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A site-specific antibody produced with a novel immunization procedure by induction of tolerance to cross-reacting determinants and its utilization in clinical research.

Research Project

Project/Area Number 61870026
Research Category

Grant-in-Aid for Developmental Scientific Research

Allocation TypeSingle-year Grants
Research Field Immunology
Research InstitutionDivision of Oncogenesis,Department of Oncology, Biomedical Research Center, Osaka University Medical School

Principal Investigator

HAMAOKA Toshiyuki  Div. Oncogenesis, Biomedical Res. Center, Osaka Univ. Med.Sch; Professor, 医学部, 教授 (60028529)

Co-Investigator(Kenkyū-buntansha) ONO Shiro  Div.Oncogenesis,Biomedical Res.Center,Osaka Univ.Med.Sch.,Instructor, 医学部, 助手 (80127208)
TATEISHI Kayoko  1st Dept. Biochem., Sch.of Medicine, Fukuoka Univ.; Instructor, 医学部, 助手 (60179728)
Project Period (FY) 1986 – 1988
Project Status Completed (Fiscal Year 1988)
Budget Amount *help
¥30,500,000 (Direct Cost: ¥30,500,000)
Fiscal Year 1988: ¥9,000,000 (Direct Cost: ¥9,000,000)
Fiscal Year 1987: ¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 1986: ¥13,500,000 (Direct Cost: ¥13,500,000)
KeywordsSite-specific antibody / Immunological tolerance / copolymer of D-glutamic acid and D-lysine (D-GL) / Cholecystokinin (CCK) / Neurokinin / Glucose-6-phosphate dehydrogenase (G6PD) / Sugar chain structure / 糖鎖構造 / Dーグルタミン酸Dーリジン重合体(DーGL) / グルコース6リン酸デヒドロゲナーゼ(G6PD) / 特異抗体作製法 / 神経ペプチド / HLA-DR
Research Abstract

In this study, a novel immunization procedure to produce a site-specific antibody to a ligand of clinical significance with low cross-reactivity was developed and utilized. the method involved the induction of B-lymphocyte tolerance to the cross-reacting determinants on molecules of the ligand in question by treatment of animals with the cross-reacting determinant-d-gl conjugate and immunization with the ligand containing the requisite determinants. 1. Cholecystokinin (CCK)-8-specific antibody was successfully induced by using this immunization procedure, and it was found that the antibody detects biologically active CCK itself but not CCK-precursor and CCK-degradates. 2. By using this CCK-8-specific antibody, CCK was found to widely distribute in central nervous system, except primary sensory neurons, including mesencephalic dopamine neurons and in their projection areas. In addition, CCK levels were significantly reduced in temporal, parietal and occipital cortex of brain of eck fist … More ula dogs and dimethylnitrosamine-treated dogs which were prepared as experimental models of hepatic encphalopathy. Phenylalanine and tyrosine were increased in cortex of these animals. Amounts of reduction of CCK, however, did not correlate with those of increment of the aromatic amino acids in cortex of these models. Thus, these results imply that reduced levels of CCK are elicited by the mechanism distinct from that inducing increase of false neurotransmitter. 3. Neurokinin A- and neurokinin B-specific antibodies were firstly developed by using the abovedevised immunization procedure. Radioimmunoassays using these specific antisera allowed us to measure these neurokinins directly. Measurements of immunoreactive neurokinin A and B in different rat brain regions and spinal cord revealed that they are present with various ratios depending on the region. 4. By utilizing the novel immunization procedure, we are trying to establish the following sitespecific antibodies: antibodies which enable us to distinguish A and B allele of human glucose-6-phosphate dehydrogenase, and antibodies which enable us to distinguish the tumor-related change in in sugar moiety of human choriogonadotropin. Less

Report

(3 results)
  • 1988 Annual Research Report   Final Research Report Summary
  • 1986 Annual Research Report
  • Research Products

    (40 results)

All Other

All Publications (40 results)

  • [Publications] T.Hamaoka: Ann. Rev. Immunol. 4. 167-204 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] A.Funakoshi: Am.J.Gastroenterol. 81. 1174-1178 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] I.Nakano: Reg.Peptides. 14. 229-236 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] I.Nakano: Gastroenterologia Japonica. 22. 748-755 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] I.Nakano: Reg.Peptides. 23. 153-159 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] T.Kosaka: Brain Res.409. 403-408 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] T.Hayakawa: Res.Exp.Med.188. 19-25 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] T.Hokfelt: J.Chem.Neuroanatomy. 1. 11-52 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] S.Sato: Reg.Peptides. (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] K.Tateishi: Reg.Peptides. (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] A.Nagashima: (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] T.Hamaoka: "Cellular, Molecular and Genetic Approaches to Immunodiagnosis and Immunotherapy" University of Tokyo Press, 11 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] T.Hamaoka: "Regulation of B-cell diffenetiation: Inteactions of factors and corresponding receptors" Ann. Rev. Immunol.4. 167-204 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] A.Funakoshi: "High plasma cholecystokinin levels in patients with chronic pancreafifis having abdominal pain" Am. J. Gastroenterol.81. 1174-1178 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] I. Nakano: "High plasma cholecystokinin response following mgestion of test meal by patients with non-msulin dependent dtabefes mellifus" Reg. Peptides.14. 229-236 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] I. Nakano: "Diurinal profile of pancreatic exocrine secretion and plasma levels of gut hormones (cholecystokinin and pancreatic palypeptide)" Gastroenterologia Japonica. 22. 748-755 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] I. Nakano: "Gastrin-releasing peptide stimulates cholecystokinin secretion in perfused rat dusdenum" Reg. Peptides. 23. 153-159 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] T. Kosaka: "an aspect of the organizational principle of the -aminobutyric acidergic system in the central cortex" Brain Res.409. 403-408 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] T. Hayakawa: "Meal-stimulated cholecystokinin release and exocrine pancreatic secretion in dogs" Res. Exp. Med.188. 19-25 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] T. Hokfelt: "Immunohistochemical studies on cholecystokinin-immunoreactive neurons in the rat using sequence specific antisera and with special reference to the caudate nucleus and primary sensory neurons" J. Chem. Neuroanatomy. 1. 11-52 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] S. Sato: "Marked depression of brain cholecystokinin and vasoactive infestinal polypeptide levels in Eck fisfula dogs" Reg. Peptides. (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] K. Tateichi: "Establishment of highly specific radioimmunoassays for neurokinin A and neurokinin B and determination of tissue distribution of respective peptides in rat central neuous system" Reg. Peptides. (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] A. Nagashima: "Cardiovascular roles of tachykinin peptides in the nucleus fractus solitarii of rats" Brain Res.(1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] T. Hamaoka: Cellular,Molecular and Genetic Approaches to Immunodiagnosts and Immunothermpy. University of Tokyo Press, 11 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Itsuro Nakano: Regulatory Peptides. 23. 153-159 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Toshio Kosaka: Brain Research. 409. 403-408 (1987)

    • Related Report
      1988 Annual Research Report
  • [Publications] T.Hayakawa: Res.Exp.Med.188. 19-25 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Tomas Hokfelt: J.Chemical Neuroanatomy. 1. 11-52 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Shunichi Sato: Regulatory Peptides. (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] Kayoko Tateishi: Regulatory Peptides. (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] Toshiyuki Hamaoka: "I-A-restricted B-B cell interaction and its relation to autoimmurity In "B cell development" Eds.O.Witte,M.Howard,N.Klinman" Alan R.Liss,Inc.,N.Y., 13 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Toshiyuki Hamaoka: "T-T cell interaction for the augmented induction of anti-tumor protective immunity and its application to active smmunotherapy in tumor-bearing hosts. In "Ganr Monograph in Cancer" Japan scientific Societies Press,Tokyo University Park Press,Baltsmore, 10 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Toshiyuki Hamaoka: Annual Review of Immunology. 4. 167-204 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Itsuro Nakano: Regulatory Peptides. 14. 229-236 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Akihiro Funakoshi: The American Journal of Gastroenterology. 81. 1174-1179 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Shiro Ono: The Journal of Immunology. 137. 187-196 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Shiro Ono: The Journal of Immunology. 137. 1149-1156 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Yoshiya Katoh: The Journal of Immunology. 137. 2871-2877 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Toshiyuki Hamaoka: "Cellular,Molecular and Genetic Approaches to Immunoliagnosis and Immunotherapy" University of Tokyo Press, (1987)

    • Related Report
      1986 Annual Research Report
  • [Publications] Toshiyuki Hamaoka: "New Horizons in Animal Models for Autoimmune Desease" Academic Press, (1987)

    • Related Report
      1986 Annual Research Report

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Published: 1987-03-31   Modified: 2016-04-21  

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