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Pathophysiologic Study on Ocular Surface using tears

Research Project

Project/Area Number 18591937
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Ophthalmology
Research InstitutionNihon University

Principal Investigator

SAWA Mitsuru  Nihon University, School of Medicine, Professor (40010475)

Co-Investigator(Kenkyū-buntansha) IWATA Mitsuhiro  Nihon University, School of Medicine, Lecturer (50193751)
INADA Noriko  Nihon University, School of Medicine, Lecturer (10307837)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordstears / Ocular surface disease / Allereic conjunctival disease / Herpetic keratitis / Antigen-specific antibody / Eosinophil cationic protein / Enzyme-linked immunosorbent assay / Clinical examination methods / アレルギー結膜疾患 / Eosinophil cationic protein (ECP) / アレルギー・ぜんそく / 細胞・組織 / 分析科学 / マイクロアレイ
Research Abstract

The purpose of the study was to investigate the pathophysiology of the ocular surface in patients with allergic conjunctivitis (ACD) and to develop clinical test methods using tears. The tears were sampled using filter paper method. The following studies were performed with the grant in aid
1. Investigation of cytokine profile using an antibody array method : The antibody array plate for 40 bioactive substances including cytokines was used to analyze tears. It was revealed that cytokine profile is useful to determine a pathophysiology in ACD
2. Antigen-specific secretory IgA (sIgA) in tears : House dust specific sIgA and total sIgA were analyzed. The ratio between them was determined to be a clinical index to evaluate the severity of ACD
3. Concentration of soluble interleukin-6 (sIL-6) and its receptor in tears : The concentration of sIL-6 was determined by ELISA and gp130 and Impression cytology and glyceraldehydes-3-phosphate dehydrogenase (G3PDH) mRNA were detected using impression cy … More tology and RT-PCR method was determined. It was concluded that the concentration of sIL-6 is an index of pathophysiology of ACD
4. A determination of clinical score : Clinical findings in ACD were categorized into three groups ; sever, moderate and minor. The efficacy of categorized findings was approved in the study
5. Eosinophil cationic protein (ECP) in tears : The concentration ECP in tears determined by EIA method was evaluated in various ACD to analyze the pathophysiology in ACD
6. Cytokine and chemokine profile in tears : Cytokine and chemokine profile determined by protein array method were analyzed between patients with vernal keratoconjunctivits and those with giant papillary conjunctivitis. No remarkable difference in profiles was found in both groups
7. Development of clinically applicable kit to determine ECP and IgE in tears
8. Development of herpes simplex virus (HSV)-specific IgA antibody kit : The clinical efficacy of the developed kit is approved to be an index to diagnose a stromal type HSV keratitis. Less

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (54 results)

All 2008 2007 2006 Other

All Journal Article (23 results) (of which Peer Reviewed: 10 results) Presentation (29 results) Book (2 results)

  • [Journal Article] Atlas of Slit-lamp Microscopy2008

    • Author(s)
      Sawa, M., Kishi, S., Suzuki, Y., Shoji, J
    • Journal Title

      Nakayama Shoten

      Pages: 192-192

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Concentration of soluble interleukin-6 receptors in tears of allergic con-junctival disease patients2007

    • Author(s)
      Shoji J, Sawa M
    • Journal Title

      Jpn J Ophthalmol 51

      Pages: 332-337

    • NAID

      10019829836

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Evaluation of totaI and allergen-specific secretory igA in tears of allergic conjunctival disease patients2007

    • Author(s)
      Inada N, Sawa M
    • Journal Title

      Jpn J Ophthalmol 51

      Pages: 338-342

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Upregulation of matrix metalloproteinase inhibitor fluid of patients with recurrent corneal erosion2007

    • Author(s)
      Sakimoto T, Sawa M
    • Journal Title

      Jpn J Ophthalmol 51

      Pages: 343-346

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] 両眼の壊死性強膜炎の1例2007

    • Author(s)
      岡島 泰彦, 稲田 紀子, 澤 充
    • Journal Title

      眼科 49

      Pages: 357-361

    • NAID

      40015383614

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] フレアメーター(FM-600)の有用性の検討フレアメーター(FM-500)との臨床比較試験2007

    • Author(s)
      岡島 泰彦, 崎本 丹, 三井 正博, 中島 正巳, 嘉村 由美, 澤 充
    • Journal Title

      眼科 49

      Pages: 1095-1100

    • NAID

      40015593644

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] 抗体アレイ法を用いたアレルギー性結膜炎におけるサイトカインプロフィールの検討2007

    • Author(s)
      庄司 純, 後藤 亜紀, 川口 敦里, 稲田 紀子, 澤 充
    • Journal Title

      眼科 49

      Pages: 1101-1110

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] シリコーンハイドロゲルレンズ(HiDk)の臨床試験報告2007

    • Author(s)
      忍田 太紀, 伏見 典子, 澤 充, 土至 田宏, 太田 亜紀, 工藤 大介, 高橋 康造, 村上 昌
    • Journal Title

      日コレ誌 49

      Pages: 35-43

    • NAID

      10020150317

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Concetration of soluble interleukin-6 receptors in Tears of allergic conjunctivital disease patients2007

    • Author(s)
      Shoji, J., Sawa, M., et. al.
    • Journal Title

      Jpn J Ophthalmol 51

      Pages: 332-337

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Evaluation of total and allergen2007

    • Author(s)
      Inada, N., Sawa, M., et. al.
    • Journal Title

      specific secretory igA in tears of allergic conjunctival disease patients Jpn J Ophthalmol 51

      Pages: 338-342

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Upregulation of matrix metallo proteinase inhibitor fluid of patients with recurrent corneal erosion2007

    • Author(s)
      Sakimoto, T., Sawa, M., et. al.
    • Journal Title

      Jpn J Ophthalmol 51

      Pages: 343-346

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] A case of bilateral necrotizing scleritis2007

    • Author(s)
      Okajima, Y., Inada, N., Sawa, M
    • Journal Title

      Ganka 49

      Pages: 357-361

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Clinical study on efficacy of flaremeter (FM-600). Comparative study with flare (FM-500)2007

    • Author(s)
      Okajima, Y., Sakimoto, A., Mitsui, M., Sawa, M., et. al.
    • Journal Title

      Ganka 49

      Pages: 1095-1100

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Clinical trial study for silicone hydrogel Lens (HiDK)2007

    • Author(s)
      Oshida, T., Fushimi, N., Sawa, M., et. al.
    • Journal Title

      Nihon Contact Lens J 49

      Pages: 35-43

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Concentration of soluble interleukin-6 receptors in tears of allergic con-junctival disease patients2007

    • Author(s)
      Shoji J, Sawa M, et. al.
    • Journal Title

      Jpn J Ophthalmol 51

    • NAID

      10019829836

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of total and allergen-specific secretory igA in tears of allergic conjunctival disease patients2007

    • Author(s)
      Inada N, Sawa M, et. al.
    • Journal Title

      Jpn J Ophthalmol 51

    • NAID

      10019829861

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Upregulation of matrix metalloproteinase inhibitor fluid of patients with recurrent corneal erosion2007

    • Author(s)
      Sakimoto T, Sawa M, et. al.
    • Journal Title

      Jpn J Ophthalmol 51

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 抗体アレイ法を用いたアレルギー性結膜炎におけるサイトカインプロフィールの検討2007

    • Author(s)
      庄司 純, 後藤亜希, 川口敦里, 稲田紀子, 澤 充
    • Journal Title

      眼科 49巻7号(In Press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 臨床医学の展望2006 眼科学.2006

    • Author(s)
      澤 充
    • Journal Title

      日本医事新報 4271号

      Pages: 46-52

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 総説 アイバンク活動の現状と展望2006

    • Author(s)
      澤 充
    • Journal Title

      日本の眼科 77巻1号

      Pages: 11-14

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 角膜移植講座 角膜移植に必要なドナーの既往疾患.2006

    • Author(s)
      三井正博, 澤 充
    • Journal Title

      Eye Bank Journal 10-2

      Pages: 12-19

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 角膜移植講座 全身疾患と眼2006

    • Author(s)
      澤 充
    • Journal Title

      Eye Bank Journal 10-3

      Pages: 28-35

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cytokine profile in allergic conjunc-Tivitis by antibody-array method

    • Author(s)
      Shoji, J., Goto, A., Kawaguchi, A., Sawa, M
    • Journal Title

      Ganka 49

      Pages: 1101-1110

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] コンタクトレンズ装用者にみられた点状角膜炎の検討2007

    • Author(s)
      大西 貴子, 庄司 純, 中神 尚子, 伏見 典子, 澤 充
    • Organizer
      第87回日大眼科症例検討会
    • Place of Presentation
      東京
    • Year and Date
      2007-12-06
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 院内角膜ドナーの特性と移植予後2007

    • Author(s)
      中島 基弘, 忍田 太紀, 澤 充
    • Organizer
      第479回日大医学会例会
    • Place of Presentation
      東京
    • Year and Date
      2007-11-17
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Clinical features and surgical outcome of donated cornea in our own hospital 479th Nihon University Medical Conference2007

    • Author(s)
      Nakashima, M., Oshida, T., Sawa, M
    • Place of Presentation
      Tokyo
    • Year and Date
      2007-11-17
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Clinical investigation of punctuated keratitis in patients with contact lens wea2007

    • Author(s)
      Onishi, T., Shoji, J., Sawa, M., et. al.
    • Organizer
      479th Nihon University Medical Conference
    • Place of Presentation
      Tokyo
    • Year and Date
      2007-11-17
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ヘルペス性角結膜疾患に対するReal-time PCR法の検討2007

    • Author(s)
      川口 敦里, 庄司 純, 稲田 紀子, 澤 充
    • Organizer
      第61回日本臨床眼科学会
    • Place of Presentation
      京都
    • Year and Date
      2007-10-11
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] レーザー虹彩切開術による水庖性角膜症の施行理由と視力予後2007

    • Author(s)
      忍田 太紀, 伏見 典子, 崎元 卓, 澤 充
    • Organizer
      第61回日本臨床眼科学会
    • Place of Presentation
      京都
    • Year and Date
      2007-10-11
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 春季カタルにおける結膜上皮のヒスタミンH_1レセプターmRNAの発見の検討2007

    • Author(s)
      原田 奈月子, 庄司 純, 茂田 今日子, 稲田 紀子, 澤 充
    • Organizer
      第61回日本臨床眼科学会
    • Place of Presentation
      京都
    • Year and Date
      2007-10-11
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Study on real-time PCR method in herpetic keratoconjunctival diseases Meeting2007

    • Author(s)
      Kawaguchi, A., Shoji, J., Inada, N., Sawa, M
    • Organizer
      61th Japan Clinical Ophthalmolgy Meeting
    • Place of Presentation
      Kyoto
    • Year and Date
      2007-10-11
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Indication criteria of laser iridotomy causing bullous keratopathy and visual prognosis2007

    • Author(s)
      Oshida, T., Fushimi, N., Skimoto, Ta., Sawa, M
    • Organizer
      61th Japan Clinical Ophthalmolgy Metting
    • Place of Presentation
      Kyoto
    • Year and Date
      2007-10-11
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Study on expression of histamine H1 receptor messenger RNA in conjunctival epithelim in vernal keratoconjuctivitis2007

    • Author(s)
      Harada, N., Shoji, J., Inada, N., et. al.
    • Organizer
      61th Japan Clinical Ophthalmolgy Metting
    • Place of Presentation
      Kyoto
    • Year and Date
      2007-10-11
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Pathophysiogic study on allergic conjunctivitis and contact lens wear2007

    • Author(s)
      Sawa M, Syoji J
    • Organizer
      CLAO Meeting
    • Place of Presentation
      Las Vegas,USA
    • Year and Date
      2007-10-05
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Pathophysiogic study on allergic conjunctivitis and contact lens wear2007

    • Author(s)
      Sawa, M., Shoji, J
    • Organizer
      CLAO Meeting
    • Place of Presentation
      Las Vegas, U.S.A
    • Year and Date
      2007-10-05
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] パピロックミニ点眼液0.1%により治療した春季カタル5例の検討2007

    • Author(s)
      原田 奈月子, 茂田 京子, 稲田 紀子, 庄司 純, 澤 充
    • Organizer
      スリーサム・イン東京第41回日本眼炎症学会
    • Place of Presentation
      東京
    • Year and Date
      2007-07-06
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Dotblotting法を用いたアレルギー性結膜疾患にたいする涙液中抗原特異的IgE抗体の検討2007

    • Author(s)
      立花 敦子, 稲田 紀子, 加藤 博司, 庄司 純, 澤 充
    • Organizer
      スリーサム・イン東京第41回日本眼炎症学会
    • Place of Presentation
      東京
    • Year and Date
      2007-07-06
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Five cases of vernal kertoconjunctivitis undergoing Pappilock Mini 0.1% eyedrop2007

    • Author(s)
      Harada, N., Shigeta, K., Inada, N., et. al.
    • Organizer
      41th Japan Immunology Society Meeting
    • Place of Presentation
      Tokyo
    • Year and Date
      2007-07-06
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Study on antigen-specific IgE in allergic conjunctivitis by Dot blotting methods2007

    • Author(s)
      Tachibana, A., Inada, N., Kato, H., et. al.
    • Organizer
      41th Japan Immunology Society Meeting
    • Place of Presentation
      Tokyo
    • Year and Date
      2007-07-06
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] TACE(ADAM17)involvement in corneal wound hiealing2007

    • Author(s)
      Sakimoto T, Yamada A, Sawa M
    • Organizer
      The Association for Research in Vision and Ophthalmology
    • Place of Presentation
      Fort Lauderdale Florida,U.S.A.
    • Year and Date
      2007-05-06
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] TACE(ADAM17) involvement in corneal wound hiealing2007

    • Author(s)
      Sakimoto, T., Yamada, A., Sawa, M
    • Organizer
      The Association for Research in Vision and Ophthalmology
    • Place of Presentation
      Fort Lauderdale Florida, U.S.A
    • Year and Date
      2007-05-06
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] TACE(ADAM17)involvement in corneal wound hiealing2007

    • Author(s)
      Sakimoto T, Yamada A, Sawa M
    • Organizer
      The Association for Research in Vision and Ophthalmology
    • Place of Presentation
      Fort Lauderdale Florida, U. S. A.
    • Year and Date
      2007-05-06
    • Related Report
      2007 Annual Research Report
  • [Presentation] Pathological study and treatment outcome of immune recovery uveitis in patient complicated with acquired immunodeficiency syndrome(AIDS)2007

    • Author(s)
      Nakajima M, Iwata M, Arakawa M, Uchiyama M, Sawa M
    • Organizer
      Asia-ARVO
    • Place of Presentation
      Singappore
    • Year and Date
      2007-03-04
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Pathological study and treatment outcome of immune recovery uveitis in patient complicated with acquired immunodeficiency syndrome (AIDS)2007

    • Author(s)
      Nakajima, M., Iwata, M., Sawa, M., et. al.
    • Organizer
      Asia- ARVOAsia- ARVO
    • Place of Presentation
      Singapore
    • Year and Date
      2007-03-04
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] マウス角膜創傷治癒におけるtumor necrosis factor転換酵素発現の検討2007

    • Author(s)
      崎元 暢, 澤 充
    • Organizer
      第31回角膜カンファランス・第23回日本角膜移植学会
    • Place of Presentation
      宮崎
    • Year and Date
      2007-02-08
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 角膜周辺部浸潤を合併した川崎病の1例2007

    • Author(s)
      菅谷 哲史, 崎元 暢、澤 充
    • Organizer
      第31回角膜カンファランス・第23回日本角膜移植学会
    • Place of Presentation
      宮崎
    • Year and Date
      2007-02-08
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 角膜移植手術後の不可逆性散瞳例2007

    • Author(s)
      大西 貴子, 崎元 暢, 澤 充
    • Organizer
      第31回角膜カンファランス・第23回日本角膜移植学会
    • Place of Presentation
      宮崎
    • Year and Date
      2007-02-08
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] アレルギー性結膜疾患における涙液中IL-16の検討2007

    • Author(s)
      後藤 亜紀, 庄司 純, 稲田 紀子, 澤 充
    • Organizer
      第31回角膜カンファランス・第23回日本角膜移植学会
    • Place of Presentation
      宮崎
    • Year and Date
      2007-02-08
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Study on expression of tumor necrosis Factor converting enzyme in corneal wound healing in mouse2007

    • Author(s)
      Sakimoto, T., Sawa, M
    • Organizer
      31th Corneal Conference/23rd Japan Keratoplasty Conference
    • Place of Presentation
      Miyazaki
    • Year and Date
      2007-02-08
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] A case of Kawasaki disease with corneal peripheral infiltration2007

    • Author(s)
      Sugaya, S., Sakimoto, T., Sawa, M
    • Organizer
      31th Corneal Conference/23rd Japan Keratoplasty Conference
    • Place of Presentation
      Miyazaki
    • Year and Date
      2007-02-08
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Irreversible mydriasis after Corneal transplantation2007

    • Author(s)
      Oonishi, T., Sakimoto, T., Sawa, M
    • Organizer
      31th Corneal Conference/23rd Japan Keratoplasty Conference
    • Place of Presentation
      Miyazaki
    • Year and Date
      2007-02-08
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] IL-16 in tears in allergic conjunctivits2007

    • Author(s)
      Goto, A., Shoji, J., Inada, N., Sawa, M
    • Organizer
      31th Corneal Conference/23rd Japan Keratoplasty Conference
    • Place of Presentation
      Miyazaki
    • Year and Date
      2007-02-08
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 細隙灯顕微鏡アトラス2008

    • Author(s)
      澤 充、岸 章治、鈴木 康之、庄司 純
    • Total Pages
      192
    • Publisher
      中山書店
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 細隙灯顕微鏡アトラス2008

    • Author(s)
      澤 充、岸章治、鈴木康之、庄司 純
    • Total Pages
      192
    • Publisher
      中山書店
    • Related Report
      2007 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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