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In vivo MS analysis of drug-resistant pneumococci and research on the development of new antibacterial drugs

Research Project

Project/Area Number 20H03858
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 57020:Oral pathobiological science-related
Research InstitutionNiigata University

Principal Investigator

Terao Yutaka  新潟大学, 医歯学系, 教授 (50397717)

Co-Investigator(Kenkyū-buntansha) 中馬 吉郎  新潟大学, 自然科学系, 研究教授 (40372263)
土門 久哲  新潟大学, 医歯学系, 准教授 (00594350)
前川 知樹  新潟大学, 医歯学系, 研究教授 (50625168)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2022: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2021: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2020: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
KeywordsStreptococcus pneumoniae / 肺炎球菌
Outline of Research at the Start

耐性肺炎球菌の肺感染マウス系を確立後,肺胞中の耐性菌とマウスの両分子群をiTRAQ-MS/MS法で網羅同定した後,耐性菌とマウスの両分子群の動態を多分子同時解析装置で詳細分析する.そして,肺炎の重症化に関与する分子を治療標的として選出し,萌芽研究のin vitro系で確立し,特許出願したDNA立体化技術を用い,in vivo系において耐性肺炎球菌の病原因子のみを特異的に制御する抗菌薬の開発を期す.

Outline of Final Research Achievements

Pneumonia and aspiration pneumonia are becoming more severe due to the increase in drug-resistant bacteria. The applicant has independently analyzed the conflict between neutrophils and pathogenic bacteria. In this study, we aimed to analyze the mechanism of aggravation of pneumonia caused by resistant pneumococci in vivo, which is still unclear in detail, and to establish a basis for the treatment of pneumonia caused by resistant bacteria. Specifically, after establishing a lung-infected mouse strain with resistant pneumococci, we comprehensively identified both the resistant bacteria and mouse molecular groups in the alveoli using the iTRAQ-MS/MS method. The dynamics of the reaction were analyzed in detail using a multi-molecule simultaneous analysis device. We then selected molecules involved in the aggravation of pneumonia as therapeutic targets, and selected antibacterial agents that specifically control only the pathogenic factors of resistant pneumococci.

Academic Significance and Societal Importance of the Research Achievements

高齢社会の到来および薬剤耐性菌の増加により,誤嚥性肺炎や肺炎の患者数・死亡者数が急増している.そして,現行の肺炎球菌ワクチンには30%未満の防御効果しかないことが,最新知見で明らかとなっている.さらには,切札の抗菌薬も奏効しないことが世界的に報告されつつある.そこで,数年前から厚生労働省は,周術期患者の口腔清掃に保険点数を新設し,誤嚥性肺炎の予防を図る取組を推進している.しかしながら,歯ブラシ等による口腔清掃以外の誤嚥性肺炎や薬剤耐性肺炎球菌への対応は国内外で進んでおらず,国民健康の観点から,薬剤耐性肺炎球菌を制御する新たな基礎研究や創薬研究が必須と考えた.

Report

(4 results)
  • 2023 Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (55 results)

All 2023 2022 2021 2020 Other

All Int'l Joint Research (2 results) Journal Article (25 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 25 results,  Open Access: 7 results) Presentation (15 results) (of which Invited: 2 results) Book (13 results)

  • [Int'l Joint Research] University of Leeds/University of Manchester(英国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] University of Bonn/Fraunhofer Institute for TEM(ドイツ)

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Ozone ultrafine bubble water exhibits bactericidal activity against pathogenic bacteria in the oral cavity and upper airway and disinfects contaminated healthcare equipment.2023

    • Author(s)
      Takizawa F, Domon H, Hiyoshi T, Tamura H, Shimizu K, Maekawa T, Tabeta K, Ushida A, Terao Y
    • Journal Title

      PLOS ONE

      Volume: 18(4)

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pneumococcal proteins ClpC and UvrC as novel host plasminogen binding factors.2023

    • Author(s)
      Hirayama S, Yasui Y, Sasagawa K, Domon H, Terao Y
    • Journal Title

      Microbiology and Immunology

      Volume: 67(2) Pages: 99-104

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Erythromycin restores osteoblast differentiation and osteogenesis suppressed by Porphyromonas gingivalis lipopolysaccharide.2023

    • Author(s)
      Tamura H, Maekawa T, Domon H, Sirisereephap K, Isono T, Hirayama S, Hiyoshi T, Sasagawa K, Takizawa F, Maeda T, Terao Y, Tabeta K
    • Journal Title

      Pharmaceuticals

      Volume: 16(2) Pages: 303-303

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Degradation of EGFR on lung epithelial cells by neutrophil elastase contributes to the aggravation of pneumococcal pneumonia.2023

    • Author(s)
      Isono T, Hirayama S, Domon H, Maekawa T, Tamura H, Hiyoshi T, Sirisereephap K, Takenaka S, Noiri Y, Terao Y
    • Journal Title

      Journal of Biological Chemistry, in press

      Volume: 0 Pages: 0-0

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neutrophil elastase aggravates periodontitis by disrupting gingival epithelial barrier via cleaving cell adhesion molecules.2022

    • Author(s)
      Hiyoshi T, Domon H, Maekawa T, Tamura H, Isono T, Hirayama S, Sasagawa K, Takizawa F, Tabeta K, Terao Y
    • Journal Title

      Scientific Reports

      Volume: 12 Pages: 8159-8159

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Triosephosphate isomerase of Streptococcus pneumoniae is released extracellularly by autolysis and binds to host plasminogen to promote its activation.2022

    • Author(s)
      Hirayama S, Domon H, Hiyoshi T, Isono T, Tamura H, Sasagawa K, Takizawa F, Terao Y
    • Journal Title

      FEBS Open Bio

      Volume: 12(6) Pages: 1206-1219

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Osteoimmunology in periodontitis: Local proteins and compounds to alleviate periodontitis.2022

    • Author(s)
      Sirisereephap K, Maekawa T, Tamura H, Hiyoshi T, Domon H, Isono T, Terao Y, Maeda T, Tabeta K
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23(10) Pages: 5540-5540

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The role of genetically modified human feeder cells in maintaining the integrity of primary cultured human deciduous dental pulp cells.2022

    • Author(s)
      Ibano N, Inada E, Otake S, Kiyokawa Y, Sakata K, Sato M, Kubota N, Noguchi H, Iwase Y, Murakami T, Sawami T, Kakihara Y, Maeda T, Terunuma M, Terao Y, Saitoh S
    • Journal Title

      Journal of Clinical Medicine

      Volume: 11(20) Pages: 6087-6087

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Matcha green tea exhibits bactericidal activity against Streptococcus pneumoniae and inhibits functional pneumolysin.2021

    • Author(s)
      Sasagawa K, Domon H, Sakagami R, Hirayama S, Maekawa T, Isono T, Hiyoshi T, Tamura H, Takizawa F, Fukushima Y, Tabeta K, Terao Y
    • Journal Title

      Antibiotics

      Volume: 10(12) Pages: 1550-1550

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clarithromycin inhibits pneumolysin production via downregulation of ply gene transcription despite autolysis activation.2021

    • Author(s)
      Domon H, Isono T, Hiyoshi T, Tamura H, Sasagawa K, Maekawa T, Hirayama S, Yanagihara K, Terao Y
    • Journal Title

      Microbiology Spectrum

      Volume: 9(2)

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of erythromycin on osteoclasts and bone resorption via DEL-1 induction in mice.2021

    • Author(s)
      Tamura H, Maekawa T, Domon H, Hiyoshi T, Hirayama S, Isono T, Sasagawa K, Yonezawa D, Takahashi N, Oda M, Maeda T, Tabeta K, Terao Y
    • Journal Title

      Antibiotics

      Volume: 10 Pages: 312-312

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The role of neutrophils and neutrophil elastase in pneumococcal pneumonia.2021

    • Author(s)
      Domon H, Terao Y
    • Journal Title

      Front Cell Infect Microbiol.

      Volume: 11 Pages: 615959-615959

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Proteolytic cleavage of HLA class II by human neutrophil elastase in pneumococcal pneumonia.2021

    • Author(s)
      Domon H, Maekawa T, Isono T, Furuta K, Kaito C, Terao Y
    • Journal Title

      Sci Rep

      Volume: 11 Pages: 2432-2432

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rice peptide with amino acid substitution inhibits biofilm formation by Porphyromonas gingivalis and Fusobacterium nucleatum.2021

    • Author(s)
      Matsugishi A, Aoki-Nonaka Y, Yokoji-Takeuchi M, Yamada-Hara M, Mikami M, Hayatsu M, Terao Y, Domon H, Taniguchi M, Takahashi N, Yamazaki K, Tabeta K
    • Journal Title

      Arch Oral Biol

      Volume: 121(1) Pages: 104956-104956

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The proinflammatory cytokine IL-36γ is a global discriminator of harmless microbes and invasive pathogens within epithelial tissues.2020

    • Author(s)
      Macleod T, Ainscough JS, Hesse C, Konzok S, Braun A, Buhl A, Wenzel J, Bowyer P, Terao Y, Herrick S, Wittmann M, Stacey M
    • Journal Title

      Cell Rep

      Volume: 33(11) Pages: 108515-108515

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Treatment of severe pneumonia by hinokitiol in a murine antibiotic-resistant pneumococcal pneumonia model.2020

    • Author(s)
      Isono T, Domon H, Nagai K, Maekawa T, Tamura H, Hiyoshi T, Yanagihara K, Kunitomo E, Takenaka S, Noiri Y, Terao Y
    • Journal Title

      PLOS ONE

      Volume: 15(10) Pages: 240329-240329

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Erythromycin inhibits neutrophilic inflammation and mucosal disease by upregulating DEL-1.2020

    • Author(s)
      Maekawa T, Tamura H, Domon H, Hiyoshi T, Isono T, Yonezawa D, Hayashi N, Takahashi N, Tabeta K, Maeda T, Oda M, Ziogas A, Alexaki VI, Chavakis T, Terao Y, Hajishengallis G
    • Journal Title

      JCI Insight

      Volume: 5(15) Pages: 136706-136706

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Sulfated vizantin inhibits biofilm maturation by Streptococcus mutans.2020

    • Author(s)
      Oda M, Kurosawa M, Yamamoto H, Domon H, Takenaka S, Osumi T, Maekawa T, Yamasaki N, Terao Y
    • Journal Title

      Microbiol Immunol

      Volume: 64(7) Pages: 493-501

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Innate immune responses in serum and cerebrospinal fluid from neonates and infants infected with parechovirus-A3 or enteroviruses.2020

    • Author(s)
      Habuka R, Aizawa Y, Izumita R, Domon H, Terao Y, Takihara H, Okuda S, Saitoh A
    • Journal Title

      J Infect Dis

      Volume: 222(4) Pages: 681-689

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of sub-minimum inhibitory concentration of chlorhexidine gluconate on development of in vitro multi-species biofilms. Biofouling.2020

    • Author(s)
      Suzuki Y, Ohsumi T, Isono T, Nagata R, Hasegawa T, Takenaka S, Terao Y, Noiri Y
    • Journal Title

      Biofouling

      Volume: 336(2) Pages: 146-158

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Animal model of periodontitis ― Analysis of experimental ligature-induced periodontitis model in mice ―.2020

    • Author(s)
      Tamura H, Maekawa T, Hiyoshi T, Terao Y:
    • Journal Title

      Methods Mol Biol

      Volume: 2210 Pages: 237-250

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protective effect of hinokitiol against periodontal bone loss in ligature induced experimental periodontitis in mice.2020

    • Author(s)
      Hiyoshi T, Domon H, Maekawa T, Yonezawa D, Kunitomo E, Tabeta K, Terao Y
    • Journal Title

      Arch Oral Biol

      Volume: 112(4) Pages: 104679-104679

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of a novel glass ionomer cement containing flour-zinc-silicate fillers on biofilm formation and dentin ion incorporation.2020

    • Author(s)
      Hasegawa T, Takenaka S, Ohsumi T, Ida T, Ohshima H, Terao Y, Traithawit N, Maeda T, Noiri Y
    • Journal Title

      Clin Oral Investig

      Volume: 24(2) Pages: 963-970

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Antibacterial activity of hinokitiol against both antibiotic-resistant and -susceptible pathogenic bacteria predominant in the oral cavity and upper airways.2020

    • Author(s)
      Domon H, Hiyoshi T, Maekawa T, Yonezawa D, Tamura H, Kawabata S, Yanagihara K, Kimura O, Kunitomo E, Terao Y
    • Journal Title

      Microbiol Immunol

      Volume: 63 Pages: 213-222

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adjunct use of mouth rinses with a sonic toothbrush accelerates the detachment of a Streptococcus mutans biofilm: an in vitro study.2020

    • Author(s)
      Ohsumi T, Takenaka S, Sakaue Y, Suzuki Y, Nagata R, Hasegawa T, Ohshima H, Terao Y, Noiri Y
    • Journal Title

      BMC Oral Health

      Volume: 20 Pages: 161-161

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Presentation] オゾンウルトラファインバブル水による口腔細菌に対する殺菌作用2022

    • Author(s)
      滝澤史雄,土門久哲,前川知樹,牛田晃臣,平山 悟,日吉 巧,田村 光,磯野俊仁,笹川花梨,樋渡 忠,瀬戸光一,寺尾 豊,多部田康一
    • Organizer
      第65回春季歯周病学会学術大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 肺炎球菌ニューモリシンの発現に対するマクロライドの作用解析.2022

    • Author(s)
      土門久哲,磯野俊仁,日吉 巧,田村 光,笹川花梨,前川知樹,平山 悟,_原克紀,寺尾 豊
    • Organizer
      第95回日本細菌学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 肺炎球菌トリオースリン酸イソメラーゼは宿主プラスミノーゲンに結合し活性化を促進する.2022

    • Author(s)
      平山 悟,土門久哲,日吉 巧,磯野俊仁,田村 光,笹川花梨,滝澤史雄,寺尾 豊
    • Organizer
      第95回日本細菌学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 身の回りのウイルスや細菌について.2021

    • Author(s)
      寺尾 豊
    • Organizer
      特別支援学校総合学習,茨城県立霞ヶ浦聾学校
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 肺炎球菌に対する抹茶成分の作用解析.2021

    • Author(s)
      笹川花梨,土門久哲,平山 悟,前川知樹, 磯野俊仁,日吉 巧, 田村 光,寺尾 豊
    • Organizer
      第63回歯科基礎医学会学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] エリスロマイシンのDel-1誘導による骨免疫制御作用の解析.2021

    • Author(s)
      田村 光,土門久哲, 日吉 巧,前田健康,多部田康一,寺尾 豊,前川知樹
    • Organizer
      第6回日本骨免疫学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 肺炎球菌性肺炎モデルマウスにおけるヒノキチオール気管内投与の治療効果.2021

    • Author(s)
      磯野俊仁,土門久哲,前川知樹,田村 光,日吉 巧,柳原克紀,國友栄治,寺尾 豊
    • Organizer
      第94回日本細菌学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 抹茶を用いた肺炎の予防・治療研究.2021

    • Author(s)
      寺尾 豊,笹川花梨,坂上莉奈,磯野俊仁,土門久哲
    • Organizer
      抹茶と健康研究会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 中球エラスターゼによる歯周病重症化メカニズム解析と新規治療法への応用.2020

    • Author(s)
      日吉 巧,土門久哲,前川知樹,田村 光,米澤大輔,多部田 康一,寺尾 豊
    • Organizer
      令和2年度新潟歯学会第2回例会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Erythromycin regulates bone metabolism through induction of Del-1.2020

    • Author(s)
      Tamura H, Maekawa T, Domon H, Hiyoshi T, Isono T, Yonezawa D, Maeda T, Terao Y, Tabeta K
    • Organizer
      第63回秋季日本歯周病学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 好中球エラスターゼによる歯周炎重症化メカニズム解析.2020

    • Author(s)
      日吉 巧,土門久哲,前川知樹,田村 光,磯野俊仁,寺尾 豊,多部田康一
    • Organizer
      第63回秋季日本歯周病学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] エリスロマイシンによるDel-1誘導を介した骨代謝の制御.2020

    • Author(s)
      田村 光,前川知樹,土門久哲,日吉 巧,前田健康,寺尾 豊
    • Organizer
      第62回歯科基礎医学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ヒノキチオールの抗菌活性および抗炎症作用によるマウス歯牙結紮歯周炎モデル骨吸収抑制作用の解析.2020

    • Author(s)
      日吉 巧,土門久哲,前川知樹,田村 光,國友栄治,寺尾 豊
    • Organizer
      第62回歯科基礎医学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 宿主由来エラスターゼはHLAクラスII発現を抑制する.2020

    • Author(s)
      土門久哲,前川知樹,寺尾 豊
    • Organizer
      第62回歯科基礎医学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] マウス歯牙結紮歯周炎モデルにおけるヒノキチオールの骨吸収抑制作用の解析.2020

    • Author(s)
      日吉 巧,土門久哲,前川知樹,田村 光,米澤大輔,國友栄治,寺尾 豊,多部田康一
    • Organizer
      第63回春季歯周病学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Book] 微生物学.歯科衛生士書き込み式学習ノート1 専門基礎科目編 人体の構造と機能/歯・口腔の構造と機能/疾病の成り立ち及び回復過程の促進 2023年版2023

    • Author(s)
      寺尾 豊(分担執筆)
    • Total Pages
      354
    • Publisher
      医歯薬出版
    • Related Report
      2022 Annual Research Report
  • [Book] 歯科衛生学シリーズ 微生物学 第2版2023

    • Author(s)
      寺尾 豊(編集・分担執筆)
    • Publisher
      医歯薬出版
    • Related Report
      2022 Annual Research Report
  • [Book] 標準微生物学 第15版2023

    • Author(s)
      寺尾 豊(分担執筆)
    • Publisher
      医学書院
    • Related Report
      2022 Annual Research Report
  • [Book] パーフェクトマスター 口腔微生物学・免疫学 第2版2022

    • Author(s)
      寺尾 豊
    • Total Pages
      103
    • Publisher
      医歯薬出版
    • Related Report
      2022 Annual Research Report
  • [Book] 口腔微生物学・免疫学 第5版第2刷2022

    • Author(s)
      寺尾 豊(編集・分担執筆)
    • Total Pages
      315
    • Publisher
      医歯薬出版
    • Related Report
      2022 Annual Research Report
  • [Book] 微生物学.歯科衛生士書き込み式学習ノート1 専門基礎科目編 人体の構造と機能/歯・口腔の構造と機能/疾病の成り立ち及び回復過程の促進 第2版 改訂第3刷2022

    • Author(s)
      寺尾 豊(分担執筆)
    • Total Pages
      302
    • Publisher
      医歯薬出版
    • Related Report
      2021 Annual Research Report
  • [Book] パーフェクトマスター 口腔微生物学・免疫学 改訂第3刷2021

    • Author(s)
      寺尾 豊
    • Total Pages
      93
    • Publisher
      医歯薬出版
    • Related Report
      2021 Annual Research Report
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    • Author(s)
      寺尾 豊(分担執筆)
    • Total Pages
      315
    • Publisher
      医歯薬出版
    • Related Report
      2021 Annual Research Report
  • [Book] 微生物学.歯科衛生士書き込み式学習ノート?@ 専門基礎科目編 人体の構造と機能/歯・口腔の構造と機能/疾病の成り立ち及び回復過程の促進 第2版 改訂第3刷2021

    • Author(s)
      寺尾 豊(分担執筆)
    • Total Pages
      302
    • Publisher
      医歯薬出版
    • Related Report
      2020 Annual Research Report
  • [Book] 口腔微生物学・免疫学 第4版 改訂第6刷2020

    • Author(s)
      寺尾 豊(分担執筆)
    • Total Pages
      303
    • Publisher
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    • Related Report
      2020 Annual Research Report
  • [Book] パーフェクトマスター 口腔微生物学・免疫学 改訂第2刷2020

    • Author(s)
      寺尾 豊
    • Total Pages
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    • Related Report
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    • Author(s)
      寺尾 豊
    • Total Pages
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    • Total Pages
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    • Publisher
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    • Related Report
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Published: 2020-04-28   Modified: 2025-01-30  

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