Project/Area Number |
61870026
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Research Category |
Grant-in-Aid for Developmental Scientific Research
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Allocation Type | Single-year Grants |
Research Field |
Immunology
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Research Institution | Division 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)
|
Keywords | Site-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
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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
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