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1992 Fiscal Year Final Research Report Summary

THE DEVELOPMENT OF A NEW CLINICAL PARAMETER FOR DIAGNOSIS OF PERIODONTAL DISEASES AND THE NEW DRUG DESIGN

Research Project

Project/Area Number 02557072
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Functional basic dentistry
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

YAMAMOTO Kenji  KYUSHU UNIV. DENTAL PHARMACOLOGY PROFESSOR, 歯学部, 教授 (40091326)

Co-Investigator(Kenkyū-buntansha) NAKANISHI Hiroshi  KYUSHU UNIV. PHARMACOLOGY INSTRUCTOR, 歯学部, 助手 (20155774)
AOKI Yosuke  THE INSTITUTE OF PUBLIC HEALTH BIOCHEMISTRY AND NUTRITION DIRECTOR, 栄養生花学部, 部長 (80049030)
IKAI Atsushi  TOKYO INSTITUTE OF TECHNOLOGY BIOLOGICAL SCIENCES PROFESSOR, 理学部, 教授 (50011713)
KATO Ihachi  NAGASAKI UNIV. PERIODONTOLOGY, PROFESSOR, 歯学部, 教授 (30005087)
Project Period (FY) 1990 – 1992
KeywordsPERIODONTITIS / GINGIVITIS / CATHEPSIN B / CATHEPSIN H / CATHEPSIN L / CATHEPSIN G / MEDULLASIN / GINGIVAL CREVICULAR FLUID
Research Abstract

Although a number of clinical parameters are now used for diagnosis of periodontal diseases, there exists the practical difficulty as to which parameters should be used to assess the rate of progress of the disease, the present disease activity and the need for treatment. is generally accepted that analysis of gingival crevicular fluid (GCF) can provide information of association between specific metabolic change and disease status and that a variety of proteolytic enzymes in GCF play an important role in pathogenesis of periodontal disease. The present work was designed to clarify the roles of lysosomal proteinases including cathepsins B, H, L, D, G, and medullasin in pathological destructive process of periodontal tissues and to put the knowledge of the GCF levels of these enzymes to practical use for diagnosis of periodontal diseases. For this purpose, we prepared the specific antibodies to each enzyme purified from human sources and determined the levels of enzymes in GCF from chronic adult periodontitis patients and experimental gingivitis subjects by enzyme immunoassay. The results indicate that the cysteine proteinases cathepsins B, H, and L are selectively released into gingival crevices at a relatively mild stage of periodontitis and their levels in GCF are positively correlated with the severity of the disease. However, no significant amounts of these enzymes are found in GCF from experimental gingivitis subjects. The serine proteinases medullasin and cathepsin G in GCF are also shown to increase with the severity of periodontitis and to decrease by periodontal treatment. Interestingly, large amounts of medullasin was detected in GCF from experimental gingivitis subjects. The results indicate that these lysosomal proteinases participate in the progression of periodontitis and that the dynamics of these enzymes in GCF is useul for determining the present disease activity and the disease progression.

  • Research Products

    (44 results)

All Other

All Publications (44 results)

  • [Publications] Tetsuya GOTO: "Immunocytochemical localization of cathepsin D in the rat osteoclast." Histochemistry. 97. 13-18 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hideaki SAKAI: "Synthesis and intracellular distribution of cathepsins E and D in differentiating murine Friend erythroleukemia cells." Arch.Biochem.Biophys.294. 412-417 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hideaki SAKAI: "Distribution of two distinct intracellular aspartic proteinases,cathepsins D and E,in rat oral tissues as demonstrated by discriminative antibodies." Jpn.J.Oral Biol.34. 317-324 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kazushi KUNIMATSU: "Possible functions of human neutrophil serine proteinases,medullasin and cathepsin G, in periodontal tissue breakdown." J.Periodont. Res. 28. (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tetsuya GOTO: "Immunohistochemical localization of cathepsins B, D and L in the rat osteoclast." Histochemistry. (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tamotsu KIYOSHIMA: "Immunohistochemical localization of cathepsins B and D in the synovial lining cells of the normal rat temporomandibular joint." Arch.Oral Biol.38. (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takayuki TSUKUBA: "Isolation and characterization of recombinant human cathepsin E expressed in Chinese hamster ovary cells." J.Biol. Chem.268. (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mitsue TAKEDA-EZAKI: "Isolation and biochemical characterization of procathepsin E from human erythrocyte membranes." Arch.Biochem. Biophys.(1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kenji HARA: "Purification of aspartic proteinases from rat epidermis." J.Invest. Dermatol.100. (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiroshi NAKANISHI: "Transient forebrain ischemia induces increased expression and specific localization of cathepsins E and D in rat hippocampus" Exp.Neurol.(1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kenji YAMAMOTO: "Biological Functions of Proteases and Inhibitors" Japan Scientific Societies Press,Tokyo, (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 山本 健二: "蛋白分解酵素" 学会出版センター, (1993)

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      「研究成果報告書概要(和文)」より
  • [Publications] 山本 健二: "カテプシンEの生合成と活性制御(ミニレビュー)" 日本学化学会, (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Kunimatsu, K.Yamamoto, E.Ichimaru, Y.Kato, and I.Kato: "Cathepsins B,H and L activities in gingival crevicular fluid from chronic adult periodontitis patients and experimental gingivitis subjects." J.Periodont.Res.25,No.2. 69-73 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Kunimatsu, E.Ichimaru, I.Kato, Y.Kato, Y.Sonoda, Y.Aoki and K.Yamamoto: "Granulocyte medullasin levels in gingival crevicular fluid from chronic adult periodontitis patients and experimental gingivitis subjects." J.Periodont.Res.25,No.6. 352-357 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Okano, Y.Aoki, H.Shimizu, and M.Naruto: "Functional expression of human elastase (HLE)/medullasin in eucaryotic cells." Biochem.Biophys.Res.Commun.167. 1326-1332 (1990)

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      「研究成果報告書概要(欧文)」より
  • [Publications] T.Saku, H.Sakai, N.Tsuda, H.Okabe, Y.Kato, and K.Yamamoto: "Cathepsins D and E in normal, metaplastic, dysplastic, and carcinomatous gastric tissue : an immunohistochemical study." Gut. 31. 1250-1255 (1990)

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      「研究成果報告書概要(欧文)」より
  • [Publications] H.Nakanishi, K.Ukai, T.Nakagawa, S.Watanabe, O.Kamata, and K.Yamamoto: "Enhancement of NMDA receptor-mediated synaptic potential evoked in rat medial-amygdala neuron following olfactory bulbectomy." Brain Res.532,No.1. 69-75 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] E.Ichimaru, H.Sakai, T.Saku, K.Kunimatsu, Y.Kato, I.Kato, and K.Yamamoto: "Characterization of hemoglobin-hydrolyzing acidic proteinases in human and rat neutrophils." J.Biochem.108,No.6. 1009-1015 (1990)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Aoki, H.Kimura, T.Hase, T.Shimazu, and M.Naruto: "Low molecular weight peptide inhibitors of medullasin : purification and structure." J.Enzyme Inhibition. 3. 279-287 (1990)

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      「研究成果報告書概要(欧文)」より
  • [Publications] T.Saku, H.Sakai, Y.Shibata, Y.Kato, and K.Yamamoto: "An immunocytochemical study on distinct intracellular localization of cathepsin E and cathepsin D in human gastric cells and various rat cells." J.Biochem.110,No.6. 956-964 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Nakanishi, O.Kamata, K.Ukai, and K.Yamamoto: "Inhibitory effects of NMDA receptor antagonists on hypoxia-induced seizures in dietary Mg^<2+>-deficient mice." Eur.J.Biochem.204,No.1. 29-34 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Nakanishi, and K.Yamamoto: "NMDA receptor mediated neurotransmission in the basal ganglia and limbic system of the rat. NMDA Receptor Related Agents;" Biochemistry,Pharmacology and Behavior (T.Kameyama, T.Nabeshima, and E.F.Domino, eds.). NPP Books,Ann Arbor. 141-151 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Sakai, T.Saku, Y.Kato, and K.Yamamoto: "Immunohistochemical and immuno-cytochemical localization of cathepsin E compared with cathepsin D." Structure and Function of the Aspartic Proteinases (B.M.Dunn,ed.). Plenum Pless,New York. 361-364 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Yamamoto, H.Sakai, E.Ueno, and Y.Kato: "Biological significance and activity control of cathepsin E compared with cathepsin D." Structure and Function of the Aspartic Proteinases (B.M.Dunn,ed.). Plenum Press,New York. 297-306 (1991)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Aoki, T.Hase, and A.Ikai: "Interaction of a_2-macroglobulin and medullasin (a serine protease in bone marrow cells)." Biol.Chem.Hoppe-Seyler 372. 129 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Aoki, and T.Hase: "The primary structure and elastinolytic activity of medullasin" (a serine Biochem.Biophys.Res.Commun.protease of bone marrow).178. 501-506 (1991)

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      「研究成果報告書概要(欧文)」より
  • [Publications] T.Shindo, S.Koizumi, Y.Kataoka, S.Watanabe, K.Yamamoto, and H.Nakanishi: "Inhibitory effect of NMDA on dopaminergic transmission in a slice preparation of rat globus pallidus." Jpn.J.Pharmacol. 58,No.1. 79-82 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Nakanishi, K.Yamamoto, and H.Kita: "Lateral hypothalamus and local stimulation induced postsynaptic responses in zona incerta neurons in an in vitro slice preparation of the rat." Brain Res.583. 287-291 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Goto, T.Tsukuba, N.Ayasaka, K.Yamamoto, and T.Tanaka: "Immunocytochemical localization of cathepsin D in the rat osteoclast." Histochemistry. 97,No.1. 13-18 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Sakai, Y.Kato, and K.Yamamoto: "Synthesis and intracellular distribution of cathepsins E and D in differentiating murine Friend erythroleukemia cells." Arch.Biochem.Biophys.294,No.2. 412-417 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Sakai, T.Saku, Y.Kato, and K.Yamamoto: "Distribution of two distinct intracellular aspartic proteinases, cathepsins D and E, in rat oral tissues as demonstrated by discriminative antibodies." Jpn.J.Oral Biol.34,No.3. 317-324 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Aoki, T.Hase, K.Oshimi, and K.Suzuki: "Induction of activated killer cells from human lymphocytes by medullasin (a serine protease in bone marrow cells)." Immunology. 75. 481-487 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Aoki: "Medullasin, a serine protease, as a new target for anti-inflammatory drug design." Drug News & Perspectives. 5,No.9. 534-541 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Osada, K.Ookata, S.B.P.Athauda,K., K.Takahashi, and A.Ikai: "The active site titration of proteinases by using a_2-macroglobulin and high-performance liquid chromatography." Anal.Biochem.207,No.1. 76-79 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Arakawa, K.Umemura, and A.Ikai: "Protein images obtained by STM, AFM and TEM." Nature. 358. 171-173 (1992)

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      「研究成果報告書概要(欧文)」より
  • [Publications] T.Tsukuba, H.Hori, T.Azuma, T.Takahashi, R.T.Taggart, A.Akamine, M.Ezaki, H.Nakanishi, H.Sakai, and K.Yamamoto: "Isolation and characterization of recombinant human cathepsin E expressed in Chinese hamster ovary cells." J.Biol.Chem.268,No.9. (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Kiyoshima, T.Tsukuba, M.A.Kido, H.Tashiro, K.Yamamoto, and T.Tanaka: "Immunohistochemical localization of cathepsins B and D in the synovial cells of the normal rat temporomandibular joint." Arch.Oral Biol.38. (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Goto, T.Tsukuba, T.Kiyoshima, Y.Nishimura, K.Kato, K.Yamamoto, and T.Tanaka: "Immunohistochemical localization of cathepsins B,D and L in the rat osteoclast." Histochemistry. 99. (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Takeda-Ezaki, and K.Yamamoto: "Isolation and biochemical characterization of pro-cathepsin E from human erythrocyte membranes." Arch.Biochem.Biophys.(1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Hara, K.Fukuyama, H.Sakai, K.Yamamoto, and W.L.Epstein: "Purification of aspartic proteinases from rat epidermis." J.Invest.Dermatol.100. (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Nakanishi, T.Tsukuba, T.Kondo, T.Tanaka, and K.Yamamoto: "Transient forebrain ischemia induces increased expression and specific localization of cathepsins E and D in rat hippocampus and neostriatum." Exp.Neurol.(1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Kunimatsu, N.Mine, I.Kato, T.Hase, Y.Aoki, and K.Yamamoto: "Possible functions of human neutrophil serine proteinses, medullasin and cathepsin G, in periodontal tissue breakdown." J.Periodont.Res.28. (1933)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Yamamoto, H.Sakai, M.Ezaki, and Y.Kato: "Biosynthesis, processing and localization of cathepsin E." Biological Functions of Proteases and Inhibitors (N.Katunuma, K.Suzuki, J.Travis, and H.Fritz, eds.) Japan Scientific Societies Press, Tokyo. (1993)

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      「研究成果報告書概要(欧文)」より

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Published: 1994-03-24  

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