線溶因子の構造と機能

　線溶因子は種々の状況下で構造と機能を変化させ、線溶活性の調節に寄与している。

主な業績

• Hoki S, Suzuki Y, Umemura K, Urano T.Enhancement of fibrinolysis by gel-filtered platelets and its quenching by cytochalasin B and GPIIb/IIIa antagonists.Pharmacological Reports 61(5),877-84, 2009
• Tanaka A, Suzuki Y, Sugihara K, Kanayama N, Urano T. Inactivation of plasminogen activator inhibitor type 1 by activated factor XII plays a role in the enhancement of fibrinolysis by contact factorsin-vitro.Life Scineces 85(5/6), 220-225, 2009
• Nakamura R, Umemura K, Hashimoto H, Urano T.Less pronounced enhancement of thrombin-dependent inactivation of plasminogen activator inhibitor type 1 by low molecular weight heparin compared with unfractionated heparin. Thromb Haemost 95, 637-42, 2006
• Hryszko T, and Urano T. Activated Protein C enhances tPA-catalyzed Glu-plasminogen activation in the presence of poly-D-lysine.Thrombosis & Haemostasis 92(4), 891-2, 2004
• Urano T, Castellino FJ, Ihara H, Suzuki Y, Ohta M, Suzuki K, Mogami H. Activated protein C attenuates coagulation-associated over　expression of fibrinolytic activity by suppressing the thrombin-dependent inactivation of PAI-1. Journal of Thrombosis and Hemostasis 1, 2615-2620, 2003
• Urano T., Ihara H., Umemura K., Suzuki Y., Oike M., Akita S., Tsukamoto Y., Suzuki I. and Takada A.　　The profibrinolytic enzyme subtilisin NAT purified from Bacillus subtilis cleaves and inactivates plasminogen activator inhibitor type 1.J Biol Chem 276(27): 24690-24696, 2001
• Urano, T., Ihara, H., Takada, Y., Fujie, M. and Takada, A.The cleavage and inactivation of plasminogen activator inhibitor type 1 and a2-antiplasmin by reptilase, a thrombin-like venom enzyme.Blood Coagulation & Fibrinolysis 11(2), 145-153, 2000
• Urano, T., Serizawa, K., Takada, Y., Ny, T. and Takada, A.Heparin and heparan sulphate enhancement of the inhibitory activity of plasminogen activator inhibitor type 1 toward urokinase type plasminogen activator.Biochim. Byophys. Acta 1201, 217-222, 1994
• Kojima, Y., Urano, T., Kojima, K., Serizawa, K., Takada, Y. and Takada, A.The Significant Enhancement of Fibrinolysis by Calcium Ion in a Cell Free System. : The Shortening of Euglobulin Clot Lysis Time by Calcium Ion.Thromb. Haemostas.72(1), 113-118, 1994
• Takada, Y., Urano, T. and Takada, A.Effect of heparan sulfate analogue or other sulfated polysaccharides on the activation of plasminogen by t-PA or u-PA.Thromb. Res.73(5), 301-311, 1994
• Takada, Y., Urano, T. and Takada, A.Conformational change of plasminogen: Effects of N-terminal peptides of Glu-plasminogen.Thromb. Res.70; 151-159, 1993
• Urano T., Strandberg L., Johansson L. B-A., Ny T.A substrate-like form of plasminogen activator inhibitor type 1: Conversions between different forms by sodium dodecyl sulphate.Eur. J. Biochem.209, 985-992, 1992
• Kawamura, I. Watanabe, T. Urano, Y. Takada and A. Takada.The effects of polysaccharides on plasminogen activation by single chain-tissue plasminogen activator.Thromb. Res.62, 481-490, 1991
• T. Urano, Y. Takada and A. Takada.Stimulation of the amidolytic activity of single chain tissue-type of plasminogen activator by fibrinogen degradation products : possible binding sites on single chain tissue plasminogen activator molecule.Biochim. Biophys. Acta 1077; 245-252, 1991.
• Urano, T., de Serrano, V. S., Urano, S. and Castellino, F. J.Stimulation by fibrinogen of the amidolytic activity of single-chain tissue plasminogen activator.Arch Biochem. Biophys.270(1): 356-362, 1989.
• Urano, T., de Serrano, V. S. Gaffney, P. J. and Castellino F. J.Effectors of the activation of human [Glu1] plasminogen by human tissue plasminogen activator.Biochemistry 27:6522-6528, 1988.
• Urano, T., de Serrano, V. S., Chibber, B. A. K. and Castellino, F. J.The control of the urokinase-catalyzed activation of human glutamic acid 1-plasminogen by positive and negative effectors.J. Biol. Chem.262(33): 15959-15964, 1987.
• Urano, T., Chibber, B. A. K. and Castellino, F. J.The reciprocal effects of e-aminohexanoic acid and chloride ion on the activation of human (Glu1) plasminogen by human urokinase.Proc. Natl. Acad. Sci. USA84: 4031-4034, 1987.

線溶因子と凝固因子の相互作用による線溶反応の調節 †

　血管が損傷したり組織が破壊されると、その部位からの血液の流出を阻止するために凝固系が働き血液が固まります。この系が正常に働かないと血友病等 のような、異常出血が認められるわけです。また過剰に働いて正常な血管の中でも固まると、脳梗塞や心筋梗塞になります。できた血液の固まり（凝血塊）は、 出血が止まり組織の修復が完了すると速やかに溶解して取り除かれます。これを線維素溶解（線溶）現象と呼びます。早く溶け過ぎると出血しますし、遅いと末 梢の循環不全や梗塞をおこします。
　このような凝固と線溶の連携プレ－は巧みな指揮者に導かれるオ－ケストラような趣（？）があります。あたかも神様あるいは指揮者が全体の現象を調 節しているように見えますが、実際は個々の反応にブレ－キとアクセルがあり、周囲の状況に応じて速度が調節されているようです。時には凝固系のアクセルが 線溶系のブレ－キになり、また時には線溶系においてもアクセルのように働くのです。この現象をとらえてある人（時）は、「血栓はすぐに溶けては困るから、 種々の機構で線溶から守られている」と言い、またある人（時）は、「血栓は速やかに除去されないと困るから、血栓ができるとすぐに線溶系が活性化される機 構がある」と言います。無論全く正反対のことですが、どのような実験データでも説明できる便利な言葉です。我々は「溶けなければならないときには溶けたく なって溶ける」と禅問答さながらに考えて仏（血栓）の声に耳を澄ませながら機構の解明を楽しんでおります。

主な業績

• Suzuki Y, Yasui Y, Brzoska T, Mogami H, Urano T.Surface-retained tPA is essential for effective fibrinolysis on vascular endothelial cells.Blood in press
• Hoki S, Suzuki Y, Umemura K, Urano T.Enhancement of fibrinolysis by gel-filtered platelets and its quenching by cytochalasin B and GPIIb/IIIa antagonists.Pharmacological Reports 61(5),877-84, 2009
• Tanaka A, Suzuki Y, Sugihara K, Kanayama N, Urano T. Inactivation of plasminogen activator inhibitor type 1 by activated factor XII plays a role in the enhancement of fibrinolysis by contact factorsin-vitro.Life Scineces 85(5/6), 220-225, 2009
• Suzuki Y, Mogami H, Ihara Y, Urano T. Unique secretory dynamics of tissue plasminogen activator and its modulation by plasminogen activator inhibitor-1 in vascular endothelial cells. Blood 113, 470-478, 2009
• Hayashi T, Mogami H, Murakami Y, Nakamura T, Kanayama N, Konno K, UranoT. Real-time analysis of platelet aggregation and procoagulant activity during thrombus formation in vivo.Pflugers Archiv-European Journal of Physiology 456(6), 1239-51, 2008
• Nakamura R, Umemura K, Hashimoto H, Urano T.Less pronounced enhancement of thrombin-dependent inactivation of plasminogen activator inhibitor type 1 by low molecular weight heparin compared with unfractionated heparin. Thromb Haemost 95, 637-42, 2006
• Hryszko T, Inaba K, Ihara H, Suzuki Y, Mogami H, Urano T. Nafamostat attenuated the impairment of fibrinolysis in animal sepsis model by suppressing the increase of plasminogen activator inhibitor type 1. The Journal of Trauma, Injury, Infection and Critical Care 60(4), 859-64, 2006
• Hryszko T, and Urano T. Activated Protein C enhances tPA-catalyzed Glu-plasminogen activation in the presence of poly-D-lysine.Thrombosis & Haemostasis 92(4), 891-2, 2004
• Urano T, Castellino FJ, Ihara H, Suzuki Y, Ohta M, Suzuki K, Mogami H. Activated protein C attenuates coagulation-associated over　expression of fibrinolytic activity by suppressing the thrombin-dependent inactivation of PAI-1. Journal of Thrombosis and Hemostasis 1, 2615-2620, 2003
• Takahashi, H., Urano, T., Takada, Y., Nagai, N. and Takada, A. Neutrophil Elastase May Play a Key Role in the Development of Symptomatic DIC and Multiple Organ Failure in Patients with Head Injury. J. Trauma 49, 86-91, 2000
• Urano, T., Ihara, H., Suzuki, Y., Takada, Y. and Takada. A. Coagulation Associated Enhancement of Fibrinolytic Activity Via a Neutralization of PAI-1 Activity. Semin. Thromb. Hemost. 26(1), 39-42, 2000
• Urano, T., Ihara, H., Suzuki, Y., Nagai, N., Takada, Y. and Takada, A. Soluble thrombomodulin quenches thrombin-mediated neutralization of PAI-1 activity and inhibits fibrinolysis through a TAFI independent mechanism.Fibrinolysis & Proteolysis 13(6), 264-271, 1999
• Takahashi, H., Urano, T., Nagai, N., Takada, Y. and Takada, A. Progressive expansion of hypertensive intracerebral hemorrhage by coagulopathy.Am. J. Hematology 59, 110-114, 1998
• Takahashi, H., Urano, T., Nagai, N., Takada, Y. and Takada, A. Hyperfibrinolytic Activity After Head Injury Is Induced By Elevated tPA Activity. Fibrinolysis and Proteolysis 12(2), 113-118, 1998
• Urano, T., Nagai, N., Matsuura, M., Ihara, H., Takada Y. and Takada, A. Human thrombin and calcium bound factor Xa significantly shorten tPA-induced fibrin clot lysis time via neutralization of plasminogen activator inhibitor type 1 activity. Thromb Haemost 80, 161-166, 1998
• Takahashi, H., Urano, T., Takada, Y., Nagai, N. and Takada. Fibrinolytic parameters as an admission prognostic marker of head injury in patients who talk and deteriorate. J. Neurosurgery 86, 768-772, 1997
• Urano T., Ihara H., Takada Y., Nagai N. and Takada A. The inhibition of human factor Xa by plasminogen activator inhibitor type 1 in the presence of calcium ion, and its enhancement by heparin and vitronectin. Biochim. Biophys. Acta 1298, 199-208, 1996
• Wu, K., Urano, T., Ihara, H., Takada, Y., Fujie, M., Shikimori, M., Hashimoto, K. and Takada, A. The Cleavage and Inactivation of Plasminogen Activator Inhibitor Type 1 by Neutrophil Elastase: The Evaluation of Its Physiological Relevance in Fibrinolysis. Blood 86, 1056-1061, 1995
• Urano, T., de Serrano, V. S., Urano, S. and Castellino, F. J. Stimulation by fibrinogen of the amidolytic activity of single-chain tissue plasminogen activator. Arch Biochem. Biophys. 270(1): 356-362, 1989.
• Urano, T., Kamiya, T., Sakaguchi, S., Takada, Y. and Takada, A. Fibrinogenolysis and fibrinolysis in normal volunteers and patients with thrombosis after infusion of urokinase. Thromb. Res. 39(2): 145-155, 1985.
• Urano, T. Takada, Y. and Takada, A. The enhanced activation of Glu- and Lys-plasminogen by urokinase in the presence of fibrin or Des A Fibrin as measured by the release of Ba peptide and FDP. Thromb. Res. 36(5): 429-435, 1984.
• Takada A. and Takada Y. Effects of w-aminoacids and clot formation on the activation by urokinase of various plasminogen preparations.Thromb. Res. 18(1/2): 167-176, 1980
• Takada, A., Urano, T. and Takada, Y. Influence of coagulation on the activation of plasminogen by streptokinase and urokinase.Thrombos. Haemostas. 42(3): 901-908, 1979
• Takada A. and Takada Y. Studies on SK-potentiator of plasminogen in human plasma. Thrombos. Res. 13(2): 325-335, 1978

癌の増殖・浸潤能の線溶因子による修飾 †

　plasminogen activator の中で uPA はその特異受容体 (uPAR) とともに、癌細胞で多く発現し、癌の浸潤・増殖に深く関わっている。
　当初はその蛋白分解活性による組織破壊が主な役割と考えられていたが、最近、細胞と細胞外基質の接着を修飾し、細胞の移動に深く関わることが明らかになってきた。

主要業績

• Fujie M, Nakamura S, Asai K, Niimi T, Yamashita J, Kiyofuji K, Shibata K, Suzuki M, Aoshima R, Urano T and Yamashita M. A novel phospha sugar analogue: synthesis and evaluation of 2,3-dibromo-　3-methyl-1-phenylphospholane 1-oxide as a new class of potential panti-proliterative materials for leukemia cells.Heterocyclic Communications in press
• Yashiro K, Matsumoto Y, Ihara H, Suzuki Y, Kondo K,Urano T,Umemura K. Involvement of platelet activation by P2Y12 receptor in the development of transplant arteriosclerosis in mice.Transplantation, 87(3), 660-667, 2009
• Suwa D, Konno H, Tanaka T, Urano T. Intraperitoneal Infusion of Recombinant Plasminogen Activator inhibitor Type 2 Induced Apoptosis in Implanted Human Colon Cancer and Inhibited its Growth and Liver Metastasis.Anticancer Research 28(2A), 693-698, 2008
• Hryszko T, Suzuki Y, Mogami H, Urano T. Protein S attenuates the invasive potential of THP-1 cells by interfering with plasminogen binding on cell surface via a protein C-independent mechanism. FEBS Letters 579(27), 6023-6, 2005
• Hryszko T, Inaba K, Ihara H, Suzuki Y, Mogami H, Urano T. Nafamostat attenuated the impairment of fibrinolysis in animal sepsis model by suppressing the increase of plasminogen activator inhibitor type 1. The Journal of Trauma, Injury, Infection and Critical Care 60(4), 859-64, 2006
• Terada H, Urano T, Konno H.　Association of interleukin-8 and plasminogen activator system in the progression of colorectal cancer.Eur. Surg. Res. 37, 166-172, 2005
• Inaba K, Suzuki S, Ihara H, Sakaguchi T, Baba S, Urano T, Konno H, Nakamura S. Sexual dimorphism in endotoxin susceptibility after partial hepatectomy in rats. J Hepatol 42(5), 719-27, 2005
• Takahashi H, Nagai N and Urano T. Role of tissue plasminogen activator/plasmin cascade in delayed neuronal death after transient forebrain ischemia. Neuroscience Letters 381, 189-193, 2005
• TakahashiT, SuzukiK, IharaH, MogamiH, KazuiT and UranoT. Plasminogen activator inhibitor-1 promotes fibrosarcoma cell migration by modifying cellular attachment to vitronectin viaavb5integrin. Semin Thromb Hemost. 31(3), 356-363, 2005
• Zhao BQ, Ikeda Y, Ihara H, Urano T, Fan WY, Mikawa S, Suzuki Y, Kondo K, Sato K, Nagai N and Umemura K. Essential role of endogenous tissue plasminogen activator through matrix metalloproteinase 9 induction and expression on heparin-produced cerebral hemorrhage after cerebral ischemia in mice. Blood 103(7), 2610-2616, 2004
• Konno H, Abe J, Kaneko T, Baba M, Shoji A, Sunayama K, Kamiya K, Tanaka T, Suzuki S, Nakamura S, Urano T. Urokinase receptor and vascular endothelial growth factor are synergistically associated with the liver metastasis of colorectal cancer.Jpn J Cancer Res. 92(5): 516-523, 2001
• Fujii, M., Hayakawa, H., Urano, T., Sato, A., Chida, K., Nakamura, H. and Takada, A. Relevance of tissue factor and tissue factor pathway inhibitor for hypercoagulable state in the lungs of patients with idiopathic pulmonary fibrosis. Thromb. Res. 99, 111-117, 2000
• Abe, J., Urano, T., Konno, H., Erhan, Y., Tanaka, T., Nishino, N., Takada, A. and Nakamura, S. Larger and more invasive colo-rectal cancer contained larger amounts of plasminogen activator inhibitor type 1 and its relative ratio over urokinase receptor correlated well with tumor size. Cancer 86(12), 2602-2611, 1999
• Morita, S., Sato, A., Hayakawa, H., Ihara, H., Urano, T., Takada, Y. and Takada A. Cancer Cells Overexpress mRNA of Urokinase-Type Plasminogen Activator, Its Receptor And Inhibitors In Human Non-Small-Cell Lung Cancer Tissue: Analysis By Northern Blotting And In Situ Hybridization. Int J Cancer 78, 286-292, 1998
• Imokawa, S., Sato, A., Hayakawa, H., Kotani, M., Urano, T., Takada, A. Tissue factor expression and fibrin deposition in the lungs of patients with idiopathic pulmonary fibrosis and systemic sclerosis. American Journal of Respiratory & Critical Care Medicine, 156(2 Pt1):631-6, 1997
• Nagayama, M., Sato, A., Hayakawa, H., Urano, T., Takada, Y. and Takada, A. Plasminogen activators and their inhibitors in non-small cell lung cancer: Low content of type 2 plasminogen activator inhibitor associated with tumor dissemination. Cancer 73(5), 1398-1405, 1994
• Sumiyoshi, K. Serizawa, T. Urano, Y. Takada, A. Takada and S. Baba. Plasminogen activator system in human breast cancer. Int. J. Cancer 50, 345-348, 1992.
• Nakamura, M., Konnno, H., Tanaka, T., Maruo, Y., Nishino, N., Aoki, K., Baba, S., Sakaguchi, S., Takada, Y. and Takada, A. Possible role of plasminogen activator inhibitor 2 in the prevention of the metastasis of gastric cancer tissues. Thromb. Res. 65: 709-719, 1992
• Sumiyoshi, S. Baba, S. Sakaguchi, T. Urano, Y. Takada and A. Takada. Increase in levels of plasminogen activator and type-1 plasminogen activator inhibitor in human breast cancer: possible roles in tumor progression and metastasis. Thromb. Res. 63, 59-71, 1991
• Nishino N., Aoki K., Tokura Y. Sakaguchi S., Fujie M., Sugawara Y., Takada Y. and Takada A. Measurement of urinary trypsin inhibitor in urine, plasma and cancer tissues of patients with stomach cancer. Haemostasis 19(2): 112-119, 1989

血管内線溶活性 調節機構と線溶因子の発現の調節機構 †

　血管内線溶活性は主要な PA である tPA とそのインヒビターである PAI-1 により調節されている。その産生は種々の生理的な要因により変化し、血中レベルは大きな日内変動を示したり、外傷・手術の影響を受けたり、また血中脂肪レベルなどの影響を受ける。これにより血管内線溶活性が大きく変化しうることを報告してきた。

主な業績

• Hoki S, Suzuki Y, Umemura K, Urano T.Enhancement of fibrinolysis by gel-filtered platelets and its quenching by cytochalasin B and GPIIb/IIIa antagonists.Pharmacological Reports61(5),877-84, 2009
• Tanaka A, Suzuki Y, Sugihara K, Kanayama N, Urano T. Inactivation of plasminogen activator inhibitor type 1 by activated factor XII plays a role in the enhancement of fibrinolysis by contact factors in-vitro.Life Scineces 85(5/6), 220-225, 2009
• Suzuki Y, Mogami H, Ihara Y, Urano T. Unique secretory dynamics of tissue plasminogen activator and its modulation by plasminogen activator inhibitor-1 in vascular endothelial cells. Blood 113, 470-478, 2009
• Hayashi T, Mogami H, Murakami Y, Nakamura T, Kanayama N, Konno K, UranoT. Real-time analysis of platelet aggregation and procoagulant activity during thrombus formation in vivo.Pflugers Archiv-European Journal of Physiology 456(6), 1239-51, 2008
• Nakamura R, Umemura K, Hashimoto H, Urano T.Less pronounced enhancement of thrombin-dependent inactivation of plasminogen activator inhibitor type 1 by low molecular weight heparin compared with unfractionated heparin. Thromb Haemost 95, 637-42, 2006''''
• Hryszko T, and Urano T. Activated Protein C enhances tPA-catalyzed Glu-plasminogen activation in the presence of poly-D-lysine.Thrombosis & Haemostasis 92(4), 891-2, 2004
• Zhao BQ, Ikeda Y, Ihara H, Urano T, Fan WY, Mikawa S, Suzuki Y, Kondo K, Sato K, Nagai N and Umemura K. Essential role of endogenous tissue plasminogen activator through matrix metalloproteinase 9 induction and expression on heparin-produced cerebral hemorrhage after cerebral ischemia in mice. Blood 103(7), 2610-2616, 2004
• Suzuki Y, Kondo K, Matsumoto Y, Zhao BQ, Otsuguro K, Maeda T, Tsukamoto Y, Urano T, Umemura K. Dietary supplementation of fermented soybean, natto, suppresses intimal thickening and modulates the lysis of mural thrombi after endothelial injury in rat femoral artery.Life Sci 73(10), 1289-98, 2003
• Sakata K, Pawlak R, Urano T and Takada A Effects of a longterm pharmacological interruption of the rennin-angiotensin system on the fibrinolytic system in essential hypertension. Pathophysiology of Haemostasis and Thrombosis. 32, 67-75, 2002
• Suzuki Y, Kondo K, Ichise H, Tsukamoto Y, Urano T and Umemura. K. Dietary supplementation with fermented soybeans suppresses intimal thickening. Nutrition. 19 (3), 261-264, 2003
• YoshidaM, NaitoY, UranoT, TakadaA and Takada Y. L-158,809 and (D-Ala7)-angiotensin I/II (1-7) decrease PAI-1 release from human umbilical vein endothelial cells. Thromb. Res. 105(6), 531-536, 2002
• Aoki K, Aikawa N, Sekine K, Yamazaki M, Mimura T, Urano T and Takada A. Elevation of plasma free PAI-1 levels as an integrated endothelial response to severe burs. Burns 27, 569-575, 2001
• Yoshino A, Suzuki K, Urano T, Aoki K, Takada Y and Takada A Enhanced secretion of tissue plasminogen activator by simultaneous use of retinoic acid and ascorbic acid from tissue cultured gastroepiploic artery. Life Sciences70, 1461-1470, 2002
• Ihara, H., Urano, T., Takada, A. and Loskutoff D. J. Induction of plasminogen activator inhibitor-1 (PAI-1) gene expression in adipocytes by thiazolidinediones. FASEB J.15(7):1233-1235, 2001
• Urano T., Suzuki Y., Arakida M., Kanamori M. and Takada A. The expression of exercise-induced tPA activity in blood is regulated by the basal level of PAI-1. Thromb. Haemost. 85, 751-752, 2001
• Suzuki, Y., Urano, T., Ihara, H., Nakajima, T., Nagai, N., Takada, Y., Taminato, T. and Takada, A. Bezafibrate attenuates the overexpression of plasminogen activator inhibitor-1 messenger RNA by a combination of mono-unsaturated fatty acid and insulin in HepG2 cells. Life Sciences in press
• Ahaneku, J.E., Sakata, K., Urano, T., Takada, Y. and Takada, A. Influence of baseline values on lipids, lipoproteins and fibrinolytic parameters during treatment of hypertension with cilnidipine. Pharmaclogical Research 41(1), 81-84, 2000
• Ahaneku, J.E., Sakata, K., Urano, T., Takada, Y. and Takada, A. Influence of baseline values on lipids, lipoproteins and fibrinolytic parameters during amlodipine treatment of hypertension in Japanese. Pharmaclogical Research 41(1), 75-79, 2000
• Sakata, K., Shirotani, M., Yoshida, H., Urano, T., Takada, Y. and Takada, A. Differential effects of analapril and nitrendipine on the fibrinolytic system in essential hypertension. Am. Heart J. 137 (6), 1094-1099, 1999
• Takada, Y., Urano, T., Takahashi, H., Nagai, N. and Takada, A. Effects of electric footshock and water immersion restraint stresses on fibrinolytic parameters in the plasma of rats. Thromb. Res. 89, 107-114, 1998.
• Nagai, N., Urano, T., Takada, Y. and Takada, A. Reperfusion after venous occlusion caused transient increase in plasminogen activator inhibitor-1 in systemic circulation.Clinical and Applied Thrombosis/Hemostasis, 4(2), 133-137, 1998
• Rydzewski, A., Urano, T., Nagai, N., Takada, Y., Katoh-Oishi, Y., Taminato, T., Yoshimi, T. and Takada, A. Diurnal variation in serum remnant-loke lipoproteins, platelet aggregation and fibrinolysis in healthy volunteers.Haemostasis, 27, 305-314, 1997
• Urano, T., Nishikawa, T., Nagai, N., Takada, Y. and Takada, A. Amounts of tPA and PAI-1 in the euglobulin fraction obtained at different pH: Their relation to the euglobulin clot lysis time. Thromb. Res. 88(1), 75-80, 1997
• Mochizuki M., Takada Y., Urano T., Nagai N., Nakano T., Nakajima K. and Takada A. The in vitro effects of chylomicron remnant and very low density lipoprotein remnant on platelet aggregation in blood obtained from healthy persons. Thromb Res. 81(5), 583-593, 1996
• Malyszko J., Urano T., Knofler R., Takada Y. and Takada A. Effects of short term treatment with mevalotin on platelet aggregation, fibrinolysis, peripheral serotonergic system and serum lipids in Japanese monkeys.Thromb. Res. 81(2), 397-402, 1996
• Takada, A., Takada, Y. and Urano, T. The physiological aspects of fibrinolysis.Thromb. Res. 76(1); 1-31, 1994. (Review)
• Aoki, K., Nishino, N., Baba, S., Urano, T. and Takada, A. Postoperative changes in plasma tissue-type plasminogen activator and type 1 plasminogen activator inhibitor. Surg Today Jpn J Surg 24, 1039-1043, 1994
• Malyszko, J., Urano, T., Knofler, R., Ihara, H., Shimoyama, I., Uemura, K., Takada, Y. and Takada, A. Correlation between platelet aggregation, fibrinolysis, peripheral and central serotonergic measures in subhuman primates.Atherosclerosis 110, 63-68, 1994
• Malyszko, J., Urano, T., Knofler, R., Ihara, H., Takada, Y. and Takada, A. Relationships between serum lipids, serotonin, platelet aggregation and some fibrinolytic parameters in humans. Life Sciences 55(21), 1619-1623, 1994
• Malyszko, J., Urano, T., Knofler, R., Taminato, A., Yoshimi, T., Takada, Y. and Talkada, A. Daily variations of platelet aggregation in relation to blood and plasma serotonin in diabetes. Thromb. Res. 75(5), 569-576, 1994
• Malyszko, J., Urano, T., Takada, Y. and Takada, A. Stress dependent changes in fibrinolysis, serotonin and platelet aggregation in rats.Life Sci. 54(17): 1275-1280, 1994
• Malyszko, J., Urano, T., Takada, Y. and Takada, A. Time-dependent changes in platelet aggregation, fibrinolytic activity, and peripheral serotnergic measures in rats subjected to water-immersion restraint stress. Haemostasis 24, 236-242, 1994
• Urano T., Malyszko J., Serizawa K., Kozima Y., Takada Y. and Takada A. Electric-foot-shock induced the supression of fibrinolytic activity in rats. Thromb. Res. 74(6): 595-603, 1994
• Takada, Y., Urano, T., Watanabe, I., Taminato, A., Yoshimi, T., Takada, A. Changes in fibrinolytic parameters in male patients with type 2 (non insulin dependent) diabetes mellitus. Thromb. Res. 71, 405-415, 1993.
• Urano, T., Kojima, Y., Takahashi, M., Serizawa, K., Sakakibara, K., Takada, Y. and Takada, A. Impaired fibrinolysis in hypertension and obesity due to high plasminogen activator inhibitor-1 level in plasma. Jpn. J. Physiol. 43, 221-228, 1993
• Sakata, K., Hoshino, T., Yoshida, H., Ono, N., Ohtani, S., Yokoyama, S., Mori, N., Kaburagi, T., Kurata, C., Urano, T., Takada, Y. and Takada, A. Circadian fluctuations of tissue plasminogen activator antigen and plasminogen activator inhibitor-1 antigens in vasospastic angina. Am. Heart J. 124(4): 854-860, 1992
• Urano, T. Sumiyoshi, K. Pietraszek, M. H. Takada, Y. and Takada, A. PAI-1 plays an important role in the expression of t-PA activity in the euglobulin clot lysis by controlling the concentration of free t-PA.Thrombos. Haemostas. 66(4) 474-478, 1991
• Takada, A., Urano, T., Takada, Y. The regulation of the activation of the fibrinolysis system. [Review] Advances in Experimental Medicine & Biology 281(209), 209-222, 1990
• Urano T., Sakakibara K., Rydzewski A., Urano S., Takada Y. and Takada A. Relationships between euglobulin clot lysis time and the plasma levels of tissue plasminogen activator inhibitor 1. Thrombos. Haemostas. 63; 82-86, 1990

中枢神経系 におけるPA-plasmin systemの役割の研究 †

　中枢神経系でも線溶系因子は、神経系ネットワークの形成及び再編成に重要な役割を果たしています。

主な業績

• Nagai, N. and Urano, T. Role of tPA in the neural system. In Recent Advances in Thrombosis and Hemostasis. Edited by K. Tanaka and E.W. Davie. Springer, Tokyo, (2008) pp 314-327.
• Takahashi H, Takada Y, Urano T and Takada A. 5-HT4 receptors in the hippocampus modulate rat locomotor activity. Hippocampus 12, 304-310, 2002
• Nagai N, Zhao BQ, Suzuki Y, Ihara H, Urano T, Takada A, Umemura K.Tissue-type plasminogen activator has paradoxical roles in focal cerebral ischemic injury by thrombotic middle cerebral artery occlusion with mild or severe photochemical damage in mice. J Cereb Blood Flow Metab. 22, 648-651, 2002
• Pawlak R-, NagaiN, UranoT, Napiorkowska-PawlakD, IharaH, TakadaY , Collen D.and TakadaA. Rapid, specific and active site-catalyzed effect of tissue-plasminogen activator on hippocampus-dependent learning in mice. Neuroscience 113(4), 995-1001, 2002
• Pawlak R, Napiorkowska-Pawlak D, Takada Y, Urano T, Nagai N, Ihara H, Takada A. The differential effect of angiotensin II and angiotensin 1-7 on norepinephrine, epinephrine, and dopamine concentrations in rat hypothalamus: the involvement of angiotensin receptors. Brain Res Bull. 54(6): 689-694, 2001
• Takahashi H, Takada Y, Urano T, Takada A. Dissociation of systemic and hippocampal modulation of rat locomotor activity by 5-HT(2C) receptors. Neurosci Res. 40(1): 97-103, 2001
• Nagai N., YamamotoS., TsuboiT., IharaH., UranoT., TakadaY., TerakawaS. and TakadaA. Tissue-type plasminogen activator enhances neuronal death induced by oxygen-glucose-deprivation in culture. J Cereb Blood Flow Metab. 21(6): 631-634. 2001
• Endo A, Hashimoto K, Takada Y, Takada A.　The activation of the tissue plasminogen activator-plasmin system induced in the mouse hippocampus after injection of trimethyltin: Poosible proteolysis of highly polysialated NCAM.Jpn. J. Physiol. 49(5): 463-466 , 1999
• Endo, A., Nagai, N., Urano, T., Takada, Y., Hashimoto, K. and Takada, Y. Proteolysis of neuronal cell adhesion molecule by the tissue plasminogen activator-plasmin system after kainate injection in the mouse hippocampus.Neuroscience Research 33, 1-8, 1999
• Nagai, N., Urano, T., Endo, A., Takahashi, H., Takada, Y. and Takada, A. Neuronal degeneration and a decrease in laminin-like immunoreactivity is associated with elevated tissue-type plasminogen activator in the rat hippocampus after kainic acid injection.Neuroscience Research 33, 147-154, 1999
• Endo, A., Nagai, N., Urano, T., Ihara, H., Takada, Y. and Takada, A. Proteolysis of highly polysialylated NCAM by the tissue plasminogen activator-plasmin system in rats.Neuroscience Letters, 246, 37-40, 1998.

細胞内信号伝達機構 †

　細胞内信号伝達機構も、second messengerが複雑に絡み合い、細胞機能調節を時空間的に巧妙に調節しているようです。最上准教授を中心に、これもまた可視化技術を駆使して、目を凝らして、見つめております。

主な業績

• Adachi E, Kazoe Y, Sato Y, Suzuki Y, Urano T, Ueyama T, Saito N, Nikolaev VO, LohseMJ,Tominaga M, Mogami H.A technique for monitoring multiple signals with a combination of prism-based total internal reflection fluorescence microscopy and epifluorescence microscopy Pflugers Arch - Eur J Physiol 459(1),227-34, 2009

• Suzuki Y, Zhang H, Saito N, Urano T, Kojima N, Mogami H.Glucagon-Like Peptide 1 Activates Protein Kinase C Through a Ca2+-Dependent Phospholipase C Activation in Insulin-Secreting Cells. J Biol Chem 281(39), 28499-28507, 2006

• Mogami H, Zhang H, Suzuki Y, Urano T, Saito N, Kojima I, and Petersen OH. Decoding of short-lived Ca2+influx signals into long-term substrate phosphorylation through activation of two distinct classes of protein kinase C. J Biol Chem 278(11), 9896-9904, 2003