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Development of the Enzyme Immunoassay Systems for the Substances Involved in the Cause of Alzheimer's Disease

Research Project

Project/Area Number 63870036
Research Category

Grant-in-Aid for Developmental Scientific Research

Allocation TypeSingle-year Grants
Research Field Neurology
Research InstitutionGifu Pharmaceutical University

Principal Investigator

HAYASHI Kyozo  Gifu Pharmaceutical University Pharmacy Professor, 薬学部, 教授 (00029935)

Co-Investigator(Kenkyū-buntansha) HIRATANI Hajime  JCR Pharmaceuticals Co., Ltd., Biotechnology Research Laboratories, Head, 研究所長
ADACHI Tetsuo  Gifu Pharmaceutical University Pharmacy, Lecturer, 薬学部, 助手 (40137063)
HIRANO Kazuyuki  Gifu Pharmaceutical University Pharmacy, Associate Professor, 薬学部, 助教授 (90057365)
FURUKAWA Shoei  National Institute of Neuroscience Department of Neuroimmunology, Head, 神経センター神経研究所, 室長 (90159129)
NISHITANI Hiroshi  Utano National Hospital, President, 院長
森 和俊  岐阜薬科大学, 薬学部, 助手 (70182194)
Project Period (FY) 1988 – 1989
Project Status Completed (Fiscal Year 1989)
Budget Amount *help
¥10,400,000 (Direct Cost: ¥10,400,000)
Fiscal Year 1989: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1988: ¥7,600,000 (Direct Cost: ¥7,600,000)
KeywordsAlzhermer's disease / cholinergic nerve cells / nerve growth factor (NGF) / superoxide dismutase (SOD) / enzyme immunoassay system (EIA) / antibody / diagnosis / astoglial cells / 老人痴呆塩 / 抗体 / 診断 / 神経成長促進因子 / 線維芽細胞成長因子 / アミロイド蛋白 / 老人痴呆 / 測定感度 / 早期診断
Research Abstract

Alzheimer's disease is a disease of unknown cause that is characterized by a progressive loss of memory and other cognitive functions, leading to a severe form of dementia and ultimately death. Neuropathologically, senile plaques and neurofibrillary tangles constitute the main features of Alzheimer's disease and it appears likely that they lead to the neuronal degeneration that characterizes the disease. One of the most consistent neuropathdlogical findings is the degeneration of magnocellular cholinergic nerve cells in the nucleus basalis of Meynert. Nerve growth factor (NGF) administration reduces the basal forebrain cholinergic neuron atrophy and the spatual memory impairment that are associated with normal aging in rats. Purpose of this research was thus to develop the highly sensitive enzyme immunoassay (EIA) systems for various neurotrophic factors involved in the cause of Alzhei mer's disease and to apply these developed EIA systems for the diagnosis of the Alzheimer's disease.
M … More ajor results are summarized as follows; (1) We developed the purification procedures for many biologically active substances, which are concerned in the cause of the disease, including NGF, epidermal growth factor (EGF), superoxide dismutase (SOD), pletelet-derived growth factor (PDGF), etc. (2) By using the highly purified these substances, we prepared their monoclonal and polyclonal antibodies against rabbits of mice. (3) By using these antibodies prepared, we developed their highly sensitive, simple, and reliable two-site enzyme immunoassay systems. The minimum amounts of these substances detected by these enzyme immunoassay systems were approximately 10-15 pg/ml when a 100 pg aliquot of the sample was used. Good reproducibilities of within- and between-assay series and excellent recovery of exogenous substances from serum were observed. (4) We demonstrated that catecholamines increased the NGF content in medium conditioned by mouse L-M fibroblast cells and mouse astroglial cells. In this research, we demonstrated that catecholamines enhanced NGF synthesis of L-M cells and astroglial cells by increasing the cellular content of NGF MRNA and the affects of catecholamines were not mediated by adrenergic receptors. Coenzyme Q and vitamin K analogues also found to stimutate the NGF synthesis of astroglial cells. Less

Report

(3 results)
  • 1989 Annual Research Report   Final Research Report Summary
  • 1988 Annual Research Report
  • Research Products

    (46 results)

All Other

All Publications (46 results)

  • [Publications] 長谷寛二,福田善弘,国立裕之,境祐二,平岩望,姫野泰雄,小林和恵,黒部真章,林恭三,井村裕夫: "肝胆道疾患におけるヒト胆汁中hEGF様免疫活性について" 日本消化器病学会雑誌. 85. 2610-2617 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 古川美子,林恭三: "神経再生" 医学のあゆみ. 145. 323-329 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 林恭三: "神経成長促進因子(1)" 化学と薬学の教室. 24-29 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 林恭三: "神経成長促進因子(2)" 化学と薬学の教室. 34-39 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 林恭三: "ヒト神経成長因子(hNGF)およびその受容体" 化学. 40. 700-701 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 林恭三,古川昭栄,古川美子: "中枢神経系における神経成長因子の生合成と機能" 日本応用酵素協会誌.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 古川美子,古川昭栄,林恭三: "神経成長因子" 現代化学.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 古川美子,古川昭栄,林恭三: "精神疾患の生物学的研究(稲永和豊編)" 医学書院, 473 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 林恭三: "脳の神経栄養因子と先天性代謝異常(永津俊治ら編)" 平凡社, 261 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 林恭三: "新生化学実験講座 第11巻 神経生化学(日本生化学会編)"

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Yasuhiro Nakata, Hiroshi Nomoto, Ikuma Takahashi, Yoshiko Furukawa, Shoei Furukawa, and Kyozo Hayashi: "Comparison of the biochemical and immnological properties of nerve growth factors from various animals." J.Clin.Biochem.Nutr., 4, 73-86 (1988).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Ichizo Shinoda, Rie Takeuchi, Masayuki Kurobe, Shoei Furukawa, and Kyozo Hayashi: "Molecular nature of beta-nerve growth factor (NGF)-like immunoreactive substance(s) in mouse plasma." J.Clin.Biochem.Nutr., 5, 135-144 (1988).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Ichizo Shinoda, Noriaki Tokida, Masayuki Kurobe, Shoei Furukawa, and Kyozo Hayashi: "Identification of epidermal growth factor in mouse abdominal effusion." Biochem.Int., 16, 53-58 (1988).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Daisuke Kohda, Chie Kodama, Ryoichi Kase, Hiroshi Nomoto, Kyozo Hayashi, and Fuyuhiko Inagami: "A Comparative ^1H NMR study of mouse alpha(1-53) and beta(2-53) epidermal growth factors." Biochem.Int., 16, 647-654 (1988).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Ichizo Shinoda, Noriaki Tokida, Masayuki Kurobe, Shoei Furukawa, and Kyozo Hayashi: "Demonstration of a considerable amount of mouse epidermal growth factor in aqueous humor." Biochem.Int., 16, 243-248 (1988).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Yukihiro Takemoto, Kouji Tsukitani, Hiroyuki Oosumi, Masahiko Mori, Kazumitu Kobayashi, Masayuki Kurobe, and Kyozo Hayashi: "Immunohistochemical localization of human epidermal growth factor/gamma-urogastrone in submandibular glands and in their obstructive lesions." Acta Histochem.Cytochem., 21, 291-300 (1988).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kazutoshi Mori, Ritsuko Fujii, Noriyoshi Kida, Mitsuhiro Ohta, and Kyozo Hayashi: "Identification of a polypeptide secreted by human breast cancer cells (MCF-7) as the human estrogen-responsive gene (pS2) product." Biochem.Biophys.Res.Commun., 155, 366-372 (1988).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kazutoshi Mori, Tomoaki Yoshimura, Shigeru Ibaragi, Masayuki Kurobe, Shoei Furukawa, Kayoko Kurosawa, Masakazu Katoh, Shigeaki Tanaka, and Kyozo Hayashi: "Abberant synthesis and secretion of a human epidermal growth factor-like immunoreactive factor by human breast cancer cells." J.Clin.Biochem.Nutr., 4, 49-64 (1988).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Noriaki Tokida, Masayuki Kurobe, Shoei Furukawa, and Kyozo Hayashi: "Epidermal growth factor-like immunoreactive substance(s) in human platelets." J.Clin.Biochem.Nutr., 5, 51-57 (1988).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Noriaki Tokida, Ichizo Shinoda, Masayuki Kurobe, Yukihiro Tatemoto, Masahiko Mori, and Kyozo Hayashi: "Effect of scialoadenectomy on the level of circulating mouse epidermal growth factor (mEGF) and on the reproductive function in male mice." J.Clin.Biochem.Nutr., 5, 221-229 (1988).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Daisuke Kohda, Nobuhiro Go, Kyozo Hayashi, and Fuyuhiko Inagami: "Tertiary structure of mouse epidermal growth factor determined by two-dimensional ^1H NMR." J.Biochem., 103(5), 741-743 (1988).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Masayuki Kurobe, Masao Kohno, Nobuo Yoshida, and Kyozo Hayashi: "Development of monoclonal antibody-based enzyme immunoassay for human pancreatic secretory trypsin inhibitor (PSTI) suitable for clinical tests." J.Clin.Biochem.Nutr., 5(2), 173-181 (1988).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Masayuki Kurobe, Masao Kono, Nobuo Yoshida, and Kyozo Hayashi: "A sensitive two-site enzyme immunoassay for human pancreatic secretary trypsin inhibitor (PSTI) using monoclonal antibody." Clin.Chim.Acta, 178, 205-214 (1988).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Tetsuo Adachi, Yoshiko Usami, Tatsuo Kishi, Kazuyuki Hirano, and Kyozo Hayashi: "An enzyme immunoassay for cuprozinc superoxide dismutase using monoclonal antibody." J.Immunol.Methods, 109(1), 93-101 (1988).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Yoshiko Furukawa, Noboru Tomioka, Wakao Sato, Eijiro Satoyoshi, Kyozo Hayashi, and Shoei Furukawa: "Catecholamines increase nerve growth factor mRNA content in both mouse astroglial cells and fibroblast cells." FEBS Lett., 247(2), 463-467 (1989).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Junichi Koga, Satoshi Nishimuro, Hiroyuki Shirono, Chitose Ito, Yoshiki Yamamoto, Akio Matsuo, Masayuki Kurobe, Kyozo Hayashi: "Monoclonal antibodies specific for high molecular weight form of human epidermal growth factor." Biochem.Int., 19(2), 445-452 (1989).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Rie Takeuchi, Katuhito Murase, Yoshiko Furukawa, Shoei Furukawa and Kyozo Hayashi: "Stimulation of nerve growth factor synthesis/secretion by 1.4-benzoquinone and its derivatives in cultured mouse astroglial cells." FEBS Lett.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Toshio Oda, Mitsuhiro Ohta, Seiji Inoue, Kiyoshi Ikeda, Shoei Furukawa, and Kyozo Hayashi: "Amino Acid sequence of nerve growth factor purified from the venom of the formosan cobra Naja naja atra." Biochem.Int.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Takekazu Ohi, Shoei Furukawa, Kyozo Hayashi, and Shigeru Matsukura: "Ganglioside stimulation of nerve growth factor synthesis in cultured rat Schwann cells." Biochem.Int.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kyozo Hayashi, Masashi Itoh, Kazutoshi Mori, Noriyoshi Kida, and Masayuki Kurobe: "Improved procedure for purification of human plateletderived growth factor." J.Clin.Biochem.Nutr.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Takashi Chijiwa, Atsushi Mishima, Masatoshi Hagiwara, Mamoru Sano, Kyozo Hayashi, Tsutomu Inoue, Kenji Naito, Tadashi Toshioka, and Hiroyoshi Hidaka: "Inhibition of forskolin-induced neurite outgrowth and protein phosphorylation by newly synthesized selective inhibitors of cyclic AMP dependent protein kinase, H-89, in PC12D pheochromocytoma cells."

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Yoshiko Furukawa, Nobuyuki Fukazawa, Yukio Miyama, Kyozo Hayashi, and Shoei Furukawa: "Stimulatory effect of 4-alkylcatechols and their diacetylated derivatives on the synthesis of nerve growth factor." Biochem.Pharmacol.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 林恭三: "神経成長促進因子(1)" 化学と薬学の教室. 24-29 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 林恭三: "神経成長促進因子(2)" 化学と薬学の教室. 34-39 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 林恭三: "ヒト神経成長因子(hNGF)およびその受容体" 化学. 40. 700-701 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 林恭三,古川昭栄,古川美子: "中枢神経系における神経成長因子の生合成の機能" 日本応用酵素協会誌.

    • Related Report
      1989 Annual Research Report
  • [Publications] 古川美子,古川昭栄,林恭三: "精神疾患の生物学的研究(稲永和豊編)" 医学書院, 473 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 林恭三: "脳の神経栄養因子と先天性代謝異常(永津俊治ら編)" 平凡社, 261 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] D.Kohda;N.Go;K.Hayashi;F.Inagaki: Journal of Biochemistry. 103. 741-743 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] I.Shinoda;R.Takeuchi;M.Kurobe;S.Furukawa;K.Hayashi: Journal of Clinical Biochemistry and Nutrition. 5. 135-144 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] N.Tokida;M.Kurobe;S.Furukawa;K.Hayashi: Journal of Clinical Biochemistry and Nutrition. 5. 51-57 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Y.Nakata;H.Nomoto;I.Takahashi;Y.Furukawa;S.Furukawa;K.Hayashi: Journal of Clinical Biochemistry and Nutrition. 4. 73-86 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] I.Shinoda;N.Tokida;M.Kurobe;S.Furukawa;K.Hayashi: Biochemistry International. 17. 243-248 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] D.Kohda;C.Kodama;R.Kase;H.Nomoto;K.Hayashi;F.Inagaki: Biochemistry International. 16. 647-654 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 林恭三: "ニューロサイエンスー神経成長促進因子とそのレセブター" 医歯薬出版, 323-329 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 古川美子、古川昭栄、林恭三: "精神疾患の生物学的研究ー神経成長因子の生化学" 医学書院, 327-351 (1988)

    • Related Report
      1988 Annual Research Report

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Published: 1988-04-01   Modified: 2018-02-02  

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