1997 年度実績報告書

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

研究課題/領域番号	08045063
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
キーワード	antisense / antisense display / nucleoside / ribozyme / liposome / aptamer
研究概要	本研究の目的は、金沢大学と米国・ニューヨーク州立大学バッファロ-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の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の化学・薬学・医学生物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である。本年度研究は概ね当初計画通り順調に振興し、以下の成果を得た。 (1)日本側分担者は、アンチセンス法に基づいた新しい機能性遺伝子スクリーニング法を開発し、アンチセンスディスプレイ法と命名した。本法により、血管新生に関係すると考えられる新しい遺伝子が分離された。 (2)米国側分担者は、薬物動態力学モデルを確立し、各種低分子製剤の用量-作用連関を明らかにした。 (3)英国側分担者は、抗血液凝固活性をもつヌクレオチド誘導体の開発に成功するとともに、ヘアピン型リボザイムの標的RNA切断活性におよぼす2価金属イオンの役割を明らかにした。 (4)日本側代表者が英国を訪問し、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った。 (5)米国側分担者2名が来日し、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-作用に関する研究打合せを行った。

研究成果
(26件)

すべてその他

すべて文献書誌 (26件)

[文献書誌] Yamagishi, S.: "Advanced glycation endproducts-driven angiogeneses in vitro." J.Biol.Chem.272. 8723-8730 (1997)
[文献書誌] Hayashi, Y.: "Induction of vanous blood-brain properties in non-neutal endothelial cells by close apposition to co-cultured astrocytes." Glia. 19. 13-26 (1997)
[文献書誌] Yonemura, Y.: "A possible role of cytokines in the formation of peritoneal dissemination." Int.J.Oncology. 11. 349-358 (1997)
[文献書誌] Ogawa, H.: "Functional properties of the unc-64 gene encoding a Caenorhabditis elegans syntaxin." J.Biol.Chem.273. 2192-2198 (1998)
[文献書誌] Yamagishi, S.: "Advanced glycation endproducts inhibit prostacyclin production and induce plasminogen activator inhibitor-1 in human microvascular endothelial cells." Diabetologia. (in press). (1998)
[文献書誌] Segawa, Y.: "Upregulation of retinal vascular endothelial growth factor mRNAs in spontaneously diabetic rats without ophthalmoscopic retinopathy." Ophthalmic Res. (in press). (1998)
[文献書誌] Kaneko, T.: "Cytidine kinase : A novel pyrimidine ribonucleoside phosphorylating enzyme in Escherichia coli." Nucleosides & Nucleotides. (in press). (1998)
[文献書誌] Yamagishi, S.: "AGE and endothelial cells." Journal od Atherosclerosis and Thrombosis. (in press). (1998)
[文献書誌] Booth, B.P.: "Nitroglycerin-inhibited whole blood aggregation is partially mediated by calcitonin gene-related peptide-a neurogenic mechanism." Br.J.Pharmacol.122. 577-583 (1997)
[文献書誌] Bauer, J.A.: "Application of pharmacodynamic modeling for designing time-variant dosing regimens to overcome nitroglycerin tolerance in experimental heart failure." Pharm.Res.14. 1140-1145 (1997)
[文献書誌] Bauer, J.A.: "Vascular and hemodynamic differences between organic nitrates and nitrites." J.Pharmacol.Exp.Ther.280. 326-331 (1997)
[文献書誌] Oh, Y.K.: "Impact of Mycobacterium Avium infection on macrophage-liposome interaction." J.Liposome Research. 7. 101-114 (1997)
[文献書誌] Balasubramanian, S.V.: "Salicylic acid induces changes in the physical properties of model and native kidney membranes" J.Pharm.Sci.86. 199-204 (1997)
[文献書誌] Sharma, U.S.: "Liposome-mediated therapy of intracranial brain tumors in a ratmodel." Pharm.Res.14. 992-998 (1997)
[文献書誌] Oh, Y.K.: "Cellular retention of liposome-delivered anionic compounds modulated by a probenecid-sensitive anion transporter." Pharm.Res.14. 1203-1209 (1997)
[文献書誌] Ramanathan, M.: "Integration of intemet-based technologies as learning tools in a pharmacoutical calculations course" Am.J.Pharmaceutical Educ.61. 141-148 (1997)
[文献書誌] Ramanathan, M.: "Flow cytometry applications in pharmacodynamics and drug delivery." Pharmaceutical Research. 14. 1106-1114 (1997)
[文献書誌] Ramanathan, M.: "Integration of Intemet-based technologies as learning tools in a pharmaceutical calculations course." Am.J.Pharmaceutical Educ.61. 141-148 (1997)
[文献書誌] Ramanathan, M.: "A physicochemical modeling approach for estimating the stability of soluble receptor bound tumor necrosis factor-α." Cytokine. 9. 19-26 (1997)
[文献書誌] Ramanathan, M.: "Analysis of intracellular Th1 cytokine secretion data using parametric methodology." Cytometry. 32(in press). (1998)
[文献書誌] Parikh, H.H.: "Accuracy and sample size dependence of the model-based,parametric method for analyzing of flow cytometric Th1 cytokine data." Cytometry. (in press). (1998)
[文献書誌] Guranowski, A.: "Adenosine 5'-tetraphosphate phosphohydrolase from yellow lupin seeds : purification to homogeneity and some properties." Biochem,J.328. 257-262 (1997)
[文献書誌] Delaney, S.M.: "Diadenosine polyphosphates inhibit adenosine kinase activity but decrease levels of endogenous adenosine in rat brain." Eur J Pharmacol. 332. 35-42 (1997)
[文献書誌] Frith, J.C.: "Clodronase and liposome-encapsulated clodronate are metabolized to a toxic ATP analog,adenosine 5'- (beta,gamma-dichloromethylene) triphosphate,bymammalian cells in vitro." J.Bone Miner Res.12. 1358-1367 (1997)
[文献書誌] Chan, S.W.: "PC P1,P4-dithio-P2,P3-monochloromethylene diadenosine 5',5'''-P1,P4-tetraphosphate : a novel antiplatelet agent." Proc.Natl.Acad.Sci.U.S.A.94. 4034-4039 (1997)
[文献書誌] Young, K.J.: "Metal ions play a passive role in the hairpin ribozyme catalysed reaction." Nucleic Acids Res.25. 3760-3766 (1997)

1997 年度 実績報告書

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

研究代表者

山本 博 金沢大学, 医学部, 教授 (00115198)

研究成果

[文献書誌] Yamagishi, S.: "Advanced glycation endproducts-driven angiogeneses in vitro." J.Biol.Chem.272. 8723-8730 (1997)

[文献書誌] Hayashi, Y.: "Induction of vanous blood-brain properties in non-neutal endothelial cells by close apposition to co-cultured astrocytes." Glia. 19. 13-26 (1997)

[文献書誌] Yonemura, Y.: "A possible role of cytokines in the formation of peritoneal dissemination." Int.J.Oncology. 11. 349-358 (1997)

[文献書誌] Ogawa, H.: "Functional properties of the unc-64 gene encoding a Caenorhabditis elegans syntaxin." J.Biol.Chem.273. 2192-2198 (1998)

[文献書誌] Yamagishi, S.: "Advanced glycation endproducts inhibit prostacyclin production and induce plasminogen activator inhibitor-1 in human microvascular endothelial cells." Diabetologia. (in press). (1998)

[文献書誌] Segawa, Y.: "Upregulation of retinal vascular endothelial growth factor mRNAs in spontaneously diabetic rats without ophthalmoscopic retinopathy." Ophthalmic Res. (in press). (1998)

[文献書誌] Kaneko, T.: "Cytidine kinase : A novel pyrimidine ribonucleoside phosphorylating enzyme in Escherichia coli." Nucleosides & Nucleotides. (in press). (1998)

[文献書誌] Yamagishi, S.: "AGE and endothelial cells." Journal od Atherosclerosis and Thrombosis. (in press). (1998)

[文献書誌] Booth, B.P.: "Nitroglycerin-inhibited whole blood aggregation is partially mediated by calcitonin gene-related peptide-a neurogenic mechanism." Br.J.Pharmacol.122. 577-583 (1997)

[文献書誌] Bauer, J.A.: "Application of pharmacodynamic modeling for designing time-variant dosing regimens to overcome nitroglycerin tolerance in experimental heart failure." Pharm.Res.14. 1140-1145 (1997)

[文献書誌] Bauer, J.A.: "Vascular and hemodynamic differences between organic nitrates and nitrites." J.Pharmacol.Exp.Ther.280. 326-331 (1997)

[文献書誌] Oh, Y.K.: "Impact of Mycobacterium Avium infection on macrophage-liposome interaction." J.Liposome Research. 7. 101-114 (1997)

[文献書誌] Balasubramanian, S.V.: "Salicylic acid induces changes in the physical properties of model and native kidney membranes" J.Pharm.Sci.86. 199-204 (1997)

[文献書誌] Sharma, U.S.: "Liposome-mediated therapy of intracranial brain tumors in a ratmodel." Pharm.Res.14. 992-998 (1997)

[文献書誌] Oh, Y.K.: "Cellular retention of liposome-delivered anionic compounds modulated by a probenecid-sensitive anion transporter." Pharm.Res.14. 1203-1209 (1997)

[文献書誌] Ramanathan, M.: "Integration of intemet-based technologies as learning tools in a pharmacoutical calculations course" Am.J.Pharmaceutical Educ.61. 141-148 (1997)

[文献書誌] Ramanathan, M.: "Flow cytometry applications in pharmacodynamics and drug delivery." Pharmaceutical Research. 14. 1106-1114 (1997)

[文献書誌] Ramanathan, M.: "Integration of Intemet-based technologies as learning tools in a pharmaceutical calculations course." Am.J.Pharmaceutical Educ.61. 141-148 (1997)

[文献書誌] Ramanathan, M.: "A physicochemical modeling approach for estimating the stability of soluble receptor bound tumor necrosis factor-α." Cytokine. 9. 19-26 (1997)

[文献書誌] Ramanathan, M.: "Analysis of intracellular Th1 cytokine secretion data using parametric methodology." Cytometry. 32(in press). (1998)

[文献書誌] Parikh, H.H.: "Accuracy and sample size dependence of the model-based,parametric method for analyzing of flow cytometric Th1 cytokine data." Cytometry. (in press). (1998)

[文献書誌] Guranowski, A.: "Adenosine 5'-tetraphosphate phosphohydrolase from yellow lupin seeds : purification to homogeneity and some properties." Biochem,J.328. 257-262 (1997)

[文献書誌] Delaney, S.M.: "Diadenosine polyphosphates inhibit adenosine kinase activity but decrease levels of endogenous adenosine in rat brain." Eur J Pharmacol. 332. 35-42 (1997)

[文献書誌] Frith, J.C.: "Clodronase and liposome-encapsulated clodronate are metabolized to a toxic ATP analog,adenosine 5'- (beta,gamma-dichloromethylene) triphosphate,bymammalian cells in vitro." J.Bone Miner Res.12. 1358-1367 (1997)

[文献書誌] Chan, S.W.: "PC P1,P4-dithio-P2,P3-monochloromethylene diadenosine 5',5'''-P1,P4-tetraphosphate : a novel antiplatelet agent." Proc.Natl.Acad.Sci.U.S.A.94. 4034-4039 (1997)

[文献書誌] Young, K.J.: "Metal ions play a passive role in the hairpin ribozyme catalysed reaction." Nucleic Acids Res.25. 3760-3766 (1997)

1997 年度実績報告書

山本博金沢大学, 医学部, 教授 (00115198)