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2013 Fiscal Year Research-status Report

プロテアソーム活性低下に起因する自己炎症病態の解明

Research Project

Project/Area Number 25461478
Research Category

Grant-in-Aid for Scientific Research (C)

Research InstitutionNagasaki University

Principal Investigator

有馬 和彦  長崎大学, 医歯(薬)学総合研究科, 講師 (30423635)

Co-Investigator(Kenkyū-buntansha) 井田 弘明  久留米大学, 医学部, 教授 (60363496)
Project Period (FY) 2013-04-01 – 2016-03-31
Keywordsシグナル伝達
Research Abstract

網羅的細胞内シグナル伝達物質の転写量比較 健常細胞を複数の異なる濃度のプロテアソーム阻害剤(MG-132, Lactacystin, Epoxomicin, MG-115, MG-262)存在下に培養を行った。各薬剤の異なる濃度でプロテアソーム活性を測定し、培養可能な細胞死を起こさない薬剤濃度を得た。中條―西村症候群患者由来細胞と健常細胞を10%子牛血清存在下で培養し、血清刺激を起点として培養液交換後の時間経過で遺伝子転写産物試料を採取した。
遺伝子転写産物はSYBR Greenを利用した定量的リアルタイムPCRで行い、複数の内性対照遺伝子転写産物から算出されるBestKeeper指数で補正を行い解析した。82種類の網羅的遺伝子点車両の比較を行い、19種類の遺伝子転写産物の有意な増加と2種類の遺伝子転写産物の有意な低下が認められた。プロテアソームの活性低下が様々な影響を与えていることが示唆された。
新規自己炎症病態の展開的検索 既にその特異的かつ著明な濃度上昇を来すIP-10に加えて52種類のシグナル伝達物質に関連するサイトカイン・ケモカインの血清中濃度測定を行う。マルチサスペンジョンアレイを用いた血清中タンパク質測定系の基礎検討行った。血清中の測定対象物質は定量可能な測定範囲内にあり、測定方法は次期段階の目的を達成することが可能であることを確認した。この段階を通じて、プロテアソーム活性低下に起因する自己炎症病態が他の炎症性疾患に存在する可能性を検証する。

Current Status of Research Progress
Current Status of Research Progress

3: Progress in research has been slightly delayed.

Reason

段階四の新規自己炎症病態の展開的検索の準備段階もあり、進行が遅れている。

Strategy for Future Research Activity

今後の研究の推進は予定通りに行う。
段階2.細胞内シグナル伝達物質の質的検討
段階3.細胞内シグナル伝達物質群の時間経過的検討
段階4.新規自己炎症病態の展開的検索

Expenditure Plans for the Next FY Research Funding

計画はやや遅れているが、次段階の基礎検討を含め進行している。おおむね計画は遂行されている。
次年度の基礎検討は終了しており、速やかな計画遂行が期待される。

  • Research Products

    (14 results)

All 2014 2013 Other

All Journal Article (9 results) (of which Peer Reviewed: 9 results) Presentation (4 results) Remarks (1 results)

  • [Journal Article] Associations between renal impairment and anemia in older, rural Japanese men: the Nagasaki Island study.2014

    • Author(s)
      Shimizu Y, Sato S, Koyamatsu J, Yamanashi H, Nagayoshi M, Kadota K, Tamai M, Arima K, Yamasaki H, Kusano Y, Takamura N, Maeda T.
    • Journal Title

      J Physiol Anthropol.

      Volume: 33 Pages: 7

    • Peer Reviewed
  • [Journal Article] Association between the hemoglobin levels and hypertension in relation to the BMI status in a rural Japanese population: the Nagasaki Islands Study2014

    • Author(s)
      Shimizu Y, Nakazato M, Sekita T, Kadota K, Arima K, Yamasaki H, Takamura N, Aoyagi K, Maeda T.
    • Journal Title

      Intern Med

      Volume: 53 Pages: 435-440

    • Peer Reviewed
  • [Journal Article] Subclinical carotid atherosclerosis and hyperuricemia in relation to renal impairment in a rural Japanese population: the Nagasaki Islands study.2014

    • Author(s)
      Shimizu Y, Sato S, Koyamatsu J, Yamanashi H, Tamai M, Kadota K, Arima K, Yamasaki H, Takamura N, Aoyagi K, Maeda T.
    • Journal Title

      Atherosclerosis

      Volume: 233 Pages: 525-529

    • DOI

      10.1016/j.atherosclerosis.2014.01.033.

    • Peer Reviewed
  • [Journal Article] Ultrasonographic examination of rheumatoid arthritis patients who are free of physical synovitis: power Doppler subclinical synovitis is associated with bone erosion.2014

    • Author(s)
      Kawashiri SY, Suzuki T, Nakashima Y, Horai Y, Okada A, Iwamoto N, Ichinose K, Tamai M, Arima K, Nakamura H, Origuchi T, Uetani M, Aoyagi K, Eguchi K, Kawakami A.
    • Journal Title

      Rheumatology (Oxford)

      Volume: 53 Pages: 562-569

    • DOI

      10.1093/rheumatology/ket405.

    • Peer Reviewed
  • [Journal Article] Falls are associated with stroke, arthritis and multiple medications among community-dwelling elderly persons in Japan.2013

    • Author(s)
      Mizukami S, Arima K, Abe Y, Kanagae M, Kusano Y, Niino N, Aoyagi K.
    • Journal Title

      Tohoku J Exp Med.

      Volume: 231 Pages: 299-303

    • Peer Reviewed
  • [Journal Article] Relationship between adult height and body weight and risk of carotid atherosclerosis assessed in terms of carotid intima-media thickness: the Nagasaki Islands study.2013

    • Author(s)
      Shimizu Y, Nakazato M, Sekita T, Kadota K, Arima K, Yamasaki H, Goto H, Shirahama S, Takamura N, Aoyagi K, Maeda T.
    • Journal Title

      J Physiol Anthropol.

      Volume: 32 Pages: 19

    • DOI

      10.1186/1880-6805-32-19.

    • Peer Reviewed
  • [Journal Article] Free thyroxine (FT4) and anemia in relation to drinking status of Japanese men: the Nagasaki islands study.2013

    • Author(s)
      Shimizu Y, Nakazato M, Sekita T, Kadota K, Arima K, Yamasaki H, Goto H, Takamura N, Aoyagi K, Maeda T.
    • Journal Title

      Endocr J.

      Volume: 60 Pages: 1029-1034

    • Peer Reviewed
  • [Journal Article] An elderly patient with chronic active Epstein-Barr virus infection with mixed cryoglobulinemia and review of the literature.2013

    • Author(s)
      Ichinose K, Origuchi T, Tashiro N, Kawashiri SY, Iwamoto N, Fujikawa K, Aramaki T, Arima K, Tamai M, Yamasaki S, Nakamura H, Moriuchi H, Kawakami A.
    • Journal Title

      Mod Rheumatol.

      Volume: 23 Pages: 1022-1028

    • DOI

      10.1007/s10165-012-0731-9.

    • Peer Reviewed
  • [Journal Article] Significant improvement in MRI-proven bone edema is associated with protection from structural damage in very early RA patients managed using the tight control approach.2013

    • Author(s)
      Kita J, Tamai M, Arima K, Kawashiri SY, Horai Y, Iwamoto N, Okada A, Koga T, Nakashima Y, Suzuki T, Yamasaki S, Nakamura H, Origuchi T, Ida H, Aoyagi K, Uetani M, Eguchi K, Kawakami A.
    • Journal Title

      Mod Rheumatol.

      Volume: 23 Pages: 254-259

    • DOI

      10.1007/s10165-012-0646-5.

    • Peer Reviewed
  • [Presentation] STRINGENT THERAPIES IMPROVE BOTH RADIOGRAPHIC AND CLINICAL OUTCOME IN EARLY-STAGE RA PATIENTS FROM JAPANESE POPULATION: LONGITUDINAL STUDY FROM NAGASAKI EARLY ARTHRITIS COHORT2013

    • Author(s)
      M. Tamai, Y. Nakashima, T. Suzuki, J. Kita, A. Okada, S.-Y. Kawashiri, N. Iwamoto, K. Ichinose, K. Arima, H. Nakamura, T. Origuchi, M. Uetani, K. Aoyagi, K. Eguchi, A. Kawakami
    • Organizer
      European League against rheumatism 2013
    • Place of Presentation
      Madrid, Spain
    • Year and Date
      20130612-20130615
  • [Presentation] AUTOMATED BREAST VOLUME SCANNER (ABVS), A NEW AUTOMATED ULTRASONIC DEVICE, IS USEFUL TO EXAMINE JOINT INJURY IN PATIENTS WITH RHEUMATOID ARTHRITIS2013

    • Author(s)
      S.-Y. Kawashiri, T. Suzuki, Y. Nakashima, Y. Horai, A. Okada, N. Iwamoto, K. Ichinose, M. Tamai, K. Arima, H. Nakamura, T. Origuchi, M. Uetani, K. Aoyagi, K. Eguchi, A. Kawakami
    • Organizer
      European League against rheumatism 2013
    • Place of Presentation
      Madrid, Spain
    • Year and Date
      20130612-20130615
  • [Presentation] THE SEVERITY OF SYNOVIAL INFLAMMATION ASSESSED BY MUSCULOSKELETAL ULTRASONOGRAPHY CORRELATES WITH THAT OF OSTEITIS ASSESSED BY MAGNETIC RESONANCE IMAGING IN PATIENTS WITH RHEUMATOID ARTHRITIS2013

    • Author(s)
      S.-Y. Kawashiri, T. Suzuki, Y. Nakashima, Y. Horai, A. Okada, N. Iwamoto, K. Ichinose, K. Arima, M. Tamai, H. Nakamura, T. Origuchi, M. Uetani, K. Aoyagi, K. Eguchi, A. Kawakami
    • Organizer
      European League against rheumatism 2013
    • Place of Presentation
      Madrid, Spain
    • Year and Date
      20130612-20130615
  • [Presentation] THE SEVERITY OF SYNOVIAL INFLAMMATION ASSESSED BY MUSCULOSKELETAL ULTRASONOGRAPHY CORRELATES WITH THAT OF OSTEITIS ASSESSED BY MAGNETIC RESONANCE IMAGING IN PATIENTS WITH RHEUMATOID ARTHRITIS - Guided Poster Tours2013

    • Author(s)
      S.-Y. Kawashiri, T. Suzuki, Y. Nakashima, Y. Horai, A. Okada, N. Iwamoto, K. Ichinose, K. Arima, M. Tamai, H. Nakamura, T. Origuchi, M. Uetani, K. Aoyagi, K. Eguchi, A. Kawakami
    • Organizer
      European League against rheumatism 2013
    • Place of Presentation
      Madrid, Spain
    • Year and Date
      20130612-20130615
  • [Remarks] 長崎大学公衆衛生学分野

    • URL

      www.med.nagasaki-u.ac.jp/public-h/‎

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Published: 2015-05-28  

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