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Elucidation of complement cold activation and cryoglobulin formation associated with HCV infection.

Research Project

Project/Area Number 08672653
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory medicine
Research InstitutionOsaka Medical College

Principal Investigator

SHIMIZU Akira  Osaka Medical College, Department of Clinical Pathology, Professor, 医学部, 教授 (00028581)

Co-Investigator(Kenkyū-buntansha) NAKANISHI Toyofumi  Osaka Medical College, Department of Clinical Pathology, Assistant Professor, 医学部, 講師 (10247843)
NAKAGAWA Toshimasa  Osaka Medical College, Department of Clinical Pathology, Associate Professor, 医学部, 助教授 (30237226)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
Keywordscomplement CH50 / cold acfivation(CA) / HCV intection / rheumatoid factor / liver cirrhosis / non-Hodgkin's lymphoma / IL-2 receptor / cryoglobulin / cold activation (CA) / C型肝炎 / 補体寒冷活性化 / クリオグロブリン / リウマトイド因子 / コールドアクチベーション / HCV / 可溶性IL-2レセプター / 非ホジキンリンパ腫 / 質量分析 / トランスサイレチン
Research Abstract

Since the mid 1970's the in vitro activation of the classical complement pathway at a low temperature has been accepted as cold activation (CA) of the complement (1). We have proved that this activation is strongly associated with HCV infection (2). The complement may be activated by an immune complex formed at a low temperature and this may be related to cryoglobulin. The incidence of positive cases for RF among patients with HCV antibody was higher than among cases without HCV antibody (3). In addition, the incidence of RF positivity among cases showing cold activation was higher than among those with no cold activation (3). Sera of HCV antibody positive and cold activation positive showed a high incidence of elevation of RF during storage at low temperature (4) but the elevation was suppressed by addition of guinea pig serum as a complement source or in a buffer with a higher ionic strength. In the presence of HCV infection, a subset (or subsets) of B-lymphocytes proliferates and a clone (or clones) of B-cells excreting a particular type of RF may expand.
It has been reported that the incidence of HCV infection is high in a group with non-Hodgkin's lymphoma (NHL) and serum levels of soluble interleukin-2 receptors (slL-2R) are increased in NHL patients and relate to the tumor burden. It has also been reported that HCV-related NHL complicating mixed cryoglobulinaemia represents a particular patient's subset in which particular genetic and / or environmental factors can also be involved. We measured slL-2R, and HCV in 44 NHL and 5 adult T cell leukemia patients. HCV antibody and/or HCV-RNA were positive in 330% cases. Surprisingly, the levels of slL-2R in HCV positive cases were significantly low when compared to those in HCV negative cases. HCV infection may cause expansion and neoplastic transformation of a particular clone of lymphocytes.

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (38 results)

All Other

All Publications (38 results)

  • [Publications] Ikuo Koyama, et al: "Hepatitis C virus, rheumatoid factor, complement cold activation, in alcoholic patients." Bulletin of the Osaka Medical College. 44(2). 1-7 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hideto Nakajima, et al: "High incidence of cold activation of complement in patients with hepatitis C virus infection." Bulletin of the Osaka Medical College. 43(1). 15-19 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 小山郁夫, 他: "アルコール長期多飲者における抗HCV抗体と血清補体価" 臨床病理. 45(6). 585-589 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 上田一仁, 他: "HCV感染とクリオグロブリン血症" 生物試料分析. 20(4). 287-292 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 清水 章: "HCV感染と低温補体活性化の関連" 医学のあゆみ. 180(8). 535-537 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kazuhito Ueda, et al: "Rheumatoid factor in the serum of hepatitis C virus-infected patients : an increase in the titre during cold storage." Ann.Clin.Biochem.33. 438-442 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Akira Shimizu, et al: "Advances in Mass Spectrometry, Vol.14" Elsevier Science B.V., 405-418 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kazuhito Ueda, Toshimasa Nakagawa, Akira Shimizu, Hideto Nakajima, Akira Fukuda and Nakaaki Ohsawa: "Rheumatoid factor in the serum of hepatitis C virus-infected patients : an increase in the titre during cold storage." Ann.Clin.Biochem.33. 438-442 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hideto Nakajima, Akira Fukuda, Nakaaki Ohsawa, Kazuhito Ueda, Toshimasa Nakagawa and Akira Shimizu: "High incidence of cold activation of complement in patients with hepatitis C virus infection." Bulletin of the Osaka Medical College. 43(1). 15-19 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Michiyo Hatanaka, et al.: "Cellular distribution of a GPI-anchored complement regulatory protein CD59 : homodimerization on the surface of HeLa and CD59-transfected CHO cells." J.Biochem.123. 579-586 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Michiyo Hatanaka, et al.: "Expression of caveoloin-1 in human T cell leukemia cell lines.Biochem." Biophys.Res.Commun.253. 382-387 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Toyofumi Nakanishi, et al.: "A new hemoglobin variant found during HbA1c measurement : Hb Hokusetsu [beta52(D3)Asp*Gly]." Hemoglobin. 22(4). 355-371 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masahiko Kishikawa, et al.: "A new nonamyloid transthyretin variant, G101S,detected by electrospray ionization/mass spectrometry." Hum.Mutat., Mutation in Brief, #201, Online. (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Toyofumi Nakanishi, et al.: "Simple and defined method to detect the SOD-1 mutants from patients with familial amyotrophic lateral sclerosis by mass spectrometry." J.Neurosci.Methods. 81. 41-44 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ikuo Koyama and Akira Shimizu: "Hepatitis C virus, rheumatoid factor, complement cold activation, in alcoholic patients." Bulletin of the Osaka Medical College. 44(2). 1-7 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] I.Koyama,et al.: "Hepatitis C virus,rheumatoid factor,complement cold activation and cirrhosis progression,in alcoholic patients." Bulletin Osaka Medical College. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Hatanaka,et al.: "Expression of caveoloin-1 in human T cell leukemia cell lines." Biochem.Biophys.Res.Commun.253. 382-387 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Nakanishi,et al.: "A new hemoglobin variant found during HbAlc measurement : Hb Hokusetsu〔β52(D3)Asp-Gly〕." Hemoglobin. 22(4). 355-371 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Kishikawa,et al.: "A new nonamyloid transthyretin variant,G101S,detected by electrospray ionization/mass spectrometry." Hum.Mutat.,Mutation in Brief,♯201,Online. (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Nakanishi,et al.: "Simple and defined method to detect the SOD-1 mutants from patients with familial amyotrophic lateral sclerosis by mass spectrometry." J.Neurosci.Methods. 81. 41-44 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Hatanaka,et al.: "Cellular distribution of a GPI-anchored complement regulatory protein CD59 : homodimerization on the surface of HeLa and CD59-transfected CHO cells." J.Biochem.123. 579-586 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] A.Shimizu,et al.: "Advances in Mass Spectrometry,Vol.14" Elsevier Science B.V., 405-418 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kazuhito Ueda, et al: "The association between hepatitis C virus infection and in vitro activation of the complement system." Annals of Clinical Biochemistry. 30. 565-569 (1993)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kazuhito Ueda, et al: "The association of comoplement activation at a low temperature with hepatitis C virus infection in comparison with cryoqlobulin." Clinical and Experimental lmmunology. 101. 284-287 (1995)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kazuhito Ueda, et al: "Rheumatoid factor in the serum of hepatitis C virus-infected patients:an increase in the titer during cold storage." Annals of Clinical Biochemistry. 33. 438-442 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Toyofumi Nakanishi, et al: "Electrospray ionization-tandem mass spectrometry analysis of peptides derived by enzymatic digestion of oxidized globin subunits:an improved method to determine..." Journal of The American Society for Mass Spectrometry. 7. 1040-1049 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ayako Miyazaki, et al: "Post-translational modification from methionine to aspartic acid residue on a variant hemoglobin,Hb Bristol,a proof by ESl-MS-MS." Journal of Mass Spectrometry. 31. 1311-1313 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 清水 章: "HCV感染と低温補体活性化の関連" 医学のあゆみ. 180・8. 535-537 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 上田 一仁, 他: "HCV感染とクリオグロブリン血症" 生物試料分析. 20・4. 287-292 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 小山 郁夫, 他: "アルコール長期多飲者における抗HCV抗体と血清補体価" 臨床病理. 45・6. 585-589 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kazuhito Ueda, et al: "Quality Control in the Clinical Laboratory '95" Excerpta Medica,Ltd.Tokyo, 501 (1995)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kazuhito Ueda,et al: "The association between hepatitis C virus infection and in vitro activation of the complement system." Annals of Clinical Biochemistry. 30. 565-569 (1993)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kazuhito Ueda,et al: "The association of complement activation at a low temperature with hepatitis C virus infection in comparison with cryoglobulin." Clinical and Experimental Immunology. 101. 284-287 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kazuhito Ueda,et al: "Rheumatoid factor in the serum of hepatitis C virus-infected patients : an increase in the titer during cold storage." Annals of Clinical Biochemistry. 33. 438-442 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Toyofumi Nakanishi,et al: "Electrospray ionization-tandem mass spectrometry analysis of peptides derived by enzymatic digestion of oxidized globin subunits : an improved method to determine…" Journal of The American Society for Mass Spectrometry. 7. 1040-1049 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ayako Miyazaki,et al: "Post-translational modification from methionine to aspartic acid residue on a variant hemoglobin,Hb Bristol,a proof by ESI-MS-MS." Journal of Mass Spectrometry. 31. 1311-1313 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 清水章: "HCV感染と低温補体活性化の関連" 医学のあゆみ. 180(8). 535-537 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kazuhito Ueda,et al: "Quality Control in the Clinical Laboratory '95" Excerpta Medica,Ltd. Tokyo, 501 (1995)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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