Analysis of lymphoplasmacyte infiltrating fibrotic lung lesion using samples from human lung diseases and RA lung model in D1CC mice

• Project/Area Number: 25461175
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Nippon Medical School
• Principal Investigator: terasaki yasuhiro 日本医科大学, 医学部, 准教授 (50332870)
• Co-Investigator(Kenkyū-buntansha): MATSUI Shoko 富山大学, 学内共同利用施設等, 教授 (40334726) ; TERASAKI Mika 日本医科大学, 医学部, 助教 (50372785) ; MIYAKE Koichi 日本医科大学, 医学部, 准教授 (90267211)
• Co-Investigator(Renkei-kenkyūsha): KANAZAWA Satoshi 名古屋市立大学, 医学(系)研究科, 助教 (90347401) ; KUNUGI Shinobu 日本医科大学, 医学部, 講師 (30350036)
• Research Collaborator: OGURA Takashi
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: リンパ球増殖性肺疾患 / IgG4関連肺病変 / Castleman’s disease / RA肺モデル / D1CCマウス / 高濃度水素水 / Sp-D / 抗酸化作用 / リンパ球増殖性肺疾患 / RA肺モデル / 高濃度水素分子 / IgG4 / Castleman's disease / リウマチ / D1CC / 水素治療 / マイクロダイセクション / 遺伝子治療

Outline of Final Research Achievements

Although both lesions had lymphoplasmacyte infiltrated lesion, lung lesions of IgG4-related disease was characterized by active fibrosis with eosinophilic infiltration within lymphatic stroma itself with obstructive vasculitis, whereas lung lesion of idiopathic multicentric Castleman's disease was marked lymphoplasmacyte proliferating lesions mainly in the alveolar area adjacent to lymphatic stroma and sometimes conspicuous cyst formation. These clinicopathological features may help differentiate them and influence their prognoses.
RA lung model in D1CC mice is very similar to RA lung in humans with inflammatory cells infiltration and alveolitis as lymphangiitic distribution and would be valuable model for investing general pathophysiology of chronic interstitial pneumonias in humans. H2 treatment protected the lung damage with reduction of the increased levels of serum SP-D, CT image density as well as histological changes, thus would be valuable for protection against RA induced lung.

Research Products

• [Journal Article] Pulmonary mucosa-associated lymphoid tissue lymphoma associated with pulmonary sarcoidosis: a case report and literature review. (2016)
  • Author(s): Kokuho N, Terasaki Y, Urushiyama H, Terasaki M, Kunugi S, Morimoto T, Azuma A, Usuda J, Gemma A, Eishi Y, Shimizu A.
  • Journal Title: Hum Pathol. Volume: 51 Pages: 57-63
  • DOI: 10.1016/j.humpath.2015.12.019
  • Peer Reviewed / Open Access
• [Journal Article] Inter-Observer Agreement of Usual Interstitial Pneumonia Diagnosis Correlated with Patient Outcome (2016)
  • Author(s): Hashisako M､Tanaka T, Terasaki Y. Uekusa T, Hayashi T, Kondou Y, Taniguchi H, Fukuoka J
  • Journal Title: Archives of Pathology Laboratory Medicine Volume: in press
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Osteogenesis imperfecta associated with dendriform pulmonary ossification. (2016)
  • Author(s): Morikawa M, Fukuda Y, Terasaki Y, Itoh H, Demura Y, Sasaki M, Imamura Y, Honjo C, Umeda Y, Anzai M, Ameshima S, Ishizaki T, Ishizuka T
  • Journal Title: Am J Respir Crit Care Med Volume: 193 Pages: 460-461
  • Peer Reviewed / Open Access
• [Journal Article] Role of α1 and α2 chains of type IV collagen in early fibrotic lesions of idiopathic interstitial pneumonias and migration of lung fibroblasts. (2015)
  • Author(s): Urushiyama H, Terasaki Y, Nagasaka S, Terasaki M, Kunugi S, Nagase T, Fukuda Y, Shimizu A.
  • Journal Title: Lab Invest Volume: 95 Issue: 8 Pages: 872-885
  • DOI: 10.1038/labinvest.2015.66
  • Peer Reviewed / Open Access
• [Journal Article] Uterine leiomyosarcoma with osteoclast-like giant cells associated with high expression of receptor activator of nuclear factor κB ligand (2015)
  • Author(s): Terasaki M, Terasaki Y, Yoneyama K, Kuwahara N, Wakamatsu K, Nagahama K, Kunugi S, Takeshita T, Shimizu A
  • Journal Title: Hum Pathol Volume: 46 Pages: 1679-1684
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) as a novel marker in T1 high-grade and T2 bladder cancer patients receiving neoadjuvant chemotherapy. (2015)
  • Author(s): Nomura S, Suzuki Y, Takahashi R, Terasaki M, Kimata R, Terasaki Y, Hamasaki T, Kimura G, Shimizu A, Kondo Y.
  • Journal Title: BMC Urol. Volume: 15 Issue: 1 Pages: 53-53
  • DOI: 10.1186/s12894-015-0040-7
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Role of α1 and α2 chains of type IV collagen in early fibrotic lesions of idiopathic interstitial pneumonias and migration of lung fibroblasts (2015)
  • Author(s): Hirokazu Urushiyama, Yasuhiro Terasaki, Shinya Nagasaka, Mika Terasaki, Shinobu Kunugi, Takahide Nagase, Yuh Fukuda, and Akira Shimizu
  • Journal Title: Laboratory Investigation Volume: in press
  • Peer Reviewed
• [Journal Article] Uterine leiomyosarcoma with osteoclast-like giant cells associated with high expression of receptor activator for nuclear factor κB ligand ( ANKL) (2015)
  • Author(s): Mika Terasaki, M.D., Ph.D; Yasuhiro Terasaki, MD, PhD; Koichi Yoneyama, MD, PhD;
  • Journal Title: Human Pathology Volume: in press
  • Peer Reviewed
• [Journal Article] Immunoglobulin G4-related lung disease: clinicoradiological and pathological features. (2013)
  • Author(s): Matsui S, Hebisawa A, Sakai F, Yamamoto H, Terasaki Y,,, Kurihara Y, Waseda Y, Kawamura T, Miyashita T, Inoue H, Hata N, Kawabata Y, Ogura T
  • Journal Title: Respirology Volume: 18 Issue: 3 Pages: 480-487
  • DOI: 10.1111/resp.12016
  • Peer Reviewed
• [Journal Article] Role of survivin in acute lung injury: epithelial cells of mice and humans. (2013)
  • Author(s): Terasaki Y, Terasaki M, Urushiyama H, Nagasaka S,Kungi S, et al.
  • Journal Title: Lab Invest Volume: 93 Issue: 10 Pages: 1147-1163
  • DOI: 10.1038/labinvest.2013.103
  • Peer Reviewed
• [Journal Article] The difference of neovascularization in early intra-alveolar fibrosis between nonspecific interstitial pneumonia and usual interstitial pneumonia. (2013)
  • Author(s): Takahashi M, Kunugi S, Terasaki Y, Terasaki M, Urushiyama H, Kuwahara N, Wakamatsu K, Nakayama T, Fukuda Y.
  • Journal Title: Pathol Int. Volume: May;63(5) Issue: 5 Pages: 237-44
  • DOI: 10.1111/pin.12058
  • Peer Reviewed
• [Journal Article] A mucin-rich variant of salivary duct carcinoma with a prominent mucinous component, a tumor that mimics mucinous adenocarcinoma. (2013)
  • Author(s): Terasaki M, Terasaki Y, Wakamatsu K, Takahashi M, Kunugi S, Urushiyama H, Sakanushi A, Okubo K, Fukuda Y.
  • Journal Title: Oral Surg Oral Med Oral Pathol Oral Radiol. Volume: Sep;116(3) Issue: 3 Pages: e210-e214
  • DOI: 10.1016/j.oooo.2013.01.002
  • Peer Reviewed
• [Journal Article] Renal inflammatory changes in acute hepatic failure-associated acute kidney injury. (2013)
  • Author(s): Shimizu A, Ishii E, Masuda Y, Sato A, Piao H, Kunugi S, Takahashi M, Terasaki M, Nagasaka S, Terasaki Y, Ohashi R, Morioka T, Fukuda Y.
  • Journal Title: Am J Nephrol. Volume: 37 Issue: 4 Pages: 378-88
  • DOI: 10.1159/000348567
  • Peer Reviewed
• [Journal Article] Surgical technique of orthotopic liver transplantation in rats: the Kamada technique and a new splint technique for hepatic artery reconstruction. (2013)
  • Author(s): Ishii E, Shimizu A, Takahashi M, Terasaki M, Kunugi S, Nagasaka S, Terasaki Y, Ohashi R, Masuda Y, Fukuda Y.
  • Journal Title: J Nippon Med Sch Volume: 0(1) Pages: 4-15
  • NAID: 130004147203
• [Journal Article] びまん性肺粒状網状影を呈するMicronodular pneumocyte hyperplasia (MNPH)の１例 (2013)
  • Author(s): 寺﨑泰弘、寺﨑美佳、一門和也、竹屋元裕、福田悠
  • Journal Title: 日医大医会誌 Volume: 第9巻2号 Pages: 42-43
• [Presentation] The process of development of lung fibrosis in the Rheumatoid Arthritis lung model and the effect of H2 treatment in D1CC mice. (2016)
  • Author(s): Yasuhiro Terasaki, Nariaki Kokuho, Mika Terasaki, Shinobu Kunugi, Hirokazu Urushiyama, Motoyo Maruyama, Toshio Akimoto,Satoshi Kanazawa
  • Organizer: ATS (American Thoracic Society) International Conference
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2016-05-13
  • Int'l Joint Research
• [Presentation] Localized pulmonary crystal-storing histiocytosis complicating pulmonary mucosa-associated lymphoid tissue lymphoma. TBLB study was key step for final diagnosis. (2016)
  • Author(s): Nariaki Kokuho, Shinobu Kunugi, Naomi Onda, Hirokazu Urushiyama, Mika Terasaki, Arata Azuma, Hino Mitunori, Akihiko Gemma, Yasuhiro Terasaki
  • Organizer: ATS (American Thoracic Society) International Conference
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2016-05-13
  • Int'l Joint Research
• [Presentation] A case of sarcomatoid mesothelioma with osteosarcomatous element of the pleura (2016)
  • Author(s): Terasaki M, Terasaki Y, Kokuho N, Kunugi S, Nagahama K, Urushiyama H, Kajimoto Y, Shimizu A
  • Organizer: ATS (American Thoracic Society) International Conference
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2016-05-13
  • Int'l Joint Research
• [Presentation] Role of 1 and 2 chains of Type IV Collagen in Early Fibrotic Lesions of Idiopathic Interstitial Pneumonias and Migration of Lung Fibroblasts (2015)
  • Author(s): Y. Terasaki, H. Urushiyama, N. Kokuho, M. Terasaki, S. Kunugi, Y. Fukuda, and A. Shimizu
  • Organizer: ATS (American Thoracic Society) International Conference
  • Place of Presentation: Denver, USA
  • Year and Date: 2015-05-15
  • Int'l Joint Research
• [Presentation] リウマチ肺モデルD1CCマウスの肺病変の病理形態学的に解析と高濃度水素 分子(H2)水素水の病変に対する効果 (2015)
  • Author(s): 寺崎泰弘、漆山博、國保成暁、寺崎美佳、功刀しのぶ、金沢智、清水章
  • Organizer: 日本病理学会総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-04-30
• [Presentation] 破骨細胞様巨細胞を伴う子宮平滑筋肉腫の１例 (2015)
  • Author(s): 寺崎美佳,寺崎泰弘,米山剛一,長濱清隆,若松恭子,桑原尚美,功刀しのぶ,梶本雄介,漆山博和，國保茂暁,竹下俊行
  • Organizer: 日本病理学会総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-04-30
• [Presentation] サルコイドーシス経過中に発症した肺MALTomaの1例 (2015)
  • Author(s): 國保 成暁, 漆山 博和, 梶本 雄介, 長濱 清隆, 寺崎 美佳, 功刀 しのぶ, 益田 幸成, 寺崎 泰弘, 江石 義信, 清水 章
  • Organizer: 日本病理学会総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-04-30
• [Presentation] 間質性肺炎の早期線維化巣におけるIV型コラーゲンの沈着と線維芽細胞遊走についての解析 (2015)
  • Author(s): 漆山 博和 寺﨑 泰弘 永坂 真也 國保 成暁 寺崎美佳 功刀 しのぶ 清水 章
  • Organizer: 日本呼吸器学会総会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2015-04-17
• [Presentation] 水素水は抗炎症効果によりゲフィチニブによる肺障害を抑制する (2015)
  • Author(s): 池谷真澄､渡名喜梢､鈴木徹也,大城樹実､寺崎泰弘,高橋眞由美､川口英夫､服部成介､大澤郁朗
  • Organizer: 第５回分子状水素医学シンポジウム
  • Place of Presentation: 名古屋
  • Year and Date: 2015-03-21 – 2015-03-22
• [Presentation] ステロイド休薬と休業により自然軽快した自己免疫性肺胞蛋白症（PAP）の 1 例 (2014)
  • Author(s): 清水理光 、三浦由記子 、根井貴仁 、林 宏紀 、国保成暁、 功刀しのぶ 、寺崎泰弘 、齋藤好信 、弦間昭彦 、吾妻安良太
  • Organizer: 第 212 回日本呼吸器学会関東地方会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-22
• [Presentation] Hydrogen-supplemented drinking water protects against naphthalene-gefitinib induced lung injury from inflammation-associated oxidative stress. (2014)
  • Author(s): Y. Terasaki, T. Suzuki, I. Ohsawa, H. Urushiyama, M. Terasaki, M. Takahashi, S. Kunugi, A. Ishikawa, N. Kuwahara, N.. Kokuho, A. Shimizu
  • Organizer: ATS (Americam Thoracic Sciety) International Conference
  • Place of Presentation: San Diego
  • Year and Date: 2014-05-16 – 2014-05-21
• [Presentation] 高濃度水素水によるゲフィチニブの急性肺傷害抑制 (2014)
  • Author(s): 寺崎泰弘、大澤郁朗、鈴木徹也、渡名喜梢、漆山博和、寺﨑美佳、功刀しのぶ、福田 悠、清水 章
  • Organizer: 日本病理学会総会（第103回）
  • Place of Presentation: 広島
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] IV型コラーゲン関連血管新生抑制因子の肺線維芽細胞遊走への影響と間質性肺炎早期線維化巣での発現の解析 (2014)
  • Author(s): 漆山博和, 寺﨑泰弘, 寺﨑美佳, 永坂真也, 高橋美紀子、功刀しのぶ, 益田幸成, 清水 章
  • Organizer: 日本病理学会総会（第103回）
  • Place of Presentation: 広島
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 子宮ポリープ状異型腺筋腫 (atypical polypoid adenomyoma)および子宮類内膜癌におけるsurvivin発現の検討 (2014)
  • Author(s): 寺崎 美佳、寺崎 泰弘、若松 恭子、桑原 尚美、永坂 真也、高橋 美紀子、功刀しのぶ、漆山 博和、野村 俊一郎、益田 幸成、清水 章
  • Organizer: 日本病理学会総会（第103回）
  • Place of Presentation: 広島
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 気腫合併肺線維症の病理組織学的検討：分類不能型間質性肺炎に焦点をあてて (2014)
  • Author(s): 武村民子、蛇澤 晶、寺崎泰弘、小橋陽一郎、村上知之、熊坂利夫、田畑和宏, 福岡順也, 藤井丈士、河端美則、小倉高志
  • Organizer: 日本病理学会総会（第103回）
  • Place of Presentation: 広島
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 高濃度水素水はゲフィチニブの薬効を阻害することなく急性肺障害を抑制する (2014)
  • Author(s): 渡名喜梢、鈴木徹也、寺崎泰弘、村上弥生、高橋真由美、川口英夫、大澤郁朗
  • Organizer: 第4回分子状水素医学シンポジウム
  • Place of Presentation: きゅりあん 小ホール（東京）
• [Presentation] 診断に苦慮した肝細胞癌肺転移の一切除例 (2014)
  • Author(s): 竹内真吾、石角太一郎、井上達哉、飯島慶仁、揖斐孝之、寺崎美佳、寺崎泰弘、臼田実男
  • Organizer: 第169回日本肺癌学会関東支部会
  • Place of Presentation: 京王プラザホテル
• [Presentation] Comparison of pathological features of The lung lesions of systemic IgG4-related disease and multicentric Castleman's disease (2013)
  • Author(s): Y. Terasaki, S. Ikushima, Y. Ichimura, M. Ujita, Y. Matsuzawa, M. Arita, K. Tomii, Y. Komase, I. Ohwan, T. Kawamura, S. Izumi, M. Murakami, H. Ishimoto, H. Kimura, M. Bando, N. Hada, N. Nishimoto, S. Matsui, T. Ogura
  • Organizer: ATS (Americam Thoracic Sciety) International Conference
  • Place of Presentation: Philadelphia, USA
• [Presentation] gG4関連肺病変とMulticentric Castleman's disease (MCD) 肺病変の病理学的比較検討 (2013)
  • Author(s): 寺崎泰弘、蛇澤晶、河端美則、熊坂利夫、武村民子、大田泰徳、福田悠
  • Organizer: 第102回 日本病理学会総会
  • Place of Presentation: ロイトン札幌
  • Invited
• [Presentation] 間質性肺炎の早期線維化巣におけるIV型コラーゲンの線維芽細胞遊走に関する機能についての解析 (2013)
  • Author(s): 漆山博和, 寺﨑泰弘, 寺﨑美佳, 永坂真也, 高橋美紀子, 功刀しのぶ, 益田幸成, 清水 章, 福田 悠
  • Organizer: 第102回 日本病理学会総会
  • Place of Presentation: ロイトン札幌
• [Presentation] 左顎下腺に発生したmucin-rich variant salivary duct carcinomaの一例 (2013)
  • Author(s): 寺崎美佳、寺崎泰弘、若松恭子、漆山博和、高橋美紀子、功刀しのぶ、福田悠
  • Organizer: 第102回 日本病理学会総会
  • Place of Presentation: ロイトン札幌
• [Presentation] 高濃度水素水によるゲフィチニブの急性肺傷害抑制 (2013)
  • Author(s): 鈴木徹也、寺崎泰弘、渡名喜梢、大澤郁朗
  • Organizer: 第36回日本基礎老化学会
  • Place of Presentation: 大阪国際会議場
• [Presentation] 器質化肺炎の診断で治療され10年後の再燃によりIgG4関連肺疾患が疑われた一例 (2013)
  • Author(s): 小林有紀,清水理,光林宏紀,田中徹,藤田和恵,齋藤好信,吾妻安良太,弦間昭彦 寺﨑泰弘,功刀しのぶ,福田 悠
  • Organizer: 第164回日本結核病学会関東支部会
  • Place of Presentation: キッセイ文化ホール長野県
• [Book] びまん性肺疾患の分類と診断 病理診断と問題点 内科 (2016)
  • Author(s): 寺﨑 泰弘, 國保 成暁, 寺崎美佳, 功刀 しのぶ
  • Total Pages: 4
  • Publisher: 南江堂
• [Book] 上気道 集中講義 病理学 改訂第２版 (2016)
  • Author(s): 寺崎泰弘
  • Total Pages: 3
  • Publisher: メジカルビュー社
• [Book] 肺 集中講義 病理学 改訂第２版 (2016)
  • Author(s): 寺崎泰弘
  • Total Pages: 9
  • Publisher: メジカルビュー社
• [Book] 胸膜・縦隔 集中講義 病理学 改訂第２版 (2016)
  • Author(s): 寺崎泰弘
  • Total Pages: 2
  • Publisher: メジカルビュー社
• [Book] 間質性肺炎の早期線維化巣におけるcanstatinの発現とその作用の解析 びまん性肺疾患に関する調査研究 平成27年度研究報告書 (2015)
  • Author(s): 漆山博和, 寺崎泰弘, 山内康宏, 國保成暁, 寺崎美佳, 功刀しのぶ, 長瀬隆英
  • Total Pages: 9
  • Publisher: 厚生労働省難治性疾患政策研究事業
• [Book] びまん性肺疾患に関する新規戦略的研究 平成26年度研究報告書 D1CCマウスリウマチモデルの肺病変の病理形態学的に解析と高濃度水素分子(H2)水飲水の病変に対する効果 (2015)
  • Author(s): 寺崎 泰弘、國保成暁、漆山 博和、寺崎 美佳、功刀 しのぶ、丸山 基世、秋元敏雄、金澤 智
  • Total Pages: 8
  • Publisher: 厚労省科学研究委託業務難治性疾患実用化研究事業
• [Book] 日本胸部臨床 ATS/ERS 2013 IIPs分類と今後の課題：病理学的な概説と今後の課題 (2014)
  • Author(s): 寺﨑泰弘, 漆山博和, 福田悠
  • Total Pages: 12
  • Publisher: 克誠堂出版株式会社
• [Book] 病理と臨床 リンパ増殖性肺疾患 (2014)
  • Author(s): 寺﨑泰弘
  • Total Pages: 8
  • Publisher: 文光堂
• [Book] 間質性肺炎診療マニュアル 改訂第２版. II-C 特発性間質性肺炎の鑑別診断のポイント (2014)
  • Author(s): 寺﨑 泰弘、福田悠
  • Total Pages: 8
  • Publisher: 南光堂
• [Book] 肺・呼吸器領域のIgG4関連疾患の特徴と鑑別、病理学的診断基準にむけて (2014)
  • Author(s): 寺﨑泰弘、松井祥子、蛇澤晶、酒井文和、山本洋、栗原泰之、早稲田優子、河村哲治、宮下知子、井上博雅、羽田憲彦、増渕裕朗、杉野圭史、岸潤、小林英夫、石田正之、土屋裕、甲田賢治、漆山博和、國保成暁、寺﨑美佳、功刀しのぶ、河端美則、小倉高志、東京びまん性肺疾患研究会
  • Total Pages: 9
  • Publisher: びまん性肺疾患に関する調査研究 平成25 年度研究報告書
• [Remarks] 肺病変を有するMCDの臨床・画像・病理学的検討
  • URL: http://college.nms.ac.jp/files/college/ichiran_20150114.pdf