Integrative study on the biological response modifications by arginine-related molecules including NO and ADMA

• Project/Area Number: 19591201
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: University of Fukui
• Principal Investigator: TSUKAHARA Hirokazu University of Fukui, 医学部・附属病院, 講師 (90207340)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2007: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: 成育医学 / arginine / asymmetric dimethylarginine / citrulline / nitric oxide / oxidative stress / urea cycle / heme oxygenase

Research Abstract

生体にはL-arginine/NO synthase/NO系とprotein-arginine methyltransferase(PRMT)/ADMA/dimethylarginine dimethylaminohydrolase(DDAH)系が並立し、相互作用しながら血管機能・酸化還元環境を制御することを、様々な小児患者を対象に複数のバイオマーカーを計測することで示した。

Research Products

• [Journal Article] Sustaining hypercitrullinemia, hypercholesterolemia and augmented oxidative stress in Japanese children with aspartate/glutamate carrier isoform 2-citrin- deficiency even during the silent period (2009)
  • Author(s): Nagasaka H, Okano Y, Tsukahara H, Shigematsu Y, Momoi T, Yorifuji J, Miida T, Ohura T, Kobayashi K, Saheki T, Hirano K, Takayanagi M, Yorifuji T
  • Journal Title: Mol Genet Metab 97(1) Pages: 21-26
  • Peer Reviewed
• [Journal Article] Evaluation of endogenous nitric oxide synthesis in congenital urea cycle enzyme defects (2009)
  • Author(s): Nagasaka H, Tsukahara H, Yorifuji T, Miida T, Murayama K, Tsuruoka T, Takatani T, Kanazawa M, Kobayashi K, Okano Y, Takayanagi M
  • Journal Title: Metabolism 58(3) Pages: 278-282
  • Peer Reviewed
• [Journal Article] Effects of bezafibrate on dyslipidemia with cholestasis in children with familial intrahepatic cholestasis-1 deficiency manifesting progressive familial intrahepatic cholestasis (2009)
  • Author(s): Nagasaka H, Yorifuji T, Hirano K, Ota A, Toyama-Nakagawa Y, Takatani T, Tsukahara H, Kobayashi K, Takayanagi M, Inomata Y, Uemoto S, Miida T
  • Journal Title: Metabolism 58(1) Pages: 48-54
  • Peer Reviewed
• [Journal Article] 超早産児のナトリウム補充に関する検討 : 晩期循環不全発症予防における電解質管理の重要性 (2009)
  • Author(s): 徳力周子, 巨田尚子, 古畑律代, 田村知史, 川谷正男, 畑郁江, 塚原宏一, 眞弓光文
  • Journal Title: 発達腎研究会誌 (in press)
• [Journal Article] 早産児の慢性肺疾患における酸化ストレスの病態学的意義についての検討 : CO-HbとMet-Hbを指標として (2009)
  • Author(s): 徳力周子, 塚原宏一, 巨田尚子, 田村知史, 小倉一将, 川谷正男, 畑郁江, 眞弓光文
  • Journal Title: 小児科臨床 62(5) Pages: 925-930
  • Peer Reviewed
• [Journal Article] 知っておきたい泌尿器科の知識(その1)-2. 周産期における腎機能の発達 (2009)
  • Author(s): 塚原宏一, 巨田尚子, 徳力周子, 森夕起子
  • Journal Title: 小児外科 41(2) Pages: 98-103
• [Journal Article] Clinical significance of the balance between the L-arginine/NOS/NO pathway and the PRMT/ADMA/DDAH pathway (2008)
  • Author(s): Tsukahara H, Ohta N, Tokuriki S, Tamura S, Toyo-oka M, Nishijima K, Orisaka M, Kotsuji F, Ohta N, Kawakami H, Sekine K, Nagasaka H, Mayumi M
  • Journal Title: J Dev Nephrol 16(1) Pages: 21-28
• [Journal Article] Fluctuation of lipoprotein metabolism linked with bile acid-activated liver nuclear receptors in Alagille syndrome (2008)
  • Author(s): Nagasaka H, Miida T, Hirano K, Ota A, Murayama K, Yorifuji T, Kobayashi K, Takatani T, Tsukahara H, Hui SP, Takayanagi M, Chiba H
  • Journal Title: Atherosclerosis 198(2) Pages: 434-440
  • Peer Reviewed
• [Journal Article] Reduced apolipoprotein E-rich high-density lipoprotein level at birth is restored to the normal range in patients with familial hypercholesterolemia in the first year of life (2008)
  • Author(s): Nagasaka H, Miida T, Hirano K, Ota A, Yorifuji T, Takatani T, Tsukahara H, Takayanagi M, Hui SP, Kobayashi K, Chiba H
  • Journal Title: J Clin Endocrinol Metab 93(3) Pages: 779-783
  • Peer Reviewed
• [Journal Article] Determination of asymmetric dimethylarginine, an endogenous nitric oxide synthase inhibitor, in umbilical blood (2008)
  • Author(s): Tsukahara H, Ohta N, Tokuriki S, Nishijima K, Kotsuji F, Kawakami H, Ohta N, Sekine K, Nagasaka H, Mayumi M
  • Journal Title: Metabolism 57(2) Pages: 215-220
  • Peer Reviewed
• [Journal Article] High levels of growth factors in human breast milk (2008)
  • Author(s): Kobata R, Tsukahara H, Ohshima Y, Ohta N, Tokuriki S, Tamura S, Mayumi M
  • Journal Title: Early Hum Dev 84(1) Pages: 67-69
  • Peer Reviewed
• [Journal Article] 動脈管早期閉鎖により新生児遷延性肺高血圧症をきたした1例 (2008)
  • Author(s): 巨田尚子, 田村知史, 徳力周子, 小倉一将, 畑郁江, 塚原宏一, 鈴木千代, 西島浩二, 折坂誠, 小辻文和, 眞弓光文
  • Journal Title: 小児科臨床 61(8) Pages: 1685-1689
  • Peer Reviewed
• [Journal Article] 超早産児での晩期循環不全発症予防におけるナトリウム補充の重要性 (2008)
  • Author(s): 徳力周子, 塚原宏一, 古畑律代, 巨田尚子, 田村知史, 鈴木孝二, 畑郁江, 眞弓光文
  • Journal Title: 小児科臨床 61(8) Pages: 1679-1684
  • Peer Reviewed
• [Journal Article] 座談会 : AKIの早期診断・早期治療へ向けて (2008)
  • Author(s): 野入英世, 伊西洋二, 塚原宏一, 菅谷健
  • Journal Title: 内科 102(1) Pages: 115-124
• [Journal Article] 新生児の循環の適応生理 : 新生児の心臓血管ホルモンの適応生理 (2008)
  • Author(s): 塚原宏一
  • Journal Title: Neonatal Care 21(5) Pages: 437-444
• [Journal Article] 慢性腎臓病の予防に向けた腎機能検査 : 小児医療における腎機能評価 (2008)
  • Author(s): 塚原宏一
  • Journal Title: 臨床化学 37(1) Pages: 35-44
• [Journal Article] Determination of asymmetric diraethylarginine, an endogenous nitric oxide synthase inhibitor. in umbilical blood (2008)
  • Author(s): Tsukahara H, et al.
  • Journal Title: Metabolism 57 Pages: 215-220
  • Peer Reviewed
• [Journal Article] Reduced apolipoprotein E-rich high-density lipoprotein level at birth is restored to the normal range in patients with familial hypercholesterolemia in the first year of life (2008)
  • Author(s): Nagasaka H, et al.
  • Journal Title: J Clin Endocrinol Metab 93 Pages: 779-783
  • Peer Reviewed
• [Journal Article] Evaluation of endogenous nitric oxide synthesis in congenital urea cycle enzyme defects (2008)
  • Author(s): Nagasaka H, et al.
  • Journal Title: Metabolism 58 Pages: 278-282
  • Peer Reviewed
• [Journal Article] High levels of growth factors in human breast milk (2008)
  • Author(s): Kobata R, et. al.
  • Journal Title: Early Hum Dev 84 Pages: 67-69
  • Peer Reviewed
• [Journal Article] Determination of asymmetric dimethylarginine, an endogenous nitric oxide synthase inhibitor, in umbilical blood (2008)
  • Author(s): Tsukahara H, et. al.
  • Journal Title: Metabolism 57 Pages: 215-220
  • Peer Reviewed
• [Journal Article] Leukotriene D4 enhances the function of endothelin-1-primed fibroblasts (2007)
  • Author(s): Tokuriki S, Ohshima Y, Yamada A, Ohta N, Tsukahara H, Mayumi M
  • Journal Title: Clin Immunol 125(1) Pages: 88-94
  • Peer Reviewed
• [Journal Article] Depletion of high-density lipoprotein and appearance of triglyceride-rich low-density lipoprotein in a Japanese patient with FIC1 deficiency manifesting benign recurrent intrahepatic cholestasis (2007)
  • Author(s): Nagasaka H, Chiba H, Hui SP, Takikawa H, Miida T, Takayanagi M, Yorifuji T, Hasegawa M, Ota A, Hirano K, Kikuchi H, Tsukahara H, Kobayashi K
  • Journal Title: J Pediatr Gastroenterol Nutr 45(1) Pages: 96-105
  • Peer Reviewed
• [Journal Article] Biomarkers for oxidative stress : Clinical application in pediatric medicine (2007)
  • Author(s): Tsukahara H
  • Journal Title: Curr Med Chem 14(3) Pages: 339-351
  • NAID: 120000807657
  • Peer Reviewed
• [Journal Article] Procedures for prevention of perinatal group B streptococcal diseases : A multicenter questionnaire survey of hospitals in the Kyoto Neonatal Disease Study Group, Japan (2007)
  • Author(s): Matsubara K, Kawai M, Nakahata T, Kato F, Tsukahara H, Yamakawa M, Hashimoto K, Shimada S, Maeda S, Okumura M, Kanaoka H
  • Journal Title: J Infect Chemother 13(1) Pages: 59-62
  • NAID: 10018552919
  • Peer Reviewed
• [Journal Article] Lowest effective dose of dexamethasone in the respiratory care of very preterm infants (2007)
  • Author(s): Tsukahara H, Mayumi M
  • Journal Title: Early Hum Dev 83(1) Pages: 3-3
  • NAID: 120000807736
  • Peer Reviewed
• [Journal Article] 先天性腎尿路異常症患者における酸化ストレス環境の評価 : 当院の年齢別基準値に基づいて (2007)
  • Author(s): 塚原宏一, 平岡政弘, 森夕起子, 巨田尚子, 徳力周子, 川谷正男, 長坂博範, 川上寿子, 関根恭一, 眞弓光文
  • Journal Title: 小児腎臓病学会雑誌 20(2) Pages: 131-135
  • NAID: 10025701128
  • Peer Reviewed
• [Journal Article] 酸化ストレスとレドックス制御 (2007)
  • Author(s): 塚原宏一
  • Journal Title: 総合臨床 56(10) Pages: 2915-2918
• [Journal Article] エリスロポイエチン高値の生体応答学的意義について (2007)
  • Author(s): 塚原宏一, 小倉一将, 古畑律代, 田村知史, 眞弓光文, 西島浩二, 宿南憲一, 小辻文和, 上野正樹
  • Journal Title: 発達腎研究会誌 15(1) Pages: 25-33
• [Journal Article] 慢性腎臓病-CKDキャンペーンをめぐる話題. 国内外のCKDに対するエビデンス : 小児CKD (2007)
  • Author(s): 塚原宏一
  • Journal Title: 内科 100(1) Pages: 79-83
• [Journal Article] Biomarkers for oxidative stress: Clinical application in pediatric medicine (2007)
  • Author(s): Tsukahara H
  • Journal Title: Curr Med Chem 14 Pages: 339-351
  • NAID: 120000807657
  • Peer Reviewed
• [Journal Article] Nitric oxide metabolism in asymptomatic preschool children with congenital anomalous portal veins presenting porto-systemic venous shunt flow
  • Author(s): Takatani T, Nagasaka H, Sugamoto K, Aizawa M, Miida T, Yorifuji T, Tajima G, Sakura N, Murayama K, Sanayama T, Okano Y, Mayumi M, Kobayashi K, Hirano K, Takayanagi M, Tsukahara H
  • Journal Title: Metabolism 2009 (in press)
  • Peer Reviewed
• [Journal Article] Lipoprotein profiles in children with two common cholesteryl ester transfer protein gene mutations, D442G and I14A, during the first year of life
  • Author(s): Nagasaka H, Yorifuji T, Momoi T, Yorifuji J, Hirano K, Ota A, Takatani T, Tsukahara H, Takayanagi M, Kobayashi K, Chiba H, Sato Y, Miida T
  • Journal Title: Clin Chim Acta 2009 (in press)
  • Peer Reviewed
• [Presentation] 酸化ストレスマーカーの現況と今後の展開(特別講演) (2008)
  • Author(s): 塚原宏一
  • Organizer: 第82回日本感染症学会総会
  • Place of Presentation: 松江
  • Year and Date: 2008-04-18
• [Presentation] 先天性腎尿路異常症患者における酸化ストレス環境の評価 (2008)
  • Author(s): 塚原宏一
  • Organizer: 第55回日本臨床検査医学会学術集会
  • Place of Presentation: 名古屋
• [Presentation] 尿素サイクル異常症とNO産生 (2008)
  • Author(s): 長坂博範, 塚原宏一, 依藤亨, 岡野善行, 村山圭, 高柳正樹
  • Organizer: 第50回日本先天代謝異常学会
  • Place of Presentation: 米子
• [Presentation] 酸化ストレスマーカーの臨床応用 (2008)
  • Author(s): 塚原宏一, 森夕起子, 眞弓光文
  • Organizer: 第16回中部小児腎臓病研究会
  • Place of Presentation: 松本
• [Presentation] Activating mutation of heme oxygenase(HO)-1 : A novel disease entity characterized by microcytic, hemolytic anemia, a defect of bilirubin synthesis and hereditary hemophagocytic lymphohistiocytosis (2007)
  • Author(s): Greil J, Verga-Falzacappa M, Tsukahara H, Behnisch W, Heimpel H, Schneider M, Janka G, Claus M, Muckenthaler M, Kulozik AE
  • Organizer: 49th Annual Meeting of American Society of Hematology
  • Place of Presentation: Georgia, USA
• [Presentation] Congenital porto-systemic venous shuntの病的意義 (2007)
  • Author(s): 長坂博範, 塚原宏一, 村山圭, 高柳正樹
  • Organizer: 第49回日本先天代謝異常学会
  • Place of Presentation: 山形
• [Presentation] TNF-alphaによるヒト肺微小血管内皮細胞での接着分子・ケモカイン発現過剰に対するレドックス制御の抗炎症性効果 (2007)
  • Author(s): 塚原宏一, 眞弓光文
  • Organizer: 第39回日本小児感染症学会総会・学術集会
  • Place of Presentation: 横浜
• [Presentation] Oxidative stress status in children with congenital renal anomalies (2007)
  • Author(s): Tsukahara H, Hiraoka M, Mori Y, Tamura S, Kawakami H, Sekine K, Mayumi M
  • Organizer: 40th AnnualMeeting of American Society of Nephrology
  • Place of Presentation: San Francisco USA
• [Presentation] ヒトにおけるL-arginine/NOS/NO系とPRMT/ADMA/DDAH系のバランスの生理学的意義について (2007)
  • Author(s): 塚原宏一, 巨田尚子, 田村知史, 眞弓光文, 西島浩二, 折坂誠, 小辻文和, 長坂博範, 川上寿子, 太田徳仁, 関根恭一
  • Organizer: 第16回発達腎研究会
  • Place of Presentation: 東京
• [Presentation] 先天性腎尿路異常症患者における酸化ストレス環境の評価 : 当院の正常参考値に基づいて (2007)
  • Author(s): 塚原宏一, 平岡政弘, 森夕起子, 眞弓光文, 川上寿子, 関根恭一
  • Organizer: 第42回日本小児腎臓病学会学術集会
  • Place of Presentation: 横浜
• [Presentation] Oxidative stress status in children with congenital renal anomalies (2007)
  • Author(s): Tsukahara H, et. al.
  • Organizer: 40th Annual Meeting of American Society of Nephrology
  • Place of Presentation: 米国サンフランシスコ