogeneiey frcnia variety o{ Gssues have___ -_ been reported. The-particulate-enzyme has been plrifie3u apparent hoinogeneity from an urchiasperm hut,to date, homogeneous.preparationi of particulate guanylate cyctase _ -from mammalian tissues Aave-naThesh obtained. Here ae-report our-eiiarts Jn-purifying_ _ -- particulate guar.ylatz cyclase-a3out S,-2Q0- to 51.000-fetd_frem ho_m63eaotzs rof -rat_lung. - _ Portiors of this work have apBeared iP abstrac_t form. - _ Waldm3n, S. A., Chang, L.-Y., and bfurad, F. frzpav,aNve Bfncr,e:histry 15(3ja03=1i9, 19g5.- 135 - j -_ - ~- _ __- - _ -- - ~ - ~ _ j _ _---- 1 - _ _ - - - f.'
Page 16: eta98c00
_ eoesis[4ni witk ihe :r:rosa:ic•r: r:e:hanisra. The ts'c constants at 3Q°c~-arel 4 x_i0I _8nd - E rx-il>s r<+:-$1 r r aU:' ELL:r hv _tip!'==J ,TeY resy2cN*'el -- ~i e aiSl:';.ys - suggest-that this fariEe rea tto. oP `i?s r hsi2 with hvdc peroxites •nay "hxve ir?ipcrsant - conse4uence: with rc=fir.ct ca th.z pulmo:sry texiei>.y of NO•, .n smoggy air. -- - '_ Tryor• K'. A:. Castle,l..,and C'inirch, O. L. . -Jo!utiafojt65-Rmer;,Z*a ~hemicc:~c~.ie3y+-4fil;:ii; ~l?.i985. -- - - - -- - - - Otk,el suPyvr.r ?7atio;iat Snstitutessf Health. - From the ^epartmens of Chemistry a:td Pioc.•smistry, I ouisiana State_ iir•:verxiry, Paren _itou,e. -/>iFCFiA1QLSM3 OF t''I~iAe E[?'E SA±v c`OYif,'z7Y. TaE Iti?. CT S'ATTON OF_ - HUb17.i: 8=t YR'4Ts:NASE IUtiETI7(sc PO' NiTRIC (LXI_fJEi;'sUpR.Fl`F_ - ~MIXTURFS IN A:R_ A mixturz of nitric axide{?}(1) snd isuhreeeire air 3as been s?udied 3 a cnw:e4 fo- gas-94a•se eigare :e smo:e We ha~e showc:-that-th s odel ays?e+: duplieates nEatiy ai the pro[_'tieS_ of [ijarfii 3m k.. iGeJ il:he i..aLationJf ilm~r-a_3,-Vrate:nli- -_ --mhbiio;-.ja;9r~. i}rs-tu_y,-tuffered-soL.:on oe--IY: wzr e-p3sed to-perfs_o~ air_ - s.ontaining-7r_.'3 t:aE-NO n2 4rdo&' ts-pc •sc.--3 r,b---,g o` t•e h+0,'ai•/i=_ D.2r s rea;a-uirecty thrdui~n Fiu-ee;eu pr3t_ u sc htr:or.3-cae e- cFP".-ts, un3e:bo-a~f -io..s~of - - _trS_b wry <-ap --TL:s ri trac€evat . is-ec•, a aved--•+'he: al°I_ is e<~sed to aQd~cni aztracis of' Lie-2:7;airlisoprene meatuce. Poth G;fer• ex~~sure and expos?.re ta_ aau'ous extracts, ttoweve€, cause-¢!Pi.to undergo a slew loss of acti-rity-that_coetinues for-severtf da.sa:-t?e prctein isieccbsred in the buffer_solutions. Gas-pkave cigarette- _ smoke hrs afready tsen-show tocause-ihts same r+.4-ph,ae_ inacli~a :en of a1Pi. --- The insttr-a.=.a oa atPr by the „de? system ts dePendea: on the C es-nee of oxygen in [he gas-strxata, suggesting th3 ihe_ o.*.idatien of ritric.cxta_ Fa _ci??agcc- d=osid? -- air is_is`o)s d,ry the t:naa°id:--ef t .a-ia- g-sv'eiea. ~e u,?,;c- of t'.:ese-- __apecies remains to be_de?eraine.t; however, s+,^.all alkoxy! or wnwl ralical:,',ech as a_- sp n-trappahie from_ gas pt:2se smok._ as svelE as sro:n thr NO.atr,/isoprene sy-tem?- ~_ da nc: Cy,^.ez to :aaCtnate oiP,. D pcs_:biiity is _thaCthe r aet_valinb -Veu ,-- - met3+.table comi;ourds-fotmed by radica processtr-ia thz BaE phaae-of 2•sot:: cigarett= -smo!~e and o1r mo:;-: system._ Our data suggest thae one gossib:e=class of species is_ - peroxYnit9ates: -pry•»r.W..k.•I}?ofey..MTM.indCRurc2, i.F - -- ---- --- - - Chemecol-Biologicrej_!rirerart+.'ees 34:173-?g;,_19g5. _ Ot5er -srryCnr N_aliona -n ~titutes u-}e 1_a and Nf :ona, ~ Four.dsiion - for _- Cancer Resiatch. - - ~ - - -- - - - . . _ . ~ - _t ivee..ty, Paior. - . Frem tht Fieparfni.=saf r'hEmtst-l•-ar] Uu_i.;eeri!ri siur-iur.a Ezce ~- Rouge. ~ , ._ ... _ _. -
Page 17: eta98c00
- ,- -_- 1NRE,'T€NYAllOtl OF H'v':AAN Ai9uA. 1-?•°.O7P:ASE lC<iir-giTOk EY -CIGAREITE SMOKE: EFFFi~7 OF SMOKE PHASF. AND EUFFER !n order to resolve a disczepancy icr the literah-re, -we.ha.e e-amined the-in ritro inactivation of human al-proteinase inhibitor by d^ect eaposures either to who!e cigarette smoke or to flltered (i.e., gas-phase) smoke.Wyss-and coworkers_ reported that _ whole sa:oke does not i=acti+ate rhe protein, whereas we rep..Red that gas-phase smoke now find that direct exposure to gas-phase cigarette smoke causes a siightly ~_ dccs. We _ - greater inactivation or the pr t in rFan expo u• to w} e c sarer r rno- ,- esz -o s•at '•o.i sr xe less a g inan s ges phase our €ariier s g ~ confirm n g g r smoke. This dtf ere ce howsver do=s c t exc a e dran a1 fre n. bet .e c - p.enous ftsiatnas-ana r•ose el 16'yss snd vcu•crY rs Tnt esip nauon for -th_ d,s,repan.c;- !,=~ I:es ic'the nature of the bufeera-used. Wyss ar'd •.o•r.orkers ¢:ed :ris buffer and ihe_ use -_ of Trt; 40.ncnes the acCVahua pr^tes9 almvst c'_+raplCt°-"-y. :Jur expert,9.ents used - - phosphate bulier_- We s[g$.3t t:at'Stu-ts an ani~ftnbl0 bi•i:er fJF':iC ln eEper!mFnts - that probe the effects of cigarette smoke. Tf-ycr,W.-A_and Dpoay, A& 3' - n( E-~niac3ory_11'rse~s~ L?1:9E1-443, i9ga< Americ~a Rzview Otirer_ suepori.• Natronar f stitnte< of-:Leaith ant- National- Foundati -: for Car Fr>z.n the ryeyartres:_.s of Chem_ist-s a,. P.,,.hesr y•~.csisanx S.a.E Bston -:touge• _ FItEE-nADICAL -CHEIdI . ~kY t5 CICAP ~.77E 5[rTOKE P''*1D 'i S 7J;eICO OGICAz. iM° Ir.?TIG N`- _ _. •- .. - . .. - C garetrx smoke 63niat s ta- eer different apstatio_o of tsee -ad cats n e m. the _- S tar aud ane .a the gx 35=. - The-'ar~lhy`S .., trs 3~ n rE z_e--el S rr `re _- ~- : :adicafa w.ha:e +de~+sfl ,pr ncpa! sd€ al a. 4-_i•+ /hycr u ru•r+ ltj_/ryi~eompler he d m tbe t., r rz ix. Xsar g tia hQx:i i: a 4 e_~x _ system that u..aQa4te or r~~ctng m y z2cy7 h i Poance sup •4ztde v ntuany -~ = ieading_to hy3rogen_t__ocUUe and fy3 scyl rad c I-addtt n e haFe sna n that - the prin tpa3 adical tn ,ar c rt 7• D'R -it v!r posas-_t; by ova en:_birvmg ~ - 7F-gas phsse of agzreae smozrcontatnc ~+nail cxyge and carwi centered-__ - r_- - radicals -that are moch mo~ resctivethan are-_the -s±r-nha5e-nriisais.- These {as-prase -- 't ndicals 3o not a. is^ ea he-47ac,e b rather o e v- d.:ce a steae - s ac by the _ '- oxida[io- of I'i0 io h9r, rhica .be:r resets with .ea_ti.: Necle ir, sToke uch a; I-_ :soprene.-_CVe suggest that t;:_-se raditals an'd thr metasstable prnaucts derivec from these - n9 cal actlons ma respo :',e for hs-ira n-ro of r. y orei::ase nh n c•_ '-y--- ~ ` fresh smek 4 C yarette sntoke oxldtzei thiols 5 disulrldex .v - gge_st the acti. e oxsdant- are lvO_ . -- and NOs The efiect~ £ s•nn.e :.n 3,v d~eroa at on are c r~ pt_x, and fr u dscuss d _ F-- We a?so dscusi the test .Aog.- 33 urpE- a to .s for the radita s in rnoke in t.,rms_ Gf _a. _ ~_ Ecn;'ser of r;dical-vm_e ated.3.;cas p-ocess „::n Ird-ng-er.tpS. m., an: cance-. ~ -- Church, D. F. and Prvor, W. A. ~ _ -Enriron_mentai7ltn-lrhF¢rspeai.~es6a:111-126,1965~ -~'- _ - _ - }fi __154 r=
Page 18: eta98c00
i9tke.- s:Tr?a:r: F;s[ionsl mstitutes of Healtk and-i'eterar•s-Acmib:i;tration. - _ Fron:_the t)epartr<=ats af-Medicire~nd Pharoacoiosy, ~tanflr:. University, Stahford, - . CAA and Vete a!s hd,:ialsr t x-_ Me.dicai £en1P+, Palo +Itu; CA: LUNG: CHA`rtA:."TSRI-£ATION AND C OkfPARISON W:TH SihUB[.'t - -HIGHLY PciRjF:ED _PARTICSiLATE GUAh1rLA:E-CYCf:ASE FROM-AAT~ rLAiLLriY-.7L - differences;n subceliu7ar d'uftib_t:ca, Phaica! .^aracte;aics zu~ antigenlcit;. - - :.aar stal ]esit a._hodgh ch..ir rcsia.tia•g - ru .ure is Swe gent_;esu{;inra-in generated to the Soiuble edzyme:_ Wiiile both forms of the enzyme cBuld-be Peguiaf d by __ _ the focmat;on of miaed- disn;rdes, the parGou3ate enzyme was reiativ=ly ir.s^esiiive in in hibit,ion by cystir_ - Witir GT? as-s_bstrate, .'ti fcrns of the anzyT.e-demoastrat_d_ typical kihetics, and-with GTP anaioEues; aegat:ve coope.---tiv?y was obseeved with both _- - enz7me forms. i'hes;_data sur;or; the wggestios that the two f„rnis of guaryiate syciase - particutaie gu,,tyiate cyct_e_d:d nercross-react wirh a nu:aber o€ -Monoc lo?al asitibodiP' Guanr.ate cyaiasa v.•as purificd t000-fold front-washed-rat -Lng- paaicuizte - fra.tions to a Gtt•2 specific activity of-SQn-rm- t_ t;y lic GMP- pfod u+Jm::/nig yrteln by a combination of deterge.nt extraction and shromatography on cr.ncaaavaiin A-Sephara5e, GTt} agarc•se, and- blue -agarose. Particulate guanylate cyciase has a caolecular weight a` 216;C~•4 daEtons, a S;okes radius of 48A an.d a--sedimentation _coetficiera of 9.4, while the soluble form has a molecular weight of 150 00t: daltoos, a Stokes radius ef ia.a; a1ti a sedin:er,tatioa _oefficient.o:` :+.@. Khere€s the particuhae-- eazy:ne-ii a glycopr>tein_ with a specific affsni¢y fcr --cncanavaGn A and -wheat germ agglntinin, Fhe eolub'a foFmof-guanyiate cycl-se d"€d_zwtbiad+o these=le-t;ns. Purifird - _ ?Valdman, S: A.. Le~ric'r.i, 1._ic., Char,g, L. Y: and MuFed, bfofefufar and CeRuf. &rv;iemitirv3T15518G. 19g3'. -` - - :Nher ;uppori: -NaGnhal]rititutes oiHellt.`t•-5nd y'ctaraas-.Admrristratsoo. - Stanford, CA.."d Vetera_ ns AAxi::rttatinr.-M_dicaF Center; Palo Alto, CA. - From ihe Departmint€o.`-Medicintand Pharracologv; Statefurd Uruve?sity; - -RELAXATION OF V ASCULAF SA1t"iOTHs'.RUSCLE: fiOi=E OFCYCLiC GMP-- -ENDJTH£L1JM-b.'-.PEI4DENT AND NITRrjypy;~1DILATOR=f1vDUC€v^ - . The mechanist:s-by which endothefium-dep:ndert-re:a*anL and :rrarovas._diiacors ^.yclic GMP levels. As pointed out above, the use of various ;nhibitors of fatty acid radical is responsible for activat:on of smocth muscle guanyi2te :.vclase and increases in -endotheiium. The mJdefin Figure Isuggests that an oxidized f^tty acid or a derived fiee - ---factor suggests that-at least some of this process-ng eccurs before its release frum t.h.e in either ti7e er.dothela cell or srnottu ^uscl= c?Il, rh< tabilifybf the Eedothdial r.laxan.r _ muscle c6m[sor.eai tc cau,e.-relazatian. Whilc=.he ur•satvr+_:ed fatty acid may be oxidized - metabotite is thought to he the'endorheli-oi relaxant factor' that interatts with the smooth interaction-with their apprbpriate receptors, arr-thought to act:vate chosoholipase As and - --aurss=the-_release ot-an -insaturatec Catty acid. The released cnsat'.r=!id fattr acid or a observations it s,im:n;rized .n_F;g: 5. The eadothehuni-dependent vasodilators,--througk .aase re;;;rar,anof :•a.cula-smooth cuscle ht•s beeo reviewed.-^: ir,edel-szplaiaing-th-~_ - 133
Page 19: eta98c00
r_ALFSODULItI.'-i.Ak.': iAi1H7E ION EkCY7ANC.E KINET]CS -_ A ruw.iievysts-app :us -uii_abie fo -dM1~sfssd} o€-4ibh-a''.:rctY .o_etai bituiing- _-proteins haa be n 1i±zd tu sttd,-eaimM-.ia-sn.e[a1 excha:i~c em°tics. C€tnendul:s _ la4!td with Eo-13_' -and : a-133 +.s-uiaipzed aea;;at t-j'fer c=;asaiairr; -vareous _campet_eg metal iom. The_ rate oF meta•=.cian6e :+as-moeitorec by a gammz-ray. seinti!fation deteetEr. Tae kinetics of exchange are first order aad the ra?^s fa!! into two- )r) in on~ and the lanthanides Ec1H1; -and L3(t categories: Ca(iI) aoe Cd(H) Gd(4t11 in - - , , - - - _. --.the other.. ~ --- ~- _ -- - - -- - . cuccigross, 7. c. Doniteli,_C.. acd Ne(san rl 1e•'rnc^ Pr2st Aei}:ng, China, np.. AGA-d00, 1985 - - r om rlte Departmeh; of Cher:vrv- Ciaik r n:veisity Worces'ktA. - " -ACOAqFA+?A tVEsTL%DYYsE-T HtD,"G`ITIOPii:7 N:C_OTINEAN_7I'r_'"- _ -- _ _- __ METAS^=I7EsIN':'H8E.E7Y8FiEDSrP.FtTNS'3?`_hliCE-- __ 7$e dispcstttrn:;,C vcottne_caii6ne nrar:,;oLi?ts N ox d€ wa :avestigated in male_ __ _r<;8'-:, DBA and"-ri mce-:ctiowing3r -- in.e_ 2c ...cottne- l:J tr:gzrst), :he __ '_ h..lf ii.~es E}r t nxiu.a in bIrrC'; Voerz 4,o_.a, n. --The r,,ic elin;isxi_nr -af -. =_- -- - - _-.cotice was accrrir,oanied Ey C- r.ad ac ur-ss s so:-. cf - t^etabr ites; _ r.,azima: _'- _-cencant•guons -"C_tns,ne:re icatlaod--FZtbtte 56A=ng,ar u:~.erE a_cF:e ed=tn i~ man 3.d__- = u soti!t~-N-c~s ~ f's agiml JC ii axic f?3 mfn. 'fh€ f3_:n b ood ~~s ?QL -® 718 -_ -= ms~-Porcatiame ar' :?_4-m rrfoni€o_ iin N Ocid='. Tne ts.va!ues f-r nicot:ne int roraia -= ra s_m, ar to to e:a tx.'er•9 5ur tS vat sfar t°v^ ; v r we e siight arger t_53 to 9.2 - -~- -- __ -m } d wtert a:. d-ffere•t c vs-rc :ig f:cart A i ge atra'n-:e r d difference-r he= ~_ . - -_ts f r coaniTs was fos.;ti; t t n'•F aLwiite vas n iinat d t em she blpri Gi.DBA m-z_at- _ e•tlv at:ou ore Sal` _he aa e determin d°o tne Q n r£tratna - e t.~ `or_ nxar: ne - -- N oa:de rss hver raa d f-rem 12.7 to ?7 mr he + lue +.cre s g.f antlv 4es nt wt h s^S78' fTBA aii i C3H mtc . St<atv rFatcd d f.~eoces u re a so Sser+en :n -_ re ponse o cS enrc oosure to crgarette sm,rae 3 he { o njec?e-d n ot n apne re^ ,o -- E- sttgh Iy decr .rsed :- CS'/ L and DE.4 ar ce ot aca-s tne a,.e.iby S*')t li:•ers or C3H --/ - ID C2 -^:nSafed o a .ynrr0 grolJ - - - - ii __- tz'e en D- P N..rn Y.: ! an -Fhoe,pson 7 A - - - - - _ _- _ _ . -~ . Drug Afrl anhsn 3rtJ 6:~v_rrs~! crr T t6)ts•roa Crfi0.,-744d _- _ From thf Sch.3ol of 7i:armac;, Univer:tY L( Coiorado, Boulder. ISE3iATloiw Ah:_D A:1Ai. YSI~ C_F N-O?C;DE-.META Y r: iT`-4r` -O F TEtT:A1l` __ sT,i1NES: Q4A~d`f€:.4TIC^7 Or Nt^~_T h-.- ::-QX Dt-1-3~idxT10N"SP'r iYf!C« _To invest: a e,.Fe_fo-mation anG el rri ratton_LY- tcGf ne-' h-g;ed5 (6k0 es __ -_m ice treated w'S s;ingfe injecti,a-of rt onrs• se!rsitive and se!-etive me:heds-x-er? - d^veioped to 4uantitate this potar and hea:-atsiEe metabol;ie. The compound was isolated _ front tissue horooge~,,3ees-as a dodc-pl-stfate ion pair wixh Cra exiractior, cartridges and -_ana'r,zed cn-an amine bbaded-phase high-perfoimanci• liVidchrotnatographic .olumn-- -= w:•,h amobile-phas&coasist:5g of isopropxr,oi-w+_.er,-Ovez'-t rr:oreries of IHNC-+ese - _ 64-7046 from bioloqleal media. _ Severai methMs of - detection - svere tcaiuated; - n_dioi2beiing - was necessarF -[o achieve the sensitivity- =eqoired _-for - j39 0 M Q f r
Page 20: eta98c00
-- sgaittet.[hoss"rere_Dtor3 imnSiinatiiciciSa;ed cr,t!scsridic recW6a. Thestd3EE sugges+ that _ some degree of strusturaP-hortology exises__'bettweea'rustarini< c_hoEinergic rec4rstors - anG ct-adrenergiE rece5tors. - . Wnier.I.C:. Eddy, 'J: }_riil'- L ,td-.. aed-Fryer, C.M. Proceedings or th-e--Fational Acudew€Y oi _- a_r,•ences of ih= flnite4-- Srr'es of -_ :4r.terka @12'2 .76; 15'&9. -- - ' - -- . _ - _ q:her suppsrt: Ameriran Heart Association.= _Froa: the DeDartlnerto( A'nlecu: : imh anotcgy, Ro-svel7 Park M-nsrra'. Insti -.e,-?se-,- Yor's State_UeVaritttent ot`=Healtfi. 13uff_1^,and t?±e-Depaftment-0f_ Cenetics, A!ber Ett~:einCoL€gfoflN2d+sire Th-,5rcnz,'NY--, - c-RYINGAR;ITOXLYnLfX_'KS EXCITATtJRY SYNAPTIC TRANSt.:'S41ON- _- _ FiETWE€N-CERCAL'-SEN'SCRY NEURONES AND-GYANT IiJTERNE'Ui<ON€ 2. OF T HE COCKROACfIrPERI.a'.-ANE{:t ahlER!CAN.1.-. i_ ALtoradiog v;ihic--lcca!izat.ion- nC an--tsrt-a-bum~a.-arr.in_ bindi+g --comDone^.v -- revea!e3that speci`-ic binding was ae.tributedmairJy irrthe neuroDi;e and to s_ome-ei<ten( -- in the Der_iD!'e_ry of_tf~e Ser_ainal-abdnmina'. garglion of the c~ ktnacts yeriplaserc amrrScona . 2. -Actioc potentiais_recorded lrom the axon-of Gt 2 under_current-cla,aD- -..fiditions were P~Ot af:EEted t%y exDosar2 ru 1.D X 1C-61F n-~ansafnlJE=n. -- - - - 3. Excitatory pastsyrautica.dtec;ials :e..^rded firnm-G,?. rfcked BY-s;r:viaton oi - - vercal sen,ory eet.•ones,-wer,. ns'Y.;ve to btck by ret;ti.e7y concentrations of-u-bungar7,toxin. -The time-course !'or blockade was found to dePend on toxii%ccacentratioeand frequency of affereiit uimula(ion. -- - ' d. Excitatory po:'~ynaDtic Dotent:afs recorded from Gt 2 wers not affected by _ exposure to I.6X 10"xRi quinuctidiny! uenziLte. - 5. We conclude that at !eas: ? Dertion of the 'snc*-biangarotcxin binding- €omfiOnent rtpresertTs eh^_linsrgiC=receD'oj`-- ^r'ch have a_p=:isyna.iCc furt. ion at synap5e:-betweeB e cai`Se]sory nearone-a3F9-Gi-2. - - - -. - : - - -- ?.attelle, D: +'ue, B.,Pelhate. ?+t:;-C-ep1er. F. f, an!La Journai ci FxDerir,.en;a! Biology 147:d73-4g9,'.983. - - _ Othe, support: Ciba-fcuidatien-Anglo-Frencf: Exchange 9xrsary and the U,.R: National -Scier.c€FounQation: - - -~__ - - " - . ---- --... . - Erom Lke fi.lt" i,init' or 7nsect-?Jeu ophy -oWkY-snd-P armacolegy, -DeDar[.^.tenr-of .-?2olog_1; Camtridge 1=aiversay.-Cam3tidge, Fr.,K.; Leboratoirr de-Phrsiofogier Fzculte _-de Medecin€,-Uaiversite-d`Angers;-France;-and th_e-_DeDartnmnt of Genetics,--AI^uea EinsteigCollege-of 5iedicine; 4'heBroax, NK CHRONIC INHALAi7ON STiiDIES°IN M:CE L F.4CtLITIES-AND` - .. -_ EQUIPMENT FOR"R'OS£-ONLV• EXf'OS'JR£ T0.e:~GARETTE S.^.iOKz -- -- Faeiiities- ande.uipruent are described for largo-scz!e-, leng-term--'no=-e-oniy' = inhalation exposure of mice le ~whol= cgacette-smoke.- ExDerimentat=Drocedures and 127 - - ®
Page 21: eta98c00
--Win;luist, R.#--, Faison,. E. P., Waldman., & A., Sch-aar.z, !C,-h?ucC. F. and Rapc•port, R. Proeeedings o! the ~halir.?.: .t.-mfe.nr -a,f vuie.ees of :hz UniieG S:a!^.t o= Axerica $1[ - --765Y7538, 1984.- -. L ~ _ - . -- OlFrrac•Ol~rt-Nati.,nailrsti;ute~~f-?lealt?~.asd~'eterans_Admi3istratien.= _ - -Frorrthe Oepar_tment of_ Cardiotia;cu:ar Ph_arrns~olog.,-M4rck :ncti;u:e for iherapeutic Research, We.t Pcicty PA; Uepartment- oC-Madicine-as•dPEarmacniogy, Sianford 1)ni~ersity, SSanf2rc,:£A:.and Yeterxru Admenistratinnhtedical Cancer, Paio Aitn,.CA. _ MFC HP,NISh9S-i,F AGENi?SiN' TR:PHOSPNATP.-, THRG5±BI.~-, AhD - -- - _- 7f'iYPStN-INT_rUe€D 3F1A7€ATR?h' JF RAT THOryAGIt-' RURTA - -- The mecha isms _by which aden ,ine tripho :.F a , thromb c, and t=y; _in -cause_ -relaxation u~ vascu:ec rnoothmuscle were invrstigated.. Retaxat:on af the rat eiwracic ._ aorta with adenpsinee tripl:osyie_ate,thromrvir.,--aiid/or.tryF~;ir wdsassociated with -- increased - ieveis -of . cyclic -guanosine - mcnophosphate m -Soth -timti- and - corcentration-dependent manr:ars. ThrOmhio_ and t_rypsir dic3 .o: alter_cyclic _ajer,osine -_ mOnophosptnate leveis s~her0a: ~derJs:ne-_ iriD'spr?l.p i:icre.seG.faiic ad_eri5ine 5 -.;,-F~~ : ~-, . -I ~ :- - ~ {~- _. a.,, - t -- h ~. 1 h I h -ntor.op osp ata_ .e.~-a~ ..r s,gnt_a~aii r.-.a..a[.on:accuree~. .erso;- e >n3c' els~rn - ,. a t --abolished-adenosi?etrip':c':P ate-; Fhre.r-b .-t and tr pssr.-induced el=xateon' and the -_ - 236ciated t't rease_1 ]e.YiS Of cy;,'tic n. ^stide3- e'i-la,.il -a d~~ t.x the-e Yg2orewa3 9•-.o - inhibiLd bv tx;osure to.-_nordiF.ydtoguaiaret:c :~;, a iipo jgenasz 'iphlbi sr, -•.nd-- - _- eico;atetra;not., acid,-a :,ipo_xygen3;e and cyclo.ixygcnase;:nhib r- th:;;meth cir, a- - --cyc:ooxygenasa triibirr potentiateti.ra:aAation to.these agE,rts whe_rease the i^,creased -- -= --- -levels o!:. Cyclic _~nuctEOt:3es.- due -in - aCenosi.^.e .IipnoSFbate . y:pre unaltered. - ---6ion3ophr.na.y! bromide, a pho:p+o'IiDue -irr-inuibitas, dECrea3ei- Celai3tion aue to _ adenosme trtphosphate, thromr:n, and trypsin and the associated mcr,~ased-Pavels-of - _ cyclic~ nndec_idey--Rea.ovsl-o:-ex•.:~reth;la:- aiciun. ws ~: also pzesumarfr inhibits -- phosphntiprse As, crrvcnt^d the eievated levcls of cyclic nurle0iides snd_the inhibiiory __ -_effects-of adenosine,triphospbate and.irypsin an con«ac.ian. in couirast, sodium -- nr.oprusside :ndncsd ,elaz'ticn snd/or -increas€d level; cf cyclic guanosir.e -°Jtlonophosphat2 -weie-u.^:alte'.Eu'.-by _nordlhydrogi,ii3reGc Scid, eicosatetrayno?c- ac ;d. _ branophenaayl-bro^ai5e, and removal Of extraciliular SaCi_m. 7lfter lncubat:on- of intactt€ssue.-.vith r4P-oar•op:,asphas6, the patterss of ;.rste+:: phesphorSlaN.cn_ censad b;. ' %Sda- asine. t ,phos,;n+ts. thrombii.,-gid 1ry,,sir. -a -.distingni-habls_ fm , -thoxe= of -aCetylchOl3ne, `:odsn.:-rs:!rCprli-9,de and g-nroiHJ cyc;.fi-gnanoT„C m]upphQSpIatt. Ah - - these agents dechosphoryla:ed myosie light chain.- Thus, thc p-esenr study supports the -hypethesis that relsxationjnduced.by-adenosine triphosphate, thromhin and trypsin is _ ai%diated throught£e formation qf an-endothe:al facto:= which_elevaaes eyctic gusnosine - monophosphate-.leyels and--cause€= cyclic _euanosirz mor.ophosph-,te-dependent protein phosphorylatibn-asd dephesghorylaticn„f rnyosin light chain. -- Rapopv'.Y, P rr . 1~:22ai. - P4:.B:. and Flsrca. f.-.- r'rculuan.3r.eerck?33te:464-479,14.4 - ON:er supporr National-=r_ ststutas of.Heahh,-4etcrans Adrr listra-to :; National Researci: v - Se 'ce Award ____ I~i-- -From the Dep rtrnt.~ts-ot +tedicine and 'harveac ky 4tar.ro [.. tvern;: c--: ooI-oT -Medicir.e,-Stanfusd,.CA, and Vet=-rans .Fdministratior tAetlical Center, Palo Alto, CA. -- i35 ~-- Y _ ~- ~ Pv ~
Page 22: eta98c00
-____ -_ ~ I STIRUMC3RAL-.3EGLidRtFiEN'TzFOR#LLflSfE¢Ir`.ACCEVA'_`uR3-CERAT--` - L[VER7.`-iCR•'.3<„-OPvfAi 3=tiYDRO.YY-3-F!ETHYLGi.UTARYiC'O':rvZ;"ME A - REDUCTfcSE -: SZV[ral corsJOunu3-cJIItalning +ari.=u5 struetural n€oleYr25 of NAD_(?AH),- were _-esam:ned ss-possib!e effectors o! rat [ivsr- 3-hydroxy-3-methyld!utaryl- eoerzyme A - - reductse ac-.:ivity :?sficrosomai rrdur_tze wa: aftivaredwith <.i siN-G`--H, assaved ycth abcscu-at ng-NADPf cor +-~2t n arrr' --.crcasrrg aat --~tit of he teucd corrpourds -_ Under hese- condit ons [Fe esseat ' and t uf rcxe s u n e reqslsd. to - tle tenca y c^.han< the a tivitp of tr educta.e r 0a: of 5AMPkh n the 2' ro tton of the nucleot,de u hgsphorylated, rhis 'los]enc ac¢v mc c. dirrm 'ed -- -, -. 2' _ _ - 8ie:ke.•rcear.d oioP~r srk-` iese nCai:~irmr ru;or,_..Zi(',1.4_c-~rs7,!ys' Rcitetman, 3. and`Shea%-:er: i.. - , Aviv nr:erstiy, ti:at•_._ --~- f=rom t]g,Depaitmen ef r.che. st•y,, i*. Ge_'-gF S. Wise Fa^;tlty of'LifE Science ALLOSrER.C ACT-iJAT!ONGF,.ATLi+ES+NRt:3trOSOiYAL --_- F IC--- t-HYD20k`[ 3-7vIE s .Y*P~i;t3'TAPc` COER rrc1F A-RED,^._aASF..G" NICOTI* AMIDE ADE i_ ~- _ -NADH and N.ADt au- r:_ei.hcr _substrat^s nor in!rtri<.or.- of _3-Svd_ro.y - ?-methy[g!ctarY coen.yrrt:=A (Nt,°GCoA; reoactice--in-cn.nzentra*ions u] to d~n.d__- Addition_+sf either- N ADIf or hJAD =nFarttert t?+T_-aciivi:y of_-eat Eiver .a'aciusoma _ - I--, redu.ta..- s r NADH''aredvo affect tnea iivn e2 t-' f;eeu. tiaw s>lublv.Len.V,m• I The _ desrree ,,; enhxne-.^[er,t of en y~€ . av €v oy \ sD` decreas 3 as GSH - --- concen~tten_-rn tlre ~ av rcreas d. Ado,r,en nf S~f i._9 NADH u-the acsaytcmv.rted- - the sigmeid;.; r+2i':I ces:Hcinr: 03-^;ADPs-de.:-::denr, kinetic cu= = of ;he micosoma -_ ~ - reductasr- int? MicFael-s tfentealrretics-_(1-> M criefficienr --1.+)---;'ur<heuTcre, the -_ _ ~ kinetic currss- were ss ft°@.-er Y;e +Eft -iesclle+3 in an-ut:.-to-35% --decreasa in _ ;h- - -_ - ~-- -_eoncerrs at o. of_NADr{ re,tuirrn [c, obtair hai:-ma~ima.! -elnr,t3t (>" =) in Tre n*xsence of 500 u.a.f NADH. Agatr- t:es effect- -r NADr, was drm.inhed as .£iSH - oresn aions 1- increared The•__ re..rly denscns z e hat nD(-si rs an a1to..errc- ti ^tor of [_ HM3 L.w duciase •Fhe-cresu tn o i ia:cae th YR4r i,FA .ducta has 4r1DIH) -. tlll__ tmdmS ci*c( ) - sstin f ar €he :,a alu.c NA^FH 5r.. ,} Ttie 3ourncl_~ B:olos a7_ l:einis! ~.2541'=2i16029-1q032;~i9S4 ---- ' - - - _ -- From mG I'Jepaitmen€ of E e;tiFn t~--~,h_x G=orge ~.-Yise~-Fa i,y of L_i[c xtc ~ces-,- ._ _ _ _ ,. ~--~ Avr vi~nv rsaty.-IsraeL _ REDUCED GLUl'A I-i3Q.h[E tN C}^NESE }i.KMSTrR-0YA5`Y CELLS -. - _ -- - PRJTECTS-kGs.{NS IYrC-fEVAT{ON-OF 3 7r.YDR03EY=.f sfETHYLi UrAU:?.--- -_ COENZY.~rE A RE.^--UL'£ASt-@Y T rv!EfU'RPTQETHh.TJOLDISULF[DE - When the disulFide ~ of 2-merczptoethanol- (ESSEi is added to tht medium of _c_!tueedCh:nese hamster ovyry_(CHO) ceil>, a t:ne and-concentratiun deTend<.^.r rzlease _ ef 2-mercaytaetY:anoi ~ to- Etie TCdiurt is a.errved. -The _reductio* of ESSE to _ 2=aercaytoe:3rsnoi uy :N!s i,-a 3aturahirC:ress; the-ati: be:ng sn9roximat.!p-3J y..ckr -_ C ~
Page 23: eta98c00
_ -2lease ~Gd me'..~bGlisum_ tl2£ Do: a1l0`~n_~ g; os others to {lfedicl [be. structure 4C the acFive af either the 1:pCZyRena,, or P-d59-patftc+ay,._ mater:ai. To date the oest xvidxAce.?uggests lhat the unsaturated fatty acid is a prvcuct lournal oJCye!ic Nuc:ec.:de andProtei.Pho,P7ory+atiort 2esearcn 9Fd-5;::gI-295, 19.3. Rapo?ori, R. l.f. and Mt3ad, ~-t'.'. -- - - Medieine, 53anford,-CA, and Yeterans AdmiristraEion Medical Certer, Palo Alto;-C-A..-._ __ From-tSe De7artmeets-c£=Med:cine and-Pharmacoiogy, Stanford University Schxl of - Other srPp!r_ _Irationa3'?6atiiutei.gf.i:eaeth and=yreterans A,imin±siration. -. GUAN:'LATE CYCLASETND-ELEVATFSCYCLICi.h3P=INRAT TiS.S'_%E7 - - . A T R:AL NATRiURmC : AC_'CsR SELECTIVE.Y.4CT±YATES-PARTiC'I7LATt- guar,y"aee cyc, u9iie beift treatn_nt bad no-effect._ Ac umulation of ^ycJ:c_QTiP-in :. __ kidney miaceszn daaaa.~ a et-mu..ted hy-ANN pcn a;o:. of guany?aiecycl_:r, _These=-, data suggest a-ro€ ]o p'tr:a'ate gLanylate . Yclas=- in the..mo/ecular a.echaaisms -underaying the'Dhyst ogicat'2:fecte of ANF uca as vBseu:ar re:asatior., natriu.esis and --tissuzs~'aa-net -actz.ated br ANF Tr,+psic trea me>'t o:_A NV prevent_sd;lst astixaiion -?i - - and li.5r b'_-not rr =t' F'~;t_Jr brarf=. `ilniL'b-E ganyl3te CvstaSe oFi!al-'d -fa)m: these--_. homogenares o` rat Y!dney. _ Acttvattcn of particulate guanylate cycia;e by p14t'- was alse--_ abserved in-particuiate hactim:s irorn homsger.ates of r`t sortz, ?estes, :rtestine, f;ir~g- - in a concentratioo- and't:me-d€pende.:e fastiioR in crride- membmne:i ~obtatr~d- itar_r .-_-.- _ _ . _ acctte!-1a:;nrt at-a sym[hetie peptide cautainiog the _;niaa scid.sequenqd and himiogicai activily of strial hat 3reti== fsetor (RNF?. ANF aa,eivated particu:ate gu hy ate cyctase - A strdy Fas --doce "ea ihe effecfs on guarYlate cyclr.a- and .c3--lic CTk9_ - - diuresu. - - .°/aldman, 5. A., Rapoport, A. 10. and ?furnd• TkelorunctoJ-Biolo%+crd Crpmiatry e39(23::J4332-€933i,19g4. Frcra-tRe-Departmentro: A:adicne und_PharmacciiaY, $tanfr•raa {inivx-air-~ Schoai ut- Atedicine, Stanford, CA, aad Veterans Admimstratioa Medical Center- Paio Altn, tA. = Other s.p~rt: National tast;tutes of Liealth a_naVete-r3nz Adm>ri.aratiua.-= - CYCLA3E IN V.ASi.ULAR sxiuJTH SIUSCLf- - -- - ., - INDEPENDENT RELA)±471S5N AND A,C'3VATE5-fAR'_'fCULATE E',UANYLAT.=. _ A T RI.4L-TJAT)tIUR-c T 7C Fk" -"I'4R ELICIT3 AN ENDOTHEI"iUM-- _ - kvxs-o•_' eGivfiPwilh 5i. chang€ in the levels ot' ~A1.7P. - The AN%-indueed _ increases in ._ -function_alty desi:mjed. Tha-reL"cztions-were-etmForailY -~srciated-with. -increa.ses in_-- -- retaxe_ }soated -n.bbtt- aorpe±egtnet+ta tn_ wn:=n t.he esdotheltum-,was.sr.hrr :9taet_ or _A?ic-amino acid iy"ttfieti -pePfid2: frixgmertt of a:,ai natriurs[i = facter-(A.NF) particulate guanyfate cyclasg.. tissue levels_oCcCtYfP. AN?appears.to ir:_creast v-ascirlat cGMPleve_lsry activatiun ef. - (endothelium-independer.tp. -ssx'ilator effect of-.iiJF may be.mfdi>ted- via ircreased, - cyciau,- having no effect Ae -th: 3olublc form of- the_-cnzyme: Thus, -lhe-_ direzt _ oEtarnen-- for soeiu"a nllroFresstde. AN: selectively sct:vated - gart,culate: guany:zte -- cCMP q}osphodie,a;erae v,hibit5r Pvtp$-22,948. -Qtralitativelr :imi;ar rz-su€~ were - RiSE5' were a3a ob3Erved m Sortte seg?nc t3 pretreated wf:h caicium-EZee buLfer or th^. -- 13d_
Page 24: eta98c00
EM ?rher sup?n^.' iYa_ttcnal ias!i:a-~>cF=NSaE,+ and,Fhe rv°s:oaal Fo_vnd+ticl :or Cancer zZesea~chY From thr-L'epart _-~ai_a eF ~hemisery 8nu' ~irri:hen:istrY, i,auisiana `-tate si_n:'=~rx ;y: Ba[o~ _ -UTTERIIVE B Or:i3_FLOW A'r °-_:AT.,CF39Lthf:RE R_ iPONSE T^ REPETt%IVE NICOTfNE EXPOSIRE IN T4E PREGNANT EW'E- In orde t, ein+-itate nueran s.r.ilk[na _experuaents }-ree designed o- aetcrm:rE what _-dose. Z.t - mco ire-.:it- me <<;.~nant sF.etp- .FUui.: preciace -those- p%=sTS:.c:ine concen?r[ir oservSd'sr Y[uenansneoK rs ansto m-asure.uterine blwd fvow and_r7asma a t i.fic'a+rti es en rc;p;nc cr ce,rtit - ex7o,yr> (es:v 30_minutes)._to that nicorine "_das:,_ seve?< - r.ca:!;- e~..:k€3sriaed pretnast .s7+eev- eq+:ipped with - --_efeetrom_agne[s fh~'a c;ooes a•caa7 u, t._rire arteries, ye cbre-.ved tha[ s nicotinc - dose of 0.2 mg,•'mir: Fa> 5 nsinutss resslts i--.en. ?i=ia nic_:i,x co+~ce:~crario:s of -i3 :- - -> L' ng/sl .SEM ~a-y 77'. immediarc:f-rallawing iMvsioa. This dCSL ot nicoti*!e >ras :hen-_ _-:r.i'ussd i62rv 3(f mmutes±or 4haar.-, ar,d xii-'auots oLblood-were G:u vn immediatdy _ before and after,:.ic_otirs^ infus:on_.For_¢etermination of-g?as;ta catetSrlamisus- No--_- ..__.;igniGcaai akerasi+:;s ic p=as[na c,r,ineRhrine- and-norccir.cphriae were obse3ved ;h:aughoul-~eez~l'-rim_r,iafa w-it),andro-signiiicani c]ianges in-uteruie-bioo_d flow _ -=occur.edatahYtiin:d_u.'ingth?experireent(^-3•.").-A'ecoe4.ttide[ta:theiei-R spesies - --diffefeacc_ bet+e±r sh=€p -aisd- .__.ea re-__m4 3c -ia<- n_ icotis:c f resi€oid - Cvr CateclOiaTtr•.c rereEse: .6'r,rt:3. R:. Cgnover. W. H., r; T C., and Van 4'cnaki,. :f.-_ lmericen ia~ a n~ ..hst tres 151(7pBS5 ~$'i i7($.'.- su:DNR U.~.'PuDfr.-k]ea[.'nServ.c.. - Ftom the Deyartmen: o: Reprodrictivefied_icinr„-l,r.iversiat-af_Ce]iForniaat San Died.; 5/-7[00l of Metrcin_ry xni rhr 73sparccent x-Rio-eh;,rr cry, @r~ndetr €.~r._vers~iy ~'al~am, _ ___ - T4sATh1ENT VF.`L#ni2r3':_'s-MeM°t^,9r+E5 FOF< SIh90LTANF_.,^.L;.L'IALY'°s[S - -- . -Diarysu- memoraoee u:.ed f?r sinultanel+. 5__ dta- sis- onecntration -requireu - p}etreatmem tq-remn-a us-absor6inz=am;me::.ds-Lached-Lo+S: tF menioranes and to _ - reduiF the absorptidr> of pritein to the meaihranes_ Th s-va; a:cornFiis!;d- wi+h sodium _ -carbonateznditha6i<ti or with `sutfur,rer.avai sclu s,.'---Froten deteetniaaeiov were - naade :vit'rr a+r o-&radfoi e+retar,. reactr?n a%1 w•ih u abior'os m~. at 28£-nm ~ 57fsbie _ - men!-:ancmpo e;!= canributed :c at3errar.e av spectra_and xitered :he ravo of 80/260=am aF,arb=, cz--S at~(ta^.rous t[a ysls xiucoace4tratica-en €he micro pro+sin _ dtalv?^--spncc-.t,a:cr- a,.vara?tr,,= comLa+inB.--~Dspect{ of .5:+t^.-ICYer 4ialysis=_ and = ul,rartlErat+an estik5] is rapi;i-rgn[c er o;--_al[€-frorsl the pr[.tcir; x51'atic_na.- ;rier - treatrqen, of ine^iYranes ediieed -cncer aiieties -in recenta[e.e rccoveries, ei'minated - se.•-absorbing componenes of menCraaes, and improved *ecoverias of proteia.- _-- - --(2ieFr,,;r:c. V. Z:. St. Denis; R, acd C uhen, E_ - dnalyi:ca,' dixnea°istry 145:3c3-35Q 1985. - -_ From the Pacific Northwes; kesearch Founaa[ion, Seats!e, WA.-- _ Id3-- _ i
Page 25: eta98c00
previously aemonsl7tesd nat 3 ttiT i a m nt of rne perncneai rra roDhag>s results to a two- to flve-fold 1 zse tc-'F a aepo C+~ pSc phryl pio det aaert -nrote.n - - _ kinase CiYe now re,/.>rc L at thls .tfe_C ~ss_ c•_'epen„e t.t3crt cont ]u:l.g protei,. Macrophage°activaticsfor-;usnric{dal-rcicro5icidai--fur,ctio:-s can Lit achievsd :a- - - part by tr=atmsot with -reaotobinaqi -ieterferr.rr gavima ('rFFiTF -irm vurn- tr?e have - _ (ei;her braai or s:'rmufe od) h2d co,ztparabie y;m .olaes.-'Mazimum v.lociFy (Ymax) was _ - increased both by 4FNry tre>Knent and also by ;timulation with UG 6r PM1:A. The m^jo_r C.yARA^fFR:ZATIOFI Os PROTEItJ-KSNASE C':4CT[Y:Tv` IN F\TERFERrIh- GAMhSATREATEDMUR:N€-PERl7r-yNE..ti:-hiACROP:fAGtS synthesis, since ereatmect-w;th cyclobeximide under condirsns-w~here eorma: Froteie synthesis was-+nhibited by g+e.ater than 95% -had no effect r.pon the devclopmee.t of increased enz`sme attivi::. -Eiaeiination of Ca+t a.:.l-phosph.u::Bidrz~lt:iremects revealed no d€fferences-$e:w=een=eari:ire-iscl5ied fro^tcorttro!-cr iFN--treated ceI:s could not be - di;•,ingufshed-ia terTSU; t.hs• eiacvgiycL:cl iBC}or piwrbol diester {PMA) :on.ceatraaon - _ requ :e-?_fo> stitnuhtnr 4_`- acti ity-=- YSnett -ana.,vsis=i,f_ thriaTP-- a., subst:at=j -- - Goncentr3iion.-fieCead^nce-`~uai€o:F'! :hat-both con'ro' and treateQ- enz,rne prlJaratioi? -- ;=- _ differeace which-spuld-be di=ceie e. be-ween pr.te.rr kfna.x-r da i"ed uont= corrlr4 -` s INrnishir th ver<uf-f-tezted-!e:ro41a8es-aa te reagntudofe re,nonse ta ' _o: PMA;- - SFN± trea;:!rcnt increased :h?-stiu:utation index ti.e-_ ratio of hazal to stimula:ed atfivitvl - -by a fantor of two- tn fnuT=toid. TbeSe :E3L'I[a gng yt tha:-'1: 3'io - YYer$IL• .niQ:J:at1n9 vl e51it ^$ prot l Rlneid re 3- e ll' !.=28cfrr.-:aaty IL 'v^_rFY_1[~ '_rFY_1[~' _ when ext;{ised tOan"apF npT2RstiC11§aR[! ~ 9ectoa, D.L.,-,fdam=: L3.O. _end ilamiitm,T~.-- - -- Jol:rnol cf Ceilu7rv Physiclogi 125:c8?-d91, i9R5. - O:Fer rrvivr!~ tlnitad-SateS Pubnc-i;e2:th 5arvdce.--= - From the ,.^-_.,partmen_EE-of--PZdiatrics,'Paf_h_`:ogy a:c Microbiology-.n::unologX: Duke ___ - - -- - r Uhirersit9r JurFain,N" '_ - -. - - _ - - - - ~- -- - - IDENT:F?CATION uF Tii& L-YAiPMOFC`sFE SOLC$LE-7MS4UNE RPSfPOh'SE i- - SVPPRESSOt3.-;N l,`RINE-OF eL'EPflROTIC CH?LDREPI _ ~ n'l51f n-~~~ uCV~'~Vi11. ~~RU!YUiC. t.xrYi.J/ -I^SYC/::,_l nJ.vG suppressed :n-rivn and -iv vn•soimmune responsiveness ef-crcertain etioiapy.--. 3ecause - iitn thW3iszase, .-a i es fram. -increased sujnresser ! 8';nv.t, has. exers`as. _]a:eil- MCNS-pu!ient< wers,-x--eec~d-for _acav€ty_c° t*.e E;inpkokioesa:uEi+=immun*seyounsF - euppressor (SIRS), -a p: duct'of -: n anavalin A--or in_+.eaercx-„^cii.~ate~ sop7iesdr_ T--- celis.- Urines from untreated MCNS p3tiens suppres;ed polyclona- plaque-for?iing celi -responsgs of tulrured spltao..tes. -lhi= soy^.ressive ac[i.vty iden[df;ed a.t human-- SIRSby'he f^Ilowin= fanctio~•at and4:ysi^al criteria (al mo=.curar.+eigh: esiir~-atAd by - - Eross-reactlvlty ws.h monuc onaa an:lmursne- ._-ann r,,. rppress. _ acavs, e _ disappeared from uri ne after is-i?iation of treatmee.t tr:n tefore re?nission of symptoms. - ~ _ gel fil:rctfon; (b)-kinetics of' suppresseai;(c) -~ihiblten-of Scppresvorr-by catalut, < _ _ lev~rnisole_, and 2-mercaprwthane}, (d) abroaatia; , s acti~itp <y acid-or crueeasc -- ~ _ - uea:uluet~ (el e.a_r;Ln _~muic_- .ege ts~.:er.nu.~Lr -uyups L _ maaS.nyn;. . -- vr --l 3iRC 'b d' , -g..- ~v •- ~ty
Page 26: eta98c00
-.= sedsitivity=to aFNa-taeGiateU supprerion:--T>•:ese daf3 suggest_that 1FNe -can soppress ._ _--immuws-re5pon.es by:twe-aif[Crext-Uathwavs sod C>at- in-t -are eae~^ ar . eells, ac:iv'arion of=auptzrezssr T cel;s is+he Zloainant pathwav'--The prs5ence ci T ce:is-mnst . - -3i:[x p:£veu5 Sircr>ir~p?re55iJn of et e5ier- hy ItIVn. - - - - ~faternntfana Joarita:-c/fmmuncF>:ormacaicgr7{i):55-71,1985. -9tF.er 5up59vs: F`.6;santo ComParry. .= Froy the Department of Pa:iSOingy-an-t - oora;crv Melicine: Th. Je.rs!i F?o`a ,a! of St. --.Ikocis.and.theixya..mantcf~:^-atE,oiaBy;-Washington t, iversY; Schoa-it<i Auedcine, St. Louis.- _ ... - _ . -.. . - - . .. -_. _ ` . - -._- _--ttv SB:T:C3N Gi 3tiA71ikALh.Ii=.i'FIG $Y fDENOSENE-Ft9GNL'Cf..EGTIDE3 . The ef ect ^f--nuGCoLde3--on nar Tai k!!!2r acli'vity in monFe sp{eefi -wy -._-1RVeT[ig.S[d: - A;lGnosiLE .ybUnLe:e4tiue5 were-io_4^d ?t'stPOng7r"inhiblt Ratniai -killer _:- aciivity, wita--a aa!? maxin-al innit5tio; at-5n ATP=concentra.:un ai 2.U yM. The -- inhibition- was highly suecifia-__ ix -Edero;ir:e - Pit.:Ruc;eotides; ade€resine- deukyrnwnu.it,otid^_s,-goanesirie deor.vribmyau.lea€i#s, and guanos;re r:bonucieotidesitad -: verylow,--if~any. ii^ibitory-effact _-F~pcsimeaL-with i`e_-.it'u iahibiters s;tewed tr.at the effect is transmitted by purroergis!eceptarfs) :oratac' en+.he-cdl surtse. or- -__ the.kitretics of t"n€ ATIa effect v~i:h the eff.cts_of €:ifJnoperazine and Quinacr2ie showed - that ATP acts late-in-the !yticsvclP,-possi'ay imriediate!y prec<<ding-tSe_prugramtning_ ..-L+rlYSU.- Kenrik:.son, T, (274rr, °.@.)- -• /mmuaology •r.Ntecs '7:17i-17d,1983.`- _ -!'irFer suppor+--U.S.-Pub!Ic iiealth Service and the National Cancer In=_titute. --- FrorG-Ebe 6epaameai_ of ?vlicrobiolog: and In~unoiogy. 3Qfi-t:'•c__C,iT,c@r .@e:earch _ -iabgratory-U- ve.i't-y_of-r'siircmia,-Berke?cy ANTi-MY-2fi: A;vA7NGi,LUNALANTIH©LyY IPf :PY,:.GOCY?E-CHEMILUM?NESCENt"s -' - - ~ - --- - -Anti=My-2t:, "~-m w -mcaocloixal -IgG1- an .tiody, wx~"is€d _agaivs- human gru.nuiorqtes-and tti -been shoza to innia~:`luzntr.o.-enhanee~ S!ec_5o-ndepe.,d€nt - -- .--chemiWninescebce rt_}e'"hun: ~n granu!ocytes?vr-aosoiytes) resDOn+l'm€ to tha so!uh[e 3ecr€rag2gaes=A23i27 -r icnortiycin ;ca!cium'onopNores:-_anG-pherbai -myristate acetate-- -:- -- (P_MA). - Anti=My-ib-.inhe;ition -n{ CL -was--re-tiessib;€ and -was der^endent on botb -. ucretatogu¢_ and rnonocloaa! antibody _-encebiratioa. - This-inhibi::on_sppeared to -E_- - directed =at --the=-compenent -oC granulrrtyte=" CL "thaf 7nSepsndent of _ NAW,P)H~oxidaie-catalYied-forma[io.n oE superox_:;e- anioir, _becaase-neither pDsoniz?d ¢ym.csan-stimulated CL -mor the -PMA-induced decrease in NRD- (P)H-assxiated _ -_ sutollaoresZence wan affested by znti-My-?5.- lu addition, iortomy;in,-ove: -a wide _ -_ mnc.entraGon raA"s~=faited-te generata any ~7zciease iR'_gr:tnulxyse antot`luo:etcence. --- TheA32187-i:.ducec-C3.-iahibited by-anti-My-25 xa9-cor_re!atea-with=its depression of .9xygen-consutaPtion'-_--Furt?!errRbrtc auti-My-ZE `-°a.5 -ne: cy.oooxic and dfnnot -itsNt- - 149
Page 27: eta98c00
"- functional pPranletei 9r the 'e>3utrop` ~' tRe'j' wish to IDeaSur& in spite U: these CO.n.ferll! ° IVoiLLce sup£SOxlde aad hypOC ,i0[OLL9 aCd. . - - ' " - -- - -- '- - - eCUwvat.ent with resa7-d-.o chernotaclie per(e-m5nca, absiitY~o d.grs.u h~.e, and abitit} to. - metho~it -of tso:att?n wrtx wau,tr-r.tSil fcncte5r.. The 7esr!t5 of-this ituAy' in__dicate-?hat - while neutrop5l yielG and pu Y wzrE ?ern:IneA by :so!a*.ior, p,.cesirr€; a(t cells were _- -rhEFt i!ai bee:' rf0 sy-memailC t0Yp2SGOC Gf i)F2-fUnCi:Onal St$:a5 Of-neJ!IOpiliS prepa:4: - by- the.yariou., met`:ud,iog a :r-i` st a-'d- } ve ecfnoared'd'-cemrr zi9 used - ~-~ - CRisham, M, k' Engbrson T. b., McCord- I- M., ahd Jones. $. P. Jmuncf cf Immwtoia8ic;tl M1fethods 82;313 -5'..^, 1983- ---Othe: supPort: The.P.^!erican Heart Assox--iation. __ rrom the De-nartnent,,af-: Biochemistry, College oi-_bEeuicine, . _ . . - -. A!abama, b?obile. AND CALMn^Ur EK - NUCLETI7DE-i.EVELS A POTLNTiAL REOUL7Tf1^Y ROLE FOR CALCIUM = -ACTIVtTION-ASSCCiATED-ALTT'RA'.lOiS INNEUTROPHiL PzR:^vei-'E _i•7ADRH-poaW -ucreact to-SC.S; 'a9.0_ and.54U-z 10-tsmeolicNl, _resmtiiveiv. - ThesE- ghorbo! mycistic ..ataSa o: =orryiieucyipF:e: plaianir.e, -neut.ophi: E'l~AsJP :- -yaa_ayured to be zg.v c 2~,~`rnali n L- oor.-acttrat e:-witis :., . n3tze ~--zy:n6;?n A,. - The concentrar;on cf-NADP . NADPH_ in resting human_neutrophils has been . - sncrc~ses4e3!yr:csao_.u^!e.r_tsdstonnen.trvxpn_are-c:a.ke•' bY-thcaGditian-of the caicicn: _ ret;uiateDnu, pyr:dy,2_suc2eotsde concenirauunan eneaca+ated reutrephii.- --- - icggestirig a roEe £o: cakium an4 calrnoGtaii atu±=p3ssibiy-prutein'kiuax €-in the - - induced ir:creases in the _!vpDP .. N ADPH-yoot. These studies are- ir.terqreted -3 and ,Y-!~-amiaokexyll-5-chiaro-l-rphtha:ec€- sufonaniide - a!so- iii:ibir 3t-imuius- aMencE --of - ot;lEr_ sainuL.-_ _~ CalmcduLn -- Entagon!sts_ - triT!uopErazi+~~r_ cztsiuatt ionopnore-:a23i8 , ie the_pres nce uf ca3c:um wil7. trigeer tha-inerea;e in the - ancagonst e-in'..^'_~ua^_tnyi3mtrs;-xtY~°-.~.~5-:nm;;ihe.x_ybea=oa?e hyd:x:ricride, whi!e- - --S9arkman, L B.r ]oh-s, T., Engerso::, T., and Joaes; H? ciocl:irnica et SecPk;sica acta Sa3:813, 1995. .?rh,r su'vpor/:-Natioza! !nstitutesof iieahh. - _ - - From the- Departmea€- oi- Bixhemistry, College o€-Medicine, Unive.rsity of South _ Atabarna; Mobile. .- rsa:or sup=rox:de pr3du^.:•tg e.nyyme in actjvale-i IeukCk`.y1es. To test the- assertion tftaC leukocytes, ha'.e been interpreted by those aut,:ars as pr!s;' iha[ xaathir•E ozidase is the `-Recent,7rudie:-txantininR Ine effecE of aiiripurnai_on bacterial ki!ling-by- :.HEMCsTAXIS, OR_ ^Ef.'RANULAT{O'J EFFECT OF ALi.C3"'ri;RIF'OL ON NEUTROPHiL SUPEROXIDE PRODUCTION, Neutrophits were found_to contain a-level oi-xanthine o_xidase in.y:fi6ent to-accourt-for thefiuz of superoxide-associated witc ueutrophi! activat:en. Allopurinbieid-nui inhibit -tJopurin4l-on r.eutrophil _funciions,_ including sutstroii de production, was studied. - ; eutrtiphils, the :anthine oxidase content of _neutroDhils wzs measWed and the effect- of SantnIDe oxragse-i5-tnvGlved N- the {RSione'!iln Cf a_qGerOxN:e-bf-.3ctivated ^.jman
Page 28: eta98c00
- Exposure of mice to low doses of ultrav-iclet radiation (UVR) in ivvo leads -to- an - inability to sensitize them-lo xontzctsensilizing rca+;Ats a! the _si.e-of_ irradia±ion,-and -thiti-depressed sensitization is accompanied bg-the_(srn;adon-af aniige:,-specific-T antigen-presenting function by UVR, and has-co.nsegaences-(cr the unders:anding-of UVR-induced cutaneous carcinogenesis. -- supp*essor (Ts) celis. - It-has_ also been demonstrated that hapten-cpup[ed epidermal cells. _- (EC)- from SdVR-(reated mice--are unable to immunize mice efficiently when - - administered subcutaneou:iy, and such ienmuni:aSion results in- the appearance of _ suppressor cells. - We report that the mu.riue epidermis containa n previously unrecog'tiud . aatigen-prexnting cell (At.1~) that is reryuired for ::e-actirrticr, ofsuppressior:, and that -- th:s APC is resistant to UV'R The dose af UVR employed is, however, sufficient to_ prevent substantial positive immur,iation _of-micY withspngeneiE. UV=irradiated hapten-coupled EZ_. -T.nese data-eAp!ain-in part-the-cSanges inducetr in epidermal - Gransteir., R. D„ Lowy, A:. andr:reene.-M."f. - The lovrnnl of /nsmur.-olog:~ .32(1)c55;-55`., 1985. OOther suPYNrr National Eye Institute, National Institutes of Health and Arthur O, and` Gallan M. Weliman Foundation. From the 53epartmentsof-DermatriCpgy and Pathology, Aarvard Medical Schoot, Massachusetts General Hospital, Boston. crucial elements in the actevation-of supprission and- thus in-deterrainidg the balance - between immunologic reactivity aad ur,responsivecess Furthormare, the UVR resistance of this set oT novel APC may be relecant to the in viva effects of UVR exposure to mice. activation is adherent and iZVR resistarit. The sets of I-i-bearing APC appear to be of this novel APC to activate afferen: suppressor cells was resistant to a dose of - __- ultraviolet radiation (UVR) sufficienF to largely'abro$ate?ne ability o( spienic APC tb immunize for a DTh° tespo.:ve. -It v<asalso fouad that t's!n previously desc.ibed sp:enic-- - Y-Ybearing ARC needed for third-order suppressor cell (Tss, -effector=suppressorr cell) - A set of 1-i-bearing _murine splenic antiger-preseating cells (ARC) has been foend - to be responsible for first'order suppressor cell (Tsl, afferent suppressor cell) activation ir. Lhe azoberrzenearsonate-.(A9A) hapter. syste : after -intraveuous administration. - -Suppressor cel'.s induced by this set of hapten=conpled cells d,,-not function in the - efferent pha.se of?he Ce?ayed hypersensitv-ity (DTH) resptn:se- The functional--ac2ivity- -- SPLF_?.})C i-d-BEAReNv _AN`fiGEN-RF:ESfNT?i:G f;EE.L_S IN A~-_',i_VA~:GN- ~'- i;FSU?F?LEJSiON=FURTHER('.Hej.RACSE°IZ.ATtON -- - - Granstein, R. B, and Greenc. M. i. Cefiu7a.? fn. muno'o8y o1:12-iJ, 19g5. Oabcr sqa?oru- Arthur O. aild-Guhan M.-:YeRman-ioandation. - From the Det+artments of Dermatotogy and_Patholo3y,-Harsard-_rvIedical Srhool and -- Massuhtaetts General Hospital, Bostoa.
Page 29: eta98c00
mouse" renal tissuz= to _ the mo::ocloda': ar•Tiiody that=resognizea_~rv cl:gpsaz_"aride . antsg-nic d€rrrc.r:zai.- -Elu."es fr;m esrzytne-tre??ed f:oz^_~ [ivue seciier:: contaisted - norma!:v -i:nmuhoiea i?r lgC in-the-:ors-of di3ers=- These c.a a tn~i ea:-- that €iG- - - treatment of rnzen se-.;ons ccuid 6e;a`ely used !o md- c- h_c.,_etv of ;e&: in -,tr:Ey Joun$ irnrmunog oFU_sQ; in Tr Ze --iissut ai±r!-thus :^+p•PSe the' ts tiiaFio[f fspecif ie monctilcnalantiSoG; binding=___- ._ Andreivs. L: P:, C9arz, B. K„_and Darcjanor. -I`4elourmc-rolHt•i.xSrFntsry c,d.'.acche'is:ry3'(7):69369E,l935.= - - - - OfAer-su;,rtmr,:-?datior.al institutes oi Heaith. z•"rom the Departme=("o+ Pathulcev as•a_ s abcrator} ?vledic. School-ofrylediiine~:Yniipdeiphia:.___-_ hi:emanr,- t-tc:vers r; -- LXALIZATI NCF=cAA`Pt!:=iK3CAhDr'--TTAACtfF?.: EFFECTs OF --- E-ADRENERGIC A64NIg75 _ - ' _ __ _ - - - - - - A-dxno sne 3 5'--cycLc- iti2r.oiSosphat@1:AA.rP} -is believ d. -u =:dediate -:be-.- _ ~ transport of c•ns, xiter; a,d-m_aous gtycoprotei.r :n the resP'ratorysraci.=-'Becacse- _ - crez>:r=af oeeasurx--ne.- s c; tcr i-s:ue `ie .. 1 e: -A nnag ot-atw T- ~_f;e<= -b-eges io <.. -=-i,.e-!fi;Fce:!=t p•,-.=ersaGnted-sta.^.,d.rd- srsri~yte-Fxsrn_a;me :ni--t- E;amsrcihe-- '-_a•.lula: lotan t:oa `nf- eAAiP :n dog and ca? L~ lseae =:?ie $ adrsnergagoaists __ erbu,alene s•' aeo+,.e.%, rl ~ard r~rt,.aoaa=t~s--A14' 3n t ted ty_; _e.-; celix-- _-of dog_sdn cat _trac`>reae=3nd in both ses-ousind muccns gla:d Ils al=ai trzcheae. - - E'vithelial goblet cells did not resDOnd_ ta-9-adrenergic agon,sts in either spcci.°s. -TF.i; = atudy piovides=inforiaation about the ioca:io.rof f+-receptors on individual celis in tlie tracr:eathates not avaiiabie from chemical assays of ei;,`.Pr cAMP or 6-raceptors in these - _ tissues.--57ur results support the hypoih-sis ihat sactetery functions in Loth vrous_and mucous subrnuecsal gland cefls-anu' ciliated epitheliaF cells; but nor goblet cells, may --'- - _- ineolvecy.lic AMP=dependent mechanisms.- Laaarus, S. C., Ba=.baum, C. B. and Gol1• W. M. - _- Ameri:me lourrrt( oJ-e%hysio[o8y;47 (Ce!•. °hysiology 16):C32'-C334,14g6. 6ther ?uppart- tiaEonal Keart, -Lung and-B1obd inst'ttute; and the- Strobel- robet _fAed_iaa!_ _ - `esearch Funu' of the_Americar• Liueg Association cu San Francisca.' -- - - - - - - From the Cardiovasc-~lar-Research_inztiiute and Departments of Pdedicine ar,d-_Anateti:y, - _- University of Catifort_ia, San Ftancisco_ IM.Y.UNOLtiCiiC RFLEA3E OF HLSTArvSiNG FkOM_DUU LUNG: C6MPAfiiSihY OF = IN VIYO AND IN 4"3TRG REgPUti3ES]N THE aAME ntiii:2zL ---- -- - -- The purposr of this ftudy was tn- comvare, for-the first ti;ex, anttgec-induced - rSistamine release frrroN: the lung in ihe iame-n2tively-allergic_uogs both in-vitro- and in =-_ -- sivno ln six dogs, inaeimal antiger.-iaduced histamine-re@a_rz from the lung correlated- _ _- elosely in vitr_oa:.d in vivo (r-0.9d), although it varied widely bzlween dogs (0%to 75,5% _ of tatal tissue-histamir.e content"similarly, the antigen coc•centraticn to produce 50Tb-of - -- mazimal_ histanine release varied sixfoh#-between dogs M0 pg]rnt to :5D pg/mq:- 7n_ each 151- - ~ it- ~ ~
Page 30: eta98c00
--_---- -- --_ -=~ - rentlY tross-)inked,-agg?egatits. Tr.e core prDte:ns are first deDosited :y the-cel, and, as a - - --- ftineticn of timE-in i§it¢iz, fiEronectiu gnd!ca!ly ceastheir surface _- S.nviar.z, E.; C. d/iss&zr. S. £oltoff-Scrt 1 r. ;3.-; and B us.ocTeiS, Cr. U:--__ _ -PF.elou;:.e!'rif=::istx'r:emiStry.,+.Md-Gpkhtmss:rp-~3(4?3Sg-~7~--19g5.-. ,- - _ - Cther tnpyorr Fauanat-Ios dtutesoftiea n and-the Davidf.pxhic,kY i?e..ry--Segal and - -the Hlumenfeld _Famiiy-Memorsal Fur.dsr-- - From -the--beDartnentsuf - Stachemistry xnd Patho o¢y:- .4lvrt -Finslein.--i.ollege a. - - Mxdicioe, The d3rortx,.'Y. -- - - !U".MVNOCIY`-IC_ ;;{Y:9ITIOP7'JF i-7LTRA`.'IOi tT F'<AfilATION-I:NDUC€_D - TUMOR SUPPRESWR CELL AC'TIHIT _. - - - -- Long-term eat:-osure of C3R-mice to ullavioiet radiation resusied in ibe formation _ - ot-supDye'.,se.--T-cells-+-hzt PrcogR<;.e ultraviolet zd:&Iion-i.GocM-regretscr-=_kin-canczri s.c a class before he ap.-earnnce of oart tumors.--Administratioa of rr.unoc!onal - antihodies [o the nrndt€ct of-shP I-;k suLregioa of the v~ayor tustxoreDatiSility- comp!ex '--._a:-lov doses of cyctoySasphamidcio vivo in: itiitedthe-dcveloumeat or actevit-s cf -these- =8-)ls. ?.is-acli.=ty ef ihv rr:vecz'onaLardiS¢-^-y^r•-a.• Nimina;ed'.y-adsorplion c.]_ Bp1,gR -(I-Sk) hu- not Ait.?n5, s9lenocYtes. '!'Fr se fir!dings provide e-ridcnce thxe ciement: _ expressing the iJtete:minan-arc iaryurtart in regulating :he host-resnonse_prio: 2_a_ahe _ t°eri de"r'EIOp.Tient L4' _B!tI2V161a': nd'lfl'ICn-i3ldeCfd-Sk!!1 ~anc'rc anmi 31!gg:9t nUvEI - -- --tha:alxutic apprs tom2iignaacies'or_dthe: diseases in~Aving=sia6Prfasor 7 ce!is in ItseirPathogene3iS.-- Qrmsteir., R_D,. Par^sh, J, r?:, McA-nliffe, D=-1.; SYalteobau6h, C., and-Greene'--Af.J- _ - •ience 224:u15 '7,-I444. ---@suer suPF'rr_! Naucoal Research Se: v5ce-A:v2.rd aad 4r hur O.-antt Lu.isn-.cN. iYellman ' Faacdatfor:. F-cm ihe Detiartmen3 3C stma.atogy and =PatholCgy, Harvard ivF u 4a:Y:.hr=1 ar.d -- -IN3sachuse3ir-General- Hosc:a[. B==s!bn,-and-I)Epattrnent- or-i.fitrociokzgy and Lmrucoio3Y. Nu'=thc%e3tua:inivfraitv SiedicaFShao'; Csi;zgo.--_ - EP@ER_MA-L .¢1vTBC'Fiv-PiFESEN-TiNG r_Ei.Y_S #N.AE"i'b'ATIOhI 0::-' -- --- St1PPR€SSION[ !DE6iTiFICAT'ION OF A NEW FUNCTIONAL TYPE OF-- - --- Ui•7TJcVTOi.ET RiiM sTiOLi-Y:E.SISTAI3T €PIG1iRMAi, C'.ELL'-' -_ recent Y¢ark,-?-+ir ,.s_=hasau.smaa. d-fa- he Presenc - .f -imm;tnutRg-cat:y _-active ele:nent_re;idsnt-in the skia, which-turs-!ed-ta the concept oC--.skiazssociate•1 - -!ymGhoid-tissue: (SALT),--Imtnucolegic=fuatior.soC these elements -have-rje€: --democs€ra_t_ed`tc• include 3ro=e35inR° and preaentation ef--antigeo-to'Ymghoe}tes by - -dendFitic cells-calle*9 epidermal -6_ngerhans--aells (LC). =-AddiGonally,= epiderrr!al ceil-derived,- .-hymocvte-activating -factor i>:TAF).= -an~ entity°--b[&chemi.^a1lY ana -= fur.ctionally-very sir..ilaror identical io interieckin I1ILl),.is eroducetr-Dy keratinocytzs.-_ _- Thus, the skir, can he'co_xsider¢d-a complex crgan in which al!s re:eYant :a the immune system are seyresentej . - - t53
Page 31: eta98c00
_ -A3!~NE3CtGNA:. LDlC3i~P`s VACCINT.A~=AiNST-STgEprnCnCfUS --- .-'- PNEUbfOiV1AH.]NFFMOiT,._- -_- sgaitn-tinfeeti1 a with_$treqtocxcus-Raeu.-ncqice. Meauremera of-the mediaa.-iethaln vose _ mice-devtlopeie a higK ta!ee ce antivody,te=ptws,•hqrylohoFine,-wh.ic}, is known_ to yrc!ect - .: A. -itiUnoc!on2}:a,nti-bliotoPe 2ntibody-euupael_ to-a ctirfiec--O+otein-luas-yy,d-to nmmunllE 31.LBfc-fp3Ee 3gdiT t al,na: $ rs+JiaCSCCYa jtieNLFsY.iae If ftlOn.- . Yacc[nated .. be used..as an antigen 3u!%`.titHLe=Cot the i?Iductine of protective imnlun.F.y, resistance pf- BA1BLc micedo :hee barer:a; cnal;enga Antibody_to an idiotopP.can thus - Of thC-bactert3-indic3ted that antA-idtotope !mmnnl2atron silinlliCantiy.-mCreased the MtNamar, Nf. K., Ward,-R. F: and Xoh7er, X. Buffal0, i:Y. - From the Depaament.oF Moieculac Ir:uttunology, Rosw.(;_Park Memorial Institute, AID.S Institute.- ~~ - - - - - - - Oacr sxPwK:-.D.C S-shlit Heal;h.Sarvics a-•d the T;tw YorF S;ate Desartx,Fn: of-lleaitS Soiertce,2i5:i32S-E32c; !9a4: -. -- - - of the aetworkb0.aeostasis of-the im;nuseayslex.-.- - -rasfunse. -.°.olleetivOlyi, these data-drsEa:hc an idiotyye-€F-Stfi- -1 -Seiper circuit a5 rart = helper cells anG.-showed :hat s€itnuietiotr o!` Ti3--idiotyX =pecJic 'FH3 ce41s- ea,-r-be _ cOrre:e[ed-t+ith_asign:ficaci-inerease'in the perreniageal-•.i5-idiotype iR-an zati-PC --- _-. ceRs byysaag two di€(eren• TNF-~+nti-:35:`;t6-;lono.: antigers :ndica€esa TH, st,eciiicir; __ _ _ _Toi_ _a 3hared diotc~. -.-T}te stabil:ty -.crer., tine- af_ tte- Txs -"w .--c;. -s;it was_ _ - demonarsted'oycemea'ingT;,t_frequcrteies-:ayouung-ard i4rnics: _ - Fiaa:ly, we addressed thz ques,:on o1f the (:+ns o'=t!i~ id,oty6_e-reeog,azing T _ _ indic tes their-snort-I:redstata._T-at:isiti durirg ~+'hsct TH; stls are st_i:nula_IIed Tpt =ce!I acttviiy -wa, ssq_?~i:wy- monitored.hy the t.se.oC -TN7-anti-T15 hybridomv - antigens. It was found that T-y, ce:L; are,iletectcd . wk ~±r•.~ •• 9r r-ng- Ni+,,:-PC-Sd-y ,:-PC-Sd-y, wF.erea°,-T--s cells becsme a U +d after. wk of_grim;,eg. _Con7pz;ativt:analysia.~f THi - in tha _presens._study,=-the T15-iaiotyZe-~ecognii:ng ='F-heSper _r•<Il circuit - was - dissected ryith respecr to-=n itor,reostasis _inte_active sDe: rficity, star-sit", ever t:me aod - effect<_ oa B call exp:ess:o¢. Ana!ysis o€-the Ty. celis by asoi:tive transfer ezperiments -_ T.NALYSIS t7F A Tgt --+ TM H't_L7E:c CE: L_ CIiiGU3T -- - -- - _ McNamara, M., Kang. C.-Y., snd %chier. H. - The iournal oJ_Imm;•,afogy I'r-s(3):1593-1c09, 1955. - - buffalc_ NY_ = From :he-GeGartmen4 of Mokcufar Immunology. Roswell Park _Fdemoria! Institute, -G:hrr_;tv'Faor:: NatiGnZ! ia,litete Oungiag: --
Page 32: eta98c00
- of- five other dogs,- terbutaline su!fate administered intravenously - saused° a dse-dependcnt inhibi!ioa of antigen-ind"-ced histamine release from lung fr3atse::ii in viYo: the maximal inhibition-praduced by 1 n?gii•S was 50-. 4:3°b (mea2+ SEM). !n these same dogs, 1? si.4 terbutatine _iecubated= with lung fragments, in -vi!rc ea,-seed _ inhibition of antlgen-induced.3ristami ne release comparable-to 1 mg/4._g terbntaLne ;. vivo. Increasing the dose of-terbutaline in Yitro produced maximal inhibition at 10"'M with no greater effect of the drug at !0-'id (71.4±3.g9b inhibition)r Ic both experimenal sitSations propranolol caused-a dosa-dependent inhibi;ion of ry-adrenergic modulation _ of Asoaris-induced rtlease of histamir.e. '.'.:i: resu!t supports the co: clusion that _ terbutal:ne produced its effects by-.aceiorts mediated by g-adren?egic receptors ar. pulmonary -raast cells. This er.perimen!al approach provides a ssitab!e preparation in which to estimate the effectl'e-dose of ag9nL_3 that modulate anti€en-indu'.ed mast cell fbn^.tioninY.vO. . - Frey, 34. 3., Chesrown. S. E,; Reed, B. R., Greenspon, L. W., Shields, R. L.; 9ourn-c, -H. R.,-3rown, !. K., and Gofd, w. X Cii..ica1 lr.,nwnotog± 74(3):'• 2d-7=9,-ISS4: - Other support: U. S. Public Hxalth Service Eu!mor.ary Specialiud Center of Research_ From the C'a:-diovascuiar Research Institute and the_ Division of Clinical Fharmacofog f, DeOartment of l.fedicine. University of California, san Francisco. - - -EXTRACELLULA!t MATRIX MICROFIBRILS ART _COM_POSEDD= CORE _ - PROTEINS CGA T ED R'IT3-1>'79RONECTi_N I, _ -- _ - - Exr oceHu!ar proteins of cultured calf aortic smooth muscle cells consist predominantly of -miaefibrif3 lu-i0 nm in diameter typisal_ of 'elasti. associated' _ - I-- microfibri!s described in many tissues. C.hemicai_and im :unocbemicai evidence is- - - i -0resented that microfibrils consist ef-at least two-proteins: core protein-arrd fibronectia Insoluble proteins rLthe micrefibrls were obtained in C:e form ofa peltet-.nd-arriibodics _- -~ r'sed ~n a`b;ts a a:nst lS ~a= om_ ~ t -T~re il~ i e -_ vd ,t1,_ `- _ s r r x nen s acL w e c [ s a m of !he fibronectinand incre~ed vis:;a!i>a:ion eF the nu-crofibr+is sv:.A ehe-absorbed ~e_G; _ doubie-label immunofluoresccnceshowed that hoih proteins occuired or~- the- sanie- microfibrils. The localization ofir,tnunoreactive sites teThe extraceLular microfibrils with fgG to fibronectinr Treatment of these cultures with urea led to partia!=dissociation . reacting with the_absorbed IgG became less i ntense. whereas that of mlcrofibrik reaciing _with IgG to fibroneetin incre2sed; irn eonf€uent cells, esseatia!iy r.ostaiging-w•as daected witF the absorbed igG, and a dense network of intensely stained microfibrils was -seen- assay,- ar,d :mqtunnstained the -iifrace!lutar ._mi<_rofibriis- in -crdru;ed cells_ . An _ immunoglpbu!in iig; fraction ~as prepared and al?soined with fibrnnec.:in.. Thr absorbed 1f=G retained its reactivity_with.the m!crofibriilar prote-ins butyvas no ionger reactrre-- with--soluble fibronectin. _.Immunoflucrescence studies -were carried out -using . the absor!:ed IgG and_IgG to soluble fibronectin. Both-antibodies =howed immuncreactive - -miciofibrils in the exlracelluia.r matrix uf-ce!1a i.~ing ghage. _-However, with increasi e- time in cu?:ure. m-thc cells reached cont,uence, the imaetnofiucrescence of -microf ibrils - microfibril!ar proteins and with soluble fibror:ectie in cnzymeanked-immunosorbent = _ o_ g., . . { : t s - _: t F -:_ e - n,a:,.o._ - - was confirmed by immunoekctror. r.icroscony. Nearly quartitative cleavagzwit.'. CCdBr- failed-to dissociate the antigenically active fragments o- fibronectin from the CPditr - _ fragments of the core proteins of tF,e mictofibrils. It was concluded that microfibrils contain core proteins~and fibro_r,ectin that-are codistributed ia insoluble, possibly cova-
Page 33: eta98c00
pharmacokinetic studies in mice. The cis and brsns isomers of-NNO were scParated on a Partisil PAC coiumn 2nd en::•-aatic :21_ecrivity was es?tuattd for the formadon of thr;e Thompson,3. A:. Noriis, Y:.I- anj Pererse». H: Jourr,mr of e7,>oerrataSrnPF.} 3s1:?-d4=i39; ]'3g`:- From tAe S]iooi a` Pltaracy, T'oi+ersit: of Co€o.-::do. - Bocider. INAL-CIYAT7ON-Or a_._tFiAN Et-F-1-`_RO"£! .p$_ INN1B1 i UR 'nY Gs.S-9HF.$_E CIvARtTT,E SMOkr: As ctxrteu irc 3his direct exp.sur of hwr,ar. ti]-;.rotP~r.=e inhibf{cr (aiPl) t3 the gL:_phaSe _^loke frJ_ncont Cig1:=S[e re£l-fG Inp-hlphaSi, inacriv2t;o? of Gl:l.- (1} __ The ai' illors 11b.`Y -rYe a 3ylLf, in t.d ~JSF n. Clasti -] nhiblLJ. J fapaclty- rhr^ 2!noJ',R of which ie dzipendert 'swa t3b^•-aTee nfi7te s.'.eRe.- Tw rap:d, cknr!'-lerm incrtiraticn is nN, seen when thtrprotein is-expTlsed-ts aGueous-extracc: ef_cigars,te smoke (as h-dd beerr_ - -done in the past):- (2)-f:ow_evar;-b_oth e_xposvre=egimens-±+roduce-a__second,--t.ow inestivatinr taaCocc,us-sv_'u -several days 'T_h_ authors-suggest :hat 8he- -ahort-term - - j _ enactio.-^ta U°duetC penz-z;miea .(7-=si •ar:eaGtiLrspesa;t:atr-fwr;ned.-".. .-- f_- rai:ca in tS* gard--a..e c°€ is una ~±te iit aqrxc•n .-a -~tiua. -rx ai:~Sa e hai•e-nat-ye:_- - ' identifred a- piec:es r qe ara]€-f•,r rh~icng-tzr:!: ir,aEtivatior-obseived-fol:owing °„ottr-- - _ - direct etqxsure ni_-p,ar2 -.•-sinoke ard .-prsux' r-, a:u.c! - estrcta.`=4r-..y,,._.bw€+_ is. -. - that th e -1 3 fira-iY01a Cn'n 3aY7Ftit 33a ree~lTSfJ~e LOO:adaF:ot` oF-aiP!- RLth- alttl:',wjt_,ap!, _ "- .'. - s5eo:e crornpottnd& tha desso;ve ?a eqaeou=_ satutwvs. -- - - _ - = -- {N!;RCSA?:ON-OF-ORvANfC: HYDROPEROXIDES BY-ti;ITi.OGiN DiOXILsEIDINITROfrFN Tl:TRAQX]DF_ - Ct.•nYl and terf usyl hYdrep-roxidcs r€_act ra3raly wi.h hv ' NzCr m nrganic solver.ts rre tne-.Ilre_sence o:'-i san to4orst th:6danrc iri ra[e1'~flh,`Cstas-tfie-inajor - peoduci•,-togettr_e. ~tt4 ce;i~ie~ a~»onts arCt•_e corresPordirv3 +iGite lR[7NfiY, atcohcl, - and csrb5ny7. compeu-nd -(acetopnenonm or--aeetar.e frorzt cumyl sr:d ter[-6u;yf - hylroperoxide, ie;pectiveiy;?. The Droducts £sont -te<i -butyl hydrnpetixidz -.are. simd-r _whether-a-ba3e is-Dr>stnio,--not-butehose fr;.aacamyf.hydicperoxi?r are rore com.]ez. The researctiers have firtmulaied?he :nirial reaction a a nitiosatidn of the -hydrrperozid._: - by-NA to give-the-Derotynitrite este_r:= This latter Epesies is onstaGle-an,3 eitlier= - __ rearrang'es'.o give the mtrais or-dissociates to-Iorm z]koiry_l radicaEsands nitrogen dimcide-- that si4;rrtate:y gives the o€h;:r ohserved-Drcducts. -T-he ki.-r-:ics:of the zeaetio:±..weiz P_vor• iF".-i:. Dociey, h''.--M.. aed ;'hare] ;_D_~r._ - . RttxRcrnical-andSiGehysicaf-Rese,irr.n Cummun?ecftocs .?2L2 ~_ - Oth2r sitrPort: Natioaal-sn=tiCUte_s-of~~ea!tli-_a;td"-the - Re_!?arCh-- - -- -- --- - - - - - -- ~- - Front the Deparint=_ets of £irrr.'sjtiv ac8 B:o,.hemi -- I - studied-b; itopDed flow anl-are co rnpiex,. eut the ir,cestigatarr conctude they are
Page 34: eta98c00
(MMUNOREAC71vi.CA?!'!_T(JNIN-GENE-RELnTEO PEATf6i AND - - 3LrRST ANCE P-COE%ISS'-i; i S"r.NSCRY ;^IEIJRnNSTc'> Ty M SPIIs.+._~. CORU - ANb iNSERAL? 1N SPINAL 3EHAV7f; P.AL RcS;'JNSES OF THE E.AT Using imr.,ur.hisrxt+ex.isfry, evide:::e:-was.-..obtaired= f:_x, ;he -~esisteace o comb:natson.Thus.SP-(uD=to 20"yg) -alone-eaused CW °inly for aa few-minutes-after : behavior was carriedoutafterir.trathecai-administratioc ef-CGRP-and SP alcne-nr-in-- _- spmai sensory neurons. -=AnaFysis-ot caurialtv-diPected-biting-and--scratching.-(CBS)~ ca!Citonin-gene-.elated peptide (CCi7P)- and iubstance P(SP)-lire iei3munare~_iivity in _ injectior., whereas SPf IOYSP vtus CC;Rp (20 yg)<au4ed-a rasp5nse with-a-duratiori upp to Neuroaricnte Lt-'ters 52:14`>-204, 1484: TshoOp-~F. A-., aadzn:her, 3_ A= Wicsenfeld-Hallin, Z. }iokfelt, T., Lundberg, 7. M., Fors<,ma^t•., W. G., dei necke, Ft the sf+sr,al cord. - _ supp7it--fcr s possiDle i...e=.n,ti,n oi-thf-two'reOEidea at-syn%ps , i., the dc~rsal horn of 40 mm. CGRP420 yg) alone had no effects in this model. Thes. £indings provide •-••••• nvr~.~,• u e ouaam sarance r;ompany, - the Xa*clinaka r.n;irL au h- 3t+ ss Nah na' Sf-rn e Founda o- _- From the DeRa•tment n r' o? e;,raFhysioi r H aoirae Hospital; EIepar:ments of Htstufegy and Pha:-mwoiog,,_rCa oLrska :nst-u e, Sto<:ic:r!m, Department of Ana?;mv Lab:i?atory fGr Celefa:n A".e:abo!sny tJep_rtmeciuor Orthopedic Stt:gerp and Medicine, - al, UnIV3rs'ty°-of.-`Leideitirg;-Federal Republic of~-i:ermany, and the Research Untvers;ty o`.-=Guirch, $witz€rta-n;f. BfOSYNTHESIS OF GLYCfyPHiNGOL'!PIOi 9Y-HUMAN M_YEL +!Iy - LEUXEMiA CELLS-_ _ . _ - '- - - - Flor_il-column chromatog2aphy. and-high-per£ovmar•.ce }iquid-chrematcgraphy sssingaa _ - [atrobeaQ-eoiur:ia. =-Cempounds with-or.* -sugar we~e analyzed hy_ thin-laver - chrorita[>graphy on borate plates. This analysis showed that_HL-60 cells synthesize only glucosylcesamde,. wkereaa'K56i--an3 -KCrI cells syn[hevze predomir:an[iy _ glucosyleeramide,-but also-asmail amouat of gaLctosy;cerarnide - Compounds with two to four sugari=were chara_terized-by.Areafriretit-with exo- and endoglyeosidases The _results showed t-t K56? :id KGi °eils aa s alar io cells-irom patients with acuze leuke;sia in exqressirg-two-series izloho aad-neolacrot oT- natura.-glycosphingoiipids,- whereas the-HL-60 cells-are similarlo mature humamrnyetoid cells in expnssing only _- one series (neolacto).- Therefore,-human myeloid leukemia cells blocked at different stages of di•`ferentiaiion vary in their ability tosynthesize neutrai giycosphi :goiipids: -- glycospningolrpids eontainirrg-one to fdur stigars vrere 9urifiedd hy-a-ccmbiratie,n of.the-= - fol!owing_methoda_: - dietsqfa,ineeihyl-Sephad€x :olerdn dro datog'adhy. aceiylaiion= °- s+ntt•,cssze., by tSree-hnman--m.etotd :eukenik-cell imes;-K'62. i<L;l,-and t3L=60, which =were -metabdlically -.rateL•d- -witfi. 1=tCigaiactose, -to- ezaiua€e- shan=,«s in :eetral -gtycospbsgoli.pi.' -synthesis-.s wit ;-myelosd- tell differe•,tiation. ---tndividual =neutral--- We have performe;t,-comGarative -studies- of --the-neutr lg1y<ospn~ng-ol:pids- --- Buehler, J., Qwan, E., DeGregoria, M. W., and Maeher, B, A. - BiocF.en:is7ry 34'6978-6?84, 1985.
Page 35: eta98c00
Uiher su,:aorl,--Natiopal irs;itutes-of Healthaud Veterans-Administra:ion. CA, aod Vete*ans A:'.m;rtistra::oh Medical Center, T3so Mto, i.A: From-the--Deyartmcns of-t•4ebicina and Ph_rmacolog"y. Stanford Jniver;ity, Stanrcrd, - -RAF ADRr.PFAL..:,-~-- - _ ' --EFFEC?'S OF AT3IOPE>n':N ON- PART iCI;L-A"fs GUAtiYi=ATE CYCLASE FROM Atriopeptin I3activated particolete ;uenytate cyclase 5-19-fold :n a.concertra±iom- --Aeeumuiatuna5fcycitcvMrtvmtr.ces.e+Paaeenal.coaez or-medana-was tncreased adrenal cortei or medulla.-,Simitar effects were nb?erved with other atriopeptin analogs. -_S:iubte guanyl3te-cycta:e_aneadenylat:e cyc.tase ia these preparations w_re-not setlvated. aedd time-dependent fashion in crude- membrnzs_obtained from :itomogenateso€ rat .o-E-fold- due lo atr.opeCtin: II activation ~of<partieulate 3uanylate cyclase.- Several - :1tu iree-~ thiol- g:our~+',- on_ nLembCaae d.+rs[e:in?-::aay- 4e__ importar.i iin atrioptpt:r - _- thici-reactivc-ageats-blGcke[r-th.ed activ3tion-of particu!ats gua:y]ace cyclsu, 3ng;esting - -teceptor-guaeylate e,elasc coupling. _ . i4"altiman.8. F:., R-apo59r:; R-M.,-iiscus,.R.R..znd.Mwad. F. - - Sioddrnr,^:a el tfiopkyeica-.4c:w525;S9g=305, 19S5. - - Otker scpporf: Veter.ns pxm;nistration. -From the Deoartrrent-of Medicinc and PharmsccW-gy, Stanforct Uruversity esbool .;f --fi!edicine:-Stanford, CA, and.!'etrrsnsAdminlaratio-^. Medicx: Ce.ter., Palo-n:°n. CA. - ROLE OFCY:.LIC-G>vtP:N RF.L A3;ATICiN-e OF Y.~.CLiLAR-Sh'f.rJTH MIJSCLE- -- of- these parametert (cGb3P,-_ cGMP-dependent `prctei7 kin~a;e and_ . prr,teia endothelium prasent:--/n contrast; the effects of the endorheiium-depender.'. agents or. -aEi autoradiograp`ny.- The effectss of nitroprassidt were observed with or a''aheue the - - wcre observed +itn both asses oi relaxanit on two-ditneriortet gel eleciroptvoresis ..id ` intp numerous smi.t•thrmusele<prptcias:--Ideptical patterns of protein phosphorylation increase cyclic:£`,MP->Jepender„ pr•.n(ein:kinsse acevity anc alter the incorporation of 'rP -'oncenSration- and-time-dependent fzsnion. With ra% ~r.~rta scgnents, ihese agent- also - -t.hrombin, and trypsin, is -assxiated with cyciic-OMP (_-GMP; accu~iation in a ~$elaxation of--rat- aortasegments_ with sridium aitroprusside and endotheleum-d^G°-ade!i-`asodiia[ors,-suc'- as aeetylct~_,iine,_histamine,-Az3:8L, TTP, -- fanorr and-resporsibie. for Kuanylate-cyclase activation_ A smooth-mus<ie- protein- with agents,suggesttng that a.metabol~t--sf arachtdonlc actd -ts, tnee er,uothehum-re'sxand chospholipase.and lipoaygenase pr.ventad-shed effect~_ of the eadcti:eiis~rs-depesde:r _ phosphorylation) _ reqtiirtd- tLe- integrity of -thee endotheliam_ Various ir:hubit2rs Jf - - common biockemicat.~and.p!<y=iofo8icat effects on sace•thmus.cle of these two ctasses of - - level of -guanylate-cydar,e- activation and c.:eMP_ accumulatiaq. vrhrrh -ecpiains the _ tadotheltum-dep°n._enx vzsodtla:er ani d:r-_ctly acting ^t?rovsscqilators conYrrgc at n:e - identified as myosin..,iight chain. A moaef is pfasen;ed suggesting that t!n, effects o- - 9ecreseds+P srlr_pySration af ter treaisr.er.t.:Nita -either class- u'• -rc/3xant3_ has been vasoddatcrs. - - Murad. F.. Rsrwport, R. M. and Fiscus, R. - Jourrtal of Carcior,zcal._r PJ:arr:otclagy7 (Supp'-3):S! I i-StlB, 19F5.
Page 36: eta98c00
- 7)tkeF ,uPCa,rt: National fn?tltutes of-Health ar:d Yeterans-Administse'lon.-- -- From the De7artme:iu-of'-Medicinsand-Ptierinacology. Stasford University Sehiel of-- - Medicm;, Ftant'ord, CS atr- Yeteran. _Ad.;inis r.o:. Iviedical Cecter,-Pa!o Altb, CA.. - _ EFFECT OF SODr'1' PQTASSIti!vl POMP I1HFr2ITOILS AND . = _ ME.MACcANE-DEi'Or 4RIZiNG AGE'+~_ J3N SO'II[iM-- - - - - NITRC'PRJSSIDE-INDL'C€t-i R LAXAT?Oh zzNq CYCLIC Gy;cNOSr!:1: -..- -. , MONGP"OSPttATE ACC'JkIUYATIOh I"r$AT A0.FTA -' - - - Th p!.r~rose ot tnu tLdY wa- t mvesri te .e -p tt9 5~;.betweea sad ur.* -- ~__ ciiroDr4assde-,~tc ~ced ela htt_ d nhtutt an a he su!- mpotaV tu r mC 5'`-:y i.c - III gLznassr,t mnP.kDhn-pha~c. FiS_„re ct .a!. _rar~._ti+,na m.i.aoe.a.-_r ,c".,.r:rc_ er_ -_ magc-esiun-free 1`;rebs-Ringer bicarb?oate' sob_,icna - D'oad %e- -wh- h-Dres_mab!_+ inhibit iLe so3i9m-4stassiitm ©ump.-br'-.o potassiutn chloride er-tetn_ethy!au¢ranium,- - memb:anz-depoiarizing age:tv, i=.hibired_ relaz.a_tiao_to-ei[:oprussi•?e.- There condi!sn. -_ had little or no_-effect os'the elevated cyslic guanesi6e mor.cphosphate !evels at -a = - concen:ratioa of niteoprussir!e (F.: yM) tha: relaaed ncrepintphrine c.:rtract:c tissues bY __ -- - 80%. -However,=at a-msSi^.1ura relaaan€ :accea:attan oi ni:roqrusride (L0-}:Mrthese _ conditions deSreascd ;he ei€vation nLcyclsgaancsine_monoPhcsphate: The inhibaion of =ele+ated cyclic_guaersine"conepho.5fihat: ie-,eis w~ indenertient ot-the er,da:hei:uar,- - ez&acellolzr crl?iu an- the cSrlicuano.,M- maeg hosphte-Cho'tod -ter;ise __ inhi.itor Mdtn 349ae --•phe`mnR+txs effu' bia'ei, at--f-poM-iims= d._ __ -= magnes um-free so'er on on e te ine .>e3 ieve:s ofcycl c guaruve nvi opFaspha.e- - - ca;!lzd by 3l:-d rs rYCn ss-der were abolUhed whn_ .:ss .e we-e incubated wit^oLi - ~i- na:epiexD .pe._or w S ao D-•' hrl e. tSe pres.ece o the o-adr.re g o occe', -'- _ --p!:entoho.intne.- €c contrast, a 6=adrtnei c blocrcer, -- - - - - - gt propvnolol;-had_no effecSc-r che=_ -- ouabain-induced iuhiSition'of e!evated tyci:c-gua_r.asine m_bneGFosphate igvels; with - norep:nephrlne prCSen:. TSe3e leslllt3 5te L`oni:atent"Iitil-theY}^ao!hei0a'..."I-!nenbrTne = eYenls re4s'!ate -cys'1rC -gLLin'wn! - MoaophC9y$ffie - synthes.9r- _ -AI - nltraJly55WC coucentratians grea:e[ tha?l-1) -i jXF, 1YefUtm3t1&n ofCyC!.f gnaboi.Re f11o::.3phdSpha[e - - - - appearseobernaptedtotbestatuenfthe-smootF-musctecet!n:eak^nearid~lM -=~€aegrity`--_ _ - - = of -the- sodium-TOta.r;.,:m 'c'.rmD- - Ftirrs:ermore: the =elevated-cy=lic guam:sine socopbosDhate=_!eveis indbced_by-nitruprrrisidr---sna9 bs'--totnpar!msnFalize3_-and, --~--- depend rg upon the er r eI!ul r coacertra! cn a-a<- h a.,sac aled wltq- sev2 al - ie.-.aicns 'fhesz7unGto ry _mctLdeacn =a lao of theze~ Lm ~en• ium DamC an6 •x -- -_= a.emb ane5y9crqoia utax-r? rveves 3c e ie t f cy i;c gux n5 h-aanoph-iphate 01 - -- sadinm-potasStYn: paulp t'rvi,l aod7o 5:..mt}ran t1Cientia3 smams t0 bedem.llstr3t2d._ ~- M,radF Raf+oqorr R Ra anF$cFwa-IZ-K: ` - Cireul.ttena Research -- - j-_° -- Othrr ss~por7: NaTi rai instiRtee of HealtYh and i'eierersAdmtr T?atian. _crorr the Depar!mene- a:`--Medicir.e= sa3 Pha-rmeialo: y, Sts'rrord- I_'R_ iver_sP_y-Sci!ool n_ f' - Medicine and'Yeterarir Ad'mi?te~t!xtitin Medical Ceater, Palo A!to; C.A-. -- 138
Page 37: eta98c00
From t`e Fep3rr_ment of FY'ho!elly -a,d{.a>iorato.y Medicine, -Theee•Yisfi ~ patafif-~:• = Louis;_and tLt: Depar me r of-Pat+ ]ogy, Was;r.ng_i r---Ctniversi,y ScAnoi if--tdeq!c - Loitis.= - of_S1RS by-3ntaci !es ions, and the cbror:i_^„ immanoniod;tated stage--of- schistosotaiasis man;om. - - Au.-,erT.M_-Freedmas, G.L_F, .; andt'o:ley. D::r. -- _. he Irrarnal e! lmmunrtogy i?i(4):27fS-27-73, IS$S.- -- - Otner suppert;-Naional Sci_ nce Fenndation, Na_rionallns_tituTes of i'_caltt and- Veteran= - - - Administration. - - From the-Department of-Pathology and 3.aboratory Afedicine„the Iavish-Hospits: of St.= i,ouis; the Department of-Pathoicgy,-f'ashington-Uni:•ersity Sclioo: of Medicine, St.- Louis;- Yeterans AdmiKittration Medicai_ Center and-Department of Micrebiniogy, 'aVO D[FFERENT PATHW.AYS OF I ANTIBODY SECRETION EKFERON 17EDIATED SUPPRESSION OF - - -Interferon s•.:ppresses_e.variety of in vicro immune r_esponses byamechanism which- has not t+een-well defined. 3=h direct suppression tied activation of-suppressor T cells - have-been suggasted as possible mecha-isms 4f-:nte;(•_ren-action, _In an attefi:pl to -- --exarn~re this questinn,-interferon-a (IFNa)-med:ated scppressioe of a plaque-fnrrriing _ -_ cell response to a T ce!1 independenS antigen by-spleen cells or by-B-;ells-waB examined; - therefore, a strong associacioh between the presence of S1RS in the s€rum, the production - -_gramflomas obtained fren: acutely infected mice did not release SIRS, There is, - in:rrtunamodu~ia4ed lesiens c:!araaeristic ofthas infections. Lxrgt, i^tense; unmodulated _from-chronica;ly infected_ mice release detcstable=teve!s_-if SIRS.---These are the - __ earlier_ infectiqas. Alsq, culturxs of isolate~, -intact, hepatic, eBg-:ocused granulomas _- sc:`:istosn::iasis mgnson; (atieast =Q.wk Gf infeea:on), but not :a the sera of mice with - senings. Ti;is report derncr.;trates ti,e presence of SIRS in the sera of mice with chronic PRODU('TIOts OF T-I3E i'+'l:fPHOK INE.SOLU3i,E IMMUNE RESPONSE -- -SUPPRt.SO (,S'RStLCRtNO.CiJROfUCEX+cRi*.iEiyTAL - SCHISTOSO d-P.S7S M 1N..c3N1- Chronic achistosomiasis -mansoni is a helrinthic infection e.har3cterized- by _ cell-mediated, antF-egg granulomatais reactions and a- variety -of associated -_ immunoregulatorq phenomena. Soluble immune response suppressor (SIRS)- is a lymphokine p.oduceG by activated-suppressor T lympho^.ytes in various experimental - _ - Vanderbilt 2!.n.i:ersay:Szhoa=..of Medicine, _NSSh%iOe;TN. of ei:her -2-mercaptoetha, ol -ie+amisole - or - monoc!onal antibodiet agaieat -the _ (FITC-BA). Howzver,-supp:essiaa of splee.nn cell responses could be bh+eked by addition responses by B calls thad-by spleen oells=-to theantigenf7udresceirated-9ruca7n-abor:u.c -- -_ _-Somewhat greater a,uantities, of IFNa were- required to suvDress plaque formiug ce7t - ' _ ) _ -1;•n:phokine.-_soluble immur.esesponsc snppres<or (S!Ri., whereas supp'es=ion of -B-cNl- i_ responses by fFNn was_unaffected by these agents. Each of these-agents interferes= with I SIRS mediated suppression of immune responses- Addition -of T cells to-B ce!1 cuHures sLmu3ated with F17C-BA did not affect the tct51-p!aque--forming cell response nor the - -I extent of suppression by- IFNa, -but it did restore 2-mercaptoethancl sensitivily to - IFNa-mediated suaoressioe. - As few as. I X l0° T-cells were effective and it was - ~_ - necessary To add T cells awithfn-5 h of adde`tion-o€ IFva to~ confer 2-mercaptoethane!
Page 38: eta98c00
_-oL1-?,ercaptaethimol per-mg ce!t jrutein-.`orhir hour upen e+9'aare-_to'250 p:a ECE - Dctan, 1. and Sh.%cqfrr. i. _ ESSE as a pertubanc.ef the GS}3 Status irn cells-is dsc.-Sed. -_ ° and th:n prevent it" from-inhibhing theredLct~e.- Cultured-ceits respnnd to FSSE =..-administration=hy-c:evatuag thcir totat and-acid-seluble-glutathione leveis. The use of : Cyto;olic-reduced-xe!eta_thinone c"an symtaneossiy exchange disulfide bs,•hdss w•.gh E,`SE addition ef gtucusa and in;ulin is-necessary-ies arde:-ta obta's=r a linear reductionrate of ---_-ESSE. - -.: The=I r3te- 3imiting-, enxymc.- ic -tiee.=steroi--.:binsynthetic --aafhway, - -=3-hydrox"s-3-tnethYtg€atatyl [aenzyme AA ieduttase (ES.=i ia inhibited -by ESSE -..-wheA 'i3olP.tGI- froLi- C b(j-~^ejl:-_ put: liJtail nGCi2ponur3ble- il]1d3 sy ntF.25i5 from -[2-?+C]-acetate-in intact cells is-not affected by zSSE--at-.coecen[rations up to 500 - fteduct.oora:e of ESSE by-ce3i5 attactie.g-ta asLOSSratu_-.',,~°;ndep?ndenr of -giacos.- and -insulin fcr per<ods -up to ~[ h.-•urs._ -zfowever, in-deiached cells, swirted ir: suspenxion; - -From-theDegar«ent of 6iochemist_y_. the 6eorgc S. ?!'"ae Fze-ulty :nr ? ite St;ience_, Te`: _ Aviv University, Csiael. - _ Jcranol of CrAufa.-?hv5so:o>p i22:ta-2n, !^-83 -A-PiD LOW pH IN_iSOi.AT-cEtkc.AlCT OF RAHe?li ADENOS[NE-lNDUCED CORONARY RELER.SEOF PROSTACYCi.iN AT NORMAL flow iaduced-tiy_ t_is=:-le acidos"rs is not r iated to an augmented for.nation of prosta.:Yclin. -Ciabattoni, G" and.lY"enmmolrr,. !. - - -- _ _ - - - - _ _ Brirrsh lourna! o,f Fharmaco!o8x-g3.357-5b3, 19" , r ~ ~ Y• • g p_ c sor e ata •p.y an v._seq~renr -[ormation nl_ prltaCyCIG, In the COfCnary ieSSel'a. Fn1Yh°rm.elhe increase in corOfw°ry" - -pre-labeled-with jteC]-ar5chidonic acid, ader•.osine (10 NM) induced a-3pecific liberetion _ of!abeled!ipid-extractablesuhstances,including6--keto-PGF . E. From these data we- conclude thaP adenosine stti'.•nulates the =_liberat:on of -- 6-keto-iR F- fromtha ia~bit hea t b ncreas'n - re-ur v'I b" d•F adenosme-mduced rr.crease :nsroronafy f!ow wa; not facilitated b9,iow pii: - -. 4. _ The base-coronarv eftlux o€-6-keto-FGF. =frotn the hearts was_-2.i-3 5 ngJmitr. Adeoosine-(if"°-19"{A:)-significanily;acititat o t}is efllux; up Is_*.S ng/n:in. - Thee?ilux of 6-keSo-fE;F~ was not changed by perru-ion witkacidic medium;either irt- _ the tissal state ar during per~usion with-adcncs:r,e. -- - - - - - - - 5. -fh: basal interatieiat efGv* of 6-keto-PGF- w~ 4.5-;.,-r.g 3/min. This effiux -- _was not affected by9erfusion of th>h^ert with adenoiin~-containing-mediem_ Ir: hearts _ - flow, aeountinj;_io about Z54o_at-itorm_l rU and a drug cobcehtra:ioa of-Ef: sk:. - The- eomparison 2o cot;tse!. Adenosine induced a-dote+!ependent iacreass-i.r the coronary - _- 3. Thabasal eorottary-flow• wa9 elevate#by a!most-70% duringhissue acidosis, in .- were rr.easure . er s+on was per o orned bo,." at pH 7.4 and 6.-: - - 2' In dthei experiments the hearts-were pre-!abaled with [rTj-arachidonic acid _ and-the coronary -eillur of radioactiviry_ and of labeled lipida--and 6-keto-PGF]Q was - determined. - L= Rabbif hearts were perfused by thr-Langer~jorff method _ with Crug=free perftuion-msdiurh- ?r w:th-a medium contoiaing a#enosine 0O-7 M- _- Jn-~i)_ and- the -_coronary and-Arans^fyocardiai-=fflux rates _oT 6=keto-yrr,stav7;ndin F (6°keEQ-PGF =~~ -d - ..- ' - "K _ _ a - ln = - !a'` f P f Orher suOOou; Smedlsh Medical Research Council. - From the Department of-Pharmacology,-Catholic Uniyersity, Rome, Italy, and the- Department of Clinwal-Piysiology at.Karoiinska Insiitut_s, Nvddinge University Hosy,tsl, --Stockhclm,Sweden. -]a5
Page 39: eta98c00
induce oxida!iv±-metabolis-M =wfieA sufd-_as,a itimula_nt_._ Bin:ting_af eiti-?:7y-Z5 tb phagxydic cclls-wa;-nnt decreased by pre-exP., r, e ceits to etineT FJ':3N- or. Ph:P:.: - Evi3enee vTresentcd tcSuggest LSai_the irinrditnl of-.ar.:i-My-.2C-s,; surface ee.>.:bata.. the czl a:.e=pe vn?tse-€ri "h,umren.9 +re and r'dP 7ty b!cr___ing-a- _ - comIDOn:Ratt+.w'ay(sj slin:ulat-d-by these o,ffeeeni secretsgogues. - - -- - warrxa; L. T. ar:d Ci+ti._. C,l: - The lournn7 o,rlmmU.w!ogy-73•1(3iak27-3g3., 19$3= Other v:pport• Nadona+:mtu:_?es of Hca!ta. = Diri;ien nf_Pediatric Or•.co:o2y, T'e lohn=-?3ockins Onco'ogy Center, The Johns -HoFkirs Fram .ne Ueyar*!nea ef.L-.viog-, Iftsity u 3er.:[iFE n a.-P i?aoeian,=,. and- th:. _TJnivers[ty.ichool of 4ledicine, Baitimore_ AN77-MY-2g: AN AMYeGRANiiiOCY7E iAO;,r9i; MONOCLONAL ANT;BODl(,- - -- BINDS TO A-SUGAR SEQUENCE IN-7 AC'['O-N-NEOTETRAISE- sialosyiv.araglob.nide, x:d iG diitai trsacc'ar;dr aeauer.ee-'u-tound a•m nignee glycoliyids - GIcNAOR1-3Ga!p-4GIc. T:is tetracacehaeide occnrs in the giyFolipic- oaraglobOside and -- layor chrr_;aatagsa,S.-7 recLign:-:s-a.eug~ ; q~e'ce-in--ts[o-'-1Leo.et.,,cse, G_?fl!-. _- leukocy[es-a.r.d eri=Arotirtes ai-zhrr..~u by radioitF.:ausozsay-o.nd :mrnlnocnainiaq-of thio-- -` cels. Anti-N?y-2g binds t¢ lev>ral r.eutcai glycni;pids aad.iessalylated 3giiosiEes of .. - to lymPnrcytea a+d minoc-tes aad ce many leuteste.:.ell-l;ne, and ;rztrerrt leukenuc. btrst- iYmphxytes:- :16wever, af,er treate-.g -.ells v:ach cec?n:inidase t:e-z-t srn.y-a1so tr.Ss -. immuno'7uor Scenc;, t-E~adsde-hua:an __grant.!ocvtes.s b_ -net -iC---t^sacytK- a.d- from t:::e:n cePs off a muuse_immuniEed-.:ith Posmal-.huma>t-granu}-„yyies.--By_ Aliti-b:y-2:=is ar 1gM-K..m,o„celnna-sn:~ );rodeced-bi-a_byi=,:dont: gr¢pared- . and gly4opn:t=_ins: Spitah•.ik, S. L.,-/:irin. G.l. e. ai:- .- O.Fer sfnr:a• Natlneal-insti£.,re. nf I€-atrn. - From th0 Nationa: InstitLte of Arthfiti3, i7iabeie5, and Digeaive and p_idney 1`+iseases, Bethesda, MD, and the Division oi-Fediatric Onco?ogy, the Onc..•iogy jCenter, ':: e]ehns Hopkins Uni-nrsity Schooi -af ~btedicipe, Ba!tiT,oee, rvfL. - _- h3IXEB GLY:;OSIDE PRET,YEATMEN? PEUL*CES.NONS,e£CfFI{' i}iNi.ING OF = ANTI@O4!fS-Tt3FftOZEN_TISSIV£ SECT' if?h`5--. _- indiacrim;:ate-binding--of uconrJ-ry-ar.tibody to allnouse ini munogicbulins; i=.,-to th^ . mouocl ma!- sntLyotiies -yieiss; iri -ge. er!. suboptimal- resilt_m primari!y -`_oec.ause- of ~3isect-_immnr.~3tn;.*.e:r[:~a3: stuts:es-.of -frozeni nsause tissues-=.i+;!b moui= of siaed--glycesidaie`s -fkiG;._ This- trfatmerS- reduced- the- eouspzcific Sackgrourd_ - - enz; matical[y. Optimal rxsiu3ts rrvere obtained foliowing a 2 hr trsaimzlit wi[S 20 rugjml Ir3sue.-To reduce this-.bonspi<cifi:.staining,itozen-,ec;iolls of mouse kii7ney w•ere- createt - monoctonari reagent aaa to -cr:aogenous rmq:unogiopulin nor.suerfically traFped -in-the- -- statmug ofthx !nterstNt-1-sPaccs' and blirod vesse!s, .hut did not_affect-ihe_ reactivity -oi structu I:rl%ccnd im .unog3ob',tiis-P., (igG) i-tht glmneruti - r aiter :!:e seactlvirv of: "' 1 }[i
Page 40: eta98c00
Urines were tes!ed fro:n ii patiens w•.ti,_6:CNS, aI3-of whom exereted SIFS. -ln-asdiEion, -- ._ SIRS in urtnes iror-a :arge group o, paa r ..gryc a pasr .e r.e o. upgresse4 immune rnspoe es _fiec foul.i in ...:pkrotuc s, narome' --- - nephrotfe syndremeagid_that t!_e prfse-_e ef Sh~in th. ~.:ine's no: acecunted fnr sole!y . ry the presenc of: pro[ii^.uria.or r.ephrosis._ Serecn rr m four-n:phro::c aa.iec€s also contained SIRS Hhe-eas neith-ersEron• n r tiri:r_frrm ~ianormal subJect; ha - SIRS activity. The systenic preseoce of SIRS in the_se four patients and the identifcation o:f _ _ _ _ _ --'tt-~l-f-S1RS~rtt:e [wo r.e3hrotic petiensh w•:h acute gtcnmxruloasphritssnd tBree_se2hrotrc patiertts w;th- _- nc^'sepFr.:i.- _ membranoproiif.rai~ve disease escr?:e; £I~S. cut --,ther nepl:raits-and 211 Fatie.lt5 did not 've5e reSUTtS indi[atee t"st E£Cretlo:l a'. S:RS ovc4rs in ceaainCa€°s C - Sch apE : Ei.ir snd Ai+-:e, :.Jl -Jorunaf ol Cl;nieailn:cstigalfen_75.3+1-.315,1'iE__.'-_ - ~ Orher.suppor vlot>_anto omyar.y. _ A5ed3cine, St Lau's.-._ - From theC~eparimest o_` Pa!hoTJ$Y aiiA La•aoraYory M dicine, Th.e IewisS -iiosp=ta: of St. Louis add the.Uepar•ments of Fea`iat A:; and Ratho[ogy, Wa.hingion i'niversitp-Sceao! o.r iNHIBI T 3ON OF S?TAJELC IbiidUME F LSFONSE _SUPPfcE`=SOR -- FCTIVSTI' Sv GRG:PTH Fa_TORS- properties o aiRS. in botS 5e.arogena;us and.homogeneous cel• pepufatmees. - -not IGF.or {L-!-; ,e.etne~ ir.hihitiri. of antibody secretion by S'-RS . tn s tem€- ana concentration-dep€ndent marn_r. 'r/ith 10 -:r.~•s of IL-2-per 0S-m! culiure, reve;sat wa• complete within 1 h.. The abiG[y oP growth faetors to interfere with 'rnhivition of cell drvrsioa uy SIRS~ wa,,zxamrned w'ith t're humau H ck !-..nkemia RP*~s:-1785 This cel:_ - iinebrnds iGFbut :3 r:o, lnown to havi celi sarface rse€piar_ io.-2l:-1er };--2. -fGF -- (0.3-!-ng[mti1 wher:-adGed t R?M!_: 8g csltyresS 6 hr 5efeie IRS ;-Intcrfered w:th - th6abt'ity o 3 k, to Tn'+~[ - fl1l-d v~qt . TakE'r t x t-e_ t1 3e 6±-Snt~~- that g_ow.h fact o.n e , rere wt-h '+ota t+_ m+neno uEf-e~srve arv1 g-ew!h trFt i.ory ~- - before or up ?c 3 hr aftee additiou of SiF.S. Further eval -ation siowed that !L-_• but Each~inhibited SiRS-med?atedswjFres€ion _eff antibceyy secretion by- cutrured mause -cp!eemceBs, :nni3ition or S Ras sivit was mvit ec!ive_when grnwt.^. fa-n^ ,vere- -added lafx in_tSe :eaure period.- iL-1_._IL-2 and _-GFaiso bixsed scpEressien by - 3RSa,r Flower GF and 1L-1 b:ock stC =s;on by - RS.. u-•en added -3-6 hr before aldition of -IRS svherea^ !L 2 blocked s.ppresaian b IRS. -when adAed lntEriI- (LL-1), mteneu5rn 2 (!i-7) and ep:de•mal growl ._ = .a. (..~ . to irs activated for.::,_SiRS-., 'cY i,yd:o!;e'i;,r_:ozide-preduced by m~cro^vha,=s. SIRSys _ :nhibi=antibcdy secretior.bY °lyTp"hocytes and ceil division by normal c•r transformed -_ _-cell lines. Effects o' purified growth.factors on si-ppressian_ of a ntitx.dY secretion s+ere -exami.^.ed to determ":_ne whether any would op,usf the inhibitory effects of SIRS- or _ F f-. , ~~F~ . Solub!E mm>_r~o-fxsfa .. uqOres /S.RS„ a pr ~tei.:_of-3f r i4~0i75• is_ _aamphokine predu:.ed `ov interfe:en- 8r.-cencanava!i! A-aUVited suppressor T ce!s and is5x€d'exeG- - Proceedings of the 'Naiionat -Academy -aT ° Sci.nres oj- the Ur•iied- - Stares ^+I Ameriea g2-52z:0=3?-'t4; 1955. Other snOlort: Sciauce Foundation and the ?Lfonsanto Compacy. 147 1

Text Control

Highlight Text:

OCR Text Alignment:

Image Control

Image Rotation:

Image Size: