Xenotransplantation as a Vector for Infection

Marian G. Michaels

doi:10.1128/9781555818043.ch10

Chapter 10 : Xenotransplantation as a Vector for Infection

VIEW AFFILIATIONS HIDE AFFILIATIONS

Affiliations: 1: Division of Allergy, Immunology, and Infectious Diseases, University of Pittsburgh School of Medicine, and The Children's Hospital of Pittsburgh, Pittsburgh, PA 15213

Content Type: Monograph

Publication Year: 2001

Category: Immunology

Book DOI: 10.1128/9781555818043

Chapter DOI: 10.1128/9781555818043.ch10

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:

Xenotransplantation as a Vector for Infection, Page 1 of 2

< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555818043/9781555811679_Chap10-1.gif /docserver/preview/fulltext/10.1128/9781555818043/9781555811679_Chap10-2.gif

Abstract:

This chapter reviews the issue of xenotransplantation as a vector for infection to humans and considers potential mechanisms for disease, screening systems, and evaluations that need to be carried out to identify these risks as the field moves forward. Knowledge of donor-associated infections after allotransplantation and of zoonotic infections is used to help estimate the potential risk of xenotransplantation. Bacterial or fungal infections in the airway of the donor can lead to disease after lung or heart-lung transplantation, and histoplasmosis has been transmitted with cadaveric kidneys. These types of acute donor-associated infections can theoretically be less of a risk after xenotransplantation as source animals can be maintained under optimal healthy conditions and surgery would be performed on an elective schedule rather than under the current time pressures of allotransplantation. In an attempt to minimize the risk of xenozoonoses and to learn how to evaluate animal-associated infections after xenotransplantation, more extensive protocols began to be developed in the early and mid-1990s that continue to be expanded upon today. Some microbes, particularly viruses, are considered to be "species specific." If this is the case, it is possible that xenotransplantation carries less risk of donor-transmitted infections than does allotransplantation. Acute viremia can lead to donor-associated infections after allotransplantation and would likewise be expected to have the same risk after xenotransplantation. Xenotransplantation may have positive implications for decreasing the risk of some infections after transplantation.

Citation: Michaels M. 2001. Xenotransplantation as a Vector for Infection, p 193-206. In Platt J (ed), Xenotransplantation. ASM Press, Washington, DC. doi: 10.1128/9781555818043.ch10

Highlighted Text: Show | Hide

Full text loading...

Figures

Xenotransplantation as a Vector for Infection

[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555818043.chap10-1,webId=/content/author/10.1128/9781555818043.chap10-1,properties={foaf_givenname=Marian G., foaf_name=Marian G. Michaels, foaf_surname=Michaels, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555818043.chap10-aff1]]}]]

Citation: Michaels M. 2001. Xenotransplantation as a Vector for Infection, p 193-206. In Platt J (ed), Xenotransplantation. ASM Press, Washington, DC. doi: 10.1128/9781555818043.ch10

/content/10.1128/9781555818043.chap10.fig10-1

Figure 1

Algorithm to determine whether to use infected animal tissue in transplantation.

10.1128/9781555818043/fig10-1_thmb.gif

10.1128/9781555818043/fig10-1.gif

Figure 1

Algorithm to determine whether to use infected animal tissue in transplantation.

Citation: Michaels M. 2001. Xenotransplantation as a Vector for Infection, p 193-206. In Platt J (ed), Xenotransplantation. ASM Press, Washington, DC. doi: 10.1128/9781555818043.ch10

References

/content/book/10.1128/9781555818043.chap10

1. Allan, J. S.,, S. R. Broussard,, M. G. Michaels,, T. E. Starzl,, K. L. Leighton,, E. M. Whitehead,, A. G. Comuzzie,, R. E. Lanford,, M. M. Leland,, W. M. Switzer,, and W. Heneine. 1998. Amplification of simian retroviral sequences from human recipients of baboon liver transplants. AIDS Res. Hum. Retrov. 14: 821– 824.

2.Anonymous. 1997. Nonhuman primate spumavirus infections among persons with occupational exposure— United States, 1996. JAMA 277: 783– 785.

3. Artenstein, A. W.,, C. B. Hicks,, B. S. Goodwin, Jr.,, and J. K. Hilliard. 1991. Human infection with B virus following a needle stick injury. Rev. Infect. Dis. 13: 288– 291.

4. Bailey, L. L.,, S. L. Nehlsen-Cannarella,, W. Concepcion,, and W. B. Jolley. 1985. Baboon-to-human xenotransplantation in a neonate. JAMA 254: 3321– 3329.

5. Benveniste, R. E.,, W. R. Morton,, E. A. Clark,, C. C. Tsai,, H. D. Ochs,, J. M. Ward,, L. Kuller,, W. B. Knott,, R. W. Hill,, M. J. Gale, et al. 1988. Inoculation of baboons and macaques with SIV/mne, a primate lentivirus closely related to HIV 2. Virology 2: 2091– 2101.

6. Cappucci, D. T. 1972. Tuberculosis from man to primates. Am. Rev. Respir. Dis. 106: 819– 823.

7. Cen, H.,, M. C. Breinig,, R. W. Atchinson,, M. Ho,, and J. L. C. McKnight. 1991. Epstein-Barr virus transmission via the donor organs in solid organ transplantation: polymerase chain reaction and restriction fragment length polymorphism analysis of IR2, IR3 and IR4. Virology 65: 976.

8. Chapman, L. E.,, T. M. Folks,, D. R. Salomon,, A. P. Patterson,, T. E. Eggerman,, and P. D. Noguchi. 1995. Xenotransplantation and xenogeneic infections. N. Engl. J. Med. 333: 1498.

9. Charamella, L. J.,, R. B. Reynolds,, L. T. Ch'ien,, and C. A. Alford, Jr. 1973. Biologic characterization of an unusual human cytomegalovirus isolated from the brain. Abstr. V 373. Ann. Meetings Amer. Soc. Med. 256.

10. Chari, R. S.,, B. H. Collins,, J. C. Magee,, M. DiMaio,, A. D. Kirk,, R. C. Harland,, R. L. McCann,, J. L. Platt,, and W. C. Meyers. 1994. Brief report: treatment of hepatic failure with ex vivo pig-liver perfusion followed by liver transplantation. N. Engl. J. Med. 331: 234– 237.

11. Chellman, G. J.,, V. S. Lukas,, E. M. Eugui,, K. P. Altera,, S. J. Almqist,, and J. K. Hilliard. 1992. Activation of B virus in chronically immunosuppressed cynomolgus monkeys. Lab. Anim. Sci. 42: 146– 151.

12. Chou, S. 1986. Acquisition of donor strains of cytomegalovirus by renal-transplant recipients. N. Engl. J. Med. 314: 1418.

13. Chou, S. 1989. Reactivation and recombination of multiple cytomegalovirus strains from individual organ donors. J. Infect. Dis. 160: 11– 15.

14. Cooper, D. K. C.,, Y. Ye,, L. L. Rolf, Jr.,, and N. Zuhdi,. 1991. The pig as a potential organ donor for man, p. 481– 499. In D. K. C. Cooper,, K. Kemp,, K. Reemtsma,, and D. J. G. White (ed.), Xenotransplantation: The Transplantation of Organs and Tissues Between Species. Springer- Verlag, Berlin, Germany.

15. Dummer, J. S.,, J. Armstrong,, J. Somers,, S. Kusne,, B. J. Carpenter,, J. T. Rosenthal,, and M. Ho. 1987. Transmission of infection with herpes simplex by renal transplantation. J. Infect. Dis. 155: 202.

16. Dummer, J. S.,, S. Erb,, M. Breinig,, M. Ho,, C. R. Rinaldo, Jr.,, P. Gupta,, M. V. Ragni,, A. Tzakis,, L. Makowka,, D. Van Thiel,, and T. E. Starzl. 1989. Infection with human immunodeficiency virus in the Pittsburgh transplant population. Transplantation 47: 134.

17. Edington, N.,, A. E. Wrathall and,, J. T. Done. 1988. Porcine cytomegalovirus (PCMV) in early gestation. Vet. Micro. 17: 117– 128.

18. Falk, L.,, F. Deinhardt,, M. Nonoyama,, L. G. Wolfe,, and C. Bergholz. 1976. Properties of a baboon lymphotropic herpesvirus related to Epstein-Barr virus. Int. J. Cancer 18: 798– 807.

19.Federal Register. 1996. Draft Public Health Service guideline on infectious disease issues in xenotransplantation. Fed. Regist. September 23, 61: 49920– 49932.

20. Fishman, J. A. 1994. Miniature swine as organ donors for man: strategies for prevention of xenotransplant-associated infections. Xenotransplantation 1: 47– 57.

21. Flugel, R. M. 1991. Spumaviruses: a group of complex retroviruses. Acquired Immune Defic. Syndromes 4: 739– 750.

22. Frazier, M. E. 1985. Evidence for retrovirus in miniature swine with radiation-induced leukemia or metaplasia. Arch. Virol. 83: 83– 97.

23. Gao, F.,, E. Bailes,, D. L. Robertson,, Y. Chen,, C. M. Rodenburg,, S. F. Michael,, L. B. Cummins,, L. O. Arthur,, M. Peeters,, G. M. Shaw,, P. M. Sharp,, and B. H. Hahn. 1999. Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes. Nature 397: 436– 441.

24. Green, M.,, and M. G. Michaels,. 1997. Infections in solid organ transplant recipients, p. 626– 634. In S. S. Long,, L. Pickering,, and C. Prober (ed.), Principles and Practice of Pediatric Infectious Diseases. Churchill Livingstone Inc., New York, N.Y.

25. Halliburton, I. W.,, R. E. Randall,, R. A. Killington,, and D. H. Watson. 1977. Some properties of recombinants between type 1 and type 2 herpes simplex viruses. J. Gen. Virol. 36: 471– 484.

26. Henderson, J. D., Jr. 1992. Diagnostic exercise: anemia in a baboon. Lab. Anim. Sci. 42: 514–515 .

27. Heneine, W. 1996. Strategies for diagnosis of xenotransplant-associated retroviral infections. Mol. Diag. 1: 255– 257.

28. Heneine, W.,, and W. M. Switzer. 1996. Highly sensitive and specific polymerase chain reaction assays for detection of baboon and pig cells following xenotransplantation in humans. Transplantation 62: 1360– 1362.

29. Heneine, W.,, A. Tibell,, W. M. Switzer,, P. Sandstrom,, G. V. Rosales,, A. Mathews,, O. Korsgren,, L. E. Chapman,, T. M. Folks,, and C. G. Groth. 1998. No evidence of infection with porcine endogenous retrovirus in recipients of porcine islet-cell xenografts. Lancet 352: 695– 699.

30. Hilliard, J. K.,, D. Black,, and R. Eberle. 1989. Simian alphaherpesviruses and their relation to the human herpes simplex viruses. Arch. Virol. 109: 83– 102.

31. Ho, M.,, and J. S. Dummer,. 1990. Risk factors and approaches to infections in transplant recipients. In G. C. Mandell,, G. R. Douglas, Jr.,, and J. E. Bennet (ed.), Principles and Practice of Infectious Diseases, 2nd ed. Churchill Livingstone, New York, N.Y.

32. Ho, M.,, G. Miller,, R. W. Atchison,, M. K. Breinig,, J. S. Dummer,, W. Andiman,, T. E. Starzl,, R. Eastman,, B. P. Griffith,, R. L. Hardesty, et al. 1985. Epstein-Barr virus infections and DNA hybridization studies in post-transplantation lymphoma and lymphoproliferative lesions: the role of primary infection. J. Infect. Dis. 152: 876.

33. Holmes, G. P.,, L. E. Chapman,, J. A. Stewart,, S. E. Straus,, J. K. Hilliard,, and D. S. Davenport 1995. Guidelines for the prevention and treatment of B-virus infections in exposed persons. Clin. Infect. Dis. 20: 421– 39.

34. Homma, T.,, P. J. Kanki,, N. W. King, Jr.,, R. D. Hunt,, M. J. O'Connell,, N. L. Letvin,, M. D. Daniel,, R. C. Desrosiers,, C. S. Yang,, and M. Essex. 1984. Lymphoma in macaques: association with virus of HTLV family. Science 225: 716– 718.

35. Huang, E.,, B. Kilpatrick,, A. Lakeman,, and C. A. Alford. 1978. Genetic analysis of a cytomegalovirus-like agent isolated from human brain. J. Virol. 26: 718– 723.

36. Huang, L.,, J. Silberman,, H. Rothschild,, and J. C. Cohen. 1989. Replication of baboon endogenous virus in human cells. J. Biol. Chem. 264: 8811– 8814.

37. Hubbard, G. B.,, K. F. Soike,, T. M. Butler,, K. D. Carey,, H. Davis,, and W. I. Butcher. 1992. An encephalomyocarditis virus epizootic in a baboon colony. Lab. Anim. Sci. 42: 233– 239.

38.InstituteofMedicine. 1996. Xenotransplantation: Science, Ethics and Public Policy. National Academy Press, Washington, D.C.

39. Isfort, R.,, D. Jones,, R. Kost,, R. Witter,, and H. Kung. 1992. Retrovirus insertion into herpesvirus in vitro and in vivo. Proc. Natl. Acad. Sci. USA 89: 991– 995.

40. Javier, R. T.,, F. Sedarati,, and J. G. Stevens. 1986. Two avirulent herpes simplex viruses generate lethal recombinants in vivo. Science 234: 746– 748.

41. Kalter, S. S.,, and R. L. Heberling. 1990. Primate viral diseases in perspective. Med. Primatol. 19: 519– 535.

42. Kennedy, I., and Advisory Group on Ethics of Xenotransplantation. 1996. Animal Tissue Into Humans. ISBN 011 321866 4. Department of Health, Publications Center, London, U.K.

43. Khabbaz, R. F.,, W. Heneine,, and J. R. George. 1994. Brief report. Infection of a laboratory worker with simian immunodeficiency virus. N. Engl. J. Med. 330: 172– 177.

44. Khabbaz, R. F.,, T. Rowe,, M. Murphey-Corb,, W. M. Heneine,, C. A. Schable,, J. R. George,, C. P. Pau,, B. S. Parekh,, M. D. Lairmore,, J. W. Curran, et al. 1992. Simian immunodeficiency virus needle stick accident in a laboratory worker. Lancet 340: 271– 273.

45. Lerche, N. W.,, J. L. Yee,, and M. B. Jennings. 1994. Establishing specific retrovirus-free breeding colonies of macaques. Lab. Anim. Sci. 44: 217– 221.

46. Le Tissuer, P.,, J. P. Stoye,, Y. Takeuchi,, C. Patience,, and R. A. Weiss. 1997. Two sets of human-tropic pig retrovirus. Nature 389: 681– 682.

47. Martin, U.,, V. Kiessig,, J. H. Blusch,, A. Haverich,, K. von der Helm,, T. Herden,, and G. Steinhoff. 1998. Expression of pig endogenous retrovirus by primary porcine endothelial cells and infection of human cells. Lancet 352: 692– 694.

48. Martin, W. J.,, K. Ahmed,, L. C. Zeng,, J. Olsen,, J. G. Seward,, and J. S. Seehrai. 1995. African green monkey origin of the atypical cytopathic 'stealth virus' isolated from a patient with chronic fatigue syndrome. Clin. Diag. Virol. 4: 93– 103.

49. Martin, W. J.,, L. C. Zeng,, K. Ahmed,, and M. Roy. 1994. Cytomegalovirus-related sequence in an atypical cytopathic virus repeatedly isolated from a patient with chronic fatigue syndrome. Am. J. Pathol. 145: 440– 451.

50. Mason, J. C.,, K. S. Ordelheide,, G. M. Grames,, T. V. Threasher,, R. D. Harris,, R. H. Dang Bui,, and M. C. T. Mackett. 1987. Toxoplasmosis in two renal transplant recipients from a single donor. Transplantation 44: 588.

51. Mayes, J. T.,, A. R. O'Connor,, W. Castellani,, and W. Carey. 1995. Transmission of Toxoplasma gondii infection by liver transplantation. Clin. Infect. Dis. 21: 511.

52. McConnell, E. E.,, P. A. Basson,, V. De Vos,, B. J. Myers,, and R. E. Kuntz. 1974. A survey of diseases among 100 free-ranging baboons from the Kruger national park, Onderstepoort. J. Vet. Res. 41: 97– 167.

53. Melby, E. C.,, and N. J. Aitman (ed.). 1976. Handbook of Laboratory Animal Science, Vol. III, P. 49. CRC Press, Boca Raton, Fla.

54. Meng, X. J.,, P. G. Halbur,, M. S. Shapiro,, S. Govindarajan,, J. D. Bruna,, I. K. Mushahwar,, R. H. Purcell,, and S. U. Emerson. 1998. Genetic and experimental evidence for cross-species infection by swine hepatitis E virus. J. Virol. 72: 9714– 9721.

55. Meng, X. J.,, R. H. Purcell,, P. G. Halbur,, J. R. Lehman,, D. M. Webb,, T. S. Tsareva,, J. S. Haynes,, B. J. Thacker,, and S. U. Emerson. 1997. A novel virus in swine is closely related to the human hepatitis E virus. Proc. Natl. Acad. Sci. USA 94: 9860– 9865.

56. Michaels, M. G. 1997. Infectious concerns of cross-species transplantation: xenozoonoses. World J. Surgery 21: 968– 974.

57. Michaels, M. G.,, D. Alcendor,, K. St. George,, C. R. Rinaldo, Jr.,, G. Ehrlich,, and H. G. Becich. 1997. Distinguishing baboon CMV from human CMV: importance for xenotransplantation. J. Infect. Dis. 176: 1476– 1483.

58. Michaels, M. G.,, and M. D. Green,. 1997. Infectious complications of heart and lung transplantation in children, p. 27– 45. In K. L. Franco (ed.), Pediatric Cardiopulmonary Transplantation. Futura Publishing Company Inc., New York, N.Y.

59. Michaels, M. G.,, J. Hilliard,, S. Deeks,, P. Gupta,, W, Heneine,, D. Pardi,, C. Kaufman,, C. Rinaldo,, K. St. George,, L. Chapman,, T. Folks,, Y. Colson,, P. Volberding,, and S. T. Ildstad. 1997. Baboon bone marrow xenotransplant in a patient with advanced HIV: a model for the evaluation of potential xenozoonoses. Proc. Inst. Hum. Virol. Annu. Meet., J. Acquired Immune Defic. Syndr. Hum. Retrovirol., Abstr. 11, p. 3.

60. Michaels, M. G.,, R. Lanford,, A. J. Demetris,, D. Chavez,, K. Brasky,, J. Fung,, and T. E. Starzl. 1996. Lack of susceptibility of baboons to infection with hepatitis B virus. Transplantation 61: 350– 351.

61. Michaels, M. G.,, J. McMichael,, K. Brasky,, S. Kalter,, R. L. Peters,, T. E. Starzl,, and R. L. Simmons. 1994. Screening donors for xenotransplantation: the potential for xenozoonoses. Transplantation 57: 1462.

62. Michaels, M. G.,, and R. L. Simmons. 1994. Xenotransplant-associated zoonoses. Transplantation 57: 1.

63. Michaels, M. G.,, E. T. Wald,, F. J. Flicker,, P. J. del Nido,, and J. Armitage. 1992. Toxoplasmosis in pediatric recipients of heart transplants. Clin. Infect. Dis. 14: 847.

64. Miller, G., 1990. Epstein-Barr virus: biology, pathogenesis, and medical aspects, p. 1921. In B. N. Fields, and D. M. Knipe (ed.), Virology, 2nd ed. Raven Press, New York, N.Y.

65. Morton, W. R.,, L. Kuller,, R. E. Benveniste,, E. A. Clark,, C. C. Tsai,, M. J. Gale,, M. E. Thouless,, J. Overbaugh,, and M. G. Katze. 1989. Transmission of the SIV in macaques and baboons. Med. Primatol. 18: 237– 245.

66. Mravak, S.,, U. Bienzle,, H. Feldmeier,, H. Hampl,, and K. Habermehl. 1987. Pseudorabies in man. Lancet 1: 501.

67. Patience, C.,, Y. Takeuchi,, and R. A. Weiss. 1997. Infection of human cells by an endogenous retrovirus of pigs. Nature Med. 3: 282– 286.

68. Pereira, B. J. G.,, E. L. Milford,, R. L. Kirkman,, and A. S. Levey. 1991. Transmission of hepatitis C virus by organ transplantation. N. Engl. J. Med. 325: 454.

69. Perot, K.,, C. M. Walker,, and R. R. Spaete. 1992. Primary chimpanzee skin fibroblast cells are fully permissive for human cytomegalovirus replication. J. Gen. Virol. 73: 3281– 3284.

70. Persing, D. H. 1996. Nucleic acid-based pathogen discovery techniques. Potential application to xenozoonoses. Molec. Diagn. 1: 243.

71. Reemtsma, K.,, B. H. McCracken,, J. U. Schlegel,, M. A. Pearl,, C. W. Pearce,, C. W. DeWitt,, P. E. Smith,, R. L. Hewitt,, R. L. Flinner,, and O. Creech, Jr. 1964. Renal heterotransplantation in man. Ann. Surg. 160: 384– 410.

72. Remington, J. S.,, R. McLeod,, and G. Desmonts,. 1995. Toxoplasmosis, p. 140– 267. In J. S. Remington, and J. O. Klein (ed.), Infectious Diseases of the Fetus and Newborn Infant, 4th ed. W. B. Saunders Co., Philadelphia, Pa.

73. Rubin, R. H. 1990. Impact of cytomegalovirus infection on organ transplant recipients. Rev. Infect. Dis. 12( Suppl. 7): S754– S766.

74. Schweizer, M.,, V. Falcone,, J. Gange,, R. Turek,, and D. Neumann-Haefelin. 1997. Simian foamy virus isolated from an accidentally infected human individual. J. Virol. 71: 4821– 4824.

75. Simonds, R. J.,, S. D. Holmberg,, R. L. Hurwitz,, T. R. Coleman,, S. Bottenfield,, L. J. Conley,, S. H. Kohlenberg,, K. G. Castro,, B. A. Dahan,, C. A. Schable,, M. A. Rayfleld,, and M. F. Rogers. 1992. Transmission of human immunodeficiency virus type I from a seronegative organ and tissue donor. N. Engl. J. Med. 326: 726.

76. Starzl, T. E.,, J. Fung,, A. Tzakis,, S. Todo,, A. J. Demetris,, I. R. Marino,, H. Doyle,, A. Zeevi,, V. Warty,, M. Michaels,, S. Kusne,, W. A. Rudert,, and M. Trucco. 1993. Baboon-to-human liver transplantation. Lancet 341: 65– 71.

77. Starzl, T. E.,, T. L. Marchioro,, G. N. Peters,, C. H. Kirkpatrick,, W. E. C. Wilson,, K. A. Porter,, D. Rifkind,, D. A. Ogden,, C. R. Hitchcock,, and W. R. Waddell. 1964. Renal heterotransplantation from baboon to man: experience with 6 cases. Transplantation 2: 752– 776.

78. Starzl, T. E.,, A. Tzakis,, J. J. Fung,, S. Todo,, A. J. Demetris,, R. Manez,, I. R. Marino,, L. Valdivia,, and N. Murase. 1994. Prospects of clinical xenotransplantation. Transplant. Proc. 26: 1082– 1088.

79. Varki, N. M.,, S. Bhuta,, T. Drake,, and D. D. Porter. 1990. Adenovirus hepatitis in two successive liver transplants in a child. Arch. Pathol. Lab. Med. 114: 106.

80. Weiss, R. A. 1988. Foamy retroviruses: a virus in search of a disease. Nature 33: 497.

81. Wilson, C. A.,, S. Wong,, J. Muller,, C. E. Davidson,, T. M. Rose,, and P. Burd. 1998. Type C retrovirus released from primary peripheral blood mononuclear cells infects human cells. J. Virol. 72: 3082– 3087.

82. Wong, S. Y.,, and D. M. Allen. 1992. Transmission of disseminated histoplasmosis via cadaveric renal transplantation: case report. Clin. Infect. Dis. 14: 232.

83. Wreghitt, T. G.,, M. Hakim,, J. J. Gray,, A. H. Balfour,, P. G. I. Stovin,, S. Stewart,, J. Scott,, and J. Wallwork. 1989. Toxoplasmosis in heart and heart and lung transplant recipients. J. Clin. Pathol. 42: 194.

84. Ye, Y.,, M. Niekrasz,, S. Kosanke,, R. Welsh,, H. D. Jordan,, J. C. Fox,, W. C. Edwards,, C. Maxwell,, and D. K. C. Cooper. 1994. The pig as a potential organ donor for man. Transplantation 57: 694– 703.