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Abstract

Azathioprine (“Imuran”) is an S-substituted 6-mercaptopurine.

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References

  • Alexandre, G.P.J., Murray, J.E., Dammin, G.J, Nolan, B.: Immunosuppressive drug therapy in canine renal and skin homografts. Transplantation 1, 432–461 (1963).

    Article  PubMed  CAS  Google Scholar 

  • Arinovtche, R., Loewi, G.: Comparison of the effects of two cytotoxic drugs and of anti- lymphocytic serum, on immune and non-immune inflammation in experimental animals. Ann. rheum. Dis. 29, 32–39 (1970).

    Article  Google Scholar 

  • Aronsen, K.F., Husberg, B., Pihl, B.: Immunosuppressive treatment in non-transplanted dogs. Azathioprine versus azathioprine-antilymphocyteimmunoglobulin-G. Acta chir. scand. 135, 475–481 (1969).

    PubMed  CAS  Google Scholar 

  • Babington, R. G., Wedeking, P.W.: The influence of cinanserin and selected pharmacologic agents on experimental allergic encephalomyelitis (EAE). J. Pharmacol, exp. Ther. 177, 454–460 (1971).

    CAS  Google Scholar 

  • Bach, J.F.: Immunosuppression by chemical agents. Transplant. Proc. 3, 27–33 (1971).

    PubMed  CAS  Google Scholar 

  • Bach, J. F.: Antigen-binding cells. In: Cell-mediated immunity. In vitro correlates, pp. 51–74. Basel: Karger 1971a.

    Google Scholar 

  • Bach, J. F., Dardenne, M.: Études sur le métabolisme de L’azathioprine. C.R. Acad. Sci. (Paris) 271, 453–456 (1970).

    CAS  Google Scholar 

  • Bach, J.F., Dardenne, M.: The metabolism of azathioprine in renal failurè. Transplantation 12, 253–259 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Bach, J.F., Dardenne, M.: Activities of immunosuppressive agents In vitro. I. Rosette inhibition by azathioprine. Rev. Europ. études clin, etbiol. 16, 770–777 (1971a).

    CAS  Google Scholar 

  • Bach, J.F., Dardenne, M.: Serum immunosuppressive activity of azathioprine in normal subjects and patients with liver diseases. Proc. roy. Soc. Med. 65, 260–263 (1972).

    CAS  Google Scholar 

  • Bach, J.F., Dardenne, M.: Antigen recognition by T lymphocytes. II. Similar effects of azathioprine, antilymphocyte serum and anti-theta serum on rosette-forming lymphocytes in normal and neonatally thymectomized mice. Cell. Immunol. 3, 11–21 (1972a).

    Article  PubMed  CAS  Google Scholar 

  • Bach, J.F., Dardenne, M., Crosnier, J.: Bone marrow-reactivity to azathioprine due to metabolism abnormality. Ann. intern. Med.

    Google Scholar 

  • Baöh, J.F., Dardenne, M., Davies, A. J.S.: Early effect of adult thymectomy. Nature (Lond.) 231, 110–111 (1971a).

    Article  Google Scholar 

  • Bach, J. F., Dardenne, M., Fournier, C.: In vitro evaluation of immunosuppressive drugs. Nature (Lond.) 222, 998–999 (1969).

    Article  CAS  Google Scholar 

  • Bach, J.F., Dardenne, M., Goldstein, A.L., Guha, A., White, A.: Appearance of T-cell markers in bone marrow rosette-forming cells after incubation with thymosin, a thymic hormone. Proc. nat. Acad. Sci. (Wash.) 68, 2734–2738 (1971).

    Article  CAS  Google Scholar 

  • Bach, M.A., Bach, J.F.: Activities of immunosuppressive agents In vitro. II. Different timing of azathioprine and methotrexate in inhibition and stimulation of mixed lymphocyte reaction. Clin. exp. Immunol. 11, 89–98 (1972).

    CAS  Google Scholar 

  • Berenbaum, M.C.: IS azathioprine a better immunosuppressive than 6-mercaptopurine ? Clin, exp. Immunol. 8, 1–8 (1971).

    CAS  Google Scholar 

  • Blancuzzi, V., Elion, G. B.: Unpublished.

    Google Scholar 

  • Bloom, B.R., Jimenez, L., MARCUS, P.I.: A plaque assay for enumerating antigen-sensitive cells in delayed-type hypersensitivity. J. exp. Med. 132, 16–30 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Board, J. A., Lee, H.M., Draper, D. A., Hume, D.M.: Pregnancy following kidney homotrans- plantation from a non-twin: Report of a case with concurrent administration of azathioprine and prednisone. Obstet. Gynec. 29, 318–323 (1967).

    Google Scholar 

  • Boll, I., Klimas, J., Willigerodt, B.: Die Wirkung von 6-Mercaptopurin und Azathioprin auf menschliches Knochenmark In vitro. Arzneimittel-Forsch. 21, 502–504 (1971).

    CAS  Google Scholar 

  • Borel, Y., Fauconnet, M., Miescher, P.A.: Effect of 6-mercaptopurine (6-MP) on different classes of antibody. J. exp. Med. 122, 263–275 (1965).

    Article  PubMed  CAS  Google Scholar 

  • Borel, Y., Schwartz, R. S.: Inhibition of immediate and delayed hypersensitivity in the rabbit by 6-mercaptopurine. J. Immunol. 92, 754–761 (1964).

    PubMed  CAS  Google Scholar 

  • Bresnick, E.: The metabolism In vitro of antitumor imidazolyl derivatives of mercaptopurines. Fed. Proc. 18, 371 (1959).

    Google Scholar 

  • Brooke, M.S.: Immunological paralysis in mice exposed to sublethal irradiation or treated with 6-mercaptopurine. Transplantation 4, 1–7 (1966).

    Article  Google Scholar 

  • Calne, R.Y.: Renal transplantation, 2nd Ed. London: Edward Arnold, Ltd. 1967.

    Google Scholar 

  • Calne, R. Y., Alexandre, G.P.J., Murray, J.E.: A study of the effects of drugs in prolonging survival of homologous renal transplants in dogs. Ann. N. Y. Acad. Sci. 99, 743–761 (1962).

    Article  PubMed  CAS  Google Scholar 

  • Caplan, R.M., Dossetor, J.B., Matjghan, G.B.: Pregnancy following cadaver kidney transplantation. Amer. J. Obstet. Gynec. 106, 644–648 (1970).

    PubMed  CAS  Google Scholar 

  • Casey, T.P.: The development of lymphomas in mice with autoimmune disorders treated with azathioprine. Blood 31, 396–399 (1968a).

    PubMed  CAS  Google Scholar 

  • Casey, T. P.: Azathioprine (Imuran) administration and development of malignant lymphomas in NZB mice. Clin. exp. Immunol. 3, 305–312 (1968b).

    CAS  Google Scholar 

  • Chalmers, A. H., Knight, P. R., Atkinson, M.R.: Conversion of azathioprine into mercapto- purine and mercaptoimidazole derivatives In vitro and during immunosuppressive therapy. Aust. J. exp. Biol. med. Sci. 45, 681–691 (1967).

    Article  PubMed  CAS  Google Scholar 

  • Chalmers, A. H., Knight, P. R., Atkinson, M.R.: 6-Thiopurines as substrates and inhibitors of purine oxidases: a pathway for conversion of azathioprine into 6-thiouric acid without release of 6-mercaptopurine. Aust. J. exp. Biol. med. Sci. 47, 263–273 (1969).

    CAS  Google Scholar 

  • Chan, G. Y., Stone, R.L.: Inhibition of nucleic acid and protein synthesis in mouse spleen cells In vitro by azathioprine. Appl. Microbiol. 20, 910–912 (1970).

    PubMed  CAS  Google Scholar 

  • Connon, A.F.: Effects of azathioprine on reproduction in rats. J. Reprod. Fértil. 18, 165–166 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Dalldorf, G., Carvalho, R.P.S., Jamara, M., Frost, P., Ehrlich, D., Marigo, C.: The lymphomas of Brazilian children. J. Amer. med. Ass. 208, 1365–1368 (1969).

    Article  CAS  Google Scholar 

  • Demiranda, P., Beacham, L.M., Ill, Creagh, T., Elion, G.B.: Metabolic fate of the imidazole moiety of azathioprine (Imuran). Abstract, Fifth International Congress on Pharmacology 55 (1972).

    Google Scholar 

  • Demiranda, P., Cinx, L. C.: Reaction of azathioprine (Imuran) with 14c-glycine in the rat. Fed. Proc. 29, 608 (1970).

    Google Scholar 

  • Denman, E.J., Denman, A.M., Greenwood, B.M., Gall, D., Heath, R.B.: Failure of cytotoxic drugs to suppress immune responses of patients with rheumatoid arthritis. Ann. rheum. Dis. 29, 220–231 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Dutton, R. W., Pearce, J.D.: A survey of the effect of metabolic antagonists on the synthesis of antibody in an in vitro system. Immunology 5, 414–423 (1962).

    PubMed  CAS  Google Scholar 

  • Eberle, P., Htxnstein, W., Perings, E.: Chromosomes in patients treated with Imuran. Hum. Genet. 6, 69–73 (1968).

    Article  CAS  Google Scholar 

  • Egger, G., Ackman, D.).: Light microscopic examination of the jejunum after long-standing azathioprine treatment. Experientia (Basel) 27, 326 (1971).

    Article  CAS  Google Scholar 

  • Elion, G. B.: Unpublished.

    Google Scholar 

  • Elion, G.B.: Biochemistry and pharmacology of purine analogues. Fed. Proc. 26, 898–904 (1967).

    PubMed  CAS  Google Scholar 

  • Elion, G.B.: Discussion. In: Miescher, P.A., Grabor, P. (Eds.): International symposium on immunopathology, Fifth, Italy, June 1967, pp. 399–401. New York: Grune and Stratton 1968.

    Google Scholar 

  • Elion, G.B.: The comparative metabolism of “Imuran” and 6-mercaptopurine (6-MP) in man. Proc. Amer. Ass. Cancer Res. 10, 21 (1969).

    Google Scholar 

  • Elion, G.B.: The significance of azathioprine metabolites. Proc. roy. Soc. Med. 65, 257–260 (1972).

    CAS  Google Scholar 

  • Elion, G. B., Benezra, F. M., Carrington, L. O., Strelitz, R. A.: Metabolic fate of 14C-azathio- prine. Fed. Proc. 29, 607 (1970).

    Google Scholar 

  • Elion, G.B., Callahan, S.W., Bieber, S., Hitchings, G.H., Rundles, R.W.: A summary of investigations with 6-[(r-methyl-4’nitro-5’-imidazolyl)] thiopurine. Cancer Chemother. Rep. 14, 93–98 (1961).

    CAS  Google Scholar 

  • Elion, G.B., Callahan, S.W., Hitchings, G.H., Ründles, R.W., Laszlo, J.: Experimental, clinical and metabolic studies of thiopurines. Cancer Chemother. Rep. 16, 197–202 (1962).

    CAS  Google Scholar 

  • Elion, G. B., Callahan, S. W., Rtjndles, R. W., Hitchings, G. H.: Relationship between metabolic fates and antitumor activities of thiopurines. Cancer Res. 23, 1207–1217 (1963).

    PubMed  CAS  Google Scholar 

  • Elion, G. B., Hitchings, G. H.: Metabolic basis for the actions of analogs of purines and pyrim- idines. In: Advances in chemotherapy, Vol. 2, pp. 91–177. New York: Academic Press 1965.

    Google Scholar 

  • Eltringham, J.R.: Effect of azathioprine and amethopterin on secondary disease in the rhesus monkey. Exp. Hematol. 10, 12–13 (1966).

    Google Scholar 

  • Floersheim, G. L., Seiler, K.: Differential effects of immunosuppressive drugs on a cutaneous graft-versus-host reaction in chickens. Transplantation 5, 1355–1370 (1967).

    Article  CAS  Google Scholar 

  • Folb, R.I., Trounce, J. R.: Immunological aspects of candida infection complicating steroid and immunosuppressive drug therapy. Lancet II, 1112–1114 (1970).

    Google Scholar 

  • Fofrnier, C., Bach, M. A., Dardenne, M., Bach, J.F.: Selective action of azathioprine on T cells. Transplant. Proc. 5, 523–526 (1973).

    Google Scholar 

  • Frankel, H.H., Yamamoto, R.S., Weisburgeb, E-K., Weisbubger, J.H.: Chronic toxicity of azathioprine and the effect of this immunosuppressant on liver tumor induction by the carcinogen N-hydroxy-N-2-fluorenylacetamide. Toxicol, appl. Pharmacol. 17, 462–480 (1970).

    CAS  Google Scholar 

  • Friedrich, U., Zeuthen, E.: Chromosomenabnormitäten und Behandlung mit Imuran (Azathioprin) nach Nierentransplantationen. Hum. Genet. 8, 289–294 (1970).

    Article  CAS  Google Scholar 

  • Gabor, E.P., Scott, J.L.: Effect of thiopurines on rat lymphoid tissues. Clin. Res. 16, 154 (1968).

    Google Scholar 

  • Gelfand, M.C., Nowakowski, A., Friedman, E.A., Knepshield, J.H.: Synergism in immunosuppression. III. Allograft rejection and humoral antibody production in intact and splenectomized mice. Transplantation 12, 377–383 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Gillibrand, P.N.: Systemic lupus erythematosus in pregnancy treated with azathioprine. Proc. roy. Soc. Med. 59, 834 (1966).

    CAS  Google Scholar 

  • Githens, J.H., Rosenkrantz, J. G., Tunnock, S.M.: Teratogenic effects of azathioprine (Imuran). J. Pediat. 66, 959–961 (1965).

    Article  PubMed  CAS  Google Scholar 

  • Glasgow, L.A.: Immunosuppression, interferon, and viral infections. Fed. Proc. 30, 1846– 1851 (1971).

    Google Scholar 

  • Gleichmann, E., Gleichmann, H., Schwabtz, R.S.: Immunologic induction of malignant lymphoma: genetic factors in the graft-versus-host model. J. nat. Cancer Inst. 49, 793–801 (1972).

    PubMed  CAS  Google Scholar 

  • Gonzalez, E.M., Kbejczy, K., Malt, R.A.: Modification of nucleic acid synthesis in regenerating liver by azathioprine. Surgery 68, 254–259 (1970).

    PubMed  CAS  Google Scholar 

  • Gotjamanos, T.: The effect of azathioprine on phagocytic activity and morphology of reticuloendothelial organs in mice. Pathology 3, 171–179 (1971).

    PubMed  CAS  Google Scholar 

  • Hambubgeb, J., Cbosnieb, J., Dobmont, J., Bach, J.F.: Renal transplantation. Theory and practice. Baltimore: Williams and Wilkins 1972.

    Google Scholar 

  • Hampel, K.E., Lackneb, A., Schulz, G., Busse, V.: Chromosomal mutations by azathioprine in human leukocytes In vitro. Z. Gastroent. 9, 47–51 (1971).

    CAS  Google Scholar 

  • Haxhe, J. J., Alexandbe, G.P. J., Kestens, P. J.: The effect of Imuran and azaserine on liver function tests in the dog. Its relation to the detection of graft rejection following liver transplantation. Arch. int. Pharmacodyn. 168, 366–372 (1967).

    CAS  Google Scholar 

  • Heine, K.M., Stobbe, H., Klatt, R., Apostoloff, E., Dutz, W.: Lymphocyte transformation tests in patients under treatment with immunosuppressive drugs. Helv. med. Acta 35, 140–145 (1969/70).

    Google Scholar 

  • Hebsh, E.M., Oppenheim, J.J.: Inhibition of In vitro lymphocyte transformation during chemotherapy in man. Cancer Res. 27, 98–105 (1967).

    Google Scholar 

  • Hill, R.H., JB., Rowlands, D.T., JB., Rifkind, D.: Infectious pulmonary disease in patients receiving immunosuppressive therapy for organ transplantation. New Engl. J. Med. 271, 1021–1027 (1964).

    Google Scholar 

  • Hibsch, M.S., Black, P.H., Tbacy, G.S., Leibowitz, S., Schwabtz, R.S.: Leukemia virus activation in chronic allogeneic disease. Proc. nat. Acad. Sci. (Wash.) 67, 1914–1917(1970).

    Google Scholar 

  • Hibsch, M.S., Phillips, S.M., Solnik, C., Black, P.H., Schwabtz, R.S., Cakpenteb, C.B.: Activation of leukemia viruses by graft-versus-host and mixed lymphocyte reactions In vitro. Proc. nat. Acad. Sci. (Wash.) 69, 1069–1072 (1972).

    Article  Google Scholar 

  • Hitchings, G. H.: Summary of informal discussion on the role of purine antagonists. Cancer Res. 23, 1218–1225 (1963).

    PubMed  CAS  Google Scholar 

  • Hitchings, G.H., Elion, G.B.: Chemical suppression of the immune response. Pharmacol. Rev. 15, 365–405 (1963).

    PubMed  CAS  Google Scholar 

  • Hitchings, G.H., Elion, G.B.: Purine analogues. In: Hochsteb, R.M., Quastel, J.H. (Eds.): Metabolic inhibitors, Vol. 1, pp. 215–237. New York: Academic Press 1963a.

    Google Scholar 

  • Hitchings, G. H., Elion, G. B.: Thiopurines as inhibitors of the immune response. In: Shugab, D. (Ed.): FEBS Symposium, Biochemical aspects of antimetabolites and of drug hydroxylation, Vol. 16, pp. 1–10. London and New York: Academic Press 1969.

    Google Scholar 

  • Hitchings, G.H., Elion, G.B.: The role of antimetabolites in immunosuppression and transplantation. Accounts chem. Res. 2, 202–209 (1969a).

    CAS  Google Scholar 

  • Hitchings, G.H., Elion, G.B.: Mechanisms of action of purine and pyrimidine analogues. In: Brodsky, I., Kahn, S.B., Moyeb, J.H. (Eds.): Cancer chemotherapy II, 22nd Hahnemann Symposium, pp. 23–32. New York: Grune and Stratton 1972.

    Google Scholar 

  • Howard, J. G.: Cellular events in the induction and loss of tolerance to pneumococcal polysaccharides. Transplant. Rev. 8, 50–75 (1972).

    PubMed  CAS  Google Scholar 

  • Hunstein, W., Pebings, E., Klose, U.: Long-term animal experiments with azathioprine (Imuran) to test its myelotoxic effect. Vehr, dtsch. Ges. inn. Med. 73, 450–453 (1967).

    CAS  Google Scholar 

  • Huseb, H. J., Mtjbphy, G.P.: The renal and hematologic effects of immunosuppression in the rhesus monkey. Survival of autotransplants following azathioprine. Amer. Surg. 32, 243– 248 (1966).

    Google Scholar 

  • Jensen, M.K.: Chromosome studies in patients treated with azathioprine and amethopterin. Acta med. scand. 182, 445–455 (1967).

    Article  PubMed  CAS  Google Scholar 

  • Kaufman, J. J., Dignam, W., Goodwin, W.E., Mabtin, D.C., Goldman, R., Maxwell, M.H.: Successful normal childbirth after kidney homotransplantation. J. Amer. med. Ass. 200, 338–341 (1967).

    Article  CAS  Google Scholar 

  • Kelley, W.N., Rosenbloom, F.M., Seegmiller, J.E.: The effects of azathioprine (Imuran) on purine synthesis in clinical disorders of purine metabolism. J. clin. Invest. 40, 1518– 1529 (1967).

    Google Scholar 

  • Kennealey, G. T., Lytton, B., Ruddle, N., Mitchell, M.S.: Modification of response to histocompatibility antigens with chemotherapeutic agents. Transplantation 12, 522–523 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Klein, G.: Immunological aspects of Burkitt’s lymphoma. Advanc. Immunol. 14, 187–243 (1971).

    Article  CAS  Google Scholar 

  • Krueger, G. R. F., Heine, U. I.: Morphogenesis of two immunologically induced mouse lymphomas. Cancer Res. 32, 573–582 (1972).

    PubMed  CAS  Google Scholar 

  • Krueger, G. R. F., Malmgren, R. A., Berard, C. W.: Malignant lymphomas and plasmacytosis in mice under prolonged immunosuppression and persistent antigenic stimulation. Transplantation 11, 138–144 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Lauro, V., Santilligiornelli, F.E., Dominici, C., Fanelli, A., Citcchia, G.: Effetti della 6-mercaptopurina e dell’azathioprina sulla fase di annidamento dell’uovo: indagine comparativa in alcune specie di roditori. Arch. Ginec. Obstet. 74, 164–177 (1969).

    CAS  Google Scholar 

  • Lee, A.K. Y., Mackay, I.R., Rowley, M. J., Yap, C.Y.: Measurement of antibody-producing capacity of flagellin in man. IV. Studies in autoimmune disease, allergy, and after azathioprine treatment. Clin. exp. Immunol. 9, 507–518 (1971).

    CAS  Google Scholar 

  • Leibowitz, H.M., Elliott, J. H.: Chemotherapeutic immunosuppression of the corneal graft reaction. II. Combined systemic antimetabolite and topical corticosteroid therapy. Arch. Ophthal. 76, 338–344 (1966).

    PubMed  CAS  Google Scholar 

  • Leung, F. C., Vas, S.I.: Effects of immunosuppressive drugs on secondary antibody response In vitro. Canad. J. Microbiol. 14, 7–11 (1968).

    Article  CAS  Google Scholar 

  • Levy, J., Barnett, E.V., Macdonald, N.S., Klinenberg, J.R., Pearson, C.M.: The effect of azathioprine on gammaglobulin synthesis in man. J. clin. Invest. 51, 2233–2238 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Malamud, D., Gonzalez, E.M., Cmu, H., Malt, R.A.: Inhibition of cell proliferation by azathioprine. Cancer Res. 82, 1226–1229 (1972).

    Google Scholar 

  • Mandel, M.A., Decosse, J.J.: Enhancement of tumor induction in mice by long term immunosuppression. Surg. Forum 21, 129–131 (1970).

    PubMed  CAS  Google Scholar 

  • McEwan, A., Petty, L.G.: Oncogenicity of immunosuppressive drugs. Lancet I, 326–327 (1972).

    Google Scholar 

  • Mellohs, R. C.: Murine leukemialike virus and the immunopathological disorders of New Zealand Black mice. J. infect. Dis. 120, 480–487 (1969).

    Article  Google Scholar 

  • Merigan, T.C., Stevens, D. A.: Viral infections in man associated with acquired immunological deficiency states. Fed. Proc. 30, 1858–1864 (1971).

    PubMed  CAS  Google Scholar 

  • Merkatz, I.R., Schwartz, G.H., David, D.S., Stenzel, K.H., Riggio, R.R., Whitsell, J.C.: Resumption of female reproductive function following renal transplantation. J. Amer. med. Ass. 216, 1749–1754 (1971).

    Article  CAS  Google Scholar 

  • Merrill, J.P.: Medical management of the transplant patient. In: Rapaport, F.T., Dausset, J. (Eds.): Human transplantation, pp. 66–79. New York: Grune and Stratton 1968.

    Google Scholar 

  • Meyer Zum Büschenfelde, K. EL, Freudenberg, J.: Tierexperimentelle Untersuchungen über die Wirkung von Azathioprin auf die Bildung zirkulierender Antikörper. Klin. Wschr. 47, 379 - 482 (1969).

    Google Scholar 

  • Miller, J. F. A. P., Basten, A., Sprent, J., Cheers, C.: Interaction between lymphocytes in immune responses. Cell. Immunol. 2, 469–495 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Miller, J. J., Cole, L. J.: Resistance of long-lived lymphocytes and plasma cells in rat lymph nodes to treatment with prednisone, cyclophosphamide, 6-mercaptopurine, and actinomy- cin D. J. exp. Med. 126, 109–125 (1967).

    Article  PubMed  CAS  Google Scholar 

  • Mitchell, C.G., Eddleston, A.L.W.F., Smith, M.G.M., Williams, R.: Serum immunosuppressive activity due to azathioprine and its relation to hepatic function after liver transplantation. Lancet I, 1196–1199 (1970).

    Google Scholar 

  • Moore, H.L., JR., Kozma, C.: Unpublished.

    Google Scholar 

  • Murray, J.E., Reid, D.E., Harrison, J.H., Merrill, J.P.: Successful pregnancies after human renal transplantation. New Engl. J. Med. 269, 341–343 (1963).

    CAS  Google Scholar 

  • Murray, J. E., Scheil, A. G. R., Moseley, R., Knight, P. R., Mcgavic, J. D., Dammin, G. J.: Analysis of mechanism of immunosuppressive drugs in renal homotransplantation. Ann. Surg. 160, 449–473 (1964).

    Article  PubMed  CAS  Google Scholar 

  • Nathan, H.C., Bieber, S., Elion, G.B., Hitchings, G.IL: Detection of agents which interfere with the immune response. Proc. Soc. exp. Biol. (N. Y.) 107, 796–799 (1961).

    CAS  Google Scholar 

  • Nyhan, W.L., Sweetman, L., Carpenter, D.G., Carter, C.H., Hoefnagel, D.: Effects of azathioprine in a disorder of uric acid metabolism and cerebral function. J. Pediat. 72, 111–118 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Obe, G.: Die Wirkung von 6-Mercaptopurin und Azathioprin auf menschliche Chromosomen In vitro. Arzneimittel-Forsch. 21, 504–505 (1971).

    CAS  Google Scholar 

  • Page, D., Posen, G., Stewart, T., Harris, J.: Immunological detection of renal allograft rejection in man. Increased deoxynucleic acid synthesis by peripheral lymphoid cells. Transplantation 12, 341–347 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Paine, K.W.E.: Personal communication.

    Google Scholar 

  • Palmer, D.L., Rifkind, D., brown, D.W.: 181I-Labeled colloidal human serum albumin in the study of reticuloendothelial system function. III. Phagocytosis and catabolism compared in normal, leukemic, and immunosuppressed human subjects. J. infect. Dis. 123, 465–469 (1971).

    CAS  Google Scholar 

  • Patkowski, J.: On the mode of action of some immunosuppressant drugs. J. Pharm. Pharmacol. 20, 957–959 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Penn, I., Halgrimson, C.G., Starzl, T.E.: De novo malignant tumors in organ transplant recipients. Transplant. Proc. 8, 773–778 (1971).

    Google Scholar 

  • Penn, I., Makowski, E., Droegemtjeller, W., Halgrimson, C.G., Starzl, T.E.: Parenthood in renal homograft recipients. J. Amer. med. Ass. 216, 1755–1761 (1971a).

    Article  CAS  Google Scholar 

  • Perper, R.J., Alvarez, B., Colombo, C., Schroder, H.: The use of a standardized adjuvant arthritis assay to differentiate between antiinflammatory and immunosuppressive agents. Proc. Soc. exp. Biol. (N.Y.) 187, 506–512 (1971).

    Google Scholar 

  • Powell, D.: Pregnancy in active chronic hepatitis on immunosuppressive therapy. Postgrad, med. J. 45, 292–294 (1969).

    Article  CAS  Google Scholar 

  • Qttadracci, L.J., Hellström, I.E., Striker, G.E., Marchioro, T.L., Hellström, K.E.: Immune mechanisms in human recipients of renal allografts. Cell. Immunol. 1, 561–566 (1970).

    Article  Google Scholar 

  • Quinn, R. P., Elion, G. B.: Unpublished.

    Google Scholar 

  • Reid, R.H., Piroesky, B., Dawson, P. J.: The influence of immunosuppression on virus-induc- ed lymphatic leukemia in mice. Transplantation 13, 61–65 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Rettber, M. D.: Accentuation of carbon tetrachloride-induced cirrhosis by azathioprine in the rat. Arch. Path. 90, 567–571 (1970).

    Google Scholar 

  • Rifkind, D.: The activation of varicella-zoster virus infections by immunosuppressive therapy. J. Lab. clin. Med. 68, 463–474 (1966).

    PubMed  CAS  Google Scholar 

  • Rifkind, D., Marchioro, T.L., Waddell, W.R., Starzl, T.E.: Infectious diseases associated with renal homotransplantation. I. Incidence, types and predisposing factors. J. Amer. med. Ass. 189, 397–407 (1964).

    CAS  Google Scholar 

  • Rosenkrantz, J.G., Githens, J.H., Cox, S.M., Kellum, D.L.: Azathioprine (Imuran) and pregnancy. Amer. J. Obstet. Gynec. 97, 387–394 (1967).

    PubMed  CAS  Google Scholar 

  • Rosenthale, M.E., Datko, L. J., Kassarich, J., Söhneid Er, F.: Chemotherapy of experimental allergic encephalomyelitis (EAE). Arch. int. Pharmacodyn. 179, 251–275 (1969).

    Google Scholar 

  • Rowley, M. J., Mackay, I.R., Mckenzie, I. F.C.: Antibody production in immunosuppressed recipients of renal allografts. Lancet II, 708–710 (1969).

    Google Scholar 

  • Rtjndles, R. W., Laszlo, J., Itoga, T., Hobson, J. B., Garrison, P. E., JR.: Clinical and hematologic study of 6-[(l-methyl-4-nitro-5-imidazolyl)thio]-purine and related compounds. Cancer Chemother. Itep. 14, 99–115 (1961).

    Google Scholar 

  • Sahiar, K., Schwartz, R.S.: Inhibition of 19 S antibody synthesis by 7 S antibodv. Science 145, 395–397 (1964).

    Article  PubMed  CAS  Google Scholar 

  • Schwartz, G.H., Stenzel, K.H., Rubin, A. L.: Depression of lymphocyte transformation by drugs In vitro. Effects of a new immunosuppressant, Cinanserin. Transplantation 8, 704– 711 (1969).

    Google Scholar 

  • Schwartz, R.S.: Immunoregulation, oncogenic viruses, and malignant lymphomas. Lancet I, 1266–1269 (1972).

    Google Scholar 

  • Schwartz, R.S., Andre, J.: The chemical suppression of immunity. Mechanism of cell and tissue damage produced by immune reactions. 2nd International symposium on immunopathology 1961, pp. 385–409. Basel: Benno Schwabe & Co. 1962.

    Google Scholar 

  • Schwartz, R.S., Beldotti, L.: The treatment of chronic murine homologous disease: a comparative study of four “immunosuppressive” agents. Transplantation 3, 79–97 (1965).

    Article  PubMed  CAS  Google Scholar 

  • Schwartz, R.S., Dameshek, W.: Drug-induced immunological tolerance. Nature (Lond.) 183, 1682–1683 (1959).

    Article  CAS  Google Scholar 

  • Schwartz, R.S., Dameshek, W.: The role of antigen dosage in drug-induced immunologic tolerance. J. Immunol. 90, 703–710 (1963).

    PubMed  CAS  Google Scholar 

  • Schwartz, R.S., Eisner, A., Dameshek, W.: The effect of 6-mercaptopurine on primary and secondary immune responses. J. clin. Invest. 38, 1394–1403 (1959).

    Article  PubMed  CAS  Google Scholar 

  • Schwartz, R. S., Stack, J., Dameshek, W.: Effect of 6-mercaptopurine on antibody production. Proc. Soc. exp. Biol. (N.Y.) 99, 164–167 (1958).

    CAS  Google Scholar 

  • Sheehan, R., Shklar, G., Tennebattm, R.: Azathioprine effects on the development of hamster pouch carcinomas. Arch. Path. 21, 264–270 (1971).

    Google Scholar 

  • Shipley, W.U.: Immunosuppressive agents and immune cytolysis In vitro. The effect of azathioprine, hydrocortisone, and radiation on antiserum and complement-mediated lysis of cultured mammalian cells. Transplantation 14, 392–395 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Silas, D.E., Nance, F.C.: Increased tolerance to high doses of azathioprine by germfree animals. Clin. Res. 16, 84 (1968).

    Google Scholar 

  • Simmons, R.L., Kjellstrand, C.M., Buselmeier, T.J., Najarian, J.S.: Current practice of renal transplantation at the University of Minnesota. Minn. Med. 54, 115–120 (1971).

    PubMed  CAS  Google Scholar 

  • Skarpa, M., Udall, V.: Unpublished.

    Google Scholar 

  • Skopinska, E., Sankowski, A., Nottza, K.: Effect of azathioprine on the development of allograft sensitivity in mice. Bull. Acad. pol. Sci. CI. 617, 85–88 (1969).

    Google Scholar 

  • Smith, J.L., Forbes, I.J.: Use of human lymphocytes in studies of drug action. Nature (Lond.) 215, 538–539 (1967).

    Article  CAS  Google Scholar 

  • Smith, J.L., Forbes, I.J.: Inhibition of protein synthesis in human lymphocytes by thiopu- rines. Aust. J. exp. Biol. med. Sci. 48, 267–276 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Sorensen, L. B.: Suppression of the shunt pathway in primary gout with azathioprine. Proc. nat. Acad. Sci. (Wash.) 55, 571–575 (1966).

    Article  CAS  Google Scholar 

  • Spiegelberg, H.L., Miescher, P.A.: The effect of 6-mercaptopurine and aminopterin on experimental immune thyroiditis in guinea pigs. J. exp. Med. 118, 869–890 (1963).

    Article  PubMed  CAS  Google Scholar 

  • Starzl, T.E.: Experience in renal transplantation. Philadelphia: W.B. Saunders (1964).

    Google Scholar 

  • Starzl, T.E., Marchioro, T.L., Porter, K.A., Taylor, P.D., Faris, T.D., Hermann, T. J., Hlad, C.L., Waddell, W.R.: Factors determining short- and long-term survival after orthotopic liver homotransplantation in the dog. Surgery 58, 131–155 (1965).

    PubMed  Google Scholar 

  • Stevens, J. E., Willoughby, D.A.: The anti-inflammatory effect of some immunosuppressive agents. J. Path. 97, 367–373 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Stinson, E.B., Bieber, C.P., Griepp, R.B., Clark, D.A., Shumway, N.E., Remington, J.S.: Infectious complications after cardiac transplantation in man. Ann. intern. Med. 74, 22–36 (1971).

    PubMed  CAS  Google Scholar 

  • Storti, E., Traldi, A., Quaglino, D.: Clinical studies on the effect of Imuran and vincristine in the treatment of leukemia. Acta Genet, med. (Roma) 17, 220–231 (1968).

    CAS  Google Scholar 

  • Sunderman, C.R., Pearson, H.A.: Growth effects of long-term antileukemic therapy. J. Pediat. 75, 1058–1062 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Swanson, M.A., Schwartz, R.S.: Immunosuppressive therapy: the relation between clinical response and immunological competence. New Eng. J. Med. 277, 163–170 (1967).

    Article  CAS  Google Scholar 

  • Thiersch, J.B.: Effect of 6-(l’, -methyl-4’-nitro-5’-imidazolyl)mercaptopurine and 2-amino-6- (1’-methyl-4/-nitro-5’-imidazolyl)mercaptopurine on the rat litter in utero. J. Reprod. Fertil. 4, 297–302 (1962).

    Article  PubMed  CAS  Google Scholar 

  • Tripathy, S.P., Mackaness, G.B.: The effect of cytotoxic agents on the passive transfer of cell-mediated immunity. J. exp. Med. 130, 17–30 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Tuchmann-Duplessis, H., Mercier-Parot, L.: Production de malformations des membres chez le Lapin par administration d’un antimetabolite: l’azathioprine. C.R. Acad. Sci. (Paris) 259, 3648–3651 (1964).

    CAS  Google Scholar 

  • Tuchmann-Dfplessis, H., Mercier-Parot, L.: Considérations sur les tests tératogènes. Différences de réaction de trois espèces animales à l’égard d’un antitumoral. C.R. Soc. Biol. (Paris) 158, 1984–1990 (1964a).

    Google Scholar 

  • Ttjchmann-Duplessis, H., Mercier-Parot, L.: Réactions provoquées chez l’embryon par deux antimétabolites chimiquement voisins. Bull, schweiz. Akad. med. Wiss. 22, 153–165 (1966).

    Google Scholar 

  • Udall, V.: Unpublished.

    Google Scholar 

  • Uyeki.M., Llacer, V.: Anti-tumour agents on antibody-forming cells In vitro. Biochem. Pharmacol. 19, 2419–2424 (1970).

    Article  Google Scholar 

  • Van Vroonhoven, T. J., Malt, R. A.: Rebound hyperplasia of regenerating liver after cessation of azathioprine. Surg. Forum 22, 339–340 (1971).

    PubMed  Google Scholar 

  • Vas, M., Lowenstein, L.: The effect of prednisone and azathioprine in mixed leucocyte culture. In: Conference and workshop on histocompatibility testing, pp. 213–215. Baltimore: Williams and Wilkins 1965.

    Google Scholar 

  • Vinegar, R.: Unpublished.

    Google Scholar 

  • Vinegar, R., Schreiber, W., Hugo, R.: Inhibitory effects of immunosuppressive agents on adjuvant arthritis (AA) and delayed skin reactions (DSR). Pharmacologist 10, 184 (1968).

    Google Scholar 

  • Vredevoe, D.L., Hayes, E.F.: Effect of antilymphocytic and antithymocytic sera on the

    Google Scholar 

  • development of mouse lymphoma. Cancer Res. 29, 1685–1690 (1969).

    Google Scholar 

  • Walford, R.L.: Generalizing biologic hypotheses and aging: an immunological approach. In: Krohn, P.L. (Ed.): Topics in biology of aging, pp. 163–169. New York: John Wiley and Sons 1966.

    Google Scholar 

  • Walford, R.L.: Immunologische Aspekte des Alterns. Klin. Wschr. 47, 599–605 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Wilson, D.B.: Quantitative studies on the behavior of sensitized lymphocytes In vitro. II. Inhibitory influence of the immune suppressor, Imuran, on the destructive reaction of sensitized lymphoid cells against homologous target cells. J. exp. Med. 122, 167–172 (1965).

    Article  PubMed  CAS  Google Scholar 

  • Worth, W.S.: Azathioprine effect on normal canine liver and kidney function. Toxicol, appl. Pharmacol. 12, 1–6 (1968).

    CAS  Google Scholar 

  • Zweiman, B., Silberberg, D. H.: In vitro lymphocyte responsiveness of human subjects receiving azathioprine. Int. Arch. Allergy 41, 428–433 (1971).

    Article  PubMed  CAS  Google Scholar 

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Elion, G.B., Hitchings, G.H. (1975). Azathioprine. In: Sartorelli, A.C., Johns, D.G. (eds) Antineoplastic and Immunosuppressive Agents. Handbuch der experimentellen Pharmakologie / Handbook of Experimental Pharmacology, vol 38 / 2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-65806-8_19

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