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Pathogenesis and etiology of cutaneous NK/T lymphoproliferative disorders

Research Project

Project/Area Number 11670843
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionOkayama University (2001)
Fukushima Medical University (1999-2000)

Principal Investigator

IWATSUKI Keiji  Okayama University Graduate School of Medicine and Dentistiry. Professor, 大学院・医歯学総合研究科, 教授 (80126797)

Co-Investigator(Kenkyū-buntansha) OONO Takashi  Okayama University Hospital, Assistant, 医学部附属病院, 助手 (80203884)
FUJIMOTO Wataru  Okayama University Hospital, Lecturer, 医学部附属病院, 講師 (50165429)
大塚 幹夫  福島県立医科大学, 医学部, 講師 (70295418)
金子 史男  福島県立医科大学, 医学部, 教授 (50001920)
菊地 智  福島県立医科大学, 医学部, 助手 (50305372)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2000: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsNK / T cell lymphoma / EB virus / latent infection / mosquito hypersensitivity / hydroa vacciniforme / リンパ腫 / NK細胞 / vIL-10 / 免疫応答 / virokine / viroceptor / EBNA遺伝子 / LMP-1遺伝子 / 皮膚NK / Tリンパ腫 / ウイルスIL-10
Research Abstract

In order to elucidate the EBV gene expression, we examined 8 patients with cutaneous EBV-related NK/T-cell lymphomas, including 6 patients with NK-cell phenotypes and 2 patients with T-cell phenotypes. All samples from the patients contained EBV nuclear antigen(EBNA)-1 mRNA which was transcribed using the Q promoter, whereas both the Q promoter and another upstream promoter (Cp/Wp) were used in 3 EBV-positive cell lines, B95.8, Raji and Jiyoye. Latent membrane protein-1 (LMP-1) mRNA was detected in 7 out of 8 patients and all cell lines, whereas EBNA-2 transcripts were found only in the cell lines. The BHRF1 (viral bcl-2 homologue) and BCRF1 (viral interleukin(vlL)-10) gene transcripts were detected in 1 (NK2) and 2 patients (NK2 and 3), respectively. The patient (NK2) with UK-cell lymphoma expressing the both transcripts died of rapid progression of the illness. No LMP-1, EBNA-2 or ZEBRA antigens were detected in the skin lesions by immunostaining although they were positive in the cell line cells.
One EBV-infected NK cellI line designated NOY-1 was established from a patient with hypersensitivity to mosquito bite associated with oligoclonal proliferation of EBV-infected NK cells in the blood. Clonal expansion of the cells was observed in the cutaneous lesions following mosquito bite. The cell line cells contained 7.5 copies of EBV-DNA, and produced high levels of IFN-gamma by stimulation.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (38 results)

All Other

All Publications (38 results)

  • [Publications] Oyama N, Iwatsuki K, Homma Y, Kaneko F.: "Induction of transcription factor AP-2 by inflammatory cytokine in human keratinocytes"J Invest Dermatol. 113. 600-606 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ito M, Ohira H, Miyata M, Suzuki T, Sato Y, Kaise S, Nishimaki T, Sakuma H, Nihei Y, Iwatsuki K, Kasukawa R: "Cytophagic histiocytic panniculitis improved by combined CHOP and cyclosporin A trealment"Intern Med. 38. 296-301 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Iwatsuki K, Xu Z-G, Ohtsuka M, Kaneko F: "Cutaneous lymphoproliferative disorders associated with Epstein-Barr virus infection : A clinical overview"J Dermatol Sci. 22. 181-195 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Xu Z-G, Iwatsuki K, Ohtsuka M, Oyama N, Matsui T, Kaneko F: "Polymorphism analysis of Epstein-Barr virus isolates from palients with cutaneous NK/T-cell lymphoproliferative disorders : A possible relation to the endemic occurrence"J Med Virol. 62. 239-246 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Oyama N, Iwatsuki K, Satoh M, Akiba H, Kaneko F: "Dermal fibroblasts are one of the therapeutic tragets for topical application of 1-alpha-25-dihydroxyvitamin D3: the possible involvement of transforming growth factor-β induction"Br J Dermatol. 143. 1140-1148 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Xu X-G, Iwatsuki K, Oyama T, Ohtsuka M, Satoh M, Kikuchi S, Akiba H, Kaneko F: "The latency pattern of Epstein-Barr virus infection and viral IL-10 expression in cutaneous NK/T-cell lymphomas"Br J Cancer. 84. 920-925 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Akiba H, Motoki Y, Satoh T, Iwatsuki K, Kaneko F: "Severe NK-cell leukopenia in a patient with trichophytic granuloma"Eur J Dermatol. 11. 58-62 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nozawa Y, Tasaki K, Ohtsuka M, Iwatsuki K, Tominaga K, Abe M: "Unusual case of cutaneous T-cell lymphoma with a prominent reactive population of B lymphocytes"j Clin Exp Hematopathol. 1. 69-72 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Satoh M, Oyama N, Akiba H, Ohtsuka M, Iwatsuki K, Kaneko F: "Hypersensitivity to mosquito bites with natural-Killer cell lymphocytosis : the possible implication of Epstein-Barr virus reactivation"Eur J Dermatol. 12. 381-384 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 山田瑞穂, 古川福美, 岩月啓氏: "皮膚科学考え方学び方"金原出版株式会社. 261 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] N. Oyama, K. Iwatsuki, Y. Homma, F. Kaneko: "Induction of transcription factor AP-2 by inflammatory cytokine in human keratinocytes."J Invest Dermatol.. 113. 600-606 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M. Ito, H. Ohira, M. Miyata, T. Suzuki, Y. Sato, S. Kaise, T. Nishimaki, H. Sakuma, Y. Nihei, K. Iwatsuki, R. Kasukawa: "Cytophagic histiocytic panniculitis improved by combined CHOP and cyclosporin A treatment."Intern Med.. 38. 296-301 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K. Iwatsuki, XuZ-G, M. Ohtsuka, F. Kaneko: "Cutaneous lymphpproliferative disorders associated with Epstein-Barr virus infection : A clinical overview."J Dermatol Sci.. 22. 181-195 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] XuZ-G, K : Iwatsuki, M. Ohtsuka, N. Oyama, T. Matsui, F. Kaneko: "Polymarphism analysis of Epstein-Barr virus isolates from palients with cutaneous NK/T-cell lymphoproliferative disorders : A possible relation to the endemic occurrence of these diseases in Japan."J Med Virol.. 62. 239-246 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] N. Oyama, K. Iwatsuki, M. Satoh, H. Akiba, F. Kaneko: "Dermal fibrobrasls are one of the Unerapeulic target for topical application of 1-alpha-25-dihydraxyvitamin D3 : the possible involvement of transforming growth factor-β induction."Br J Dermatol.. 143. 1140-1148 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] XuZ-G, K. Iwatsuki, T. Oyama, M. Ohtsuka, M. Satoh, S. Kikuchi, H. Akiba, F. Kaneko: "The latency pattern of Epstein-Barr virus infection and viral IL-10 expression in cutaneous NK/T cell lymphomas."Br J Cancer.. 84. 920-925 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H. Akiba, Y. Motoki, T. Satoh, K. Iwatsuki, F. Kaneko: "Severe NK-cell leukopenia in a patient with trichophytic granuloma"Eur J Dermatol.. 11. 58-62 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. Nozawa, K. Tasaki, M. Ohtsuka, K. Iwatsuki, K. tominaga, M. Abe: "U nusual case of cutaneous T-cell lymphoma with a prominent reactive population of β lymphocytes."J Clin Exp Hematopathol.. 1. 69-72 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M. Satoh, N. Oyama, H. Akiba, M. Ohtsuka, K. Iwatsuki, F. Kaneko: "Hypersensitivity to mosquito bites with natural-killer cell lymphocytosis: the possible implication of Epstein-Barr virus reactivation."Eur J Dermatol.. 12. 381-384 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Iwatsuki Keiji 他: "The latency pattern of Epstein-Barr virus infection and viral IL-10 expression in cutaneous NK/T-cell lymphomas"British Journal of Cancer. 84・7. 920-925 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Iwatsuki Keiji 他: "Subcorneal pustular dermatosis-type IgA pemphigus arising in a patient with Heumatoid arthritis receiving bucillamine and gold sodium thiomalate"European Journal of Dermatology. 11・1. 41-44 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Iwatsuki Keiji 他: "Severe NK-cell leukopenia in a patient with trichophytic granuloma"European Journal of Dermatology. 11・1. 58-62 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Iwatsuki Keiji 他: "Unusual case of cutaneous T-cell lymphoma with a prominent reactive population of B lymphocytes"Journal of Clinical and Experimental Hematopathology. 41・1. 69-72 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Iwatsuki Keiji 他: "Treatment of recurrent auricle pseudocyst with intralesional injection of minocycline : A report of two cases"Journal of the Academy of Dermatology. 45・4. 554-556 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Iwatsuki Keiji: "Cutaneous Lymphomas"Steinkopff. 6 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 岩月啓氏 他: "皮膚科学考え方学び方"金原出版. 261 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 岩月啓氏: "悪性リンパ腫-その分類とトピックス-"日本皮膚科学会. 26 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Iwatsuki Keiji,: "Cutaneous lymphoproliferative disorders associated with Epstein Barr virus infection : a clinical overview"Journal of Dermatological Science. 22. 181-195 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Xu Zi-Gang 他: "Polymorphism analysis of Epstein-Barr virus isolates from patients with cutaneous NK/T-cell lymphoproliferative disorders"Journal of Medical Virology. 62. 239-246 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Oyama Noritaka 他: "Novel point mutations of steroid sulfatase gene in patients with x-linked ichthyosis : transfection analysis using the mutated genes"Journal of Investigative Dermatology. 114. 1195-1199 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Akiba Hitoshi 他: "Recalcitrant trichophytic granuloma associated with severe NK cell deficiency in a SLE patient treated with corticosteroid"European Journal of Dermatology. 11. 58-62 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Xu Zi-Gang 他: "The latency pattern of Epstein-Barr virus infection and viral IL-10 expression in cutaneous NK/T-cell lymphoma."British Journal of Cancer. (印刷中).

    • Related Report
      2000 Annual Research Report
  • [Publications] Iwatsuki Keiji: "Unusual Lymphomas"Gunter Burg(印刷中).

    • Related Report
      2000 Annual Research Report
  • [Publications] Iwatsuki K,他: "Cutanecus lymphoproliferative disorders associated with Epstein -Barr virus infection :a clinical overview"Journal of Dermatdogical Science. 22. 181-195 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Xu Z-G,Iwatsuki K,他: "Polynmorphism analysis of Epstein-Barr virus isolates from patients with cutaneous NK/T-cell lymphoproliferative disorders."Journal of Medical Virology. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Iwatsuki K,他: "Epstein-Barr virus-associated cutaneous lymphoproliferative disorders."Proceedings of the 11th Korea-Japan Joint Meeting of Dermatology. 135-140 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 岩月 啓氏: "Epstein-Barrウイルスと皮膚"日皮会誌. 109. 2189-2195 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 岩月 啓氏: "代表的な節外性リンパ腫の特徴と治療:皮膚"臨床医. 88. 1876-1878 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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