アンチセンスDNAを用いた新しい診断・治療法開発に関する日米英共同研究

• 研究課題/領域番号: 08045063
• 研究種目: 国際学術研究
• 配分区分: 補助金
• 応募区分: 大学協力
• 研究分野: 医化学一般
• 研究機関: 金沢大学
• 研究代表者: 山本 博 金沢大学, 医学部, 教授 (00115198)
• 研究分担者: グラスビー ジェーン A シェフィールド大学, 化学部, 講師 ; ミカエル ブラックバーン シェフィールド大学, 生物有機化学部, 教授 ; ラマナサン ムラリ ニューヨーク州立大学, 薬学部, 助教授 ; ストロービンガー ロバー ニューヨーク州立大学, 薬学部, 助教授 ; ファン ホ・ロン ニューヨーク州立大学, 薬学部, 教授 ; BLACKBURN G.Michael Unive.of Sheffield, Dept.Chem., Professor ; FUNG Ho-Leung State Univ.of New York at Buffalo, Faculty of Health Sciences, Professor ; STRAUBINGER Robert M. State Univ.of New York at Buffalo, Faculty of Health Sciences, Associate Profess ; GRASBY J.A. Univ.of Sheffield, Dept.Chem., Lecturer ; ブラックバーン ジョージ シェフィールド大学, 生物有機化学部, 教授 ; ストロー ビンガー ロバ ニューヨーク州立大学, 薬学部, 助教授 ; ロンファン ホ ニューヨーク州立大学, 薬学部, 教授 ; BLACKBURN Je 米国, シェフィールド大学, 教授 ; GRASBY Jane 米国, シェフィールド大学, 講師 ; RAMANATHAN M 米国, ニューヨーク州立大学, 助教授 ; STRAUBINGER ロバート エム 米国, ニューヨーク州立大学, 助教授 ; FUNG HoーLeun 米国, ニューヨーク州立大学, 教授 ; 横山 邦彦 金沢大学, 医学部附属病院, 助手 (60230661) ; 米村 豊 金沢大学, 医学部附属病院, 講師 (20167042) ; 中島 恵美 金沢大学, 医学部附属病院, 助教授 (90115254) ; 市村 藤雄 金沢大学, 医学部附属病院, 教授 (40143911) ; 原田 真市 金沢大学, 医学部, 助手 (90272955) ; 米倉 秀人 金沢大学, 医学部, 助教授 (80240373)
• 研究期間 (年度): 1996 – 1998
• 研究課題ステータス: 完了 (1998年度)
• 配分額: 7,200千円 (直接経費: 7,200千円); 1998年度: 2,400千円 (直接経費: 2,400千円); 1997年度: 2,400千円 (直接経費: 2,400千円); 1996年度: 2,400千円 (直接経費: 2,400千円)
• キーワード: antisense / antisense display / nucleoside / ribozyme / liposome / aptamer / アンチセンス / がん / 血管新生 / 薬剤耐性リポソーム / リポソーム / 修飾オリゴヌクレオチド

研究概要

(目的)
本研究は、金沢大学と米国・ニューヨーク州立大学バッファロー校、英国・シェフィールド大学との学術交流協定に基づき、3大学が擁する国際的にも屈指のアンチセンスDNA研究陣を結集して、アンチセンスDNAの有機化学・生化学・薬理学・薬剤動態学に関する学際研究を格段に発展させ、特異的メッセンジャーRNAを標的とした各種疾病の新しい診断・治療原理を開発することを目的とする。
平成8-10年度研究は概ね当初計画通り順調に進行し、以下の成果を得た。
(1) 日本側分担者は、(1)がん増殖・浸潤、(2)血管新生、(3)薬剤耐性の阻止に有効と考えられるアンチセンスDNA標品を開発した。また、アンチセンス法を用いた新しい機能性遺伝子スクリーニング法を考案し、Antisense Display法と命名した。さらに、本法をヒト血管内皮細胞を用いたスクリーニングに応用し、血管新生制御に関与すると考えられる新規遺伝子の分離に成功した。
(2) 米国側分担者は、薬物動態力学モデルでの各種低分子製剤の用量-作用連関解明に基づき、修飾リポソームを用いた核酸薬品の高効率デリバリー法の開発に成功した。また、抗インターフェロン活性をもつ短鎖DNAを分離し、そのメカニズムはリガンドの高次構造を変化させるアプタマー作用によることを明らかにした。
(3) 英国側分担者は、加水分解抵抗性のホスホネート修飾オリゴヌクレオチド、抗血液凝固活性をもつヌクレオチド誘導体、Mn^<++>要求性新規ヘアピン型リボザイムの開発に成功した。
(4) 平成8年度には、日本側分担者が米国を訪問してアンチセンス薬品の動態に関する調査研究を行うとともに、英国側分担者が来日してアンチセンスDNA/RNAの化学・生物学に関するセミナーと研究打ち合わせを行った。翌9年度には、日本側代表者が英国を訪問してアンチセンスとリボザイムの化学・医学生物学に関する研究打合せを行うとともに、米国側分担者が来日してリポソームを用いたアンチセンス薬品のデリバリーとアンチセンスDNAのアプタマー作用に関する研究打合せを行った。最終年度には、日米英三国の研究分担者と研究協力者が金沢に集い、アンチセンスDNA/RNAおよびその応用に関する公開ジョイント・セミナーを開催した。

研究成果

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• [文献書誌] Ishizaki, J.: "Effect of Sequence of Adiministration on the Pharmacokinetic Interaction between the Anticholinergic Drug Biperiden and [^3H] Quinuclidinyl Benzylate of [3H] N-Methylscopolamine in Rats." J.Pharm.Pharmacol.50. 189-196 (1998)
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• [文献書誌] Ishizaki, J.: "Infuence of Ammonium Chloride on the Tissue Distribution of Anticholinergic Drugs in Rats." J.Pharm.Pharmacol.50. 761-766 (1998)
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• [文献書誌] Ishizaki, J.: "Uptake of Basic Drugs into Rat Lung Granule Fraction in Vitro." Biol.Pharm.Bull.21. 858-861 (1998)
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• [文献書誌] Tabrizi-Fard MA: "Effects of nitro-L-arginine on blood pressure and cardiac index in anesthetized rats : a pharmacokinetic-pharmacodynamic analysis." Pharm Res. 15(7). 1063-1068 (1998)
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• [文献書誌] Balasubramanian V.: "Interferon-gamma-inhibitory oligodeoxynucleotidesalter the conformation of interferon-gamma." Mol Pharmacol. 53(5). 926-932 (1998)
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• [文献書誌] Caplan NA: "Novel bisphosphonate inhibitors of phosphoglyceratekinase." Bioorg Med Chem Lett. 8(5). 515-520 (1998)
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• [文献書誌] Blackburn GM: "Two hydrolase resistant analogues of diadenosine 5', 5'P1, P3-triphosphate for studies with Fhit, the human fragile histidine triad protein." Nucleosides Nucleotides. 17(1-3). 301-308 (1998)
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• [文献書誌] 山本 博: "「細胞工学」動脈硬化+高脂血症研究ストラテジー : VEGF" 秀潤社, 464 (1996)
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• [文献書誌] 山本 博: "KEY WORD 1996-'97「炎症・免疫系」 : FltとFlk" 先端医学社, 191 (1996)
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• [文献書誌] 山岸 昌一: "「血管新生のメカニズムと疾患」 : 周皮細胞" 医薬ジャーナル社, 287 (1996)
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• [文献書誌] 山岸 昌一: "「COMPLICATION-糖尿病と血管-」創刊号 : 微小血管障害-血管新生" メディカルビュー社, (1996)
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• [文献書誌] 山岸 昌一: "「分子糖尿病学」 : 後期糖化反応生成物(AGE)による血管内皮細胞・周皮細胞傷害とその分子機構-糖尿病性細小血管症の成因・予防への新観点" 医学図書出版, 213 (1996)
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• [文献書誌] 三浦順之助: "「分子糖尿病学」 : 長期罹病IDDM患者の末梢血単球におけるAGEレセプター遺伝子の発現" 医学図書出版, 213 (1996)
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• [文献書誌] Yonemura, Y.: "Contemporary approaches toward cure of gastric cancer (Edited by Yutaka Yonemura)" Maeda Shoten Co., Ltd., 197 (1996)
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• [文献書誌] 山本 博(平賀紘一、山本博、伊達孝保、野口民夫編): "「医学のための基礎分子細胞生物学」細胞の基本構造、血管新生、老化、遺伝病(1)、遺伝病(2)" 南山堂, 122 (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] 米倉秀人(平賀紘一、山本博、伊達孝保、野口民夫編): "「医学のための基礎分子細胞生物学」インスリン・グルカゴン、血管作動性物質" 南山堂, 122 (1997)
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• [文献書誌] 山岸昌一: "「分子糖尿病学」 : Advanced Glycation Endoproductsの血管新生活性について" 医学図書出版, 262 (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] 山本靖彦: "「分子糖尿病学」 : 糖尿病-膵癌合併の分子メカニズム" 医学図書出版, 262 (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] 米村 豊: "「胃外科」 : 胃癌における遺伝子異常" 医学書院, (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] 米村 豊: "スキル胃癌-基礎と臨床- : スキル胃癌の転移再発形式" 医薬ジャーナル社, (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] 山岸昌一: "Therapeutic Research 19(2) : 糖尿病と血管新生" ライフサイエンス出版(株), 254 (1998)
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• [文献書誌] 山岸昌一: "実験医学「血管の分子医学その最前線」 : 糖尿病性網膜症の血管生物学" 羊土社, 208 (1998)
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• [文献書誌] 藤森英希: "「血管と内皮」特集 : 内皮のストレスとその応答 AGEと内皮応答" メディカルレビュー社, 100 (1998)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] 米倉秀人: "「KEY WORD 1998-2000 高血圧症・動脈硬化」 : 3章 血管新生" 先端医学社(齋籐 康、萩原俊男、馬渕 宏編), 207 (1998)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] 山本靖彦: "「現代医療」 : 糖尿病-AGE受容体" 現代医療社, 344 (1998)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Yonemura, Y.: "Peritoneal Dissemination - Molecular mechanisms and the latest therapy -" Maeda Shoten Kanazawa (Japan), (1998)
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• [文献書誌] 山岸昌一: "「メビオ」 : 糖尿病と網膜血管障害" (株)メジカルビュー社, in press (1999)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] 山岸昌一: "「組織培養工学」 : 糖尿病と血管新生" ニューサイエンス社, in press (1999)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] 山本 宏(平賀紘一、山本宏、伊達孝保、野口民夫編): "「医学のための基礎分子細胞生物学」第2版 細胞の基本構造、老化、遺伝病(1)、遺伝病(2)" 南山堂, 131 (1999)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] 米倉秀人(平賀紘一、山本博、伊達孝保、野口民夫編): "「医学のための基礎分子細胞生物学」第2版 インスリン・グルカゴン、血管作動性物質" 南山堂, 131 (1999)
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• [文献書誌] 山岸昌一(平賀紘一、山本博、伊達孝保、野口民夫編): "「医学のための基礎分子細胞生物学」第2版 血管新生" 南山堂, 131 (1999)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Kaji, M., Yonemura.Y., Harada.S., Liu, X., Terada, I.and Yamamoto, H.: "Participation of c-met in the progression of human gastric cancers ; Anti-c-met oligonucleotides inhibit proliferation or invasiveness of gastric cancer cells." Cancer Gene Therapy. 3 (6). 393-404 (1996)
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• [文献書誌] Yamagishi, S., Yamamoto, Y., Harada, S., Hsu, C.-C.and Yamamoto.H.: "Advanced glycosylation end products stimulate the growth but inhibit the prostacyclin-producing ability of endothelial cells through interactions with their receptors." FEBS Lett.384. 103-106 (1996)
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• [文献書誌] Yamamoto, Y., Yamagishi, S., Hsu, C.-C.and Yamamoto.H.: "Advanced glycation endproducts-receptor interactions stimulate the growth of human pancreatic cancer cells through the induction of platelet-derived growth factor-B." Biochem.Biophys.Res.Commun.222 (3). 700-703 (1996)
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• [文献書誌] Yonemura, Y., Kaji, M., Hirono, Y., Fushida, S., Tsugawa, K., Fujimura, T., Miyazaki, I., Harada.S., Yamamoto, H.: "Correlation between overexpression of c-met gene and the progression of gastric cancer." Int.J.Oncology. 8. 555-560 (1996)
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• [文献書誌] Hatakeyama, H., Miyamori, I., Takeda, Y., Yamamoto, H.and Mabuchi, H.: "The expression of steroidogenic enzyme genes in human vascular cells." Biochemistry and Molecular Biology International. 40 (3). 639-645 (1996)
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• [文献書誌] Hirono, Y., Fushida, S., Yonemura, Y., Yamamoto, H., Watanabe, H.and Raz, A.: "Expression of autocrine motility factor receptor correlates with disease progression in human gastric cancer." British Journal of Cancer. 74. 2003-2007 (1996)
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• [文献書誌] Yonekura, H., Anzai, T., Kato, I., Furuya, Y., Shizuta, S., Takasawa, S., and Okamoto, H.: "Identification of the five essential histidine residues for peptidylglycine monooxygenase." Biochem.Biophys.Res.Commun.218. 495-499 (1996)
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• [文献書誌] Yamada, S., Kawasaki, M., Gunji, Y., Ronan, P., Harada, S., Yamamoto, H.: "Effects of low frequency magnetic fields on DNA synthesis." IEEE Trans.on Magnetics. 32 (6). 5115-5117 (1996)
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• [文献書誌] Ishizaki, J., Yokogawa, K., Hirano, M., Nakashima, E., Sai, Y., Ohkuma, S., Ohshima, T.and Ichimura, F.: "Contribution of Lysosomes to the Subcellular Distribution of Basic Drugs in the Rat Liver" Pharm.Res.13. 902-906 (1996)
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• [文献書誌] Nakashima, E., Oya, A., Kubota, Y., Kanada, N., Matsushita, R., Takeda, K., Ichimura, F., Kuno, K., Mukaida, N., Hirose, K., Nakanishi, I., Ujiie, T.and Matsushima, K.: "A Candidate fo Cancer Gene Therapy : Mip-1alpha Gene Transfer to and Adenocarcinoma Cell Line Reduced Tumorigenicity and Induced Protective Immunity in Immunocompetent Mice." Pharm.Res.13. 1896-1901 (1996)
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• [文献書誌] Yonemura, Y.., Kinoshita, K., Fujimura, T., Fushida, S., Sawa, T., Matsuki, N., Tanaka, S., Kamata, T., Takashima, T., Miyazaki, I.: "Correlation of the histological effects and survival after neoadjuvant chemotherapy on gastric cancer patients." Hepato-Gastroenterol. 43 (11). 1260-1272 (1996)
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• [文献書誌] Fushida, S., Yonemura, Y.., Takamura, H., Hirono, Y., Miyazaki, I., Urano, T.: "Decreased expression of p16 gene in gastric cancer." Int.J.Oncl.8. 963-967 (1996)
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• [文献書誌] Yonemura, Y.., Endou, Y., Yamaguchi, T., Nojima, N., Kawamura, T., Fujimura, T., Obata, T., B.S.Kim, Miyazaki, I., Sasaki, T.: "Roles of VLA-2 and VLA-3 on the formation of peritoneal dissemination in gastric cancer" Int.J.Oncl.8. 925-931 (1996)
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• [文献書誌] Yonemura, Y., Endo, Y., Yamaguchi, T., Fujimura, T., Obata, T., Kawamura, T., Nijima, N., Miyazaki, I.Sasaki, T.: "Mechanisms of the formation of the peritoneal dissemination in gastric cancer." Int.J.Oncl.8. 795-802 (1996)
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• [文献書誌] Fujimura, T., Yonemura, Y.., Kawamura, T., Nojima, N., Satoh, T., Hirono, Y., Kinami, S., Fushida, S., Nishimura, G., Miwa, K., Miyazaki, I.: "Cytoreductive surgery and sandwich therapy with chemohyperthermic peritoneal perfusion and- intra-aortic chemotherapy for peritoneal dissemination in gastric cancer" Oncol.Rep.3. 513-517 (1996)
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• [文献書誌] Nishimura, G., Fushida, S., Fujimura, T., Yonemura, Y.., Miwa, K., Miyazaki, I.: "Intraperitoneal treatment for peritoneal dissemination of colorectal cancer." Reg Cancer Treat. 9. 60-62 (1996)
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• [文献書誌] Yonemura, Y.., Fujimura, T., Nishimura, G., Raul Falla, Sawa, T., Katayama, K., Tsugawa, K., Fushida, S., Miyazaki, I., Tanaka, M., Endou, Y., Sasaki, T.: "Effects of intraoperative chemohyperthermia in patients with gastric cancer with peritoneal dissemination." Surgery. 119 (4). 437-443 (1996)
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• [文献書誌] Ito, H., Yonemura, Y.., Fujita, H., Tsuchihara, K., Kawamura, T., Nojima.N., Fujimura, T., Nose, H., Endo, Y., Sasaki, T.: "Prognostic relevance of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitors PAI-1 and PAI-2 in gastric cancer" Virchows Arch. 427-487 (1996)
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• [文献書誌] Yonemura, Y.: "Invited commentary." World J Surg. 20. 529 (1996)
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• [文献書誌] Kinuya S,Yokoyama K,Haji K,Konishi S,Hwang EH,Michigishi T,Tonami N: "In-111 labeled leukocyte scintigraphy of infected prosthesis with Candida parapsilosis in a patient without predisposing risk factors." Clin Nucl Med 1996 Nov. 21 (11). 885-886
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• [文献書誌] Kinuya S,Yokoyama K,Michigishi T, Tonami N: "I-131 accumulation in folliculitis of the scalp." Clin Nucl Med 1996 Oct. 21 (10). 807-808
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• [文献書誌] Kinuya S,Yokoyama K,Konishi S,Tonami N,Hisada K: "Effect of induced hypertension with angiotensin II infusion on biodistribution of 111 in-labeled monoclonal antibody." Nucl Med Biol 1996 Feb. 23 (2). 137-140
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• [文献書誌] Kinuya S,Yokoyama K,Konishi S,Hwang EH,Takayama T,Michigishi T,Tonami N: "201T1 and 99Tcm-human serum albumin for assessment of the effect of hypertensive treatment with angiotensin II infusion on tumour circulation." Nucl Med Commun 1996 Feb. 17 (2). 160-163
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• [文献書誌] Watanabe N,Seto H,Yokoyama K,Matsuda H,Shimizu M,Tonami N,Hisada K,Kakishita M: "Scintigraphic study of malignant melanoma with 123I-iodoamphetamine." Nucl Med Commun 1996 Feb. 17 (2). 153-159
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• [文献書誌] Tabrizi-Fard MA,Fung HL: "Pharmacokinetics and steady-state tissue distribution of L-and D-isomers of nitroarginine in rats." Drug Metab Dispos 1996 Nov. 24 (11). 1241-1246
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• [文献書誌] Balthasar JP,Fung HL: "Inverse targeting of peritoneal tumors : selective alteration of the disposition of methotrexate through the use of anti-methotrexate antibodies and antibody fragments." J Pharm Sci 1996 Oct. 85 (10). 1035-1043
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• [文献書誌] Booth BP,Jacob S,Bauer JA,Fung HL: "Sustained antiplatelet properties of nitroglycerin during hemodynamic tolerance in rats." J Cardiovasc Pharmacol 1996 Sep. 28 (3). 432-438
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• [文献書誌] Bauer JA,Fung HL: "Arterial versus venous metabolism of nitroglycerin to nitric oxide : a possible explanation of organic nitrate venoselectivity." J Cardiovasc Pharmacol 1996 Sep. 28 (3). 371-374
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• [文献書誌] Bauer JA,Fung HL: "Specific binding of nitroglycerin to coronary artery microsomes.Evidence of a vascular nitrate binding site." Biochem Pharmacol 1996 Aug 23. 52 (4). 619-625
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• [文献書誌] Tabrizi-Fard MA,Fung HL: "Reversed-phase high-performance liquid chromatography method for the analysis of nitro-arginine in rat plasma and urine." J Chromatogr B Biomed Appl 1996 Apr 26. 679 (1-2). 7-12
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• [文献書誌] Kishnani NS, Fung HL: "Nitric oxide generation from pharmacological nitric oxide donors." Methods Enzymol. 268. 259-265 (1996)
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• [文献書誌] Balthasar JP,Fung HL: "Pharmacokinetic and pharmacodynamic optimization of intraperitoneal chemotherapy." Life Sci. 58 (7). 535-543 (1996)
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• [文献書誌] Sharma A,Sharma US,Straubinger RM: "Paclitaxel-liposomes for intracavitary therapy of intraperitoneal P388 leukemia." Cancer Lett 1996 Oct 22. 107 (2). 265-272
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• [文献書誌] Oh YK,Straubinger RM: "Intracellular fate of Mycobacterium avium : use of dual-label spectrofluorometry to investigate the influence of bacterial viability and opsonization on phagosomal pH and phagosome-lysosome interaction." Infect Immun 1996 Jan. 64 (1). 319-325
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• [文献書誌] Ramanathan M: "A pharmacokinetic approach for evaluating cytokine binding macromolecules as antagonists." Pharm Res 1996 Jan. 13 (1). 84-90
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• [文献書誌] Craven CJ,Whitehead B,Jones SK,Thulin E,Blackburn GM,Waltho JP: "Complexes formed between calmodulin and the antagonists J-8 and TFP in solution." Biochemistry 1996 Aug 13. 35 (32). 10287-10299
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• [文献書誌] Rogers MJ,Brown RJ,Hodkin V,Blackburn GM,Russell RG,Watts DJ: "Bisphosphonates are incorporated into adenine nucleotides by human aminoacyl-tRNA synthetase enzymes." Biochem Biophys Res Commun 1996 Jul 25. 224 (3). 863-869
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• [文献書誌] Wentworth P,Datta A,Blakey D,Boyle T,Partridge LJ,Blackburn GM: "Toward antibody-directed"abzyme"prodrug therapy, ADAPT : carbamate prodrug activation by a catalytic antibody and its in vitro application to human tumor cell killing." Proc Natl Acad Sci USA 1996 Jan 23. 93 (2). 799-803
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• [文献書誌] Thorogood H,Grasby JA,Connolly BA: "Influence of the phosphate backbone on the recognition and hydrolysis of DNA by the EcoRV restriction endonuclease.A study using oligodeoxynucleotide phosphorothioates." J Biol Chem 1996 Apr 12. 271 (15). 8855-8862
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• [文献書誌] Hayashi, Y., Nomura, M., Yamagishi, S., Harada, S., Yamashita, J.and Yamamoto, H.: "Induction of various blood-brain barrier properties in non-neural endothelial cells by close apposition to cocultured astrocytes." Glia. 19. 13-26 (1997)
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• [文献書誌] Yamagishi, S., Yonekura.H., Yamamoto, Y., Katsuno, K., Sato, F., Mita, I., Ooka, H., Satozawa, N., Kawakami, T., Nomura, M.and Yamamoto, H.: "Advanced glycation endproductsdriven angiogenesis in vitro : Induction of the growth and tube formation of human microvascular endothelial cells through autocrine vascular endothelial growth factor." J.Biol.Chem.272 (13). 8723-8730 (1997)
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• [文献書誌] Yonemura, Y., Endou, Y., Nojima, N., Kawamura, T., Fujita, H., Kaji, M., Ajisaka, H., Bandou, E., Sasaki, T., Yamaguchi, T., Harada, S.and Yamamoto, H.: "A possible role of cytokines in the formation of peritoneal dissemination." International Journal of Oncology. 11. 349-358 (1997)
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• [文献書誌] Noguchi, N., Takasawa, S., Nata.K., Tohgo, A., Kato, I., Ikehata, F., Yonekura, H., and Okamoto, H.: "Cyclic ADP-ribose binds to FK506-binding protein 12.6 to release Ca2+ from islet microsome." J.Biol.Chem.272. 3133-3136 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Kaneko, Y., Yamamoto, H.: "Cytidine kinase : A novel pyrimidine ribonucleoside phosphorylating enzyme in Escherichia coli." Nucleosides & Nucleotides. 16. 2111-2122 (1997)
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• [文献書誌] Kuno, K., Kanada, N., Nakashima, E., Fujiki, F., Ichimura, F.and Matsushima, K.: "Molecular Cloning of a Gene Encoding a New Type of Metalloproteinase-Disintegrin Family Protein with ThromBospondin Motifs as an Inflammation Associated Gene." J.Bio.Chem.272. 556-562 (1997)
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• [文献書誌] Ishizaki, J., Yokogawa, K., Nakashima, E.and Ichimura, F.: "Prediction of Changes in the Clinical Phamracokinetics of Basic Drugs on the Basis of Octanol-Water Partition Coefficients." J.Pharm.Pharmacol.49. 762-767 (1997)
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• [文献書誌] Ishizaki, J., Yokogawa, K., Nakashima, E.and Ichimura, F.: "Relationship Between the Hepatic Intrinsic Clearance or Blood Cell-Plasma Partition Coefficeint in the Rabbit and the Lipophilicity of Basic Drugs." J.Pharm.Pharmacol.49. 768-772 (1997)
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• [文献書誌] Shido, A., Hobayashi, H., Yamamoto, K., Kobayashi, T., Fujimura, T., Yonemura, Y..: "Peritoneal damage after continuous hyperthermic peritoneal perfusion" Annals of the New Yoek Academy of Sciences. 813. 610-612 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Yonemura, Y.., Endou, Y., Nojima, N., Kawamura, T., Fujita, H., Kaji, M., Ajisaka, H., Bandou, E., Sasaki, T., Yamaguchi, A., Harada, S., Yamamoto, H.: "A possible role of cytokines in the formation of peritoneal dissemination" Int J Oncol. 11. 349-358 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Fujimura, T., Yonemura, Y.., Ninomiya, I., Miwa, K., Miyazaki, I., Endo, Y., Ishikawa, N., Obata, T., Tanaka, M., Sasaki, T.: "Early detection of peritoneal dissemination of gastrointestinal cancers by reverse-transcriptase polymerase chain reaction" Oncology Reports. 4. 1015-1019 (1997)
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• [文献書誌] Yonemura, Y.., Nojima, N., Kawamura, T., Ajisaka, H., Taniguchi, K., Fujimura, T., Fujita, H., Fushida, S., Miyazaki, I., Endou, Y., Sasaki, T.: "Correlation of peritoneal dissemination and integrin alpha3 expression in gastric cancer" Oncology Reports. 4. 549-555 (1997)
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• [文献書誌] Ajisaka, H., Yonemura, Y.., Fujita, H., Michiwa, Y., Kawamura, T., Satoh, T., Nojima, N., Fushida, S., Fujimura, T., Miwa, K., Endo, Y., Sasaki, T.: "Association of progression and reduced expression of VLA-2 in gastric cancer." Oncology Reports. 4. 1265-1269 (1997)
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• [文献書誌] Yonemura, Y.., Nojima, N., Kaji, M., Kawamura, T., Fushida, S., Fujimura, T., Itho, H., Fujita, H., Miyazaki, I., Endou, Y., Sasaki, T., Yamamoto, H.: "E-cadherin and c-met expression as a prognostic factor in gastric cancer" Oncology Reports. 4. 743-748 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Kinuya S.Asaka S,Takeda R,Yokoyama K,Michigishi T,Tonami N.: "Visualization of bone structure with Tc-99m MIBI in a patient on hemodyalysis." Clin Nucl Med 1997 May. 22 (5). 331-332
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• [文献書誌] Kinuya S,Yokoyama K,Yamamoto W,Konishi S,Shuke N,Aburano T,Watanabe N,Takayama T,Michigisgi T,Tonami N: "Short-period-induced hypertension could improve tumor-to-nontumor ratios of radiolabeled monoclonal antibody" Nucl Med Biol 1997 Aug. 24 (6). 547-552
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• [文献書誌] Booth BP,Nolan TD,Fung HL: "Nitroglycerin-inhibited whole blood aggregation is partially mediated by calcitonin gene-related peptide - a neurogenic mechanism." Br J Pharmacol 1997 Oct. 122 (3). 577-583
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• [文献書誌] Bauer JA,Balthasar JP,Fung HL: "Application of pharmacodynamic modeling for designing time-variant dosing regimens to overcome nitroglycerin tolerance in experimental heart failure." Pharm Res 1997 Sep. 14 (9). 1140-1145
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• [文献書誌] Bauer JA, Nolan T,Fung HL: "Vascular and hemodynamic differences between organic nitrates and nitrites." J Pharmacol Exp Ther 1997 Jan. 280 (1). 326-331
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• [文献書誌] Oh YK,Straubinger RM: "Cellular retention of liposome-delivered anionic compounds modulated by a probenecid-sensitive anion transporter." Pharm Res 1997 Sep. 14 (9). 1203-1209
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• [文献書誌] Sharma US,Sharma A,Chau RI,Straubinger RM: "Liposomemediated therapy of intracranial brain tumors in a rat model." Pharm Res 1997 Aug. 14 (8). 992-998
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• [文献書誌] Balasubramanian SV,Straubinger RM,Morris ME: "Salicylic acid induces changes in the physical properties of model and native kidney membranes." J Pharm Sci 1997 Feb. 86 (2). 199-204
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• [文献書誌] Ramanathan M: "Flow cytometry applications in pharmacodynamics and drug delivery." Pharm Res 1997 Sep. 14 (9). 1106-1114
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• [文献書誌] Ramanathan M: "A physicochemical modelling approach for estimating the stability of soluble receptor-bound tumour necrosis factor-alpha." Cytokine 1997 Jan. 9 (1). 19-26
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• [文献書誌] Frith JC,Monkkonen J,Blackburn GM,Russell RG,Rogers MJ: "Clodronate and liposome-encapsulated clodronate are metabolized to a toxic ATP analog, adenosine 5'- (beta, gammadichloromethylene) triphosphate, by mammalian cells in vitro." J Bone Miner Res 1997 Sep. 12 (9). 1358-1367
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• [文献書誌] Brenner C,Pace HC,Garrison PN,Robinson AK,Rosler A,Liu XH,Blackburn GM,Croce CM,Huebner K,Barnes LD: "Purification and crystallization of complexes modeling the active state of the fragile histidine triad protein." Protein Eng 1997 Dec. 10 (12). 1461-1463
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• [文献書誌] Guranowski A,Starzynska E,Brown P,Blackburn GM: "Adenosine 5'-tetraphosphate phosphohydrolase from yellow lupin seeds : purification to homogeneity and some properties." Biochem J 1997 Nov 15. 328 (Pt 1). 257-262
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• [文献書誌] Delaney SM,Blackburn GM,Geiger JD: "Diadenosine polyphosphates inhibit adenosine kinase activity but decrease levels of endogenous adenosine in rat brain." Eur J Pharmacol 1997 Jul 30. 332 (1). 35-42
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• [文献書誌] Chan SW,Gallo SJ,Kim BK,Guo MJ,Blackburn GM,Zamecnik PC: "P1, P4-dithio-P2, P3-monochloromethylene diadenosine 5', 5'''-P1, P4-tetraphosphate : a novel antiplatelet agent." Proc Natl Acad Sci USA 1997 Apr 15. 94 (8). 4034-4039
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• [文献書誌] Young KJ,Gill F,Grasby JA: "Metal ions play a passive role in the hairpin ribozyme catalysed reaction." Nucleic Acids Res 1997 Oct 1. 25 (19). 3760-3766
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• [文献書誌] Ogawa, H., Harada, S., Sassa, T., Yamamoto, H.and Hosono, R.: "Functional properties of the unc-64 gene encoding a Caenorhabditis elegans syntaxin." J.Biol.Chem.273 (4). 2192-2198 (1998)
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• [文献書誌] Segawa, Y., Shirao, Y., Yamagishi, S., Higashida, T., Kobayashi, M., Katsuno, K., Iyobe, A., Harada, H., Sato, F., Miyata, H., Asai, H., Nishimura, A., Takahira, M., Souno, T., Segawa, Y., Maeda, K., Shima, K., Mizuno, A., Yamamoto, H.and Kawasaki, K.: "Upregulation of retinal vascular endothelial growth factor mRNAs in spontaneously diabetic rats without ophthalmoscopic retinopathy." Ophthalmic Res.30. 333-339 (1998)
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• [文献書誌] Yamagishi, S., Yonekura, H., Yamamoto, Y., Fujimori, H., and Yamamoto, H.: "AGE and Endothelial Cell." Journal of Atherosclerosis and Thrombosis. 4 (4). 141-143 (1998)
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• [文献書誌] Yamagishi, S., Fujimori, H., Yonekura, H., Yamamoto, Y.and Yamamoto, H.: "Advanced glycation endproducts inhibit prostacyclin production and induce plasminogen activator inhibitor-1 in human microvascular endothelial cells." Diabetologia. 41 (12). 1435-1441 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Nomura, M., Yamagishi, S., Harada, S., Yamashima, T., Yamashita, J., Yamamoto, H.: "Placenta growth factor (PIGF) mRNA expression in brain tumors." Journal of Neurooncology. 40 (2). 123-130 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Wada, K., Sato, H., Kinoh, H., Kajita, M., Yamamoto, H., Seki, M.: "Cloning of three Caenorhabditis elegans genes potentially encoding novel matrix metalloproteinases." Gene. 211. 57-62 (1998)
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• [文献書誌] Taniguchi, K., Yonemura, Y., Nojima, N., Hirono, Y., Fushida, S., Fujimura, T., Miwa, K., Endo, Y., Yamamoto, H., Watanabe, H.: "The relation between the growth patterns of gastric carcinoma and the expression of hepatocyte growth factor receptor (c-met) , autocrine motility factor receptor, and urokinase-type plasminogen activator receptor." Cancer. 82 (11). 2112-2122 (1998)
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• [文献書誌] Ishizaki, J., Yokogawa, K., Nakashima, E., Ohkuma, S.and Ichimura, F.: "Characteristic Subcellular Distribution, in Brain, Heart and Lung, of Biperiden, Trihexyphenidyl, and (-) -Quinuclidinyl Benzylate in Rats." Biol.Pharm.Bull.21. 67-71 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Ishizaki, J., Yokogawa, K., Nakashima, E., Takayasu, T., Ohshima, T.and Ichimura.F.: "Effect of Sequence of Adiministration on the Pharmacokinetic Interaction between the Anticholinergic Drug Biperiden and [^3H] Quinuclidinyl Benzylate or [^3H] N-Methylscopolamine in Rats." J.Pharm.Pharmacol.50. 189-196 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Ishizaki, J., Yokogawa, K., Nakashima, E., Ohkuma, S.and Ichimura, F.: "Influence of Ammonium Chloride on the Tissue Distribution of Anticholinergic Drugs in Rats." J.Pharm.Pharmacol.50. 761-766 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Ishizaki, J., Yokogawa, K., Nakashima, E., Ohkuma, S.and Ichimura, F.: "Uptake of Basic Drugs into Rat Lung Granule Fraction in Vitro." Biol.Pharm.Bull.21. 858-861 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Yonemura, Y.., Ninomiya, I., Tsugawa, K., Fushida, S., Fujimura, T., Miyazaki, I., Uchibayashi, T., Endou, Y., Sasaki, T.: "Prognostic significance of c-erbB-2 gene expression in the poorly differentiated type of adenocarcinoma of the stomach" Cancer Detection and Preventionr. 22 (2). 139-146 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Nozaki, S., Endo, Y., Kawashiri, S., Nakagawa, K., Yamamoto, E., Yonemura, Y.., Sasaki, T.: "Immunohistochemical localization of a urokinase-type plasminogen activator system in squamous cell carcinoma of the oral cavity : association with mode of invasion and lymph node metastasis" Eur.j.Cancer. 34 (1). 58-62 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Fujimura, T., Ohta, T., Kitagawa, H., Fushida, S., Nishimura, G., Yonemura, Y., Elnemr, A., Miwa, K., Nakamura, Y.: "Trypsinogen expression and early detection for peritoneal dissemination in gastric cencer" J Surg.Oncol.69 (2). 71-75 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Bando, E., Yonemura, Y.., Endou, Y., Sasaki, T., Taniguchi, K., Fujita, H., Fushida, S., Fujimura.T., Nishimura, G., Miwa, K., Seiki, M.: "Immunohistochemical study of MT-MMP tissus status in gastric carcinoma and correlation with survival analyzed by univariate and multivariate analysis." Oncol.Rep. 5 (6). 1483-1488 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Tsugawa, K., Yonemura, Y.., Hirono, Y., Fushida, S., Kaji, M., Miwa, K., Miyazaki, I., Yamamoto, H.: "Amplification of the c-met, c-erbB-2 and epidermal growth factor receptor gene in human gastric cancers : Correlation to clinical features" Oncology. 55. 475-481 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Kinuya S,Yokoyama K,Tega H,Hiramatsu T,Konishi S,Yamamoto W,Shuke N,Aburano T,Watanabe N,Takayama T,Michigishi T,Tonami N: "Rhenium-186-mercaptoacethyltriglycine labeled monoclonal antibody for radioimmunotherapy : In vitro assessment, in vivo kinetics and dosimetry in tumor-bearing nude mice" Jpn J Cancer Res 1998 Aug. 89 (8). 870-878
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Watanabe N,Yokoyama K,Kinuya S,Shuke N,Shimizu M,Futatsuya R,Michigishi T,Tonami N,Seto H,Goodwin DA: "Radiotoxicity after iodine-131 therapy for thyroid cancer using the micronucleus assay" J Nucl Med 1998 Mar. 38. 436-440
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• [文献書誌] Watanabe N,Yokoyama K,Kinuya S,Shuke N,Shimizu M,Michigishi T,Tonami N,Seto H,Goodwin DA: "Radiotoxicity after strontium-89 therapy for bone metastases using the micronucleus assay" J Nucl Med 1998 Dec. 39 (12). 2077-2079
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• [文献書誌] Booth BP,Fung HL: "Regulation of in vivo whole blood aggregation in rats by calcitonin gene related peptide." Can J Physiol Pharmacol 1998 Jul-Aug. 76 (7-8). 811-813
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Tabrizi-Fard MA,Fung HL: "Effects of nitro-L-arginine on blood pressure and cardiac index in anesthetized rats : a pharmacokinetic-pharmacodynamic analysis." Pharm Res 1998 Jul. 15 (7). 1063-1068
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Booth BP,Fung HL: "Contribution of vascular tissue to the antiplatelet activity of sodium nitroprusside." J Cardiovasc Pharmacol 1998 Jul. 32 (1). 129-133
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Edgerton M,Koshlukova SE,Lo TE,Chrzan BG,Straubinger RM,Raj PA: "Candidacidal activity of salivary histatins.Identification of a histatin 5-binding protein on Candida albicans." J Biol Chem 1998 Aug 7. 273 (32). 20438-20447
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Balasubramanian V,Nguyen LT,Balasubramanian SV,Ramanathan M: "Interferon-gamma-inhibitory oligodeoxynucleotidesalter the conformation of interferon-gamma." Mol Pharmacol 1998 May. 53 (5). 926-932
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Ramanathan M: "Analysis of intracellular Th1 cytokine secretion data using parametric methodology." Cytometry 1998 Jun 1. 32 (2). 147-156
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Williams DM,Jakeman DL,Vyle JS,Williamson MP,Blackburn GM: "Synthesis and binding of stable bisubstrate ligands for phosphoglycerate kinase." Bioorg Med Chem Lett 1998 Sep 22. 8 (18). 2603-2608
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Caplan NA,Pogson CI,Hayes DJ,Blackburn GM: "Novel bisphosphonate inhibitors of phosphoglyceratekinase." Bioorg Med Chem Lett 1998 Mar 3. 8 (5). 515-520
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Jakeman DL,Ivory AJ,Williamson MP,Blackburn GM: "Highly potent bisphosphonate ligands for phosphoglycerate kinase." J Med Chem 1998 Nov 5. 41 (23). 4439-4452
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Blackburn GM,Liu X,Rosler A,Brenner C: "Two hydrolase resistant analogues of diadenosine 5', 5'''-P1, P3-triphosphate for studies with Fhit, the human fragile histidine triad protein." Nucleosides Nucleotides 1998 Jan-Mar. 17 (1-3). 301-308
  • 説明: 「研究成果報告書概要(欧文)」より
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• [文献書誌] Tabrizi-Fard MA: "Effects of nitro-L-arginine on blood pressure and cardiac index in anesthetized rats:a pharmacokinetic-pharmacodynamic analysis." Pharm Res. 15(7). 1063-1068 (1998)
• [文献書誌] Booth BP: "Contribution of vascular tissue to the antiplatelet activity of sodium nitroprusside." J Cardovasc Pharmacol. 32(1). 129-133 (1998)
• [文献書誌] Edgerton M.: "Candidacidal activity of salivary histatins.Identificaiton of a histatin 5-binding protein on Candida albicans." J Biol Chem. 273(32). 20438-20447 (1998)
• [文献書誌] Balasubramanian V.: "Interferon-gamma-inhibitory oligodeoxynucleotidesalter the conformation of interferon-gamma." Mol pharmacol. 53(5). 926-932 (1998)
• [文献書誌] Ramanathan M: "Analysis of intracellular Th1 cytokine secretion data using parametric methodology." Cytometry. 32(2). 147-156 (1998)
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• [文献書誌] Caplan NA: "Novel bisphosphonate inhibitors of phosphoglyceratekinase." Bioorg Med Chem Lett. 8(5). 515-520 (1998)
• [文献書誌] Jakeman DL: "Highly potent bisphosphonate ligands for phosphoglycerate kinse." J Med Chem. 41(23). 4439-4452 (1998)
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• [文献書誌] 米倉秀人: "「KEY WORD 1998-2000 高血圧症・動脈硬化」:3章 血管新生" 先端医学社(斎藤 康、萩原俊男、馬渕 宏編), 207 (1998)
• [文献書誌] 山本靖彦: "「現代医療」:糖尿病-AGE受容体" 現代医療社, 344 (1998)
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• [文献書誌] 山岸昌一: "「メビオ」:糖尿病と網膜血管障害" (株)メジカルビュー社(in press), (1999)
• [文献書誌] 山岸昌一: "「組織培養工学」:糖尿病と血管新生" ニューサイエンス社(in press), (1999)
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