Induction of lethal experimental allergic encephalomyelitis in nonhuman primates and guinea pigs with human glioblastoma multiforme tissue

Darell D. Bigner M.D., Ph.D.1, Olin M. Pitts Ph.D.1, and Carol J. Wikstrand Ph.D.1
View More View Less
  • 1 Departments of Pathology, Experimental Surgery, and Microbiology, Duke University Medical Center, Durham, North Carolina
Restricted access

Purchase Now

USD  $45.00

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00
Print or Print + Online

✓ The introduction of active specific immunotherapy as an adjunct to conventional therapy of the brain-tumor patient creates the risk of the concomitant induction of experimental allergic encephalomyelitis (EAE). The lack of resolution concerning the total group of central nervous system (CNS) antigens which may be encephalitogenic, and the lack of definition of the necessary conditions for the induction of an anti-CNS myelin response complicate the design of an immunotherapeutic regimen for brain-tumor patients. We report here the ready induction of EAE in four of four guinea pigs and both of two nonhuman primates (Macaca fascicularis) with human glioblastoma multiforme (GBM) tissue injected with either complete or incomplete Freund's adjuvant (CFA, IFA). Immunization protocols utilizing encephalitogenic GBM tissue and adjuvant which did not result in EAE induction were established in both of two macaques, and the production of significant levels of antibodies specifically reactive with immunizing GBM-derived cultured cell lines in all of 12 macaques without EAE induction was demonstrated. As the lower detection limit of the sodium dodecyl sulfate-polyacrylimide gel electrophoresis (SDS-PAGE) assay for human myelin basic protein (HBP) was 0.6 µg HBP/gel, and an extract prepared from WR-GBM tumor tissue contained less than 0.6 µg of detectable HBP/25 µg of pH 3 extractable protein, and as 100 to 1000 µg of purified human basic protein (HBP) failed to induce EAE in three of three macaques, it was hypothesized that 1) GBM tissue may act as an adjuvant and markedly lower myelin basic protein (MBP) threshold doses for EAE induction, that 2) MBP encephalitogenic fragments capable of EAE induction may be present in GBM tissue but difficult to quantitate in precipitates by in vitro methods, or that 3) secondary encephalitogenic antigens unrelated to MBP may be present in GBM tissue. The threat of EAE induction and the potential difficulty of its detection in the deteriorating brain-tumor patient receiving active specific immunotherapy warrants a biological screen in immunizing CNS material in experimental animals prior to administration to patients in immunotherapy protocols.

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00

Contributor Notes

Address reprint requests to: Darell D. Bigner, M.D., Departments of Pathology and Experimental Surgery, Duke University Medical Center, Durham, North Carolina 27710.
  • 1.

    Albright L, , Seab JA, & Ommaya AK: Intracerebral delayed hypersensitivity reactions in glioblastoma multiforme patients. Cancer 39:13311336, 1977 Albright L, Seab JA, Ommaya AK: Intracerebral delayed hypersensitivity reactions in glioblastoma multiforme patients. Cancer 39:1331–1336, 1977

    • Search Google Scholar
    • Export Citation
  • 2.

    Alvord EC Jr, , Shaw C-M, & Hruby S: Myelin basic protein treatment of experimental allergic encephalomyelitis in monkeys. Ann Neurol 6:469473, 1979 Alvord EC Jr, Shaw C-M, Hruby S: Myelin basic protein treatment of experimental allergic encephalomyelitis in monkeys. Ann Neurol 6:469–473, 1979

    • Search Google Scholar
    • Export Citation
  • 3.

    Alvord EC Jr, , Shaw C-M, & Hruby S, et al. : Encephalitogen-induced inhibition of experimental allergic encephalomyelitis: prevention, suppression and therapy. Ann NY Acad Sci 122:333345, 1965 Alvord EC Jr, Shaw C-M, Hruby S, et al: Encephalitogen-induced inhibition of experimental allergic encephalomyelitis: prevention, suppression and therapy. Ann NY Acad Sci 122:333–345, 1965

    • Search Google Scholar
    • Export Citation
  • 4.

    Audibert F, & Chédid L: Distinctive adjuvanticity of synthetic analogs of mycobacterial water-soluble components. Cell Immunol 21:243249, 1976 Audibert F, Chédid L: Distinctive adjuvanticity of synthetic analogs of mycobacterial water-soluble components. Cell Immunol 21:243–249, 1976

    • Search Google Scholar
    • Export Citation
  • 5.

    Behan PO, , Kies MW, & Lisak RP: Immunologic mechanisms in experimental encephalomyelitis in nonhuman primates. Arch Neurol 29:49, 1973 Behan PO, Kies MW, Lisak RP: Immunologic mechanisms in experimental encephalomyelitis in nonhuman primates. Arch Neurol 29:4–9, 1973

    • Search Google Scholar
    • Export Citation
  • 6.

    Bernard CCA: Experimental autoimmune encephalomyelitis in mice: genetic control of susceptibility. J Immunogenet 3:263274, 1976 Bernard CCA: Experimental autoimmune encephalomyelitis in mice: genetic control of susceptibility. J Immunogenet 3:263–274, 1976

    • Search Google Scholar
    • Export Citation
  • 7.

    Bernard CCA, , Leydon J, & Mackay IR: T cell necessity in the pathogenesis of experimental autoimmune encephalomyelitis in mice. Eur J Immunol 6:655660, 1976 Bernard CCA, Leydon J, Mackay IR: T cell necessity in the pathogenesis of experimental autoimmune encephalomyelitis in mice. Eur J Immunol 6:655–660, 1976

    • Search Google Scholar
    • Export Citation
  • 8.

    Bigner DD, , Bigner SH, & Pontén J, et al. : Heterogeneity of genotypic and phenotypic characteristics of 15 permanent cell lines derived from human gliomas. J Neuropathol Exp Neurol 40 (In press, 1981 Bigner DD, Bigner SH, Pontén J, et al: Heterogeneity of genotypic and phenotypic characteristics of 15 permanent cell lines derived from human gliomas. J Neuropathol Exp Neurol 40 (In press, 1981)

    • Search Google Scholar
    • Export Citation
  • 9.

    Bigner DD, , Markesberry WR, & Pegram CN, et al. : Progressive neoplastic growth in nude mice of cultured cell lines derived from human gliomas. J Neuropathol Exp Neurol 36:593, 1977 (Abstract) Bigner DD, Markesberry WR, Pegram CN, et al: Progressive neoplastic growth in nude mice of cultured cell lines derived from human gliomas. J Neuropathol Exp Neurol 36:593, 1977 (Abstract)

    • Search Google Scholar
    • Export Citation
  • 10.

    Bigner SH, , Bullard DE, & Pegram CN, et al. : Relationship of in vitro morphologic and growth characteristics of established human glioma-derived cell lines to their tumorigenicity in athymic nude mice. J Neuropathol Exp Neurol 40 (In press, 1981) Bigner SH, Bullard DE, Pegram CN, et al: Relationship of in vitro morphologic and growth characteristics of established human glioma-derived cell lines to their tumorigenicity in athymic nude mice. J Neuropathol Exp Neurol 40 (In press, 1981)

    • Search Google Scholar
    • Export Citation
  • 11.

    Bloom HJG: Combined modality therapy for intracranial tumors. Cancer 35:111120, 1975 Bloom HJG: Combined modality therapy for intracranial tumors. Cancer 35:111–120, 1975

    • Search Google Scholar
    • Export Citation
  • 12.

    Brooks WH, & Roszman TL: Immunobiology of intracranial tumors, in Waters H (ed): Immunotherapy. The Handbook of Cancer Immunology, Vol 5. New York: Garland STPM Press, 1978, pp 345355 Brooks WH, Roszman TL: Immunobiology of intracranial tumors, in Waters H (ed): Immunotherapy. The Handbook of Cancer Immunology, Vol 5. New York: Garland STPM Press, 1978, pp 345–355

    • Search Google Scholar
    • Export Citation
  • 13.

    Burger PC, , Mahaley MS Jr, & Dudka L, et al. : The morphologic effects of radiation administered therapeutically for intracranial gliomas. A postmortem study of 25 cases. Cancer 44:12561272, 1979 Burger PC, Mahaley MS Jr, Dudka L, et al: The morphologic effects of radiation administered therapeutically for intracranial gliomas. A postmortem study of 25 cases. Cancer 44:1256–1272, 1979

    • Search Google Scholar
    • Export Citation
  • 14.

    Chedid L, , Audibert F, & Lefrancier P, et al. : Modulation of the immune response by a synthetic adjuvant and analogs. Proc Nat Acad Sci USA 73:24722475, 1976 Chedid L, Audibert F, Lefrancier P, et al: Modulation of the immune response by a synthetic adjuvant and analogs. Proc Nat Acad Sci USA 73:2472–2475, 1976

    • Search Google Scholar
    • Export Citation
  • 15.

    Cohen SR, , Brooks BR, & Herndon RM, et al. : A diagnostic index of active demyelination: myelin basic protein in cerebrospinal fluid. Ann Neurol 8:2531, 1980 Cohen SR, Brooks BR, Herndon RM, et al: A diagnostic index of active demyelination: myelin basic protein in cerebrospinal fluid. Ann Neurol 8:25–31, 1980

    • Search Google Scholar
    • Export Citation
  • 16.

    Devesa SS, & Silverman DT: Cancer incidence and mortality trends in the United States: 1935–1974. JNCI 60:545571, 1978 Devesa SS, Silverman DT: Cancer incidence and mortality trends in the United States: 1935–1974. JNCI 60:545–571, 1978

    • Search Google Scholar
    • Export Citation
  • 17.

    Driscoll BF, , Kies MW, & Alvord EC Jr: Adoptive transfer of experimental allergic encephalomyelitis (EAE): prevention of successful transfer by treatment of donors with myelin basic protein. J Immunol 114:291292, 1975 Driscoll BF, Kies MW, Alvord EC Jr: Adoptive transfer of experimental allergic encephalomyelitis (EAE): prevention of successful transfer by treatment of donors with myelin basic protein. J Immunol 114:291–292, 1975

    • Search Google Scholar
    • Export Citation
  • 18.

    Eylar EH, , Brostoff S, & Jackson J, et al. : Allergic encephalomyelitis in monkeys induced by a peptide from the Al protein. Proc Nat Acad Sci USA 69:617619, 1972 Eylar EH, Brostoff S, Jackson J, et al: Allergic encephalomyelitis in monkeys induced by a peptide from the Al protein. Proc Nat Acad Sci USA 69:617–619, 1972

    • Search Google Scholar
    • Export Citation
  • 19.

    Eylar EH, , Jackson J, & Rothenberg B, et al. : Suppression of the immune response: reversal of the disease state with antigen in allergic encephalomyelitis. Nature 236:7476, 1972 Eylar EH, Jackson J, Rothenberg B, et al: Suppression of the immune response: reversal of the disease state with antigen in allergic encephalomyelitis. Nature 236:74–76, 1972

    • Search Google Scholar
    • Export Citation
  • 20.

    Giard DJ, , Aaronson SA, & Todaro GJ, et al. : In vitro cultivation of human tumors: establishment of cell lines derived from a series of solid tumors. JNCI 51:14171423, 1973 Giard DJ, Aaronson SA, Todaro GJ, et al: In vitro cultivation of human tumors: establishment of cell lines derived from a series of solid tumors. JNCI 51:1417–1423, 1973

    • Search Google Scholar
    • Export Citation
  • 21.

    Gruenewald R, , Levine S, & Sowinski R: Experimental allergic encephalomyelitis in the rat: enhancement and suppression by synthetic polyribonucleotides. Proc Soc Exp Biol Med 154:175179, 1977 Gruenewald R, Levine S, Sowinski R: Experimental allergic encephalomyelitis in the rat: enhancement and suppression by synthetic polyribonucleotides. Proc Soc Exp Biol Med 154:175–179, 1977

    • Search Google Scholar
    • Export Citation
  • 22.

    Gutstein HS, & Cohen SR: Spinal fluid differences in experimental allergic encephalomyelitis and multiple sclerosis. Science 199:301303, 1978 Gutstein HS, Cohen SR: Spinal fluid differences in experimental allergic encephalomyelitis and multiple sclerosis. Science 199:301–303, 1978

    • Search Google Scholar
    • Export Citation
  • 23.

    Hashim GA: Myelin basic protein: structure, function and antigenic determinants. Immunol Rev 39:60107, 1978 Hashim GA: Myelin basic protein: structure, function and antigenic determinants. Immunol Rev 39:60–107, 1978

    • Search Google Scholar
    • Export Citation
  • 24.

    Hashim GA, & Schilling FJ: Prevention of experimental allergic encephalomyelitis by nonencephalitogenic basic peptides. Arch Biochem Biophys 156:287297, 1973 Hashim GA, Schilling FJ: Prevention of experimental allergic encephalomyelitis by nonencephalitogenic basic peptides. Arch Biochem Biophys 156:287–297, 1973

    • Search Google Scholar
    • Export Citation
  • 25.

    Howard JC, & Gonatas NK: Inhibition of experimental allergic encephalomyelitis in rats severely depleted of T cells. J Neuropathol Exp Neurol 34:97, 1975 (Abstract) Howard JC, Gonatas NK: Inhibition of experimental allergic encephalomyelitis in rats severely depleted of T cells. J Neuropathol Exp Neurol 34:97, 1975 (Abstract)

    • Search Google Scholar
    • Export Citation
  • 26.

    Johnson AB, , Bornstein MB, & Raine CS: Effects of antigalactocerebroside serum on organotypic CNS cultures: ultrastructural and immunocytochemical observations. J Neuropathol Exp Neurol 39:364, 1980 (Abstract) Johnson AB, Bornstein MB, Raine CS: Effects of antigalactocerebroside serum on organotypic CNS cultures: ultrastructural and immunocytochemical observations. J Neuropathol Exp Neurol 39:364, 1980 (Abstract)

    • Search Google Scholar
    • Export Citation
  • 27.

    Kibler RF, & Shapira R: Isolation and properties of an encephalitogenic protein from bovine, rabbit, and human central nervous system tissue. J Biol Chem 243:281286, 1968 Kibler RF, Shapira R: Isolation and properties of an encephalitogenic protein from bovine, rabbit, and human central nervous system tissue. J Biol Chem 243:281–286, 1968

    • Search Google Scholar
    • Export Citation
  • 28.

    Kristensson K, , Wiśniewski HM, & Bornstein MB: About demyelinating properties of humoral antibodies in experimental allergic encephalomyelitis. In vivo and in vitro studies. Acta Neuropathol 36:307314, 1976 Kristensson K, Wiśniewski HM, Bornstein MB: About demyelinating properties of humoral antibodies in experimental allergic encephalomyelitis. In vivo and in vitro studies. Acta Neuropathol 36:307–314, 1976

    • Search Google Scholar
    • Export Citation
  • 29.

    Lehrer GM, , Maker HS, & Silides DJ, et al. : Anti-whole white matter serum inhibits incorporation of glucose and galactose into the lipids of myelinating spinal cord cultures. J Neurochem 30:247251, 1978 Lehrer GM, Maker HS, Silides DJ, et al: Anti-whole white matter serum inhibits incorporation of glucose and galactose into the lipids of myelinating spinal cord cultures. J Neurochem 30:247–251, 1978

    • Search Google Scholar
    • Export Citation
  • 30.

    Levine S: Hyperacute, neutrophilic, and localized forms of experimental allergic encephalomyelitis: a review. Acta Neuropathol 28:179189, 1974 Levine S: Hyperacute, neutrophilic, and localized forms of experimental allergic encephalomyelitis: a review. Acta Neuropathol 28:179–189, 1974

    • Search Google Scholar
    • Export Citation
  • 31.

    Levinson AI, , Lisak RP, & Zweiman B, et al. : Reactive and non-reactive lymphocytes in experimental allergic encephalomyelitis. II. Characteristics of peritoneal lymphocytes responding to antigen. Immunology 33:621627, 1977 Levinson AI, Lisak RP, Zweiman B, et al: Reactive and non-reactive lymphocytes in experimental allergic encephalomyelitis. II. Characteristics of peritoneal lymphocytes responding to antigen. Immunology 33:621–627, 1977

    • Search Google Scholar
    • Export Citation
  • 32.

    MacPherson CFC, & Armstrong H: Prevention of experimental allergic encephalitis in Lewis rats by rat and bovine spinal cord proteins. Nature 266:459461, 1977 MacPherson CFC, Armstrong H: Prevention of experimental allergic encephalitis in Lewis rats by rat and bovine spinal cord proteins. Nature 266:459–461, 1977

    • Search Google Scholar
    • Export Citation
  • 33.

    Madrid RE, , Wiśniewski HM, & Iqbal K, et al. : Search for secondary antigens in the pathogenesis of relapsing experimental allergic encephalomyelitis. J Neuropathol Exp Neurol 39:373, 1980 (Abstract) Madrid RE, Wiśniewski HM, Iqbal K, et al: Search for secondary antigens in the pathogenesis of relapsing experimental allergic encephalomyelitis. J Neuropathol Exp Neurol 39:373, 1980 (Abstract)

    • Search Google Scholar
    • Export Citation
  • 34.

    Nagai Y, , Akiyama K, & Suzuki K, et al. : Minimum structural requirements for encephalitogen and for adjuvant in the induction of experimental allergic encephalomyelitis. Cell Immunol 35:158167, 1978 Nagai Y, Akiyama K, Suzuki K, et al: Minimum structural requirements for encephalitogen and for adjuvant in the induction of experimental allergic encephalomyelitis. Cell Immunol 35:158–167, 1978

    • Search Google Scholar
    • Export Citation
  • 35.

    Ommaya A: Immunotherapy of gliomas: a review. Adv Neurol 15:337357, 1976 Ommaya A: Immunotherapy of gliomas: a review. Adv Neurol 15:337–357, 1976

    • Search Google Scholar
    • Export Citation
  • 36.

    Paterson PY: The Demyelinating Diseases: Clinical and Experimental Correlates. Immunological Diseases, Vol 2. M Samter, editor. Boston: Little, Brown and Co, 1971, pp 12771299 Paterson PY: The Demyelinating Diseases: Clinical and Experimental Correlates. Immunological Diseases, Vol 2. M Samter, editor. Boston: Little, Brown and Co, 1971, pp 1277–1299

    • Search Google Scholar
    • Export Citation
  • 37.

    Paterson PY: Neuroimmunologic diseases of animals and humans. J Infect Dis 1:468482, 1979 Paterson PY: Neuroimmunologic diseases of animals and humans. J Infect Dis 1:468–482, 1979

    • Search Google Scholar
    • Export Citation
  • 38.

    Paterson PY: Transfer of allergic encephalomyelitis in rats by means of lymph node cells. J Exp Med 111:119136, 1960 Paterson PY: Transfer of allergic encephalomyelitis in rats by means of lymph node cells. J Exp Med 111:119–136, 1960

    • Search Google Scholar
    • Export Citation
  • 39.

    Pitts OM, , Barrows AA, & Day ED: An evaluation of a procedure for the isolation of myelin basic protein (BP). Prep Biochem 6:239264, 1976 Pitts OM, Barrows AA, Day ED: An evaluation of a procedure for the isolation of myelin basic protein (BP). Prep Biochem 6:239–264, 1976

    • Search Google Scholar
    • Export Citation
  • 40.

    Pontén J: Neoplastic human glia cells in culture, in Fogh J (ed): Human Tumor Cells In Vitro. New York: Plenum Press, 1975, pp 175206 Pontén J: Neoplastic human glia cells in culture, in Fogh J (ed): Human Tumor Cells In Vitro. New York: Plenum Press, 1975, pp 175–206

    • Search Google Scholar
    • Export Citation
  • 41.

    Posner JB, , Bigner DD, & D'Angelo GJ, et al. : Neoplasms, in: Subpanel Report for Long Range Strategy on Central Nervous System Neoplasms. NINCDS. DHEW Publ. No. (NIH) 79-1915. Washington, DC: US Government Printing Office, 1978, pp 173224 Posner JB, Bigner DD, D'Angelo GJ, et al: Neoplasms, in: Subpanel Report for Long Range Strategy on Central Nervous System Neoplasms. NINCDS. DHEW Publ. No. (NIH) 79–1915. Washington, DC: US Government Printing Office, 1978, pp 173–224

    • Search Google Scholar
    • Export Citation
  • 42.

    Raine CS, , Traugott U, & Farooq M, et al. : Helper antigens are needed for demyelination. J Neuropathol Exp Neurol 39:385, 1980 (Abstract) Raine CS, Traugott U, Farooq M, et al: Helper antigens are needed for demyelination. J Neuropathol Exp Neurol 39:385, 1980 (Abstract)

    • Search Google Scholar
    • Export Citation
  • 43.

    Rivers TM, & Schwentker FF: Encephalomyelitis accompanied by myelin destruction experimentally produced in monkeys. J Exp Med 61:689702, 1935 Rivers TM, Schwentker FF: Encephalomyelitis accompanied by myelin destruction experimentally produced in monkeys. J Exp Med 61:689–702, 1935

    • Search Google Scholar
    • Export Citation
  • 44.

    Smith SB, & Waksman BH: Passive transfer and labeling studies on the cell infiltrate in experimental allergic encephalomyelitis. J Pathol 99:237244, 1969 Smith SB, Waksman BH: Passive transfer and labeling studies on the cell infiltrate in experimental allergic encephalomyelitis. J Pathol 99:237–244, 1969

    • Search Google Scholar
    • Export Citation
  • 45.

    Teitelbaum D, , Webb C, & Bree M, et al. : Suppression of experimental allergic encephalomyelitis in rhesus monkeys by a synthetic basic copolymer. Clin Immunol Immunopathol 3:256262, 1974 Teitelbaum D, Webb C, Bree M, et al: Suppression of experimental allergic encephalomyelitis in rhesus monkeys by a synthetic basic copolymer. Clin Immunol Immunopathol 3:256–262, 1974

    • Search Google Scholar
    • Export Citation
  • 46.

    Traugott U, & Raine CS: Experimental allergic encephalomyelitis. Frequent sampling of blood alters disease course. Acta Neuropathol 48:171175, 1979 Traugott U, Raine CS: Experimental allergic encephalomyelitis. Frequent sampling of blood alters disease course. Acta Neuropathol 48:171–175, 1979

    • Search Google Scholar
    • Export Citation
  • 47.

    Traugott U, & Raine CS: Experimental allergic encephalomyelitis in inbred guinea pigs: correlation of decrease in early T cells with clinical signs in suppressed and unsuppressed animals. Cell Immunol 34:146155, 1977 Traugott U, Raine CS: Experimental allergic encephalomyelitis in inbred guinea pigs: correlation of decrease in early T cells with clinical signs in suppressed and unsuppressed animals. Cell Immunol 34:146–155, 1977

    • Search Google Scholar
    • Export Citation
  • 48.

    Traugott U, , Stone SH, & Raine CS: Experimental allergic encephalomyelitis—migration of early T cells from the circulation into the central nervous system. J Neurol Sci 36:5561, 1978 Traugott U, Stone SH, Raine CS: Experimental allergic encephalomyelitis—migration of early T cells from the circulation into the central nervous system. J Neurol Sci 36:55–61, 1978

    • Search Google Scholar
    • Export Citation
  • 49.

    Trouillas P: Immunologie et immunothérapie des tumeurs cérébrales. État actuel. Rev Neurol 128:2338, 1973 Trouillas P: Immunologie et immunothérapie des tumeurs cérébrales. État actuel. Rev Neurol 128:23–38, 1973

    • Search Google Scholar
    • Export Citation
  • 50.

    Walker MD, , Alexander E Jr, & Hunt WE, et al. : Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial. J Neurosurg 49:333343, 1978 Walker MD, Alexander E Jr, Hunt WE, et al: Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial. J Neurosurg 49:333–343, 1978

    • Search Google Scholar
    • Export Citation
  • 51.

    Westall FC, , Thompson M, & Lennon VA: Hyperacute autoimmune encephalomyelitis induced by a synthetic autoantigen. Nature 269:425427, 1977 Westall FC, Thompson M, Lennon VA: Hyperacute autoimmune encephalomyelitis induced by a synthetic autoantigen. Nature 269:425–427, 1977

    • Search Google Scholar
    • Export Citation
  • 52.

    Whitaker JN, , Lisak RP, & Bashir RM, et al. : Immunoreactive myelin basic protein in the cerebrospinal fluid in neurological disorders. Ann Neurol 7:5864, 1980 Whitaker JN, Lisak RP, Bashir RM, et al: Immunoreactive myelin basic protein in the cerebrospinal fluid in neurological disorders. Ann Neurol 7:58–64, 1980

    • Search Google Scholar
    • Export Citation
  • 53.

    Wikstrand CJ, & Bigner DD: Hyperimmunization of nonhuman primates with BCG-CW and cultured human glioma-derived cells: production of reactive antisera and absence of EAE induction. J Neuroimmunol 1 (In press, 1981) Wikstrand CJ, Bigner DD: Hyperimmunization of nonhuman primates with BCG-CW and cultured human glioma-derived cells: production of reactive antisera and absence of EAE induction. J Neuroimmunol 1 (In press, 1981)

    • Search Google Scholar
    • Export Citation
  • 54.

    Wikstrand CJ, & Bigner DD: Immunobiologic aspects of the brain and human gliomas. Am J Pathol 98:515568, 1980 Wikstrand CJ, Bigner DD: Immunobiologic aspects of the brain and human gliomas. Am J Pathol 98:515–568, 1980

    • Search Google Scholar
    • Export Citation
  • 55.

    Wikstrand CJ, & Bigner DD: Surface antigens of human glioma cells shared with normal adult and fetal brain. Cancer Res 39:32353243, 1979 Wikstrand CJ, Bigner DD: Surface antigens of human glioma cells shared with normal adult and fetal brain. Cancer Res 39:3235–3243, 1979

    • Search Google Scholar
    • Export Citation
  • 56.

    Yarkoni E, , Rapp HJ, & Zban B: Immunotherapy of a guinea pig hepatoma with ultrasonically prepared mycobacterial vaccines. Cancer Immunol Immunother 2:143146, 1977 Yarkoni E, Rapp HJ, Zban B: Immunotherapy of a guinea pig hepatoma with ultrasonically prepared mycobacterial vaccines. Cancer Immunol Immunother 2:143–146, 1977

    • Search Google Scholar
    • Export Citation
  • 57.

    Zimmerman HM: Brain tumors: their incidence and classification in man and their experimental production. Ann NY Acad Sci 159:337359, 1969 Zimmerman HM: Brain tumors: their incidence and classification in man and their experimental production. Ann NY Acad Sci 159:337–359, 1969

    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 320 69 7
Full Text Views 173 1 0
PDF Downloads 110 2 0
EPUB Downloads 0 0 0