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1998 Fiscal Year Final Research Report Summary

Study on Reguratory Substance of ANCA Related-Nephritis

Research Project

Project/Area Number 08671313
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

I-OKAWARA Akiko  National Institute of Infectious Diseases, Bioactive Molecules, Research worker, 生物活性物質部, 研究員 (30260277)

Co-Investigator(Kenkyū-buntansha) ARIMURA Yoshihiro  The first Dept.of Internal Medicine, Kyorin University School of Medicine, Lectu, 医学部, 講師 (40222765)
YAMAKAWA Yoshio  National Institute of Infectious Diseases, Biochemistry and Cell Biology, Head o, 細胞化学部, 室長 (50100102)
SUZUKI Kazuo  National Institute of Infectious Diseases, Bioactive Molecules, Head of Laborato, 生物活性物質部, 室長 (20192130)
Project Period (FY) 1996 – 1998
KeywordsANCA / Autoimmune diseases / MPO / Aseanostatin
Research Abstract

1) The selection of model animals
Usually, MPO activity nor MPO-ANCA are detected in normal blood. However, both of them are detected at high level in rat plasma derived from anti-glomerulo basement membrane (GBM) antibody-induced-nephritis and adjuvant-induced-arthritis. GBM-induced-nephritis rat showed high protein urine, joint swelling was detected in paw injected adjuvant.
2) The evaluation of aseanostatin, i-14 : 0 on improvement of adjuvant-induced-arthritis
Oral administration (20 mg/kg), or intraperitoneal administration (30 mg/kg) was continued to adjuvant-induced-arthritis rat for 18 days. MPO-ANCA level decreased near the normal level. On the other hand, the degree of joint swelling, change of weight of thymus and spleen, biochemical change of serum were hardly affected by administration of aseanostatin. Intraperitoneal administration of aseanostatin appeared effective on improvement of inhibition of body weight decrease, leukocyte increase, paw swelling, bone destruction, howe … More ver, similar result was detected in the group injected only solvent for 18 days. This phenomenon could be explained by the reason that injection of intraperitoneal induce inflammation at the site, then anti-inflammatory effect may produce. As a result, treatment effect of aseanostatin may be weak. Since measurement of aseanostatin as a fatty acid could not establish, concentration of aseanostatin could not clear exactly, it may be low level in serum. Moreover, effect of aseanostatin on improvement of GBM-induced-nephritis will investigate.
Summary
1) MPO-ANCA titer increased in serum derived from adjuvant-induced-arthritis rat.
2) Administration of aseanostatin decreased MPO-ANCA titer near the normal level, however it's medical effect was not enough.
3) Since MPO-ANCA is one of indicator of neutrophil activation, decrease of MPO-ANCA titer could reflect reduction of risk of arthritis. However, condition of arthrits was hardly improvement.
4) Epitope analysis would need to clarify the relationship between induction of MPO-ANCA and arthritis. Less

  • Research Products

    (36 results)

All Other

All Publications (36 results)

  • [Publications] Y.Aratani et al.: "Severe impairment in host defense against Candida albicans in mice deficient in myeloperoxidase." Infection and Immunity,in press.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Nunoi et al.: "Prevalence of inherited myeloperoxidase deficiency in Japan" Molecular Medicine Today in press.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Uchida et al.: "Expression pattern of newly recognized protein,LECT2 in hepatocellular carcinoma and its premalignant lesion." Pathology International. 49. 147-151 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] A.Kojima et al.: "Correlation between disease stage and activity of elastase of PMN origin in the serum from IgA nephropachy patients." J.Clin.Biochem.Nutr.24. 157-165 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Nagai et al.: "Systemic expression of a newly recognized protein LECT2,in human body." Pathology International. 48. 882-886 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Yamagoe et al.: "The Mouse LECT2 gene: Cloning of a cDNA,Structural Characterization and Chromosomal Localization." Gene. 216. 171-178 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamagoe,S et al.: "Molecular cloning.structural characterization and chromosomal mapping of Human LECT2 gene." Genomics. 48. 324-329 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Asagoe,K.et al.: "Down-regulation of CXCR2 expression on human polymorphonuclear leukocytes by TNF-α." J.Immunol.160. 4518-4525 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ito,M.et al.: "Preparation of recombinant six-histidine tagged human LECT2 in E.coli." Cytotechnology. 25. 235-238 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamagoe,S.et al.: "Molecular cloning of human and bovine LECT2s having a neutrophil chemotactic activity and its specific expression in the liver." Biochim.Biophys.Acta. 1396. 105-113 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kazuo Tomizawa et al.: "A Panel Set for E pitone Analysis of Myeloperoxidase (MPO)-Specific Anti-Neutrophil Cytoplasmic Antibody MPO-ANCA Using Recombinant Hexamer Hisdine-tagged MPO Deletion Mutants." J.of Clin.Immun.18(2). 141-151 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Isao Otani et al.: "Myelperoxidase Fragments Reacting with Serum from a Patient with Myeloperoxidase-Anti-Neutrophil Cytoplasmic Antibody-Positive Glomerulo-nephritis." J.Infect.Chemother.3. 164-169 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shinobu Minoshima et al.: "Increased Release of Myeloperoxidase in Vitro from Neutrophils of Patients with Myeloperoxidase-Specific Anti-Neutrophil Cytoplasmic Antibody (MPO-ANCA) Related Glomerulonephritis." Nephrology. 3. 527-534 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamagoe et al.: "Expression of a neutrophil chemotatic protein LECT2 in human hepatocytes revealed by immunochemical studies using polyclonal and monoclonal antibodies to a recombinant LECT2." Biochem.Biophys.Res.Commun.237. 116-120 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawada,M.et al.: "Induction of p27kip1 degradation and anchorage independence by Ras through the MAP kinase signaling pathway." Oncogene. 15. 629-637 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamagoe,S.et al.: "LECT2: Purification of novel human neutrophil chemotatic protein." Immunol.Lett.52. 9-13 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mohamed,A.et al.: "Production and characterization of polyclonal anti-canine interleukin-8 antibodies." J.Vet.Med.Sci.58. 219-224 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akiko Ishida-Okawara et al.: "Modulation of Degranulation and Superoxide Generation in Human Neutrophils by Unsaturated Fatty Acids of Odd Carbon Numbers." Biochimica et Biophysica Acta. 1314. 239-246 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Aratani et al.: "Severe impairment in host defense against Candida albicans in mice deficient in myeloperoxidase." Infection and Immunitiy. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Nunoi et al.: "Prevalence of inherited myeloperoxidase deficiency in Japan." Molecular Medicine Today. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Uchida et al.: "Expression pattern of newly recognized protein, LECT2 in hepatocellular carcinoma and its premalignant lesion." Pathology International. 49. 147-151 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A.Kojima et al.: "Correlation between disease stage and activity of elastase of PMN origin in the serum from IgA nephropachy patients." J.Clin.Biochem.Nutr.24. 157-165 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Nagai et al.: "Systemic expression of a newly recognized protein, LECT2, in human body." Pathology International. 48. 882-886 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Yamagoe et al.: "The Mouse LECT2 Gene : Cloningof a cDNA,Structural Characterization and Chromosomal Localization." Gene. 216. 171-178 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamagoe, S et al.: "Molecular cloning, structural characterization and chromosomal mapping of Human LECT2 gene." Genomics. 48. 324-329 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Asagoe, K.et al.: "Down-regulation of CXCR2 expression on human polymorphonuclear leukocytes by TNF-alpha" J.Immunol.160. 4518-4525 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ito, M.et al.: "Preparation of recombinant six-histidine tagged human LECT2 in E.coli." Cytotechnology. 25. 235-238 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamagoe, S.et al.: "Molecular cloning of human and bovine LECT2s having a neutrophil chemotatic activity and its specific expression in the liver." Biochim.Biophys.Acta. 1396. 105-113 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kazuo Tomizawa et al.: "A Panel Set for E pitope Analysis of Myeloperoxidase (MPO)-Specific Anti-Neutrophil Cytoplasmic Antibody MPO-ANCA Using Recombinant Hexamer Histidine-tagged MPO Deletion Mutants." J.of Clin.Immun.18(2). 141-151 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Isao Otani et al.: "Myeloperoxidase Fragments Reacting with Serum from a Patient with Myeloperoxidase-Anti-Neutrophil Cytoplasmic Antibody-Positive Glomerulo-nephritis." J.Infect.Chemother.3. 164-169 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shinobu Minoshima et al.: "Increased Release of Myeloperoxidase in Vitro from Neutrophils of Patients with Myeloperoxidase-Specific Anti-Neutrophil Cytoplasmic Antibody (MPO-ANCA) Related Glomerulonephritis." Nephrology. 3. 527-534 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamagoe et al.: "Expression of a neutrophil chemotactic protein LECT2 in human hepatocytes revealed by immunochemical studies using polyclonal and monoclonal antibodies to a recombinant LECT2." Biochem.Biophys.Res.Commun.237. 116-120 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawada, M.et al.: "Induction of p27kip1 degradation and anchorage independence by Ras through the MAP kinase signaling pathway." Oncogene. 15. 629-637 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamagoe, S.et al.: "Purification and primary amino acid sequence of a novel neutrophil chemotactic factor LECT2" Immunol.Lett.52. 9-13 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mohamed, A.et al.: "Production and characterization of polyclonal anti-canine interleukin-8 antibodies." J.Vet.Med.Sci. 58. 219-224 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akiko Ishida-Okawara et al.: "Modulation of Degranulation and Superoxide Generation in Human Neutrophils by Unsaturated Fatty Acids of Odd Carbon Numbers." Biochimica et Biophysica Acta. 1314. 239-246 (1996)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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