1999 年度実績報告書

血管炎症候群の分子メカニズムの解析と新たなる病理形態学的基盤の確立

研究課題

研究課題/領域番号	11307003
研究種目	基盤研究(A)
研究機関	愛媛大学
研究代表者	能勢眞人愛媛大学, 医学部, 教授 (70030913)
研究分担者	沼野藤夫東京医科歯科大学, 医学部, 教授 (40013958) 居石克夫九州大学, 大学院・医学研究科, 教授 (70108710) 吉木敬北海道大学, 医学部, 教授 (60220612) 由谷親夫国立循環器病センター臨床検査部, 部長宮地良樹京都大学, 大学院・医学研究科, 教授 (30127146)
キーワード	ウイルス / 接着分子 / サイトカイン / アポトーシス / 自己抗体 / 転写因子 / 感受性遺伝子 / ゲノム
研究概要	1)血管細胞の分子病理学的形質:ウイルスの関与について、ヒトERV3およびHTLV-1遺伝子導入ラット(吉木)、ヒトCMV前早期発現遺伝子過剰発現マウス(居石)を用いて解析した。細胞間、分子間のクロストークについては、皮膚由来血管内皮細胞株によるin vitro血管新生モデルを用いて炎症状態での接着分子群発現動態を解析した。(宮地)疾病特異的形態像は、高安動脈炎のvasa vasorum血管樹の構成、その血管内皮細胞の接着分子の発現を解析した。(伊藤)2)宿主の血管障害機構、修飾要因:肺高血圧における肺血管炎発症機構を内皮細胞障害機序との関連で解析した。(由谷)抗MPO抗体関連血管炎の病変分布と病理学的特性(中林)、抗リン脂質抗体症候群での血管病変の特性(松本)を解析した。膠原病患者血清による血管内皮細胞のアポトーシス誘導能について(澤井)、顕微鏡的多発動脈炎の糸球体腎炎との関連(秋草)、非定型的高安動脈炎症例による高安動脈炎の形態学的特性(能勢)について検討した。3)血管炎モデル:患児から得たC.albicans菌体抽出物でマウスに誘導される川崎病モデルの免疫組織学的解析(直江、)HTLV-I env-pX遺伝子導入ラットモデルでの局所リンパ球のTCRレパトアの解析を行った。(吉木)ヘルペスウイルス誘導動脈炎モデルで、炎症の制御に関わると考えられるPPARαの役割につきそのノックアウトマウスを用いて解析した。(沼野)MRL/1prマウスへのIRF-1遺伝子の導入による血管炎発症抑制機構を明らかにした。(能勢)4)ゲノム解析:高安動脈炎におけるHLA遺伝子近傍の領域を対象にタンデムリピートマーカーを用いてのリンケージ解析を行を行った。(沼野)MRL/1prループスマウスの血管感受性遺伝子座をマップし、その位置的候補疾患遺伝子を解析した。(能勢)5)地理病理学的特異性:川崎病についてハワイ日系人と中国の疫学的、病理学的解析を行った(直江)。高安動脈炎病理像の地理的バリエーションについて検討した。(沼野)

研究成果
(41件)

すべてその他

すべて文献書誌 (41件)

[文献書誌] Nakatsuru S,Terada M,Nishihara M,Kamogawa J,Miyazaki T,Qu WM,Morimoto K,Yazawa C,Ogasawara H,Abe Y,Fukui K,Ichien G,Ito RM,Mori: "Genetic dissection of the complex pathological manifestataions of collagen disease in MRL/1pr mice."Pathol Int. 49. 974-982 (1999)
[文献書誌] Nishihara M,Terada M,Kamogawa J,Ohashi Y,Mori S,Nakatsuru S,Nakamura Y,Nose M.: "Genetic basis of autoimmune sialoadenitis in MRL/1pr lupus mice:additive and hierarchical properties on polygenic inheritance."Arthritis Rheum. 42. 2616-2623 (1999)
[文献書誌] Nishihara H,Nose M,Hiai H,Minato N,Honjo T.: "Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor."Immunity. 11. 141-151 (1999)
[文献書誌] Ito MR,Terasaki S,Kondo E,Shiwaku H,Fukuoka Y,Nose M.: "Experimental lupus nephritis in severe combined immunodeficient (SCID)mice:remodelling of the glomerular lesions by bystander I"Clin Exp Immunol. 119(2). 340-345 (1999)
[文献書誌] Nose M,Terada M,Nishihara M,Kamogawa J,Miyazaki T,Qu W-M,Mori S,Nakatsuru S.: "Genome analysis of collagen disease in MRL/1pr mice:polygenic inheritance resulting in the complex pathological manifestations."Int J Cardiol. (in press).
[文献書誌] Nose M,Nishihara M,Kamogawa J,Terada M,Nakatsuru S.: "Genetic basis of autoimmune disease in MRL/1pr mice:Dissection of the complex pathological manifestations and their susceptibil"Rev Immunogenet. (in press).
[文献書誌] Nose M,Nishihara M,Fujii H.: "Lessons from MRL/1pr and related mouse models:Genetic basis of the complex pathological manifestations of collagen disease."Int Rev Immunol. (in press).
[文献書誌] Nakabayashi K,Kamiya Y,Nagasawa T.: "Aortitis syndrome associated with positive perinuclear antineutrophil cytoplasmic antibody."Int Cardiol. 68(in press). (1999)
[文献書誌] Katsumata K,Ikeda H,Sato M,Ishizu A,Kawarada Y,Kato H,Wakisaka A,Koike T,Yoshiki T.: "Cytokine regulation of env gene expression of human endogenous retrovirus-Rin human vascular endothelial cells."Clinical Immunol.. 93(1). 75-80 (1999)
[文献書誌] Chen Y-X,Nakashima Y,Tanaka K,Shiraishi S,Nakagawa K,Sueishi K: "Immunohistochemical expression of vascular endothelial growth factor(VEGF)/vascular permeability factor(VPG) in the atheroscler"Arterioscler Thromb Vasc Biol. 19(1). 131-139 (1999)
[文献書誌] Iwamoto H,Kiyohara Y,Fujishima M,Kato I,Nakayama K,Sueishi K,Tsuneyoshi M.: "Prevalence of Intracranial saccular aneurysms in a Japanese community based on a consecutive autopsy scries during a 30-year ob"Stroke. 30. 1390-1395 (1999)
[文献書誌] Watanabe N,Akikusa B,Park SY,Ohno H,Fassati L,Vecchietti G,Gessner JE,Schmidt RE,Verbeek JS,Ryffel B,Izui S,Saito T.: "Mast cells induce autoantibody-mediated vasculitis syndrome through tumor necrosis factor production upon triggering Fcr recept"Blood. 94(11). 3855-3863 (1999)
[文献書誌] Uzuki M,Watanabe T,Katsura Y,Sawai T.: "Quantiative histochemical study of Hyalurinic acid binding protein and the activity of uridine diphosphoglucise dehydrogenase i"Anal Quant Cytol Histol. 21. 75-80 (1999)
[文献書誌] Watanabe M,Sawai T.: "Alteration of cross-Linking amino acids of elastin in human aorta in association with dissecting aneurysm:analysis using high p"Tohoku Exp Med. 187. 291-303 (1999)
[文献書誌] Watanabe M,Takahashi M,Sawai T.: "Unusual renal involvement of polymyositis complicated with malignant hypertension."Jap J Rheum.. 9. 381-390 (1999)
[文献書誌] Kurose A,Oyama K,Murakami Y,Ohyama K,Segawa I,Sawai T.: "Dilated cardiomyopathy in Noonan syndrome:A first autopsy case."Human Pathology.(in press). (1999)
[文献書誌] Ito M,Matsunaga K,Sano K,Sakaguchi N,Hotchi M.: "Intravascular fasciitis of the forearm vein:a case report with immunohistochemical characterization."Pathol Int. 49(2). 175-179 (1999)
[文献書誌] Kitamura H,Kitamura H,Ito S,Kuwana N,Yutani C: "Epithelioid hemangioma of the temporal artery clinically mimicking temporal arteritis"Pathol Int. 49. 831-835 (1999)
[文献書誌] Ishibashi-Ueda H,Yutani C,Kuribayashi S,Takamiya M,Imakita M,Ando M.: "Late in-stent restenosis of the abdominal aorta in a patioent with Takayasu's arteritis and related pathology."Cardio Vascular & Interventional Radiology. 22. 333-336 (1999)
[文献書誌] Yamada K,Sugimoto K,Matsumoto T,Narumi K,Oshimi K.: "All-trans retinoic acid-induced vasculitis and hemonecrosis of the ileum in a patient with acute promyelocytic leukemia."Leukemia. 13(4). 647-648 (1999)
[文献書誌] Ogishima D,Matsumoto T,Nakamura Y,Yoshida K,Kuwabara Y.: "Placental pathology in systemic lupus erythematosus with antiphospholipid antibodies."Pathol Int(in press).
[文献書誌] Numano F.: "Vasovasoritis,vasculitis and artherosclerosis"Int.J.Card(in press). (2000)
[文献書誌] Baba T,Itakura K,Tanaka R,Kawasaki I,Kiyosawa M,Numano F.: "Importance of fluorescein angiographic study in a evaluating early rental chances in Takayasu disease."Jpn Opthalmol. 43. 546-552 (1999)
[文献書誌] Numano F,Gimbrone M.: "Inflammation and atherosclerosis"Atherosclerosis. V. (1999)
[文献書誌] Ishikawa O,Takahashi A,Tamura A,Miyachi Y.: "Cutaneous papules and nodules in the diagnosis of the antiphospholipid syndrome."Br J Dermatol. 140. 725-729 (1999)
[文献書誌] Ishikawa O,Abe M,i Miyachi Y.: "Herpes zoster in Japanese patients with systemic lupus eruthematosus."Clin Exp Dermatol. 24. 327-328 (1999)
[文献書誌] Kurosawa M,Inamura H,Amano H,Kanbe N,Nagata H,Furukawa,S,Miyachi Y.: "Nerve growth factor release with mast cell derived mediators in a patient with systemic mastocytosis after middle-wave ultravio"Allergy. 54. 994-998 (1999)
[文献書誌] 伊藤美津子,小野寺健,阿部弘之,三浦正悦,能勢眞人: "バルサルバ洞動脈瘤破裂に伴う大動脈弁断列にて急死した大動脈炎の一部検例"リウマチ. 39. 853-859 (1999)
[文献書誌] 能勢眞人: "血管炎の遺伝要因-モデルマウスのゲノム解析-"治療学. 33. 152-156 (1999)
[文献書誌] 能勢眞人: "血管炎モデルマウスのゲノム解析。"Bio Clinica. 14. 320-322 (1999)
[文献書誌] 能勢眞人: "自然発症疾患モデル動物:血管炎。"Molecular Medicine. 36. 32-36 (1999)
[文献書誌] 澤井高志,宇月美和: "リウマチの病理-動物モデルの病態解明と治療への応用-"病理と臨床(臨時増刊号・日本人の病気と病理学). 17. 321 (1999)
[文献書誌] 渡辺徹雄、澤井高志、佐藤成、宇月美和、里見進: "腹部大動脈瘤におけるMatrix metalloproteinase の役割。"脈管学(in press). 40. (2000)
[文献書誌] 三浦康宏、黒瀬顕、吉田浩子、井上洋西、澤井高志: "c-ANCAの低下とともに全身状態の悪化を示し、び慢性肺胞障害(DAD)で死亡したWegener肉芽腫症の一症例。"臨床リウマチ. (in press). (2000)
[文献書誌] 沼野藤夫: "高安動脈炎"治療学. 33.2. 59-62 (1999)
[文献書誌] 沼野藤夫: "血管炎における外膜の役割"血管と内皮. 9/3. 256-261 (1999)
[文献書誌] 中林公正(分担): "内科学(全身性血管炎の項)"分光堂(黒川清,松澤佑次,他編). (1999)
[文献書誌] 中林公正(分担): "わかりやすい内科学(ウェジナー肉芽腫症の項)"分光堂(井村裕夫,他編). (1999)
[文献書誌] Numano F.(分担): "Takayasu Arteritis:Fouth edition of the Oxford,Text Book of Medicine"Edited by D.Warrell,T.M.Cox,J.D.Firth.Oxford Univ.Press. (2000)
[文献書誌] Numano F.(分担): "Takayasu Arteritis,inflammatory disease of blood vessel"Edited by G.Hoffmann. (2000)
[文献書誌] Numano F.(分担): "Takayasu Arteritis,vascular manifestation of systeming autoimmune disease"Edited by Atheson R-Cervera et al CRC Press. (2000)

1999 年度 実績報告書

血管炎症候群の分子メカニズムの解析と新たなる病理形態学的基盤の確立

研究代表者

能勢 眞人 愛媛大学, 医学部, 教授 (70030913)

研究成果

[文献書誌] Nakatsuru S,Terada M,Nishihara M,Kamogawa J,Miyazaki T,Qu WM,Morimoto K,Yazawa C,Ogasawara H,Abe Y,Fukui K,Ichien G,Ito RM,Mori: "Genetic dissection of the complex pathological manifestataions of collagen disease in MRL/1pr mice."Pathol Int. 49. 974-982 (1999)

[文献書誌] Nishihara M,Terada M,Kamogawa J,Ohashi Y,Mori S,Nakatsuru S,Nakamura Y,Nose M.: "Genetic basis of autoimmune sialoadenitis in MRL/1pr lupus mice:additive and hierarchical properties on polygenic inheritance."Arthritis Rheum. 42. 2616-2623 (1999)

[文献書誌] Nishihara H,Nose M,Hiai H,Minato N,Honjo T.: "Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor."Immunity. 11. 141-151 (1999)

[文献書誌] Ito MR,Terasaki S,Kondo E,Shiwaku H,Fukuoka Y,Nose M.: "Experimental lupus nephritis in severe combined immunodeficient (SCID)mice:remodelling of the glomerular lesions by bystander I"Clin Exp Immunol. 119(2). 340-345 (1999)

[文献書誌] Nose M,Terada M,Nishihara M,Kamogawa J,Miyazaki T,Qu W-M,Mori S,Nakatsuru S.: "Genome analysis of collagen disease in MRL/1pr mice:polygenic inheritance resulting in the complex pathological manifestations."Int J Cardiol. (in press).

[文献書誌] Nose M,Nishihara M,Kamogawa J,Terada M,Nakatsuru S.: "Genetic basis of autoimmune disease in MRL/1pr mice:Dissection of the complex pathological manifestations and their susceptibil"Rev Immunogenet. (in press).

[文献書誌] Nose M,Nishihara M,Fujii H.: "Lessons from MRL/1pr and related mouse models:Genetic basis of the complex pathological manifestations of collagen disease."Int Rev Immunol. (in press).

[文献書誌] Nakabayashi K,Kamiya Y,Nagasawa T.: "Aortitis syndrome associated with positive perinuclear antineutrophil cytoplasmic antibody."Int Cardiol. 68(in press). (1999)

[文献書誌] Katsumata K,Ikeda H,Sato M,Ishizu A,Kawarada Y,Kato H,Wakisaka A,Koike T,Yoshiki T.: "Cytokine regulation of env gene expression of human endogenous retrovirus-Rin human vascular endothelial cells."Clinical Immunol.. 93(1). 75-80 (1999)

[文献書誌] Chen Y-X,Nakashima Y,Tanaka K,Shiraishi S,Nakagawa K,Sueishi K: "Immunohistochemical expression of vascular endothelial growth factor(VEGF)/vascular permeability factor(VPG) in the atheroscler"Arterioscler Thromb Vasc Biol. 19(1). 131-139 (1999)

[文献書誌] Iwamoto H,Kiyohara Y,Fujishima M,Kato I,Nakayama K,Sueishi K,Tsuneyoshi M.: "Prevalence of Intracranial saccular aneurysms in a Japanese community based on a consecutive autopsy scries during a 30-year ob"Stroke. 30. 1390-1395 (1999)

[文献書誌] Watanabe N,Akikusa B,Park SY,Ohno H,Fassati L,Vecchietti G,Gessner JE,Schmidt RE,Verbeek JS,Ryffel B,Izui S,Saito T.: "Mast cells induce autoantibody-mediated vasculitis syndrome through tumor necrosis factor production upon triggering Fcr recept"Blood. 94(11). 3855-3863 (1999)

[文献書誌] Uzuki M,Watanabe T,Katsura Y,Sawai T.: "Quantiative histochemical study of Hyalurinic acid binding protein and the activity of uridine diphosphoglucise dehydrogenase i"Anal Quant Cytol Histol. 21. 75-80 (1999)

[文献書誌] Watanabe M,Sawai T.: "Alteration of cross-Linking amino acids of elastin in human aorta in association with dissecting aneurysm:analysis using high p"Tohoku Exp Med. 187. 291-303 (1999)

[文献書誌] Watanabe M,Takahashi M,Sawai T.: "Unusual renal involvement of polymyositis complicated with malignant hypertension."Jap J Rheum.. 9. 381-390 (1999)

[文献書誌] Kurose A,Oyama K,Murakami Y,Ohyama K,Segawa I,Sawai T.: "Dilated cardiomyopathy in Noonan syndrome:A first autopsy case."Human Pathology.(in press). (1999)

[文献書誌] Ito M,Matsunaga K,Sano K,Sakaguchi N,Hotchi M.: "Intravascular fasciitis of the forearm vein:a case report with immunohistochemical characterization."Pathol Int. 49(2). 175-179 (1999)

[文献書誌] Kitamura H,Kitamura H,Ito S,Kuwana N,Yutani C: "Epithelioid hemangioma of the temporal artery clinically mimicking temporal arteritis"Pathol Int. 49. 831-835 (1999)

[文献書誌] Ishibashi-Ueda H,Yutani C,Kuribayashi S,Takamiya M,Imakita M,Ando M.: "Late in-stent restenosis of the abdominal aorta in a patioent with Takayasu's arteritis and related pathology."Cardio Vascular & Interventional Radiology. 22. 333-336 (1999)

[文献書誌] Yamada K,Sugimoto K,Matsumoto T,Narumi K,Oshimi K.: "All-trans retinoic acid-induced vasculitis and hemonecrosis of the ileum in a patient with acute promyelocytic leukemia."Leukemia. 13(4). 647-648 (1999)

[文献書誌] Ogishima D,Matsumoto T,Nakamura Y,Yoshida K,Kuwabara Y.: "Placental pathology in systemic lupus erythematosus with antiphospholipid antibodies."Pathol Int(in press).

[文献書誌] Numano F.: "Vasovasoritis,vasculitis and artherosclerosis"Int.J.Card(in press). (2000)

[文献書誌] Baba T,Itakura K,Tanaka R,Kawasaki I,Kiyosawa M,Numano F.: "Importance of fluorescein angiographic study in a evaluating early rental chances in Takayasu disease."Jpn Opthalmol. 43. 546-552 (1999)

[文献書誌] Numano F,Gimbrone M.: "Inflammation and atherosclerosis"Atherosclerosis. V. (1999)

[文献書誌] Ishikawa O,Takahashi A,Tamura A,Miyachi Y.: "Cutaneous papules and nodules in the diagnosis of the antiphospholipid syndrome."Br J Dermatol. 140. 725-729 (1999)

[文献書誌] Ishikawa O,Abe M,i Miyachi Y.: "Herpes zoster in Japanese patients with systemic lupus eruthematosus."Clin Exp Dermatol. 24. 327-328 (1999)

[文献書誌] Kurosawa M,Inamura H,Amano H,Kanbe N,Nagata H,Furukawa,S,Miyachi Y.: "Nerve growth factor release with mast cell derived mediators in a patient with systemic mastocytosis after middle-wave ultravio"Allergy. 54. 994-998 (1999)

[文献書誌] 伊藤美津子,小野寺健,阿部弘之,三浦正悦,能勢眞人: "バルサルバ洞動脈瘤破裂に伴う大動脈弁断列にて急死した大動脈炎の一部検例"リウマチ. 39. 853-859 (1999)

[文献書誌] 能勢眞人: "血管炎の遺伝要因-モデルマウスのゲノム解析-"治療学. 33. 152-156 (1999)

[文献書誌] 能勢眞人: "血管炎モデルマウスのゲノム解析。"Bio Clinica. 14. 320-322 (1999)

[文献書誌] 能勢眞人: "自然発症疾患モデル動物:血管炎。"Molecular Medicine. 36. 32-36 (1999)

[文献書誌] 澤井高志,宇月美和: "リウマチの病理-動物モデルの病態解明と治療への応用-"病理と臨床(臨時増刊号・日本人の病気と病理学). 17. 321 (1999)

[文献書誌] 渡辺徹雄、澤井高志、佐藤 成、宇月 美和、里見 進: "腹部大動脈瘤におけるMatrix metalloproteinase の役割。"脈管学(in press). 40. (2000)

[文献書誌] 三浦康宏、黒瀬 顕、吉田浩子、井上洋西、澤井高志: "c-ANCAの低下とともに全身状態の悪化を示し、び慢性肺胞障害(DAD)で死亡したWegener肉芽腫症の一症例。"臨床リウマチ. (in press). (2000)

[文献書誌] 沼野藤夫: "高安動脈炎"治療学. 33.2. 59-62 (1999)

[文献書誌] 沼野藤夫: "血管炎における外膜の役割"血管と内皮. 9/3. 256-261 (1999)

[文献書誌] 中林公正(分担): "内科学(全身性血管炎の項)"分光堂(黒川清,松澤佑次,他編). (1999)

[文献書誌] 中林公正(分担): "わかりやすい内科学(ウェジナー肉芽腫症の項)"分光堂(井村裕夫,他編). (1999)

[文献書誌] Numano F.(分担): "Takayasu Arteritis:Fouth edition of the Oxford,Text Book of Medicine"Edited by D.Warrell,T.M.Cox,J.D.Firth.Oxford Univ.Press. (2000)

[文献書誌] Numano F.(分担): "Takayasu Arteritis,inflammatory disease of blood vessel"Edited by G.Hoffmann. (2000)

[文献書誌] Numano F.(分担): "Takayasu Arteritis,vascular manifestation of systeming autoimmune disease"Edited by Atheson R-Cervera et al CRC Press. (2000)

1999 年度実績報告書

能勢眞人愛媛大学, 医学部, 教授 (70030913)

[文献書誌] 渡辺徹雄、澤井高志、佐藤成、宇月美和、里見進: "腹部大動脈瘤におけるMatrix metalloproteinase の役割。"脈管学(in press). 40. (2000)

[文献書誌] 三浦康宏、黒瀬顕、吉田浩子、井上洋西、澤井高志: "c-ANCAの低下とともに全身状態の悪化を示し、び慢性肺胞障害(DAD)で死亡したWegener肉芽腫症の一症例。"臨床リウマチ. (in press). (2000)