Pharmacologic control of smooth muscle cells in allografts

Transplant Immunology

Volumn 5, Issue 4, 1997, Pages 267-275

  Foegh, Marie L ^a,b   Ramwell, Peter W ^a  

^a GEORGETOWN UNIVERSITY MEDICAL CENTER   (United States)

^b GEORGETOWN UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANGIOPEPTIN; ARGININE; ESTRADIOL; IMMUNOSUPPRESSIVE AGENT; NITRIC OXIDE; PROSTAGLANDIN;

ALLOGRAFT; PRIORITY JOURNAL; REVIEW; SMOOTH MUSCLE FIBER;

EID: 0031470038     PISSN: 09663274     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0966-3274(97)80007-X     Document Type: Article

References (111)

1. Foegh ML, Vermani R. Molecular biology of intimal proliferation. Curr Opin Cardiol. 8:1993;938-950.
2. Ewel CH, Foegh ML. Chronic graft rejection: accelerated transplant arteriosclerosis. Immunol Rev. 134:1993;21-31.
3. Murray AG, Libby P, Pober JS. Human vascular smooth muscle cells poorly co-stimulate and actively inhibit allogeneic CD4+ T cell proliferation in vitro. J Immunol. 154:1995;151-161.
4. Suttles J, Miller RW, Moyer CF. T cell-vascular smooth muscle cell interactions: antigen-specific activation and cell cycle blockade of T helper clones by cloned vascular smooth muscle cells. Exp Cell Res. 218:1995;331-338.
5. Banskota NK, Carpentier JL, King GL. Processing and release of insulin and insulin growth factor I by macro- and microvascular endothelial cells. Endocrine. 119:1986;1904-1913.
6. Hongo M, Itoi M, Yamaguchi N, Imanishi J. Distribution of epidermal growth factors (EGF) receptors in rabbit corneal epithelial cells, keratocytes and endothelial cells and the changes induced by transforming growth factor-beta 1. Exp Eye Res. 54:1992;9-16.
7. Wilson SE, Lloyd SA. Epidermal growth factor and its receptor, basic fibroblast growth factors, transforming growth factor beta-1, and interleukin-1 alpha mRNA production in human corneal endothelial cells. Invest Ophthalmo Vis Sci. 32:1991;2747-2756.
8. Kaufman BR, Fox PL, Graham LM. Platelet-derived growth factor production by canine aortic grafts seeded with endothelial cells. J Vasc Surg. 15:1992;699-706.
9. Shaddy RE, Hansen CJ, Cowley CG. Effects of T cell on platelet-derived growth factor-like protein secretion from endothelial cells. J Heart Lung Transplant. 11:1992;48-57.
10. Kourembanas S, Faller DV. Platelet-derived growth factor production by human umbilical vein endothelial cells is regulated by basic fibroblasts growth factor. J Biol Chem. 264:1989;4456-4459.
11. Phan SH, Gharaee KM, McGarry B, Kunkel SL, Wolber FW. Regulation of rat pulmonary artery endothelial cell transforming growth factor-beta production by IL-1 beta and tumour necrosis factor alpha. J Immunol. 149:1992;103-106.
12. Hansson GK, Jonasson L, Holm J, Clowes MM, Clowes AW. Gamma-interferon regulates vascular smooth muscle proliferation and Ia antigen expression in vito and in vitro. Circ Res. 63:1988;712-719.
13. Warner SJ, Friedman GB, Libby P. Immune interferon inhibits proliferation and induces 2′-5′-oligoadenylates synthetase gene expression in human vascular smooth muscle cells. J Clin Invest. 83:1989;1174-1182.
14. Fox HS, Bond BL, Parslow TG. Oestrogen regulates the IFN-gamma promoter. J Immunol. 146:1991;4362-4367.
15. Arkins S, Rebeiz N, Brunke-Reese DL, Biragym A, Kelley KW. Interferon-gamma inhibits macrophage insulin-like growth factor-I synthesis at the transcriptional level. Molecular Endocrinol. 9:1995;350-360.
16. Gordon D, Schwartz SM, Benditt EP, Wilcox JN. Growth factors and cell proliferation in human atherosclerosis. Transplant Proc. 21:1989;3692-3694.
17. Grant MB, Wargovich TJ, Ellis EA, Caballero S, Mansour M, Pepine CJ. Localization of insulin like growth factor I and inhibition of coronary smooth muscle cell growth by somatostatin analogues in human coronary smooth muscle cells. Circulation. 89:1994;1511-517.
18. Yamamoto M, Yamamoto K. Growth regulation in primary culture of rabbit arterial smooth muscle cells by platelet derived growth factor, insulin-like growth factor-I and epidermal growth factor. Exp Cell Res. 212:1994;62-68.
19. Schiffers PMH, Fazzi GE, van Ingen Schenau D, De Mey JGR. Effects of candidate autocrine and paracrine mediators on growth responses in isolated rat arteries. Arterioscler Thromb. 14:1994;420-426.
20. Bohm M, Blasius S, Roessner A. Immunohistochemical localization of PDGF B, PDGF beta receptors and IGF-I receptors during atherogenesis. Zentralblatt für Phatologie. 140:1994;357-362.
21. Pfeifle B, Boeder H, Ditschuneit H. Interaction of receptors for insulin-like growth factor I, platelet derived growth factor, and fibroblast growth factor in rat aortic cells. Endocrinol. 120:1987;2251-2258.
22. Baserga B. IGF-I receptor as the restriction point of the cell cycle. Ann NY Acad Science. 666:1992;154-157.
23. Delafontaine P, Lou H, Alexander RW. Regulation of insulin-like growth factor I messenger RNA levels in vascular smooth muscle cells. Hypertension. 18:1991;742-747.
24. Ververis JJ, Ku L, Delafontaine P. Regulation of insulin-like growth factor I receptors on vascular smooth muscle cells by growth factors and phorbol esters. Circ Res. 72:1993;1285-1292.
25. Delafontaine P, Meng XP, Du J. Regulation of vascular smooth muscle cell insulin like growth factor-I receptors by phosphorthioate oligonucleotides: effects on cell growth and evidence that sense targeting at the ATG site increases receptor expression. J Biol Chem. 270:1995;14383-14388.
26. Delafontaine P, Ku L, Ververis JJ, Cohen C, Runge MS, Alexander RW. Epitope Mapping of the alpha chain of the insulin-like growth factor-I receptor using antipeptide antibodies. J Molec Cellular Cardiol. 26:1994;1659-1673.
27. Hayry P, Raisanen A, Ustinov J, Mennander A, Paavonen T. Somatostatin analog, lanreotide, inhibits myocyte replication and several growth factors in allograft arteriosclerosis. FASEB J. 7:1993;1055-1060.
28. Motomura N, Lou H, Maurice P, Foegh ML. Accelerating of arteriosclerosis of the rat aorta allograft by insulin growth factor-I. Transplantation. 63:1997;932-936.
29. Saito S, Motomura N, Lou H, Ramwell PW, Foegh ML. Specific effects of oestradiol on growth factor and MHC class II expression in rat aorta allograft. J Thorac Cardiovasc Surg. 114:1997;803-810.
30. Valentinis B, Bhala A, DeAngelis T, Baserga R, Cohen P. The human insulin-like growth factor (IGF) binding protein-3 inhibits the growth of fibroblasts with a target disruption of the IGF-I receptor gene. Molecular Endocrinol. 9:1995;361-367.
31. Howell M, Orskov H, Frystyk J, Flyvbjerg A, Gronbaek H, Foegh M. Lanreotide, a somatostatin analogue, reduces insulin-like growth factor I accumulation in proliferating aortic tissue in rabbits in vivo. A preliminary study. Eur J Endocrinol. 130:1994;422-425.
32. Cercek B, Fishbein MC, Forrester JS, Helfant RH, Fagin JA. Induction of insulin-like growth factor I messenger RNA in rat aorta after balloon denudation. Circ Res. 66:1990;1755-1760.
33. Bornfeldt KE, Arnquist HJ. Proliferation of vascular smooth muscle cells and regulation by insulin-like growth factor I and insulin. Diabetogia. 35:1992;104-108.
34. Bei M, Lavigne MC, Foegh ML, Ramwell PW, Clark R. Specific binding of 17 beta-oestradiol to rat coronary artery smooth muscle cells. J Steroid Biochem Mol Biol. 58:1996;83-88.
35. Lou H, Zhao Y, Delafontaine P, et al. Oestrogen effects on insulin-like growth factor-I (IGF-I) - induced cell proliferation and IGF-I expression in native and allograft vessels. Circulation. 96:1997;927-933.
36. Vargas R, Wroblewska B, Rego A, Hatch J, Ramwell PW. Oestradiol inhibits smooth muscle cells proliferation of pig coronary artery. Br J Pharmacol. 109:1993;612-617.
37. Foegh ML, Asotra S, Howell MH, Ramwell PW. Oestradiol inhibition of arterial neointimal hyperplasia after balloon injury. J Vasc Surg. 19:1993;722-726.
38. Nabulsi AA, Folsom AR, White A, et al. Association of hormone-replacement therapy with various cardiovascular risk factors in post menopausal women. N Engl J Med. 328:1993;1069-1075.
39. Manolio TA, Furberg CD, Shemanski L, et al. Associations of post-menopausal oestrogen use with cardiovascular disease and its risk factors in older women. Circulation. 88:1993;2163-2171.
40. Kafonek SD. Postmenopausal hormone replacement therapy and cardiovascular risk reduction. Drugs. 47:1994;16-24. (suppl 2).
41. Karas RH, Patterson BL, Mendelsohn ME. Human vascular smooth muscle cells contain functional oestrogen receptor. Circulation. 89:1994;1943-1950.
42. Bayard F, Clamens S, Meggetto F, Blaes N, Delsol G, Faye J. Oestrogen synthesis, oestrogen metabolism, and functional oestrogen receptors in rat arterial smooth muscle cells in culture. Endocrinol. 136:1995;1523-1529.
43. Kuiper GGJM, Carlsson B, Grandien K. Comparison of the ligand binding specificity and transcript tissue distribution of oestrogen receptor α and β Endocrinol. 138:1997;863-870.
44. Kuiper GGJM, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson JA. Cloning of a novel oestrogen receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA. 93:1996;5925-5930.
45. Mosselman S, Polman J, Dijkema R. ERß: identification and characterization of a novel human oestrogen receptor. FEBS Letters. 392:1996;49-53.
46. Dotzlaw H, Leygue E, Watson PH, Murphy LC. Expression of oestrogen receptor-beta in human breast tumours. J Clin Endocrinol Metab. 82:1996;2371-2374.
47. Rhee CY, Spaet TH, Stemerman MB, et al. Oestrogen suppression of surgically induced vascular intimal hyperplasia in rabbits. J Lab Clin Med. 90:1977;77-84.
48. Sullivan TR, Mendelsohn ME. Oestrogen inhibits the response-to-injury in a mouse carotid artery model. J Clin Invest. 96:1995;2482-2488.
49. Oparil S, Levine RL, Chen S-J, Durand J, Chen YF. Sexually dimorphic response of the balloon injured rat carotid artery to hormone treatment. Circulation. 95:1997;1301-1307.
50. Iafrati MD, Karas RH, Aronovitz M, et al. Oestrogen inhibits the vascular injury response in oestrogen receptor α-deficient mice. Nature Medicine. 3:1997;545-548.
51. Foegh M, Rego A, Lou H, Katz N, Ramwell P. Gender effects on Myointimal Hyperplasia. Transplant Proc. 27:1995;2070-2072.
52. Foegh ML, Khirabadi BS, Nakanishi T, Vargas R, Ramwell PW. Oestradiol protects against experimental cardiac transplant atherosclerosis. Transplant Proc. 19:1987;90-94. (suppl 5).
53. Cheng LP, Kuwahara M, Jacobsson J, Foegh ML. Inhibition of myointimal hyperplasia and macrophage infiltration by oestradiol in aorta allografts. Transplantation. 52:1991;967-972.
54. Jacobsson J, Cheng L, Lyke K, Kuwahara M, Kagan E, Ramwell PW, Foegh ML. Effect on oestradiol on accelerated atherosclerosis in rabbit heterotopic aortic allografts. J Heart Lung Transplant. 11:1992;1188-1193.
55. Lou H, Kodama T, Zhao J, Maurice P, Wang YN, Katz N, Foegh ML. Inhibition of transplant coronary arteriosclerosis in rabbits by chronic oestradiol treatment is associated with abolition of MHC class II antigen expression. Circulation. 94:1996;3355-3361.
56. Saito S, Motomura N, Lou H, Ramwell PW, Foegh ML. Specific effects of oestrogen on growth factors and MHC class II expression in rat aorta allograft. J Thorac Cardiovasc Surg. 114:1997;803-810.
57. Motomura N, Lou H, Hong M, Tsutsumi T, Foegh ML. Local administration of oestrogen inhibits transplant arteriosclerosis rat aorta accelerated by topical exposure to IGF-I. Transplant Proc. 29:1997;1118-1120.
58. Bettmann MA, Stemerman MB, Ransil BJ. The effect of hypophysectomy of experimental endothelial cell regrowth and intimal thickening in the rat. Circ Res. 48:1981;907-912.
59. Fingerle J, Faulmuller A, Muller G, et al. Pituitary factors in blood plasma are necessary for smooth muscle cell proliferation in response to injury in vivo. Arteriorscler Thromb. 12:1992;1488-1495.
60. Merimee J. A follow-up study of vascular disease in growth hormone deficient dwarfts with diabetes. New Engl J Med. 298:1978;1217-1222.
61. McGuire WL, Jackson JG, Figueroa JA, Shimasaki S, Powell DR, Yee D. Regulation of insulin-like growth factor binding protein (IGFBP) expression by breast cancer cells: use of IGFBP-1 as an inhibitor of insulin-like growth factor action. J Natl Cancer Inst. 84:1992;1236-1241.
62. Umayahara Y, Kawamori R, Watada H, et al. Oestrogen regulation of the insulin-like growth factor-I gene transcription involves an AP-1. J Biol Chem. 269:1994;16433-16442.
63. Lou H, Ramwell P, Foegh ML. Oestradiol down-regulates insulin-like growth factor-I receptor (IGF-IR) mRNA expression in aortic smooth muscle cells. [Abstract] Circulation. 94:1996;I-152. (suppl).
64. Mooradian DL, Fernandes B, Diglio C, Lester BR. Angiopeptin (BIM23014C) inhibits vascular smooth muscle cell migration in vivo through a G-protein mediated pathway and is associated with inhibition of cyclic-AMP accumulation. J Cardiovasc Pharmacol. 25:1995;611-618.
65. Bauters C, Belle EV, Wernert N, et al. Angiopeptin inhibits oncogene induction in rabbit aorta after balloon denudation. Circulation. 89:1994;2327-2331.
66. Foegh ML, Khirabadi BS, Chambers E, Emamoo S, Ramwell PW. Inhibition of coronary artery transplants atherosclerosis in rabbits with angiopeptin, an octapeptide. Atherosclerosis. 78:1989;229-236.
67. Fellstrom B, Dimeny E, Foegh ML, Larsson E, Wanders A, Tufveson G. Accelerated atherosclerosis in heart transplants in the rat simulating chronic vascular rejection: effects of prostacyclin and angiopeptin. Transplant Proc. 23:1991;525-528.
68. Meiser BM, Wolf S, Devens CH, et al. Continuous infusion of angiopeptin significantly reduces accelerated graft vessel disease induced by FK506 in a rat heart allograft model. Transplant Proc. 24:1992;1671-1672.
69. Mennander A, Raisanen A, Paavonen T, Hayry P. Chronic rejection in the rat aortic allograft. V. Mechanism of the angiopeptin (BIM 23014C) effect on the generation of allograft arteriosclerosis. Transplantation. 55:1993;124-128.
70. Motomura N, Foegh ML. Angiopeptin - an immunological review. Transpl Immunol. 4:1996;99-104.
71. Wahlers T, Mugge A, Oppelt P, et al. Coronary vasculopathy following cardiac transplantation and cyclosporine immunosuppression: preventive treatment with angiopeptin, a somatostatin analog. Transpl Proc. 26:1994;2741-2742.
72. Wahlers T, Mugge A, Oppelt P, et al. Preventive treatment of coronary vasculopathy in heart transplantation by inhibition of smooth muscle cell proliferation with angiopeptin. J Heart Lung Transplant. 14:1995;143-150.
73. Meiser BM, Wank K, Thiery J, et al. Prevention of treatment of graft vessel disease after heart transplantation. Transplant Proc. 27:1995;1931-1935.
74. Gang UC, Hassid A. Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J Clin Invest. 83:1989;1774-1777.
75. Palmar RMJ, Ashton DS, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature. 333:1988;664-666.
76. Thomas G, Ramwell PW. Endothelium-derived relaxing factor and the vascular role of guanidino compounds. Transplant Proc. 25:1993;2057-2060.
77. McNamara DB, Bedi B, Aurora H, Ignarro LJ, Kadowitz PJ, Akers DL. L-arginine inhibits balloon catheter-induced intimal hyperplasia. Biochem Biophys Res Com. 193:1993;291-296.
78. Taguchi J, Abe J, Okazaki H, Takuwa Y, Kurokawa K. L-arginine inhibits neointimal formation following balloon injury. Life Sciences. 53:1993;1387-1392.
79. Tarry WC, Makhoul RG. L-arginine improves endothelium-dependent vasorelaxation and reduces intimal hyperplasia after balloon angioplasty. Arteriosclerosis and Thrombosis. 14:1994;938-943.
80. Akyurek LM, Fellstrom BC, Yan Z-Q, Hansson GK, Funa K, Larsson E. Inducible and endothelial nitric oxide synthese expression during development of transplant arteriosclerosis in rat aortic grafts. Am J Pathol. 149:1996;1981-1990.
81. Langherh JM, Hoffman RA, Lancaster JR Jr., Simmons RL. Nitric oxide - a new endogeneous immunomodulator. Transplantation. 55:1993;1205-1212.
82. Langrehr JM, Murase N, Markus P, et al. Nitric oxide production in host-versus-graft and graft-versus-host reactions in the rat. J Clin Invest. 90:1992;679-683.
83. Russell ME, Wallace AF, Wyner LR, Newell JB, Karnovsky MJ. Upregulation and modulation of inducible nitric oxide synthase in rat cardiac allografts with chronic rejection and transplant arteriosclerosis. Circulation. 92:1995;457-464.
84. Worrall NK, Lazenby WK, Misko TP, et al. Modulation of in vivo alloreactivity by inhibition of inducible nitric oxide synthase. J Exp Med. 181:1995;63-70.
85. Bastian NR, Xu S, Shao XL, Shelby J, Granger D, Hibbs JB Jr. N-monomethyl-L-arginine inhibits nitric oxide production in murine cardiac allografts but does not affect graft rejection. Biochem Biophys Acta. 1226:1994;225-231.
86. Ramwell P, Thomas G. Nitric oxide and its role in transplantation. Transplant Proc. 27:1995;2074-2076.
87. Lou H, Kodoma T, Wang YN, Katz NM, Ramwell PW, Foegh ML. L-Arginine prevents cardiac transplant arteriosclerosis by modulating the vascular cell proliferative response to insulin-like growth factor-I and interleukin-6. J Heart Lung Transplant. 15:1996;1248-1257.
88. Foegh ML, Khirabadi BS, Ramwell PW. Improved rat cardiac allograft survival with nonsteroidal pharmacologic agents related to eicosanoids. Transplant Proc. 19:1987;1297-1300.
89. Mennander A, Tiisala S, Ustinov J, Raisanen A, Paavonen T, Hayry P. Chronic rejection of aorta allografts. Synthesis of the major eicosanoids by the vascular wall components, and the effect of inhibition of the thromboxane cascade. Arterioscler Thromb. 12:1992;1380-1386.
90. Foegh M, Winchester JF, Zmudka M, et al. Urinary iTXB2 in renal allograft rejection. Lancet. 2:1981;431-434.
91. Foegh ML. Immune regulation by eicosanoids. Transplant Proc. 20:1988;1158-1161.
92. Foegh ML, Hecker M, Ramwell PW. The eicosanoids: prostoglandins, thromboxomes, leukotrienes and related compounds. Katzung BG. 7th edn. Basic and clinical pharmacology. 1998;304-318 Appleton & Lange, Norwalk, CT.
93. Foegh ML. Lipid mediators in transplantation injury, acute rejection and accelerated atherosclerosis. Bailey M. Prostaglandins, leukotrienes, lipoxins, & PAF. 1991;373-381 Plenum Press, New York.
94. Frostegard J, Wu R, Giscombe R, Holm G, Lefvert AK, Nilsson J. Induction of T cellactivation by oxidized low density lipoprotein. Arterioscler Thromb. 12:1992;461-467.
95. Motomura N, Saito S, Foegh ML. Immunosuppressive property of HMG-coenzyme A reductase inhibitors. J Nephrol. 10:1997;68-76.
96. Hancock JF, Magee AI, Childs JE, Marshall CJ. All ras proteins are polyisoprenylated but only some are palmitoylated. Cell. 57:1989;1167-1177.
97. Schafer WR, Kim R, Sterne R, Thomer J, Kim S, Rine J. Genetic and pharmacological suppression of oncogenic mutations in ras genes of yeast and humans. Science. 245:1989;379-385.
98. Farnsworth CC, Wolda SL, Gelb MH, Glomset JA. Human lamin B contains a farnesylated cysteine residue. J Biol Chem. 264:1989;20422-20429.
99. Yamane HK, Farnsworth CC, Xie H, et al. G protein gamma subunits contain in all-trans-geranylageranyl-cysteine methyl ester at their carbonyl termini. Proc Natl Acad Sci USA. 87:1990;5868-5872.
100. Meiser BM, Thiery WJ, Wolf S, et al. Simvastatin decreases accelerated graft vessel disease after heart transplantation in an animal model. Transplant Proc. 25:1993;2077-2079.
101. Kahan BD. Sirolimus: a new agent for clinical renal transplantation. Transplant Proc. 29:1997;48-50.
102. Mohacsi PJ, Tuller D, Hulliger B, Wijngaard PLJ. Different inhibitory effects of immunosuppressive drugs on human and rat aorta smooth muscle and endothelial cell proliferation stimulated by platelet derived groth factor or endothelial cell growth factor. J Heart Lung Transplant. 16:1997;484-492.
103. Meiser BM, Wang J, Morris RE. Rapamycin: a new and highly active immunosuppressive macrolide with an efficacy superior to cyclosporine. Melchers F. Progress in immunology. VII:1989;1195-1198 Springer, Berlin.
104. Kuo CJ, Chung J, Fiorentino DF, Flanagan WM, Blenis J, Crabtree GR. Rapamycin selectively inhibits interleukin-2 activation of p70 S6 kinase. Nature. 358:1992;70-73.
105. Brunn GJ, Hudson CC, Sekulic A, et al. Phophorylation of the translational repressor PHAS-I by the mammalian target of rapamycin. Science. 277:1997;99-101.
106. Raisanen-Sokolowski A, Hayry P. Chronic allograft arteriosclerosis: contributing factors and molecular mechanisms in the light of experimental studies. Transplant Immunol. 4:1996;91-98.
107. Leszczynski D, Zhao Y, Yeagley TJ, Foegh ML. Direct and endothelial cell - mediated effect of cyclosporine A on the proliferation of rat smooth muscle cells in vitro. Am J Pathol. 142:1993;149-155.
108. Hayry P., Mennander A, Raisanen-Sokolowski A, et al. Pathophysiology of vascular wall changes in chronic allograft rejection. Transplant Rev. 7:1993;1-20.
109. Tai P-KK, Albers MW, Chang H, Faber LE, Schreiber SL. Association of a 59-kilodalton immunophilin with the glucocorticoid receptor complex. Science. 256:1992;1315-1318.
110. Peattie DA, Harding MW, Fleming MA, et al. Expression and characterization of human FKBP52, an immunophilin that associates with the 90-kDa heat shock protein and is a component of steroid receptor complex. Proc Natl Acad Sci. 89:1992;10974-10978.
111. Owens-Grillo JK, Hoffmann K, Hutchison KA, et al. The cyclosporin A-binding immunophilin CyP-40 and the FK506-binding immunophilin hsp56 bind to a common site on hsp90 and exist in independent cytosolic heterocomplexes with the untransformed glucocorticoid receptor. J Biol Chem. 270:1995;20479-20484.