ROLE OF CALPAIN IN PATIENTS WITH RECURRENT MISCARRIAGE

• Project/Area Number: 20591924
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Nagoya City University
• Principal Investigator: OZAKI Yasuhiko Nagoya City University, 大学院・医学研究科, 准教授 (50254280)
• Co-Investigator(Kenkyū-buntansha): SUGIURA Mayumi 名古屋市立大学, 大学院・医学研究科, 教授 (30264740)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 不育症 / 習慣流産 / 着床 / 抗リン脂質抗体症候群 / プロテオリシス / カルパイン / 子宮内膜血流量 / 抗凝固療法 / プローテオリシス / カテプシン / 子宮内膜 / 血流障害 / カルパスタチン

Research Abstract

We investigated the existence and contribution of anti-calpastatin antibody and correlation with antiphoshatidylethanolaine (anti-PE) antibody in serum of recurrent miscarriage. Subject group was patients with history of recurrent miscarriage and control group was healthy women with informed consent. We performed immunohistochemistry using mid-phase endometrium to investigate localization of calpain and calpastatin. ELISA was performed to measure anti-calpastatin antibody and PE-binding protein dependent IgG antibody in sera of non-pregnancy period in each group. Staining of μ-calpain and calpastatin were observed in the cytoplasm of stromal and epithelial cells in mid-phase endometrium but no significant differences were observed in staining patterns. Subject group of anti-calpastatin antibody in sera was 4.317±0.987 (U/ml) and control group was 3.373±0.653. Subject group was significantly higher than control group. There was no significant correlation between anti-calpastatin antibody and anti-PE antibody. The result provided that calpain-calpastatin system may plays important role in endometrium of recurrent miscarriage independently from anti-PE antibody-calpain pathway.

Research Products

• [Journal Article] Antiphosphatidylethanolamine antibodies might not be independent risk factors for further miscarriage in patients suffering recurrent pregnancy loss. (2010)
  • Author(s): Obayashi S, Ozaki Y, Sugi T, Kitaori T, Katano K, Suzuki S, Sugiura-Ogasawara M
  • Journal Title: J Reprod Immunol 85 Pages: 186-192
  • Peer Reviewed
• [Journal Article] Midline uterine defect size correlated with miscarriage of euploid embryos in recurrent cases. (2010)
  • Author(s): Sugiura-Ogasawara M, Ozaki Y, Kitaori T, Kumagai K, Suzuki S.
  • Journal Title: Fertil Steril 93 Pages: 1983-1988
  • Peer Reviewed
• [Journal Article] Japanese single women have limited knowledge of age-related reproductive time limits. (2010)
  • Author(s): Sugiura-Ogasawara M, Ozaki Y, Kaneko S, Kitaori T, Kumagai K.
  • Journal Title: Int J Gynecol Obstet 109 Pages: 75-76
  • Peer Reviewed
• [Journal Article] High cerebrospinal fluid antioxidants and interleukin 8 are protective of hypoxic brain damage in newborns. (2010)
  • Author(s): Hussein MH, Daoud GA, Kakita H, Kato S, Goto T, Kamei M, Goto K, Nobata M, Ozaki Y, Ito T, Fukuda S, Kato I, Suzuki S, Sobajima H, Hara F, Hashimoto T, Togari H.
  • Journal Title: Free Radic Res 44(4) Pages: 422-429
  • Peer Reviewed
• [Journal Article] Effect of polymyxin B-immobilized fiber hemoperfusion on respiratory impairment, hepatocellular dysfunction, and leucopenia in a neonatal sepsis model. (2010)
  • Author(s): Hussein MH, Daoud GA, Kakita H, Kato S, Goto T, Kamei M, Goto K, Ozaki Y, Ito T, Fukuda S, Kato I, Suzuki S, Hashimoto T, Togari H.
  • Journal Title: Pediatr Surg Int 26(2) Pages: 187-193
  • Peer Reviewed
• [Journal Article] Nuclear translocation and calpain-dependent reduction of Bcl-2 after neonatal cerebral hypoxia-ischemia. (2010)
  • Author(s): Zhu C, Hallin U, Ozaki Y, Grander R, Gatzinsky K, Bahr BA, Karlsson JO, Shibasaki F, Hagberg H, Blomgren K.
  • Journal Title: Brain Behav Immun 24(5) Pages: 822-830
  • Peer Reviewed
• [Journal Article] The Immunological and Oxidative Effects of Applying an Extracorporeal Circuit in a Neonatal Sepsis Model (2010)
  • Author(s): MH Hussein, Ghada A. Daoud, Hiroki Kakita, Shin Kato, Tatenubo Goto, Michi Kamei, Kenji Goto, Yasuhiko Ozaki, Tetsuya Ito, Sumio Fukuda, Ineko Kato, Satoshi Suzuki, Takashi Hashimoto, Hajime Togari
  • Journal Title: Nagoya Med.J. 50 Pages: 187-197
  • Peer Reviewed
• [Journal Article] Antiphospbatidylethanolamine antibodies might not be independent risk factors for futher miscarriage in patients suffering recurrent pregnancyloss (2010)
  • Author(s): Obayashi S, Ozaki Y, Sugiura-Ogasawara M, et al
  • Journal Title: J Reprod Immulol Volume: 85 Pages: 186-192
  • Peer Reviewed
• [Journal Article] Nuclear translocation and calpain-dependent reduction of Bcl-2 after Neonatal cerebral hypoxia-ischemia (2010)
  • Author(s): Zhu C, Ozaki Y, et al
  • Journal Title: Brain Behav Immun Volume: 24 Pages: 822-830
  • Peer Reviewed
• [Journal Article] Higher serum C5a in liver transplanted pediatric patients from female donors. (2009)
  • Author(s): MH Hussein, Ghada A Daoud, Hiroki Kakita, Shin Kato, Tatenubo Goto, Michi Kamei, Kenji Goto, Yasuhiko Ozaki, Tetsuya Ito, Sumio Fukuda, Ineko Kato, Satoshi Suzuki, Takashi Hashimoto, Hajime Togari
  • Journal Title: Fujita Med.J.
  • Peer Reviewed
• [Journal Article] Live birth rate according to maternal age and previous number of recurrent miscarriages. (2009)
  • Author(s): Sugiura-Ogasawara M, Ozaki Y,Kitaori T, Suzumori N, Obayashi S. Suzuki S
  • Journal Title: Am J Reprod Immunol 62 Pages: 314-319
  • Peer Reviewed
• [Journal Article] The polycystic ovary syndrome does not predict further miscarriage in Japanese couples experiencing recurrent miscarriages. (2009)
  • Author(s): Sugiura-Ogasawara M, Sato T, Suzumori N, Nakanishi T, Nozawa K, Ozaki Y
  • Journal Title: Am J Reprod lmmunol 61 Pages: 62-67
  • Peer Reviewed
• [Journal Article] Diagnosis and treatment methods for recurrent miscarriage cases. (2009)
  • Author(s): Sugiura-Ogasawara M, Ozaki Y, Kitaori T.
  • Journal Title: Reprod Med Biol 8 Pages: 141-144
  • NAID: 110007340007
  • Peer Reviewed
• [Journal Article] Live birth rate according to maternal age and previous number of recurrent miscarriages (2009)
  • Author(s): Sugiura-Ogasawara M, Ozaki Y, et al.
  • Journal Title: Am J Reprod lmmunol 62 Pages: 314-319
  • Peer Reviewed
• [Journal Article] Diagnosis and treatment methods for recurrent miscarriage cases (2009)
  • Author(s): Sugiura-Ogasawara M, Ozaki Y, et al.
  • Journal Title: Reprod Med Biol 8 Pages: 141-144
  • NAID: 110007340007
  • Peer Reviewed
• [Journal Article] The polycystic ovary syndrome does not predict further miscarriage in Japanese couples experiencing recurrent miscarriages (2009)
  • Author(s): Sugiura-Ogasawara M, Ozaki Y, et al.
  • Journal Title: Am J Reprod lmmunol 61 Pages: 62-67
  • Peer Reviewed
• [Journal Article] Role of μ-calpain in human decidua for recurrent miscarriage. (2008)
  • Author(s): Kumagai K, Ozaki Y, Nakanishi T, Inomata M, Furuno T, Nakanishi M, Sugiura M
  • Journal Title: Am J Reprod Immunol 59 Pages: 339-346
  • Peer Reviewed
• [Journal Article] Occasional antiphospholipid antibody positive patients with recurrent pregnancy loss also merit aspirin therapy : A retrospective cohort-control study. (2008)
  • Author(s): Sugiura-Ogasawara M, Ozaki Y, Nakanishi T, Sato T, Suzumori N, Nozawa K
  • Journal Title: Am J Reprod Immunol 59 Pages: 235-241
  • Peer Reviewed
• [Journal Article] Role of μ-calpain in human decidua for recurrent miscarriage (2008)
  • Author(s): K. Kumagai, Y. Ozaki, et al.
  • Journal Title: Am J Reprod Immunol 59 Pages: 339-346
  • Peer Reviewed
• [Journal Article] Occasional antiphospholipid antibody positive patients with recurrent pregnancy loss also merit aspirin therapy (2008)
  • Author(s): M. Sugiura-Ogasawara, Y. Ozaki, et al.
  • Journal Title: Am J Reprod Immunol 59 Pages: 235-241
  • Peer Reviewed
• [Presentation] Role of cystene proteases and inhibitors in human reproduction : Symposium, The Mechanism of implantation as an invasion of cancer. (2010)
  • Author(s): Ozaki Y, Kitaori-Nakanishi T, Nishikawa H, Sugiura M
  • Organizer: XII th International Symposium on Proteinase Inhibitors and Biological Control
  • Place of Presentation: Portoroz, Slovenia
• [Presentation] Role of gingipain produced from Porphyromonas gingivalis in preterm delivery (2010)
  • Author(s): 大林伸太郎, 尾崎康彦, 後藤志信, 水谷栄太, 杉山ちえ, 熊谷恭子, 北折珠央, 安河内篤, 川久保友世, 山本健二, 杉浦真弓
  • Organizer: 25th Annual Meeting of Japan Society for Immunology of Reproduction, International Symposium for Immunology of Reproduction
  • Place of Presentation: Osaka, Japan
• [Presentation] 反復流産患者における抗cathepsin G抗体の存在と意義(学会奨励賞) (2010)
  • Author(s): 水谷栄太、尾崎康彦、森幸野、後藤志信、杉山ちえ、大林伸太郎、熊谷恭子、北折珠央、国松歳己、杉浦真弓
  • Organizer: 第15回日本病態プロテアーゼ学会
  • Place of Presentation: 大阪
• [Presentation] ヒト卵胞液中のcathepsin Eの存在と意義(学会奨励賞) (2010)
  • Author(s): 後藤志信、尾崎康彦、森幸野、服部幸雄、佐藤剛、安河内篤、川久保友世、国松己歳、山本健二、杉浦真弓
  • Organizer: 第15回日本病態プロテアーゼ学会
  • Place of Presentation: 大阪
• [Presentation] 反復流産患者における抗cathepsin G抗体の存在と意義(高得点演題) (2010)
  • Author(s): 尾崎康彦、杉山ちえ、水谷栄太、大林伸太郎、熊谷恭子、北折珠央、杉浦真弓
  • Organizer: 第62回日本産科婦人科学会学術講演会
  • Place of Presentation: 東京
• [Presentation] Occasional antiphospholipid antibody positive patients also merit aspirin herapy in recurrent pregnancy loss. (2010)
  • Author(s): Sugiura-Ogasawara M, Obayashi S, Katano K, Ozaki Y.
  • Organizer: XIIIth International Congress on Antiphospholipid Antibody
  • Place of Presentation: Galveston, USA
• [Presentation] Role of cysteine proteases and inhibitors in human reproduction (2010)
  • Author(s): Yasuhiko Ozaki
  • Organizer: XII International Symposium on Proteinase Inhibitor and Biological Control
  • Place of Presentation: Portoroz, Slovenia Grand hotel Bernardin
• [Presentation] ワークショップ(不育症と免疫)、反復流産病態における脱落膜のシステインプロテアーゼ及びインヒピターの役割 (2009)
  • Author(s): 尾崎康彦、熊谷恭子、杉浦真弓
  • Organizer: 第24回日本生殖免疫学会総会・学術集会
  • Place of Presentation: 東京
• [Presentation] 子宮奇形をもつ反復流産患者の危険因子検索とその後の生児獲得率 (2009)
  • Author(s): 杉浦真弓、尾崎康彦、佐藤剛、岡田英斡、北折珠央、服部幸雄
  • Organizer: 第54回日本生殖医学会
  • Place of Presentation: 金沢
• [Presentation] Embryonic factors as a cause of miscarriage (2009)
  • Author(s): Sugiura. Ogasawara M, Ozaki Y, Kitaori T, Obayashi S
  • Organizer: XIX International Federation of Gynecology and Obstetrics
  • Place of Presentation: Cape Town, South Africa
• [Presentation] ワークショップ、不育症の原因としての細胞遺伝学的探索 反復流産患者において子宮奇形は胎児染色体正常流産と関係する (2009)
  • Author(s): 杉浦真弓、尾崎康彦、北折珠央、鈴森伸宏、鈴木貞夫
  • Organizer: 第54回日本人類遺伝学会大会
  • Place of Presentation: 東京
• [Presentation] 反復流産患者の妊娠初期におけるcathepsin Eの存在と意義 (2009)
  • Author(s): 尾崎康彦、小林碧、安河内篤、川久保友世、国松己歳、山本健二、杉浦真弓
  • Organizer: 第14回日本病患プロテアーゼ学会
  • Place of Presentation: 大阪
• [Presentation] ワークショップ、歯周病原因菌Porphyromonas gingivalisの早産への関与 (2009)
  • Author(s): 北折珠央、尾崎康彦、大林伸太郎、杉浦真弓
  • Organizer: 第45回日本周産期・新生児医学会
  • Place of Presentation: 名古屋
• [Presentation] The true impact of congenital uterine anomalies on reproductive outcome with recurrent miscarriage. (2009)
  • Author(s): Sugiura-Ogasawara M, Ozaki Y, Kitaori T, Kumagai K, Suzuki S
  • Organizer: 25th Annual Meeting of the European Society of Human Reproduction and Embryology
  • Place of Presentation: Amsterdam. Netherlands
• [Presentation] (高得点演題)歯周病原因菌Porphyromonas gingivalisの早産への関与 (2009)
  • Author(s): 中西珠央、尾崎康彦、大林伸太郎、熊谷恭子、杉浦真弓、川久保友世、山本健二
  • Organizer: 第61回日本産科婦人科学会学術講演会
  • Place of Presentation: 京都
• [Presentation] 反復流産患者の妊娠初期におけるcathepsin Eの存在と意義 (2009)
  • Author(s): 尾崎康彦、大林伸太郎、熊谷恭子、中西珠央、川久保友世、山本健二、杉浦真弓
  • Organizer: 第61回日本産科婦人科学会学術講演会
  • Place of Presentation: 京都
• [Presentation] 反復流産病態における脱落膜のシステインプロテアーゼ及びインヒピターの役割 (2009)
  • Author(s): 尾崎康彦
  • Organizer: 第24回日本生殖免疫学会総会・学術集会 シンポジウム
  • Place of Presentation: 東京
• [Presentation] シンポジウム、染色体相互転座をもつ不育症患者に対する着床前診断の現状 (2008)
  • Author(s): 杉浦真弓、佐藤剛、服部幸雄、北折珠央、熊谷恭子、大林伸太郎、尾崎康彦
  • Organizer: 第23回日本生殖免疫学会
  • Place of Presentation: 富山
• [Presentation] The polycystic ovary syndrome in Japanese recurrent miscarriage patients. (2008)
  • Author(s): Sugiura-Ogasawara M, Sato T, Suzumori N, Nakanishi T, Nozawa K, Ozaki Y
  • Organizer: 64th Annual Meeting of the American Society of Reproductive Medicine
  • Place of Presentation: San Francisco, CA, USA
• [Presentation] Symposium : Calpain in human reproduction : Role of calpain for apoptosis of luteal function in human granulosa cells. (2008)
  • Author(s): Yasuhiko Ozaki, Shintaro Obayashi, Kyoko Kumagai, Tamao Nakanishi, Mayumi S.Ogasawara
  • Organizer: Xl th lnternational symposium on proteinase inhibitors and biological Control
  • Place of Presentation: Portroz, Slovenia
• [Presentation] Role of Calpain-Calpastatin System and Antiphosphatidylethanolamine Antibodies in Patients with Recurrent Miscarriage. (2008)
  • Author(s): Kyoko Kumagai, Yasuhiko Ozaki, Shintaro Obayashi, Tamao Nakanishi, Mayumi S Ogasawara
  • Organizer: XIth International symposium on proteinase inhibitors and biological Control
  • Place of Presentation: Portroz, Slovenia
• [Presentation] Role of Cathepsins and Cystatins in Patients with Recurrent Miscarriage. (2008)
  • Author(s): Nakanishi T, Ozaki Y, Kumagai K, Obayashi S, Sugiura-Ogasawara M
  • Organizer: Gordon Research Conferences "Proteolytic Enzymes & Their Inhibitors"
  • Place of Presentation: New London, NH, USA
• [Presentation] Role of Calpain in Human Sperm. (2008)
  • Author(s): Ozaki Y, Obayashi S, Kumagai K, Nakanishi T, Sugiura-Ogasawara M
  • Organizer: Gordon Research Conferences "Proteolytic Enzymes & Their Inhibitors"
  • Place of Presentation: New London, NH, USA
• [Presentation] Occasional antiphospholipid antibody positive patients with recurrent miscarriage also merit aspirin therapy. (2008)
  • Author(s): Sugiura-Ogasawara M, Ozaki Y, Nakanishi T, Kumagai K, Obayashi S
  • Organizer: 28th Annual Meeting of the American Society of Reproductive Immunology
  • Place of Presentation: Chicago, IL, USA
• [Presentation] シンポジウム、膠原病の難治性臓器病変への対応「抗リン脂質抗体と不育症」 (2008)
  • Author(s): 杉浦真弓、尾崎康彦、中西珠央、熊谷恭子、大林伸太郎
  • Organizer: 第52回日本リウマチ学会
  • Place of Presentation: 札幌
• [Presentation] 着床前診断不成功であった習慣流産患者のEmotion Impact (2008)
  • Author(s): 杉浦真弓、佐藤剛、服部幸雄、中西珠央、野沢恭子、尾崎康彦
  • Organizer: 第60回日本産科婦人科学会総会・学術講演会
  • Place of Presentation: 東京
• [Presentation] Role of calpain for apoptosis of lutear function in human granulose cells (Symposium) (2008)
  • Author(s): Yasuhiko Ozaki
  • Organizer: XIth Symposium on Proteinase Inhibitors and Biological Control
  • Place of Presentation: Portoroz, Slovenia
• [Remarks] ホームページ等
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