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Emerging Therapeutic Targets Volume 3, 1999 - Issue 2
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Review

Adhesion molecules in cardiovascular disease

Joseph E Prince Baylor College of Medicine, 6565 Fannin, MS. A-601, Houston, Texas 77030, USA. Tel: +1 713 798 5034; Fax: +1 713 798 7885; [email protected]
&
Christie M Ballantyne Baylor College of Medicine, 6565 Fannin, MS. A-601, Houston, Texas 77030, USA. Tel: +1 713 798 5034; Fax: +1 713 798 7885; [email protected]
Pages 263-277 | Published online: 25 Feb 2005

Bibliography

  • AMERICAN HEART ASSOCIATION: 1999 Heart and Stroke Statistical Update. Dallas, Texas, USA (1998).
  • JACOBSON TA, SCHEIN JR, WILLIAMSON A, BALLANTYNE CM: Maximizing the cost-effectiveness of lipid-lowering therapy. Arch. Intern. Med. (1998) 158:1977–1989.
  • ROSAMOND WD, CHAMBLESS LE, FOLSOM AR et al. Trends in the incidence of myocardial infarction and inmortality due to coronary heart disease, 1987 to 1994. New Engl. J. Med. (1998) 339:861–867.
  • LEVY D, THOM TJ: Death rates from coronary disease-progress and a puzzling paradox. New Engl. J. Med. (1998) 339:915–917.
  • ROSS R: Atherosclerosis -an inflammatory disease. New Engl. J. Med. (1999) 340:115–126.
  • ••Excellent, comprehensive and current review on inflamma-tion and atherosclerosis.
  • CYBULSKY MI, GIMBRONE MA, JR.: Endothelial expres-sion of a mononuclear leukocyte adhesion molecule during atherogenesis. Science (1991) 251:788–791.
  • POSTON RN, HASKARD DO, COUCHER JR, GALL NP, JOHNSON-TIDEY RR: Expression of intercellular adhesion molecule-1 in atherosclerotic plaques. Am. J. Pathol. (1992) 140:665–673.
  • VAN DER WAL AC, DAS PK, TIGGES AJ, BECKER AE: Adhesion molecules on the endothelium and mononuclear cells in human atherosclerotic lesions. Am. J. Pathol. (1992) 141:1427–1433.
  • DAVIES MJ, GORDON JL, GEARING AJH et al. The expres-sion of the adhesion molecules ICAM-1, VCAM-1, PECAM, and E-selectin in human atherosclerosis. J. Pathol. (1993) 171:223–229.
  • O'BRIEN KD, ALLEN MD, MCDONALD TO et al. Vascularcell adhesion molecule-1 is expressed in human coronary atherosclerotic plaques. j Clin. Invest. (1993) 92:945–951.
  • WOOD KM, CADOGAN MD, RAMSHAW AL, PARUMS DV:The distribution of adhesion molecules in human atherosclerosis. Histopathology (1993) 22:437–444.
  • NAKAI K, ITOH C, KAWAZOE K et al. Concentration ofsoluble vascular cell adhesion molecule-1 (VCAM-1) correlated with expression of VCAM-1 mRNA in the human atherosclerotic aorta. Coron. Artery. Dis. (1995) 6:497–502.
  • O'BRIEN KD, MCDONALD TO, CHAIT A, ALLEN MD, ALPERS CE: Neovascular expression of E-selectin, intercellular adhesion molecule-1 in human athero-sclerosis and their relation to intimal leukocyte content. Circulation (1996) 93:672–682.
  • POSTON RN, JOHNSON-TIDEY RR: Localized adhesionof monocytes to human atherosclerotic plaques demonstrated in vitro: implications for atherogenesis. Am. J. Pathol. (1996) 149:73–80.
  • ANDERSON DC, SCHMALSTEIG FC, FINEGOLD MJ et al. The severe and moderate phenotypes of heritable Mac-1, LFA-1 deficiency: their quantitative definition and relation to leukocyte dysfunction and clinical features. J. Infect. Dis. (1985) 152:668–689.
  • KARSAN A, CORNEJO CJ, WINN RK et al. Leukocyte Adhesion Deficiency Type II is a generalized defect of de novo GDP-fucose biosynthesis. Endothelial cell fucosylation is not required for neutrophil rolling on human nonlymphoid endothelium. J. Clin. Invest. (1998) 101:2438–2445.
  • MARISCALCO MM, SMITH CW: Integrins and celladhesion molecules. In: F et al and Neonatal Physiology (2nd Edition). Polin RA, Fox WW (Eds.), Saunders, Philadel-phia, USA (1998):1980–2002.
  • CORBI AL, LARSON RS, KISHIMOTO TK, SPRINGER TA, MORTON CC: Chromosomal location of the genes encoding the leukocyte adhesion receptors LFA-1, Mac-1 and p150, 95. Identification of a gene cluster involved in cell adhesion. J. Exp. Med. (1988) 167:1597–1607.
  • COLLER BS, ANDERSON K, WEISMAN HF: New antiplatelet agents: platelet GPIlb/IIIa antagonists. Thromb. Haemost. (1995) 74:302–308.
  • TOPOL EJ, BYZOVA TV, PLOW EF: Platelet GPIlb-Illa blockers. Lancet (1999) 353:227–231.
  • LARSON RS, SPRINGER TA: Structure and function of leukocyte integrins. Immunol Rev. (1990) 114:181–217.
  • KISHIMOTO TK, LARSON RS, CORBI AL et al. The leukocyte integrins. Adv. Immunol. (1989) 46:149–182.
  • DICKESON SK, SANTORO SA: Ligand recognition by the I domain-containing integrins. Cell. Mol. Life ScL (1998) 54:556–566.
  • RUOSLAHTI E, PIERSCHBACHER MD: New perspectivesin cell adhesion: RGD and integrins. Science (1987) 238:491–497.
  • BEVILACQUA MP, NELSON RM: Selectins. J. Clin. Invest.(1993) 91:379–387.
  • MCEVER RP, BECKSTEAD JH, MOORE KL, MARSHALL-CARLSON L, BAINTON DF: GMP-140, a platelet a-granule membrane protein, is also synthesized by vascularendothelial cells and is localized in Weibel-Palade bodies. J. Clin. Invest. (1989) 84:92–99.
  • JOHNSON RC, CHAPMAN SM, DONG ZM et al. Absence of P-selectin delays fatty streak formation in mice. J. Clin. Invest. (1997) 99:1037–1043.
  • CARLOS TM, HARLAN JM: Leukocyte-endothelial adhesion molecules. Blood (1994) 84:2068–2101.
  • WANG JH, SPRINGER TA: Structural specializations of immunoglobulin superfamily members for adhesion to integrins and viruses. Immunol. Rev. (1998) 163:197–215.
  • •Comprehensive review of the structure and function of immunoglobulin superfamily members of great relevance to potential novel therapeutic targets.
  • HANNINEN A, JAAKKOLA I, JALKANEN S: Mucosal addressin is required for the development of diabetes in nonobese diabetic mice. J. Immunol. (1998) 160:6018–6025.
  • BLANKS JE, MOLL T, EYTNER R, VESTWEBER D: Stimula-tion of P-selectin glycoprotein ligand-1 on mouse neutrophils activates 02-integrin mediated cell attach-ment to ICAM-1. Eur. J. Immunol. (1998) 28:433–443.
  • SHATTIL SJ, KASHIWAGI H, PAMPORI N: Integrin signaling: the platelet paradigm. Blood (1998) 91:2645–2657.
  • TODD RF III, PETTY HR: 02 (CD11/CD18) integrins canserve as signaling partners for other leukocyte receptors. J. Lab. Orin. Med. (1997) 129:492–498.
  • •Well-written review that covers the mechanism and consequences of 'cross talk' between the different CD11/CD18 integrins.
  • COXON A, RIEU P, BARKALOW FJ et al. A novel role for the 02 integrin CD1 lb/CD18 in neutrophil apoptosis: a homeostatic mechanism in inflammation. Immunity (1996) 5:653–666.
  • ANDERSON DC, KISHIMOTO TK, SMITH CW: Leukocyte adhesion deficiency and other disorders of leukocyte adherence and motility. In: The Metabolic and Molecular Bases of Inherited Disease (7th Edition). Scriver CR, Beaudet AL, Sly WS, Valle D (Eds.), McGraw-Hill, New York, USA (1995)3955–3994.
  • WATSON RWG, ROTSTEIN OD, NATHENS AB, PARODO J, MARSHALL JC: Neutrophil apoptosis is modulated by endothelial transmigration and adhesion molecule engagement. J. Immunol (1997) 158:945–953.
  • RAINGER GE, BUCKLEY C, SIMMONS DL, NASH GB: Neutrophils rolling on immobilised platelets migrate into homotypic aggregates after activation. Thromb. Haemost. (1998) 79:1177–1183.
  • RINDER HM, BONAN JL, RINDER CS, AULT KA, SMITH BR:Dynamics of leukocyte-platelet adhesion in whole blood. Blood (1991) 78:1730–1737.
  • KONSTANTOPOULOS K, NEELAMEGHAM S, BURNS AR et al. Venous levels of shear support neutrophil-platelet adhesion and neutrophil aggregation in blood via P-selectin and 02-integrin. Circulation (1998) 98:873–882.
  • LUSCINSKAS FW, KANSAS GS, DING H et al. Monocyterolling, arrest and spreading on IL-4-activated vascular endothelium under flow is mediated via sequential action of L-selectin, 01-integrins, and 02-integrins. Cell. Biol. (1994) 125:1417–1427.
  • ABE Y, BALLANTYNE CM, SMITH CW: Functions of domain 1 and 4 of vascular cell adhesion molecule-1 in a4 integrin-dependent adhesion under static and flow conditions are differentially regulated. J. Immunol (1996) 157:5061–5069.
  • SCALIA R, APPEL JZ III, LEFER AM: Leukocyte-endothelium interaction during the early stages of hypercholesterolemia in the rabbit: role of P-selectin, ICAM-1, and VCAM-1. Arterioscler. Thromb. Vasc. Biol (1998) 18:1093–1100.
  • FROSTEGARD J, WU R, HAEGERSTRAND A et al. Mononuclear leukocytes exposed to oxidized low density lipoprotein secrete a factor that stimulates endothelial cells to express adhesion molecules. Atherosclerosis (1993) 103:213–219.
  • THORNE SA, ABBOT SE, STEVENS CR et al. Modified low density lipoprotein and cytokines mediate monocyte adhesion to smooth muscle cells. Atherosclerosis (1996) 127:167–176.
  • ALLEN S, KHAN S, AL-MOHANNA F, BATTEN P, YACOUBM: Native low density lipoprotein-induced calcium transients trigger VCAM-1 and E-selectin expression in cultured human vascular endothelial cells. J. Clin. Invest. (1998) 101:1064–1075.
  • DUPLAA C, COUFFINHAL T, LABAT L et al. Monocyte/macrophage recruitment and expression of endothelial adhesion proteins in human atheroscle-rotic lesions. Atherosclerosis (1996) 121:253–266.
  • JOHNSON RC, CHAPMAN SM, DONG ZM et al.: Absence of P-selectin delays fatty streak formation in mice. J. Clin. Invest. (1997) 99:1037–1043.
  • DONG ZM, CHAPMAN SM, BROWN AA et al. The combined role of P-and E-selectins in atherosclerosis. Clin. Invest. (1998) 102:145–152.
  • •It is demonstrated in this paper that mice deficient in both P-and E-selectin have reduced atherosclerosis.
  • NAGEH MF, SANDBERG ET, MAROTTI KR et al. Deficiency of inflammatory cell adhesion molecules protects against atherosclerosis in mice. Arterioscler. Thromb. Vasc. Biol. (1997) 17:1517–1520.
  • •This article reports that mice with a deficiency of ICAM-1 or CD18 have reduced susceptibility to diet-induced atherosclerosis.
  • HYNES RO, WAGNER DD: Genetic manipulation of vascular adhesion molecules in mice. J. Clin. Invest. (1996) 98:2193–2195.
  • HACKMAN A, ABE Y, INSULL W, JR. et al. Levels of soluble cell adhesion molecules in patients with dyslipidemia. Circulation (1996) 93:1334–1338.
  • ABE Y, EL-MASRI B, KIMBALL KT et al. Soluble cell adhesion molecules in hypertriglyceridemia and potential significance on monocyte adhesion. Arterio-scler. Thromb. Vasc. Biol. (1998) 18:723–731.
  • ROHDE LE, LEE RT, RIVERO J et al. Circulating celladhesion molecules are correlated with ultrasound-based assessment of carotid atherosclerosis. Arterio-scler. Thromb. Vasc. Biol. (1998) 18:1765–1770.
  • HWANG SJ, BALLANTYNE CM, SHARRETT AR et al. Circulating adhesion molecules VCAM-1, ICAM-1, and E-selectin in carotid atherosclerosis and incident coronary heart disease cases: the atherosclerosis risk in communities (ARIC) study. Circulation (1997) 96:4219–4225.
  • •First large prospective epidemiological study to show that increased levels of ICAM-1 were independently associated with increased risk for coronary artery disease and carotid artery disease.
  • RIDKER PM, HENNEKENS CH, ROITMAN-JOHNSON B, STAMPFER MJ, ALLEN J: Plasma concentration of soluble intercellular adhesion molecule 1 and risks of future myocardial infarction in apparently healthy men. Lancet (1998) 351:88–92.
  • RIDKER PM, GLYNN RJ, HENNEKENS CH: C-reactiveprotein adds to the predictive value of total and HDL cholesterol in determining risk of first myocardial infarction. Circulation (1998) 97:2007–2011.
  • RIDKER PM, BURING JE, SHIH J, MATIAS M, HENNEKENSCH: Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation (1998) 98:731–733.
  • ENTMAN ML, YOUKER K, SHOJI T et al. Neutrophilinduced oxidative injury of cardiac myocytes. A compartmented system requiring CD1 lb/ CD18-ICAM-1 adherence. J. Clin. Invest. (1992) 90:1335–1345.
  • YOUKER K, SMITH CW, ANDERSON DC et al. Neutrophiladherence to isolated adult cardiac myocytes: induction by cardiac lymph collected during ischemia and reperfusion. j Clin. Invest. (1992) 89:602–609.
  • SIMPSON PJ, TODD RF III, FANTONE JC et al. Reductionof experimental canine myocardial reperfusion injury by a monoclonal antibody (anti-Mol, anti-CD1 lb) that inhibits leukocyte adhesion. J. Clin. Invest. (1988) 81:624–629.
  • SEEWALDT-BECKER E, ROTHLEIN R, DAMMGEN JW: CD18 dependent adhesion of leukocytes to endothe-IMm and its relevance for cardiac reperfusion. In: Leukocyte Adhesion Molecules: Structure, Function, and Regulation. Springer TA, Anderson DC, Rosenthal AS, Rothlein R (Eds.), Springer Verlag, New York, USA (1989):138–148.
  • YAMAZAKI T, SEKO Y, TAMATANI T et al. Expression ofintercellular adhesion molecule-1 in rat heart with ischemia/reperfusion and limitation of infarct size by treatment with antibodies against cell adhesion molecules. Am. J. Pathol. (1993) 143:410–418.
  • MA XL, TSAO PS, LEFER AM: Antibody to CD-18 exertsendothelial and cardiac protective effects in myocar-dial ischemia and reperfusion. j Clin. Invest. (1991) 88:1237–1243.
  • WINN RK, LIGGITT D, VEDDER NB, PAULSON JC, HARLANJM: Anti-P-selectin monoclonal antibody attenuates reperfusion injury to the rabbit ear. J. Clin. Invest. (1993) 92:2042–2047.
  • LEFER DJ, FLYNN DM, BUDA AJ: Effects of a monoclonalantibody directed against P-selectin after myocardial ischemia and reperfusion. Am. J. Physiol (1996) 270:H88–H98.
  • MASSBERG S, ENDERS G, LEIDERER R et al. Platelet-endothelial cell interactions during ischemia/reperfu-sion: the role of P-selectin. Blood (1998) 92:507–515.
  • HOMEISTER JW, ZHANG M, FRENETTE PS et al. Overlap-ping functions of E-and P-selectin in neutrophil recruitment during acute inflammation. Blood (1998) 92:2345–2352.
  • SILVER PJ: IBT 9302 (heparinase III): a novel enzymefor the management of reperfusion injury-related vascular damage, restenosis and wound healing. Exp. Opin. Invest. Drugs. (1998) 7:1003–1014.
  • HERRMANN SM, RICARD S, NICAUD V et al. The P-selectin gene is highly polymorphic: reduced frequency of the Pro715 allele carriers in patients with myocardial infarction. Hum. Mol. Genet. (1998) 7:1277–1284.
  • ERBEL R, HAUDE M, HOPP HW et al., THE RESTENOSISSTENT STUDY GROUP: Coronary-artery stenting compared with balloon angioplasty for restenosis after initial balloon angioplasty. New Engl. J. Med. (1998) 339:1702–1704.
  • BERK BC, HARRIS K: Restenosis after percutaneous transluminal coronary angioplasty: new therapeutic insights from pathogenic mechanisms. Adv. Intern. Med. (1995) 40:445–501.
  • MINTZ GS, POPMA JJ, PICHARD AD et al. Arterial remodeling after coronary angioplasty: a serial intravascular ultrasound study. Circulation (1996) 94:35–43.
  • SERRANO CV, JR., RAMIRES JAF, VENTURINELLI M et al. Coronary angioplasty results in leukocyte and platelet activation with adhesion molecule expression: evidence of inflammatory responses in coronary angioplasty. J. Am. Coll. Cardiol. (1997) 29:1276–1283.
  • INOUE T, SAKAI Y, FUJITO T et al. Clinical significance of neutrophil adhesion molecules expression after coronary angioplasty on the development of restenosis. Thromb. Haemost. (1998) 79:54–58.
  • BARRON MK, LAKE RS, BUDA AJ, TENAGLIA AN: Intimal hyperplasia after balloon injury is attenuated by blocking selectins. Circulation (1997) 96:3587–3592.
  • SIMON DI, XU H, ORTLEPP S, ROGERS C, RAO NK: 7E3 monoclonal antibody directed against the platelet glycoprotein Ilb/Illa cross-reacts with the leukocyte integrin Mac-1 and blocks adhesion to fibrinogen and ICAM-1. Arterioscler. Thromb. Vasc. Biol. (1997) 17:528–535.
  • MICKELSON JK, ALI MN, KLEIMAN NS, et al. Chimeric7E3 Fab (ReoPro) decreases detectable CD11b onneutrophils from patients undergoing coronaryangioplasty. J. Am. Coll. Cardiol. (1999) 33:97–106.
  • SRIVATSA SS, FITZPATRICK LA, TSAO PW et al. Selectiveccv63 integrin blockade potently limits neointimal hyperplasia and lumen stenosis following deep coronary arterial stent injury: evidence for the functional importance of integrin ccv63 and osteopontin expression during neointima formation. Cardiovasc. Res. (1997) 36:408–428.
  • EPIC INVESTIGATORS: Use of a monoclonal antibodydirected against the platelet glycoprotein Hb/IIIa receptor in high-risk coronary angioplasty. NewEngl. J. Med. (1994) 330:956–961.
  • EPILOG INVESTIGATORS: Platelet glycoprotein Ilb/Illareceptor blockade and low-dose heparin during percutaneous coronary revascularization. New Engl. J. Med. (1997) 336:1689–1696.
  • PLATELET RECEPTOR INHIBITION IN ISCHEMIC SYNDROME MANAGEMENT (PRISM) STUDY INVESTIGA-TORS: A comparison of aspirin plus tiroflban with aspirin plus heparin for unstable angina. New Engl. J. Med. (1998) 338:1498–1505.
  • PURSUIT TRIAL INVESTIGATORS: Inhibition of plateletglycoprotein Ilb/Illa with eptiflbatide in patients with acute coronary syndromes. New Engl. J. Med. (1998) 339:456–443.
  • ZHAO Z-Q, LEFER DJ, SATO H et al. Monoclonalantibody to ICAM-1 preserves postischemic blood flow and reduces infarct size after ischemia-reperfusion in rabbit. J. Leukoc. Biol. (1997) 62:292–300.
  • YENARI MA, KUNIS D, SUN GH et al. Hu23F2G, anantibody recognizing the leukocyte CD11/CD18 integrin, reduces injury in a rabbit model of transient focal cerebral ischemia. Exp. Neurol (1998) 153:223–233.
  • SORIANO SG, LIPTON SA, WANG YF et al. Intercellularadhesion molecule-l-deficient mice are less suscep-tible to cerebral ischemia-reperfusion injury. Ann. Neurol (1996) 39:618–624.
  • SCHNEIDER D, BERROUSCHOT J, BRANDT T et al. Safety, pharmacokinetics and biological activity of enlimomab (anti-ICAM-1 antibody): an open-label, dose escalation study in patients hospitalized for acute stroke. Eur. Neurol. (1998) 40:78–83.
  • ENLIMOMAB ACUTE STROKE TRIAL INVESTIGATORS, SHERMAN DG: The Enlimomab Acute Stroke Trial: final results. Neurology (1997) 48:A270.
  • DEGRABA TJ: The role of inflammation after acutestroke: utility of pursuing anti-adhesion molecule therapy. Neurology (1998) 51:S62–S68.
  • •Excellent review of the therapeutic promise and clinical difficulties in pursuit of anti-adhesion molecule therapy for treatment of cerebral ischaemia.
  • KAVANAUGH AF, DAVIS LS, NICHOLS LA et al.Treatment of refractory rheumatoid arthritis with a monoclonal antibody to intercellular adhesion molecule 1. Arthritis Rheum. (1994) 37:992–999.
  • HAUG CE, COLVIN RB, DELMONICO FL et al. A Phase I trial of immunosuppression with anti-ICAM-1 (CD54) mAb in renal allograft recipients. Transplantation (1993) 55:766–773.
  • VUORTE J, LINDSBERG PJ, KASTE M et al. Anti-ICAM-1 monoclonal antibody R6.5 (enlimomab) promotes activation of neutrophils in whole blood. J. Immunol (1999) 162:2353–2357.
  • BENNETT CF, KORNBRUST D, HENRYS et al. An ICAM-1 antisense oligonucleotide prevents and reverses dextran sulfate sodium-induced colitis in mice. J. Pharmacol. Exp. Ther. (1997) 280:988–1000.
  • STEPKOWSKI SM, TU Y, CONDON TP, BENNETT CF: Blocking of heart allograft rejection by intercellular adhesion molecule-1 antisense oligonucleotides alone or in combination with other immunosuppressive modalities. J. Immunol (1994) 153:5336–5346.
  • •This article presents a novel approach toward inhibition of ICAM-1 by antisense oligonucleotides.
  • STEPKOWSKI SM, WANG ME, AMANTE A et al. Antisense ICAM-1 oligonucleotides block allograft rejection in rats. Transplant. Proc. (1997) 29:1285.
  • HALLER H, DRAGUN D, MIETHKE A et al. Antisense oligonucleotides for ICAM-1 attenuate reperfusion injury and renal failure in the rat. Kidney. Int. (1996) 50:473–480.
  • ROGERS C, EDELMAN ER, SIMON DI: A mAb to the 62-leukocyte integrin Mac-1 (CD11b/CD18) reduces intimal thickening after angioplasty or stent implanta-tion in rabbits. Proc. Natl. Acad. Sci. USA (1998) 95:10134–10139.
  • •A new approach toward reducing 'restenosis' by antibodies to Mac-1.
  • KOH KK, BUI MN, MINCEMOYER R, CANNON RO III: Effects of hormone therapy on inflammatory cell adhesion molecules in postmenopausal healthy women. Am. J. Cardiol (1997) 80:1505–1507.
  • KOH KK, CARDILLO C, BUI MN et al. Vascular effects ofestrogen and cholesterol-lowering therapies in hypercholesterolemic postmenopausal women. Circulation (1999) 99:354–360.
  • MARTIN A, FOXALL T, BLUMBERG JB, MEYDANI M: Vitamin E inhibits low-density lipoprotein-induced adhesion of monocytes to human aortic endothelial cells in vitro. Arterioscler. Thromb. Vasc. Biol. (1997) 17:429–436.
  • LU H, SMITH CW, PERRARD J et al. LFA-1 is sufficient in mediating neutrophil emigration in Mac-1-deficient mice. J. Clin. Invest. (1997) 99:1340–1340.
  • SCHMITS R, KUNDIG TM, BAKER DM et al. LFA-1-deficient mice show normal CTL responses to virus but fail to reject immunogenic tumor. J. Exp. Med. (1996) 183:1415–1426.

Websites

  • http://www.biogen.com/productinfo/ product.pipeline.html Biogen: Product Information-Biogen's Research and Development Pipeline. (1999).
  • http://www.icos.comipipeline/index.html ICOS Corporation: ICOS pipeline. (1999).
  • http://www.genentech.comipipeline/index.html Genetech, Inc.: Product Pipeline. (1999).
  • http://www.leukosite.comirdirddp.html LeokoSite, Inc.: Research and Drug Discovery. (1998).
  • http://www.integra-ls.comigrant_rsch.htm Integra LifeSciences Corporation: Grant Supported Research. (1999).
  • http://www.tbc.comiclinical.html Texas Biotechnology Corporation: Clinical Development. (1999).
  • http://www.isip.com/productsicaml.htm Isis Pharmaceuticals, Inc.: Isis Pharmaceuticals, Inc.-Cell Adhesion Molecules (CAIVIO. (1997).
  • http://www.cytelcorp.comimasterset.html Cytel Corporation. (1998).
  • http://www.bayerus.comiabout/investingiannual97/ health.html Bayer Corporation: 1997 Annual Report: Health Care and Life Sciences. (1998).

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