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Your search keyword '"Shinya, H."' showing total 19 results
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19 results on '"Shinya, H."'

1. GARFIELD-AF: risk profiles, treatment patterns and 2-year outcomes in patients with atrial fibrillation in Germany, Austria and Switzerland (DACH) compared to 32 countries in other regions worldwide

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Haas, S., Camm, J.A., Harald, D., Steffel, J., Virdone, S., Pieper, K., Brodmann, M., Schellong, S., Misselwitz, F., Kayani, G., Kakkar, A.K., Jean-Pierre, B., John Camm, A., Fitzmaurice, D.A., Fox, K.A.A., Gersh, B.J., Goldhaber, S.Z., Shinya, G., Sylvia, H., Werner, H., Mantovani, L.G., Frank, M., Pieper, K.S., Turpie, A.G.G., Martin van Eickels, Verheugt, F.W.A., Fox Bernard, K.A.A., Gersh, J., Hector, L., Luciardi Harry Gibbs, Marianne, B., Frank, C., Antonio Carlos Pereira Barretto, Connolly, S.J., John, E., Ramon, C., Zhi-Cheng, J., Petr, J., Jørn Dalsgaard Nielsen, Hany, R., Pekka, R., Jean-Yves Le Heuzey, Matyas, K., Jitendra Pal Singh Sawhney, Giancarlo, A., Giuseppe, A., Yukihiro, K., Carlos Jerjes Sánchez Díaz, Hugo Ten Cate, Dan, A., Janina, S., Elizaveta, P., Toon Wei Lim, Barry, J., Seil, O., Xavier, V., Marten, R., Jan, S., Pantep, A., Ali, O., Alex, P., Wael Al Mahmeed, David, F., Samuel, Z.G., Dayi Hu Kangning Chen, Yusheng, Z., Huaiqin, Z., Jiyan, C., Shiping, C., Daowen, W., Yuejin, Y., Weihua, L., Hui, L., Yuehui, Y., Guizhou, T., Ping, Y., Yingmin, C., Shenghu, H., Yong, W., Guosheng, F., Xin, L., Tongguo, W., Xiaoshu, C., Xiaowei, Y., Ruiping, Z., Moshui, C., Longgen, X., Ping, C., Yang, J., Ying, G., Xue, L., Zhiming, Y., Praveen Jadhavm Raghava Sarma, Govind, K., Prakash, C., Rasesh Atulbhai Pothiwala, Mohanan Padinhare Purayil, Kamaldeep, C., Veerappa Annasaheb Kothiwale, Bagirath, R., Vinod Madan Vijan, Jitendra, S., Ganapathi, B., Aziz, K., Ramdhan, M., Manojkumar, C., Sunitha, A., Vikas, B., Govindan, V., Debabrata, R., Rajashekhar, D., G Ravi Shankar, A., Sunil, K., Dinesh, J., Kartikeya, B., Vinay, K., Udigala Madappa Nagamalesh, Rajeeve Kumar Rajput, Yukihiro Koretsune Seishu Kanamori, Kenichi, Y., Koichiro, K., Yosuke, K., Keiki, Y., Fumitoshi, T., Yuji, M., Ikuo, M., Hiroo, N., Shinichi, A., Tetsuro, S., Masahiro, M., Hiroyuki, O., Susumu, A., Kei, C., Hiroaki, N., Makoto, T., Takeshi, K., Kunihiko, Y., Hiroshi, A., Takayuki, H., Megumi, O., Shiro, A., Shinichiro, K., Kenshi, K., Takashi, M., Jun, M., Yurika, O., Ryuji, S., Kazuo, G., Kotaro, M., Yoshikuni, H., Hisakazu, S., Hiroo, M., Hitoshi, K., Tsugihiro, N., Tadashi, N., Hidekazu, N., Ryuji, Z., Yoshihisa, F., Akira, Y., Hiroyuki, N., Jun, O., Yasuyuki, K., Kinshiro, M., Yutaka, W., Masanori, Y., Hiromitsu, M., Sumihisa, A., Hajime, K., Satoru, T., Katsumi, S., Hiroki, T., Ichiro, O., Takashi, K., Satoshi, H., Masamichi, G., Takuma, E., Hidetoshi, C., Kazuaki, F., Yuhei, S., Hirokuni, S., Toshihisa, N., Yoshihiko, A., Toshiro, N., Kazuhisa, S., Fumihiro, H., Naoto, Y., Masahiro, K., Toshifumi, T., Munesumi, I., Yoshitake, F., Daisuke, I., Taku, S., Tetsu, I., Norio, I., Koichi, O., Keizo, T., Yutaka, H., Motoshi, T., Hiroto, T., Shinjiro, N., Masaaki, I., Yuichiro, N., Naomasa, M., Ashida, K., Jun, A., Seishiro, M., Osamu, A., Shuji, F., Hirofumi, M., Kazuya, M., Yoshiki, H., Ichiro, S., Kotaro, O., Ichiro, T., Mitsuyuki, A., Toshihide, U., Yoshinori, G., Makoto, I., Shoji, M., Shigeru, M., Hideo, D., Mitsuru, T., Takaaki, K., Shigeo, K., Chiga, O., Masaki, S., Masami, N., Yutaka, K., Yoichi, N., Hiroshi, O., Rikimaru, O., Masato, A., Teruaki, M., Kazuhiko, N., Takafumi, M., Junichi, M., Mitsunori, A., Masako, F., Makoto, O., Tsuneo, F., Toshiya, T., Tenei, K., Hiroshi, K., Mizuho, I., Masahiro, A., Takashi, U., Hironori, O., Masahiko, I., Yoshiki, K., Atsuyuki, N., Shinobu, T., Mitsuhiro, S., Masayuki, N., Kenichiro, I., Motoyuki, I., Taro, M., Masamichi, W., Hiroaki, M., Masato, M., Fumio, O., Teruaki, K., Kuniaki, T., Masaaki, T., Morio, I., Hiroshi, W., Toshihiko, S., Shinya, H., Hiroaki, H., Mitsumoto, H., Michitaka, H., Koichi, M., Hideki, H., Nobuyoshi, S., Yukio, S., Akira, S., Kazuo, N., Tetsuro, Y., Kunio, A., Sen, A., Chiei, T., Saori, M., Hirofumi, K., Masanori, K., Shiro, N., Atsushi, T., Shuta, T., Kazuyuki, S., Akiko, M., Hiroki, S., Jin, N., Taketo, H., Takash, I., Kazuki, S., Kazuya, K., Tomobumi, K., Tsuyoshi, T., Hirosumi, S., Kiyoshi, N., Kenichi, I., Kazuo, M., Tomohiro, S., Takeshi, I., Koichi, K., Hiromichi, K., Tsutomu, T., Mamoru, H., Jisho, K., Akitoshi, S., Yoshihiro, T., Tetsuo, B., Koji, H., Masaaki, H., Koichi, H., Takao, B., Kazuaki, M., Toshihiko, K., Kunihiko, H., Toshihide, K., Akira, N., Eiji, O., Takashi, S., Hiroyoshi, H., Chikako, S., Takashi, Y., Ichiro, M., Kazunori, S., Isamu, N., Ken, T., Osamu, I., Koichi, T., Samu, U., Hirokazu, K., Takuya, O., Seizo, O., Junya, K., Toshihiko, N., Itaru, M., Yoshifusa, M., Yasuyuki, M., Kazuo, T., Hajime, H., Tetsutaro, K., Koji, M., Masaichi, N., Takashi, W., Tomoki, Y., Masato, S., Hidekazu, A., Hisanori, S., Hiroyuki, T., Nobufusa, F., Akira, O., Kentaro, Y., Kenji, A., Taku, Y., Takeaki, K., Shunji, S., Shu, S., Nitaro, S., Masayuki, W., Yosuke, N., Toru, A., Masaki, O., Tetsushi, W., Tomoko, K., Yasuo, S., Takeshi, T., Yoshihito, H., Shinichi, H., Yukihiko, A., Yoshihiro, S., Hirohide, U., Hiroshi, T., Shuichi, T., Naoto, H., Seiichi, M., Hisashi, S., Takuma, A., Yasunobu, S., Yawara, N., Osamu, M., Hideko, I., Katsumasa, N., Masatsugu, N., Kazuo, S., Toshiyuki, F., Nobuhisa, I., Shunichi, N., Kiyoharu, S., Yujin, S., Naoko, O., Teruhiko, K., Hideaki, O., Masato, E., Tsutomu, G., Makoto, H., Emiko, N., Noriyuki, N., Toshizumi, M., Shuichi, S., Katsuhiro, O., Yoko, E., Tsuyoshi, F., Haruhiko, D., Shuichi, K., Sho, N., Yuya, U., Tetsuro, F., Mitsuru, I., Takuo, O., Shunsuke, T., Hideo, I., Norihiko, S., Kiyomitsu, I., Nobuo, W., Masatake, A., Junji, D., Tetsuya, K., Masato, T., Naoya, M., Yasuaki, F., Wataru, F., Susumu, S., Akinori, F., Ryosai, N., Hiroyasu, K., Rei, F., Keijiro, N., Yoji, K., Junya, A., Kiyoshi, Y., Toshio, A., Yasuhiro, S., Tatsuo, H., Yuichiro, K., Yasuhide, S., Yukihiro, S., Shingo, M., Kojuro, M., Yasuko, S., Toyoshi, S., Fumiko, I., Toshiyuki, K., Jaeyoung, K., Hiroshi, Y., Yoichi, T., Yoko Onuki Pearce, Yasuyuki, S., Takayuki, F., Toru, N., Hideaki, K., Yoshiyuki, K., Tetsuji, I., Hironori, M., Yasufumi, M., Masahito, S., Shimato, O., Yutaka, O., Satoshi, U., Kojiro, K., Tatsuo, O., Naoki, M., Koichi, I., Atsushi, I., Tomohiro, Y., Toshihiro, G., Tsukasa, K., Atsushi, S., Etsuo, M., Toshio, T., Hiroshi, S., Shunichi, F., Tomohiro, K., Yoshiyuki, F., Hiroshi, H., Jun, N., Kiichiro, Y., Takuya, I., Takafumi, A., Chi Keong Ching Toon Wei Lim, Kelvin, W., Tan, Y., Seil Oh Hui Nam Park, Woo-Shik, K., Hyeyoung, L., Sung-Won, J., Dae Hyeok Kim, Jun, K., Dongryeol, R., Jaemin, S., Dae-Kyeong, K., Dong Ju Choi, Yong Seog Oh, Myeong-Chan, C., Hack-Lyoung, K., Hui-Kyung, J., Dong-Gu, S., Sang Weon Park, Hoon Ki Park, Sang-Jin, H., Jung Hoon Sung, Hyung-Wook, P., Gi-Byoung, N., Young Keun On, Hong Euy Lim, Jaejin, K., Tae-Joon, C., Taek Jong Hong, Seong Hoon Park, Jung Han Yoon, Nam-Ho, K., Kee-Sik, K., Byung Chun Jung, Gyo-Seung, H., Chong-Jin, K., Sakda Rungaramsin Peerapat Katekangplu, Porames, K., Thanita, B., Wanwarang, W., Pinij, K., Khanchai, S., Waraporn, T., Supalerk, P., Khanchit, L., Doungrat, C., Warangkana, B., Sirichai, C., Songkwan, S., Pisit, H., Seksan, C., Pairoj, C., Boonsert, C., Yingsak, S., Khompiya, K., Piya, M., Sasivimon, J., Ongkarn, K., Armagan Altun Ali Aydinlar, Ramazan, T., Zeki, O., Sadik, A., Durmus Yildiray Sahin, Ozcan, Y., Mehmet Birhan Yilmaz, Hasan, P., Mesut, D., Murat, S., Levent, S., Murat, E., Ertugrul, O., Dursun, A., Florencia Rolandi Adrian Cesar Ingaramo, Gustavo Alberto Sambadaro, Vanina Fernandez Caputi, Sofia Graciela Berman, Pablo, D., Andres Javier Kleiban, Nestor, C., Rodolfo Andres Ahuad Guerrero, Leonel Adalberto Di Paola, Ricardo Dario Dran, Javier, E., Matias Jose Fosco, Victor Alfredo Sinisi, Luis Rodolfo Cartasegna, Oscar Gomez Vilamajo, Jose Luis Ramos, Sonia, S., Gerardo, Z., Diego, C., Guillermo, G., Alberto Alfredo Fernandez, Mario Alberto Berli, Fabian, F., Dário Celestino Sobral Filho Jefferson Jaber, Luciana Vidal Armaganijan, Costantino Roberto Frack Costantini, André, S., Weimar Kunz Sebba Barroso de Souzaem, João David de Souza Neto, José Márcio Ribeiro, Marcelo Silveira Teixeira, Paulo, R., Leonardo, P., Daniel, M., José Carlos Moura Jorge, Adalberto Menezes Lorga Filho, Luiz, B., Marcelo Westerlund Montera, Carlos Henrique Del Carlo, Jamil Abdalla Saad, Fernando Augusto Alves da Costa, Renato, L., Gilson Roberto de Araújo, Euler Roberto Manenti, Jose Francisco Kerr Saraiva, João Carlos Ferreira Braga, Alexandre, N., Carlos, M., Dalton, P., Fernando, R., Gilmar, R., Roberto Álvaro Ramos Filho, Estêvão Lanna Figueiredo, Roberto Vieira Botelho, Cláudio Munhoz da Fontoura Tavares, Helius Carlos Finimundi, Adriano, K., César Cássio Broilo França, Fábio, A., Guido Bernardo Aranha Rosito, João Batista de Moura Xavier Moraes Junior, Rogério Tadeu Tumelero, Lilia, M., Roberto Simões de Almeida, Ney Carter do Carmo Borges, Luís Gustavo Gomes Ferreira, Ramón Corbalán Benjamin Aleck Joseh Stockins Fernandez, Humberto, M., Fernando, L., Martín Larico Gómez, Carlos, A., Carlos, C., Patricio Marin Cuevas, Alejandro, F., Claudio Bugueño Gutiérrez, Juan, A., Sergio Potthoff Cardenas, German, E., Cesar, H., Carlos, R., Germán, A., Gustavo Charme Vilches, Carlos Jerjes Sanchez Diaz Jesus Jaime Illescas Diaz, Raul Leal Cantu, Maria Guadalupe Ramos Zavala, Ricardo Cabrera Jardines, Nilda Espinola Zavaleta, Enrique Lopez Rosas, Guillermo Antonio Llamas Esperón, Gerardo, P., Ernesto Cardona Muñoz, Norberto Matadamas Hernandez, Adolfo Leyva Rendon, Norberto Garcia Hernandez, Manuel de Los Rios Ibarra, Luis Ramon Virgen Carrillo, David Lopez Villezca, Carlos Hernandez Herrera, Juan Jose Lopez Prieto, Rodolfo Gaona Rodriguez, Efrain Villeda Espinosa, David Flores Martinez, Jose Velasco Barcena, Omar Fierro Fierro, Ignacio Rodriguez Briones, Jose Luis Leiva Pons, Humberto Alvarez Lopez, Rafael Olvera Ruiz, Carlos Gerardo Cantu Brito, Eduardo Julian Jose Roberto Chuquiure Valenzuela, Roxana Reyes Sanchez, Alberto Esteban Bazzoni Ruiz, Oscar Martin Lopez Ruiz, Roberto Arriaga Nava, Jesus David Morales Cerda, Pedro Fajardo Campos, Mario Benavides Gonzalez, Marianne Brodmann Kurt Lenz, Claus, H., Johannes, F., Heinz, D., Kurt, H., Andrea, P., Michael, W., Bruno, S., Alfons, G., Wilfried, L., Sabine, E., Peter, K., Josef, S., Heribert, R., Bernhard, S., Luc Capiau Geert Vervoort, Bart, W., Geert, H., Jan, V., Dirk, F., Yohan, B., Marc, D., Olivier, X., Harry, S., John, T., Georges, M., Wim, A., Ivan, B., Michel, B., Stefan, V., Peter, V., Philippe, P., Pascal, G., Tim, B., Philippe, D., Alex, H., Joeri, V., Axel De Wolf Eva Zidkova Petr Jansky, Rudolf, S., Vilma, M., Ondrej, L., Josef, O., Lubos, K., Blazej, R., Richard, F., Jan, H., Ilja, K., Zdenek, M., Hana, B., Ondrej, J., Jana, P., Iveta, P., Vratislav, D., Michaela, H., Petr, P., Petr, R., Jindrich, S., Miroslav, N., Vaclav, D., Katarina, P., Jiri, L., Jørn Nielsen Steen Husted, Helena, D., Ulrik, H., Søren, R., Næstved, S., Arne, B., John, M., Jan, B., Jorgen, S., Ebbe, E., Thomas, L., Michael, B., Jacob, M., Morten, S., Michael, O., Pekka Raatikainen Carmela Viitanen, Franck Paganelli Joël Ohayon, Frédéric, C., Michel, G., Yannick, G., Philippe, L., Jean-Joseph, M., Mohamed Bassel Koujan, André, M., Sylvain, D., Olivier, P., Nicolas, D., Jean-Pierre, C., Maxime, G., Dominique, G., G Lokesh, A., Mathieu, Z., Pierre, A., Emmanuel, E., James, K., Pierre-Yves, F., Jean-Pierre, H., Nestor, L., Gilles, R., Igor, S., Jean-Philippe, N., Marie Hélène Mahagne, Antoine, M., Marc, B., Jean-Baptiste, C., Vincent, N., Frederic, S., Gilles, M., Jean-Paul, B., Bernard, D., Michel, M., Désiré, O., Bernard, C., Joseph, M., Etienne, B., Jean Philippe Brugnaux, Alain, F., Pierre, N., Jean-Baptiste, B., Sebastien Schellong Harald Darius, Georg, K., Andreas, K., Uwe, G., Bernd-Thomas, K., Thomas, S., Jan, P., Enno, E., Heinz-Dieter, Z., Peter, R., Christoph, A., Gerd-Ulrich, H., Holger, M., Andreas, P., Stefan, Z., Wolfgang, E., Guenter, R., Dirk, G., Norbert, L., Petra, S., Henning, W., Cosmas, W., Steffen, S., Toralf, S., Adyeri, B., Maximilian, K., Hans-Hermann, Z., Friedhelm, K., Andreas, C., Sabine, O., Torsten, L., Hermann-Josef, H., Gunter, L., Hans-Walter, B., Gunter, H., Dietrich, R., Joachim, H., Praxis Dres Werner Erdle, Wilfried, D., Janna, D., Karl-Albrecht, R., Reinhold, V., Thomas, M., Peter, M., Uwe, H., Volker, E., Heinz, H., Heinz, L., Volker, L., Heiner, M., Christian, S., Herrmann, L., Thomas, B., Gunter, B., Susanne, K., Karsten, M., Sylvia, B., Muwafeg, A., Hans-Holger, E., Carsten, S., Peter, B., Laszlo, K., Britta, S., Wilhelm, H., Jens-Uwe, R., Andras Vertes Gabor Szantai, Andras, M., Nikosz, K., Zoltan, B., Erno, K., Balazs, G., Ferenc, J., Gizella, J., Sandor, K., Zoltan, L., Zsolt, M., Bela, M., Ebrahim, N., Tamas, H., Peter, P., Gabriella, S., Sandor, V., Andras, N., Gabriella, E., Judit, F., Mihaly, E., Giuliana Martini Leone Maria Cristina, Eros, T., Rita, S., Sophie, T., Giovanni Di Minno, Marco, M., Teresa Maria Caimi, Maria, T., Roberto, C., Daniela, P., Roberto, Q., Franco, C., Raffaele, F., Vincenzo, O., Raffaele, R., Roberto, S., Raimondo De Cristofaro, Giuliana, G., Angelo De Blasio, Jorge Salerno Uriate, Flavia, L., Enrico Maria Pogliani, Grzegorz, B., Michele, A., Antonio, M., Mauro, F., Arturo, R., Luciano, F., Andrea, M., Fabrizio, G., Luca, T., Maria, S., Sergio, N., Paolo, R., Antonio, A., Claudio, B., Filippo, T., Massimo, V., Maria, D., Maria Grazia Bongiorni, Silva, S., Alessandro, C., Corrado, L., Enrico, S., Gaetano, S., Tondo, C., Paolo, G., Carmine, M., Saverio, I., Hugo Ten Cate J, H.R., Andreas, L., Henk, A., Maarten, B., Mathijs, P., Coen van Guldener, Johannes, H., S H K P, R.N., Pieter, H., Walter, H., E Groenemeijer, B., Terpstra, W., Cees, B., L V, A.B., Eivind Berge Per Anton Sirnes, Erik, G., Torstein, H., Knut, E., Arne, H., Gunnar, S., Anders, Ø., Beraki, G., Arne, S., Peter, C., Torbjørn, Ø., Svein Høegh Henrichsen, Jan Erik Otterstad, Janina Stepinska Andrzej Gieroba, Malgorzata, B., Michal, O., Beata, W., Krystyna, L., Jaroslaw, Wieslaw, S., Jerzy, K., Roman, Z., Jaroslaw, H., Lucyna, S., Lech, K., Marcin, G., Piotr, M., Maciej, O., Grzegorz, K., Malgorzata, K., Zbigniew, L., Bozenna, O., Jerzy, L., Elzbieta, Z., Agnieszka, K., Malgorzata, C., Iwona, W., Grzegorz, O., Marek, B., Marcin, O., Grazyna, G., Piotr, R., Grzegorz, S., Ryszard, S., Boguslaw, O., Piotr, K., Krzysztof, G., Krzysztof, C., Jaroslaw, J., Pawel, M., Waldemar, M., Stanislaw, M., Roman, L., Jacek, B., Teresa, R., Grzegorz, R., Ewa, D., Jadwiga, N., Jozef, L., Vera Eltishcheva Roman Libis, Gadel, K., Dmitry, B., Liudmila, E., Alexander, K., Eduard, Y., Dmitry, Z., Olga, B., Olga, M., Evgeniy, M., Konstantin, Z., Tatyana, N., Yulia, M., Elena, P., Konstantin, S., Maria, R., Yulia, S., Alla, K., Konstantin, N., Oksana, Z., Anna, Z., Victor, K., Sergey, P., Maria, P., Anton, E., Elena Aleksandrova Oksana Drapkina, Alexander, V., Oleg, N., Petr, C., Svetlana, R., Mikhail, S., Borys, K., Alexey, U., Xavier Vinolas Pere Alvarez Garcia, Maria Fernanda Lopez Fernandez, Luis Tercedor Sanchez, Salvador Tranche Iparraguirre, Pere Toran Monserrat, Emilio Marquez Contreras, Jordi Isart Rafecas, Juan Motero Carrasco, Pablo Garcia Pavia, Casimiro Gomez Pajuelo, Luis Miguel Rincon Diaz, Luis Fernando Iglesias Alonso, Angel Grande Ruiz, Jordi Merce Klein, Jose Ramon Gonzalez Juanatey, Ines Monte Collado, Herminia Palacin Piquero, Carles Brotons Cuixart, Esther Fernandez Escobar, Joan Bayo, I.L., Cecilia Corros Vicente, Manuel Vida Gutierrez, Francisco Epelde Gonzalo, Carlos Alexandre Almeida Fernandez, Encarnacion Martinez Navarro, Juan Jose Montero Alia, Maria Barreda Gonzalez, Maria Angels Moleiro Oliva, Jose Iglesias Sanmartin, Mercedes Jimenez Gonzalez, Maria Del Mar Rodriguez Alvarez, Juan Herreros Melenchon, Tomas Ripoll Vera, Manuel Jimenez Navarro, Maria Vazquez Caamano, Maria Fe Arcocha Torres, Gonzalo Marcos Gomez, Andres Iniguez Romo, Miguel Angel Prieto Diaz, Mårten Rosenqvist Alexander Wirdby, Centrumkliniken, Jan, L., Kerstin, H., Micael, E., Arnor, E., Ulf, B., Liu, B., Anders, L., Lars-Bertil, O., Mikael, G., Lars, A., Lars, B., Claes, B., Ali, H., Björn, M., Marianne, E., Åke, O., Håkan, L., Peter, S., Katarina, T., Hans, H., Pyotr, P., Fredrik, B., Ingar, T., Milita, C., Jan-Erik, K., Agneta, A., Lennart, M., Johan, E., Jörgen, T., Aida, H., Steen, J., Per, S., Jan Steffel Johann Debrunner, Juerg, H.B., Dipen, S., Iurii Rudyk Vira Tseluyko, Oleksandr, K., Svitlana, Z., Igor, K., Oleksandr, P., Iryna, K., Nestor, S., Yuriy, M., Oleksiy, U., Olena, K., Yevgeniya, S., Oleg, S., Mykola, S., Andriy, Y., Susanna, T., Ivan, F., Will Murdoch Naresh Chauhan, Daryl, G., Louise, L., Ramila, P., Philip, S., Bennett, W., Alex, C., Niranjan, P., Jhittay, P., Andrew, R., S Kainth, M., Karim, L., Kevin, D., Gill, P., Joanna, M., Laura, H., Trevor, G., Helga, W., Cumberlidge, Colin, B., Catherine, B., Kevin, J., Shoeb, S., Richard, C., Bhupinder, S., Willcock, W., Sircar, S., John, C., Gilliand, A., Roman, B., Strieder, E., Peter, H., Anne, W., Michael, S., Graham, K., Bhaskhar, V., Nigel, B., Paul, E., Clark, M., John, B., Jennifer, L., Fisher, E., Tim, F., Richard, K., Neil, P., Elizabeth, A., Michael, A., Ramesh, C., Pete, W., Simon, F., Sue, F., Julian, T., Hasan, C., Gary, T., Dawn, T., Matt, P., Claire, S., Carolyn, P., Mark, R., Angus, J., Helen, S., Hywel, J., Claire, G., Matthew, B., Philip, W., Jehad, A., Simon, W., William, L., Phil, E., Frances, S., Neil, M., Stephen, R., Yvette, S., Richard, W., Philip, P., Paul, W., Preeti, P., Andrew, G., Railton, T., Emyr, D., Jonathan, M., Marc, J., Claire, H., Thompson, R., Bijoy, S., Keith, B., Susan, B., Helen, L., David, R., Ulka, C., Ikram, H., Paul, A., Claire, J., Phil, W., Jane, E., Lisa, G., Janet, G., Alison, M., Poland, K., Conor, M., Warke, A., Paul, C., Burns, D., Smith, R., Kamath, R., Jonathan, W., Ian, H., Stephen, V., Paul, R., Hilary, P., Jayesh, P., Amar, A., Nigel, H., Richard, D., Nigel, D., Catherine, N., Mark, D., Purnima, S., Sophia, G., Charlotte, H., Raife, O., Martin, A., Mira, P., Gordon, I., Shahid, A., Catherine, R., Fiaz, C., Sabrina, K., Stephanie, S., Sharon, P., Warwick, C., Neil, R., Amy Butler Steven Coates, Ben, W., Daniel, J., Steve, W., Diane, S., Toh, W., Mark, B., Melanie, D., David, C., Sarah, D., Ben, F., Nick, H., Henry, C., Jon, S., Tim, M., Salah, E., Diane, G., Justin, W., Richard, V., Karen, F., Rob, H., Kashif, Z., Catherine, L., Rebecca, W., Paul, M., Andre, B., Philip, C., Mike, W., Mark, P., Chaminda, D., Greg, R., James, B., Polly, J., Rajesh, M., Matthew, A., Robin, F., Nicolas, T., Simon, C., Rory, R., Simon, R., Christine, A., Ann, F., Andrew, H., Simon, D., Minnal, N., Iain, M., Jane, G., Phil, S., John, S., Emma, B., Adam Blenkhorn Bhuwanendu Singh, Penny, A., William van Gaal, Walter, A., Philip, T., Ron, L., Jens, K., Andrei, C., Hosen, K., David, E., John, F., Bronte, A., Thanh, P., James, R., David, O., Sang Cheol Bae, Harry, G., Patrick, C., Greg, S., Margaret, A., Maurits, B., Astin, L., John Eikelboom Robert Luton, Milan, G., Amritanshu Shekhar Pandey, Stephen, C., Rolland, L., Philippe, B., Félix, A., Joseph, B., John, H., Germain, P., Miranda du Preez, Bradley, S., Reginald, N., Ripple, D., Tomasz, H., Andrea, L., Ratika, P., James, C., Benoit, C., Brian, R., Jorge, B., Saul, V., Sameh, F., Ahmed Mowafy Azza Katta, Mazen, T., Moustafa, N., Mohamed, S., Seif Kamal Abou Seif, Tarek, K., Ahmed Abd El-Aziz, Nasser, T., Ashraf, R., Atef, E., Mohamed Gamal El Din, Magdi, E., Adel, E., David Kettles Junaid Bayat, Heidi, S., Adrian, H., Ynez, K., Riaz, G., Thayabran, P., Michele, G., Louis van Zyl, Hendrik, T., Andrew, M., Rikus, L., Deon, G., Pindile, M., Siddique, I., Fayzal, A., Johannes, E., Shambu, M., Wessel, O., Rehana, L., Veronica, U., Wael AlAl Mahmeed AbdullahNaeemi, Ghazi, Y., Nooshin, B., Munther, A., Rajan, M., Rupesh, S., Ahmed, N., Mohamed, I., Amrish, A., Mukesh, N., Ehab, M.E., Adel, W., Rajeev, G., Michael Cox Scott Beach, Peter, D., Stephen, F., Kevin, F., Miguel, F., W Michael Kutayli, Annette, Q., Niraj, S., Vance, W., Stephen, M., Mark, A., Edwin, B., Roddy, C., Ted, G., Rodney, I., Jorge, G., Howard, N., Pamela, R., Rajneesh, R., Marcus, W., Daniel, N., Keith, F., Ihsan, H., Robert, M., Sridevi, P., Daniel, T., Charles, T., Moustafa, M., Cas, C., Walter, P., Alisha, O., George, P., Jaspal, G., James, W., and Firas, K.

Subjects
Vitamin K antagonists, Atrial fibrillation, GARFIELD-AF, Non-vitamin K antagonist oral anticoagulants, Oral anticoagulation, Phenprocoumon, Settore MED/11 - Malattie dell'Apparato Cardiovascolare
Abstract

The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is a worldwide non-interventional study of stroke prevention in patients with non-valvular AF.52,080 patients with newly diagnosed AF were prospectively enrolled from 2010 to 2016. 4121 (7.9%) of these patients were recruited in DACH [Germany (n = 3567), Austria (n = 465) and Switzerland (n = 89) combined], and 47,959 patients were from 32 countries in other regions worldwide (ORW). Hypertension was most prevalent in DACH and ORW (85.3% and 75.6%, respectively). Diabetes, hypercholesterolaemia, carotid occlusive disease and vascular disease were more prevalent in DACH patients vs ORW (27.6%, 49.4%, 5.8% and 29.0% vs 21.7%, 40.9%, 2.8% and 24.5%). The use of non-vitamin K antagonist oral anticoagulants (NOACs) increased more in DACH over time. Management of vitamin K antagonists was suboptimal in DACH and ORW (time in therapeutic range of INR ≥ 65% in 44.6% and 44.4% of patients or ≥ 70% in 36.9% and 36.0% of patients, respectively). Adjusted rates of cardiovascular mortality and MI/ACS were higher in DACH while non-haemorrhagic stroke/systemic embolism was lower after 2-year follow-up.Similarities and dissimilarities in AF management and clinical outcomes are seen in DACH and ORW. The increased use of NOAC was associated with a mismatch of risk-adapted anticoagulation (over-and-undertreatment) in DACH. Suboptimal control of INR requires educational activities in both regional groups. Higher rates of cardiovascular death in DACH may reflect the higher risk profile of these patients and lower rates of non-haemorrhagic stroke could be associated with increased NOAC use.

Published
2022

2. Prostaglandin E

Author

Takayuki, Nagano, Naohiko, Tsuda, Kenichi, Fujimura, Yuji, Ikezawa, Yuki, Higashi, and Shinya H, Kimura

Subjects
Cerebral Cortex, Methyl Ethers, Membrane Proteins, Receptors, Prostaglandin E, EP2 Subtype, Dinoprostone, Rats, Cyclooxygenase 2, Enzyme Induction, Microsomes, Cyclooxygenase 1, Animals, Azetidines, Microglia, RNA, Messenger, Rats, Wistar, Cells, Cultured, Prostaglandin-E Synthases
Abstract

Prostaglandin E

Published
2021

3. Prostaglandin E2 increases the expression of cyclooxygenase-2 in cultured rat microglia

Author

Takayuki Nagano, Yuki Higashi, Yuji Ikezawa, Kenichi Fujimura, Shinya H. Kimura, and Naohiko Tsuda

Subjects
Agonist, medicine.medical_specialty, Microglia, biology, medicine.drug_class, Chemistry, Prostaglandin E2 receptor, Immunology, Antagonist, medicine.anatomical_structure, Endocrinology, Neurology, Internal medicine, medicine, Extracellular, biology.protein, Immunology and Allergy, lipids (amino acids, peptides, and proteins), Neurology (clinical), Cyclooxygenase, Prostaglandin E2, Receptor, medicine.drug
Abstract

Prostaglandin E2 (PGE2) plays pivotal roles in controlling microglial activation with the EP2 receptor, a PGE2 receptor subtype. Activated microglia are often reported to increase cyclooxygenase (COX)-2 expression, followed by PGE2 production, but it is unclear whether extracellular PGE2 is involved in microglial PGE2 synthesis. In the present study, we report that PGE2 increases COX-2 protein in microglia. In a culture system, PGE2 at 10−6 M for 3 h increased COX-2 and microsomal PGE synthase (mPGES)-1 mRNA levels, and reduced mPGES-2, but did not affect COX-1 or cytosolic PGE synthase (cPGES) in microglia. PGE2 at 10−6 M for 3 h also increased the COX-2 protein level, but did not affect COX-1, mPGES-1, mPGES-2, or cPGES. An EP2 agonist, ONO-AE1-259-01, also increased COX-2 and mPGES-1 mRNA levels, and reduced mPGES-2, but did not affect COX-1 or cPGES, whereas an EP1 agonist, ONO-DI-004, an EP3 agonist, ONO-AE-248, and an EP4 agonist, ONO-AE1-329, had no effect. Similar to PGE2, ONO-AE1-259-01 increased the COX-2 protein level, but did not affect COX-1, mPGES-1, mPGES-2, or cPGES. In addition, the effects of PGE2 were inhibited by an EP2 antagonist, PF-04418948, but not by an EP1 antagonist, ONO-8713, an EP3 antagonist, ONO-AE3‐240, or an EP4 antagonist, ONO-AE3‐208, at 10−6 M. On the other hand, lipopolysaccharide (LPS) increased PGE2 production, but the LPS-induced PGE2 production was not affected by ONO-8713, PF-04418948, ONO-AE3‐240, or ONO-AE3‐208. These results indicate that PGE2 increases COX-2 protein in microglia through the EP2 receptor supporting the idea that extracellular PGE2 has a triggering aspect for microglial activation.

Published
2021
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4. Prostaglandin E2potentiates interferon-γ-induced nitric oxide production in cultured rat microglia

Author

Daisuke Yamanaka, Ryo Nishiyama, Satoshi Kishimoto, Yukiko Mutaguchi, Takayuki Nagano, Hirohisa Umeki, Anna Ioku, Ayaka Sanada, Shinya H. Kimura, and Motohiko Takemura

Subjects
0301 basic medicine, Agonist, biology, Chemistry, medicine.drug_class, Prostaglandin E2 receptor, Antagonist, Pharmacology, Biochemistry, Nitric oxide, Nitric oxide synthase, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, 030104 developmental biology, biology.protein, medicine, lipids (amino acids, peptides, and proteins), Cyclic adenosine monophosphate, Nitrite, Prostaglandin E2, medicine.drug
Abstract

Prostaglandin E2 (PGE2 ) plays crucial roles in managing microglial activation through the prostanoid EP2 receptor, a PGE2 receptor subtype. In this study, we report that PGE2 enhances interferon-γ (IFN-γ)-induced nitric oxide production in microglia. IFN-γ increased the release of nitrite, a metabolite of nitric oxide, which was augmented by PGE2 , although PGE2 by itself slightly affects nitrite release. The potentiating effect of PGE2 was positively associated with increased expression of inducible nitric oxide synthase. In contrast to nitrite release induced by IFN-γ, lipopolysaccharide-induced nitrite release was not affected by PGE2 . An EP2 agonist, ONO-AE1-259-01 also augmented IFN-γ-induced nitrite release, while an EP1 agonist, ONO-DI-004, an EP3 agonist, ONO-AE-248, or an EP4 agonist, ONO-AE1-329, did not. In addition, the potentiating effect of PGE2 was inhibited by an EP2 antagonist, PF-04418948, but not by an EP1 antagonist, ONO-8713, an EP3 antagonist, ONO-AE3-240, or an EP4 antagonist, ONO-AE3-208, at 10-6 M. Among the EP agonists, ONO-AE1-259-01 alone was able to accumulate cyclic adenosine monophosphate (AMP), and among the EP antagonists, PF-04418948 was the only one able to inhibit PGE2 -increased intracellular cyclic AMP accumulation. On the other hand, IFN-γ promoted phosphorylation of signal transducer and activator of transcription 1, which was not affected by PGE2 . Furthermore, other prostanoid receptor agonists, PGD2 , PGF2α , iloprost, and U-46119, slightly affected IFN-γ-induced nitrite release. These results indicate that PGE2 potentiates IFN-γ-induced nitric oxide production in microglia through the EP2 receptor, which may shed light on one of the pro-inflammatory aspects of PGE2 .

Published
2017
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5. Prostaglandin E2 increases expression of mRNA for cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in microglia

Author

Shinya H. Kimura, Yuji Ikezawa, Naohiko Tsuda, Motohiko Takemura, Takayuki Nagano, Kenichi Fujimura, and Yuki Higashi

Subjects
Messenger RNA, biology, Microglia, Chemistry, Applied Mathematics, General Mathematics, medicine.medical_treatment, Molecular biology, medicine.anatomical_structure, biology.protein, medicine, Cyclooxygenase, Microsomal Prostaglandin E Synthase-1, Prostaglandin E
Published
2020
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6. Prostaglandin E2 induces apoptosis in cultured rat microglia

Author

Shinya H. Kimura, Motohiko Takemura, and Takayuki Nagano

Subjects
Agonist, medicine.medical_specialty, Programmed cell death, Cell Survival, medicine.drug_class, Prostaglandin E2 receptor, medicine.medical_treatment, Blotting, Western, Apoptosis, DNA Fragmentation, Biology, Dinoprostone, chemistry.chemical_compound, Internal medicine, Cyclic AMP, medicine, Animals, Cyclic adenosine monophosphate, Alprostadil, Rats, Wistar, Prostaglandin E2, Molecular Biology, Cells, Cultured, L-Lactate Dehydrogenase, PROSTAGLANDIN TRANSPORTER, General Neuroscience, Receptors, Prostaglandin E, EP2 Subtype, Receptors, Prostaglandin E, EP1 Subtype, Molecular biology, Endocrinology, chemistry, Receptors, Prostaglandin E, EP3 Subtype, lipids (amino acids, peptides, and proteins), Microglia, Neurology (clinical), Poly(ADP-ribose) Polymerases, Receptors, Prostaglandin E, EP4 Subtype, Intracellular, Developmental Biology, Prostaglandin E, medicine.drug
Abstract

Prostaglandin E2 (PGE2) plays a critical role in the modulation of microglial function including migration and phagocytosis through EP2, which increases intracellular cyclic adenosine monophosphate (AMP) concentration. In the present study, we found that PGE2 reduces cell viability in microglia. PGE2 decreased 3-(4,5-dimethylthiazol-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) reduction and increased lactate dehydrogenase release, deoxyribonucleic acid fragmentation, and poly(ADP-ribose) polymerase cleavage after 24h incubation, suggesting that PGE2 induces apoptosis in these cells. An EP2 agonist, butaprost, and an EP4 agonist, PGE1 alcohol, also induced apoptosis, while an EP1 agonist, 17-phenyl trinor PGE2, or an EP3 agonist, sulprostone, at 10(-6)M did not. On the other hand, EP1-EP4 antagonists, SC-51322, AH6809, L-798106, or GW627368X, up to 10(-5)M did not affect the decrease in MTT reduction by PGE2. Intracellular cyclic AMP accumulation was induced by butaprost, but not 17-phenyl trinor PGE2, sulprostone, or PGE1 alcohol at 10(-6)M. Additionally, we previously reported that PGE2-induced intracellular cyclic AMP accumulation was reversed by AH6809. Besides EP receptors, one of other targets was thought to be prostaglandin transporter, but its inhibitors, bromocresol green or U-46619 up to 10(-5)M did not affect the decrease in MTT reduction by PGE2. These results suggest that PGE2 induces apoptosis in microglia independent of intracellular cyclic AMP concentration, and there are different mechanisms between PGE2-induced apoptosis and the modulation of microglial function.

Published
2014
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7. Prostaglandin E

Author

Takayuki, Nagano, Ryo, Nishiyama, Ayaka, Sanada, Yukiko, Mutaguchi, Anna, Ioku, Hirohisa, Umeki, Satoshi, Kishimoto, Daisuke, Yamanaka, Shinya H, Kimura, and Motohiko, Takemura

Subjects
Male, Dose-Response Relationship, Drug, Nitric Oxide Synthase Type II, Drug Synergism, Nitric Oxide, Dinoprostone, Rats, Interferon-gamma, Animals, Newborn, Animals, Female, Microglia, Rats, Wistar, Cells, Cultured, Nitrites
Abstract

Prostaglandin E

Published
2016

8. Cyclin G1 associates with MDM2 and regulates accumulation and degradation of p53 protein

Author

Hiroshi Nojima and Shinya H. Kimura

Subjects
Cyclin E, biology, Cyclin D, Cyclin A, Cyclin B, Cell Biology, Molecular biology, Cell biology, Cyclin D1, Cyclin-dependent kinase, Genetics, biology.protein, Cyclin-dependent kinase complex, Cyclin A2
Abstract

Background: Cyclin G1 is a transcriptional target of p53 and is induced by DNA damage in a p53 dependent manner. Analysis of cyclin G1 disrupted mice demonstrated that cyclin G1 is involved in many of the functions regulated by p53 such as apoptosis, growth control and check point regulation in response to DNA damage. The results suggest that the main role of cyclin G1 is to mediate or regulate the function of p53. Results: Western blot analysis revealed that the accumulation of p53 protein during the initial 24 h period following DNA damage is reduced in cyclin G1–/– cells compared to wild-type cells. This decrease in p53 accumulation could be recovered by introducing a cDNA expressing cyclin G1. Cyclin G1 interacted directly with MDM2 and promoted the formation of the ARF/MDM2 complex within the initial 24 h period following DNA damage. Furthermore, 48 h after irradiation, accumulation of p53 protein was enhanced in cyclin G1–/– cells compared to wild-type cells. In contrast, in 48 h postirradiated wild-type cells, the cyclin G1-MDM2 complex was found not to be associated with ARF but with the B′α subunit of protein phosphatase A. Conclusion: These results suggest that cyclin G1 stabilizes and promotes the degradation of p53 protein by associating, respectively, with MDM2 complexes containing ARF and PP2A.

Published
2002
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9. Cyclin G1 is involved in G2/M arrest in response to DNA damage and in growth control after damage recovery

Author

Hiroshi Nojima, Shinya H. Kimura, Akihiko Ito, Masaru Okabe, and Masahito Ikawa

Subjects
G2 Phase, Cancer Research, Cyclin E, Cell cycle checkpoint, Cyclin G1, Ultraviolet Rays, Cyclin D, Cyclin A, Cyclin B, Mitosis, Radiation Tolerance, Cyclin G, Mice, Cyclins, Genetics, Animals, Molecular Biology, Cyclin, biology, Dose-Response Relationship, Radiation, Cell cycle, Molecular biology, Mice, Mutant Strains, Mutagenesis, Insertional, Gamma Rays, biology.protein, Tumor Suppressor Protein p53, Whole-Body Irradiation, Cyclin A2, DNA Damage
Abstract

Cyclin G1 is one of the target genes of the transcription factor p53, and is induced in a p53-dependent manner in response to DNA damage. Although cyclin G1 has been implicated in a range of biological phenomena, its precise function remains unclear. Here we present an analysis of the physiological role of cyclin G1 using mice homozygous for a targeted disruption of the cyclin G1 gene. In order to clarify the role of cyclin G1 in the p53 pathway, downstream events such as apoptosis, cell growth and cell cycle checkpoint control were analysed in thymocytes and embryonic fibroblasts derived from cyclin G1-disrupted mice. No difference was detected in induction of apoptosis between mouse embryo fibroblasts (MEFs) derived from cyclin G1+/+ and cyclin G1-/- mice. Following irradiation, cyclin G1-/- MEFs proliferated more slowly and reached lower cell densities in culture dishes than cyclin G1+/+ MEFs. Analysis of cell survival showed that cyclin G1-/- MEFs were about twice as sensitive as cyclin G1+/+ MEFs to gamma radiation or UV radiation. Cyclin G1-/- mice were more sensitive to gamma radiation than wild-type mice. Flow cytometeric analysis revealed that the number of cyclin G1-/- MEFs in G2/M phase after irradiation was reduced by 50% relative to cyclin G1+/+ MEFs. Our results demonstrate that cyclin G1 plays roles in G2/M arrest, damage recovery and growth promotion after cellular stress.

Published
2001
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10. Expression of a mammalian DNA photolyase confers light-dependent repair activity and reduces mutations of UV-irradiated shuttle vectors in xeroderma pigmentosum cells

Author

Hiroshi Asahina, Hitoshi Ayaki, Mituo Ikenaga, Hiraku Takebe, Tomohisa Kato, Takeshi Todo, Takashi Yagi, Shinya H. Kimura, Masanobu Kawanishi, and Zhen Bo Han

Subjects
DNA, Complementary, Xeroderma pigmentosum, DNA Repair, Light, Cell Survival, Ultraviolet Rays, DNA repair, DNA Mutational Analysis, Genetic Vectors, Molecular Sequence Data, education, Pyrimidine dimer, Biology, Transfection, Toxicology, medicine.disease_cause, Genetics, medicine, Humans, RNA, Messenger, Photolyase, Molecular Biology, Cells, Cultured, Xeroderma Pigmentosum, Mutation, Base Sequence, Mutagenesis, DNA photolyase, medicine.disease, Molecular biology, Cell killing, Deoxyribodipyrimidine Photo-Lyase, Plasmids
Abstract

Photoreactivation is one of the DNA repair mechanisms to remove UV lesions from cellular DNA with a function of the DNA photolyase and visible light. Two types of photolyase specific for cyclobutane pyrimidine dimers (CPD) and for pyrimidine (6-4) pyrimidones (6-4PD) are found in nature, but neither is present in cells from placental mammals. To investigate the effect of the CPD-specific photolyase on killing and mutations induced by UV, we expressed a marsupial DNA photolyase in DNA repair-deficient group A xeroderma pigmentosum (XP-A) cells. Expression of the photolyase and visible light irradiation removed CPD from cellular DNA and elevated survival of the UV-irradiated XP-A cells, and also reduced mutation frequencies of UV-irradiated shuttle vector plasmids replicating in XP-A cells. The survival of UV-irradiated cells and mutation frequencies of UV-irradiated plasmids were not completely restored to the unirradiated levels by the removal of CPD. These results suggest that both CPD and other UV damage, probably 6-4PD, can lead to cell killing and mutations.

Published
1999
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11. Structure, Expression, and Chromosomal Localization of Human GAK

Author

Norikazu Yabuta, Hiromichi Tsuruga, Yuichi Endo, Hiroshi Nojima, and Shinya H. Kimura

Subjects
Male, Protein Conformation, Molecular Sequence Data, Gene Expression, Protein Serine-Threonine Kinases, Biology, Species Specificity, Pregnancy, Cyclins, Testis, Genetics, Animals, Humans, Tensin, Amino Acid Sequence, Northern blot, Cloning, Molecular, Kinase activity, Protein kinase A, In Situ Hybridization, Fluorescence, Cyclin, Sequence Homology, Amino Acid, Cyclin-dependent kinase 5, Cell Cycle, Intracellular Signaling Peptides and Proteins, Chromosome Mapping, Cell cycle, Molecular biology, Rats, Protein kinase domain, Female, Chromosomes, Human, Pair 4, HeLa Cells
Abstract

We previously cloned a rat cDNA encoding GAK, an association partner of cyclin G and CDK5. Here, we report the cloning of a cDNA encoding human GAK (1311 amino acids) and show that all of the unique motifs that characterize rat GAK, such as the presence of a Ser/Thr kinase domain, a tensin/auxilin homologous domain, and a Tyr phosphorylation target site, are conserved. The expression profiles of GAK and cyclin G during the synchronized HeLa cell cycle showed that GAK expression oscillates slightly, peaking at G1 phase, although the histone H1 kinase activity remains constant throughout the cell cycle. We also found that the kinase activity of immunoprecipitates of anti-cyclin G antibody fluctuates during the cell cycle with a peak at G1 phase, although the expression level of cyclin G remains almost constant. Northern blot analysis showed that GAK is expressed ubiquitously, with the highest level of expression being observed in the testis. By the FISH technique, we assigned the chromosomal localization of GAK to 4p16.

Published
1997
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12. GAK: a cyclin G associated kinase contains a tensin/auxilin-like domain 1

Author

Yoshihide Kanaoka, Issey Okazaki, Masako Ikeda, Hiroshi Nojima, and Shinya H. Kimura

Subjects
Leucine zipper, biology, Kinase, Cyclin D, Biophysics, Cell Biology, Auxilin, Biochemistry, Molecular biology, Structural Biology, Complementary DNA, Genetics, Cyclin-dependent kinase complex, biology.protein, Tensin, Molecular Biology, Cyclin
Abstract

We have cloned a cDNA encoding a novel association partner of cyclin G by West-Western blotting. The cDNA encodes a protein that harbors a Ser/Thr protein kinase-like catalytic domain at the N-terminal. Hence, we named it GAK (cyclin - ssociated inase). The long C-terminal extension shares homology with tensin and auxilin, and contains a leucine zipper region. Co-immunoprecipitation and Western blotting showed that GAK and cyclin G associate together in vivo. GAK also co-precipitated with CDK5, and CDK5 was found to be associated with cyclin G. We also showed by BIAcore analysis that the GAK-cyclin G interaction was direct.

Published
1997
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13. Prostaglandin E2 reduces amyloid beta-induced phagocytosis in cultured rat microglia

Author

Takayuki Nagano, Motohiko Takemura, and Shinya H. Kimura

Subjects
medicine.medical_specialty, Prostaglandin E2 receptor, medicine.medical_treatment, Phagocytosis, Blotting, Western, Prostaglandin, Dinoprostone, chemistry.chemical_compound, Internal medicine, medicine, Cyclic AMP, Animals, Cyclic adenosine monophosphate, Prostaglandin E2, Alprostadil, Molecular Biology, Cells, Cultured, Amyloid beta-Peptides, biology, Microglia, Dose-Response Relationship, Drug, General Neuroscience, Receptors, Prostaglandin E, EP2 Subtype, Peptide Fragments, Rats, Endocrinology, medicine.anatomical_structure, chemistry, Cyclooxygenase 2, biology.protein, Cyclooxygenase 1, lipids (amino acids, peptides, and proteins), Neurology (clinical), Cyclooxygenase, Developmental Biology, medicine.drug, Prostaglandin E
Abstract

Treatment with amyloid beta(1-42) (Abeta(1-42)) at 1microM for 60min increased phagocytosis of latex beads by cultured rat microglia. This increase was reduced dose-dependently by prostaglandin E(2) (PGE(2)), but PGD(2), PGF(2alpha), iloprost, or U-46619 had no effects. PGE(2) also reduced the phagocytosis of fluorescent-labeled Abeta(1-42). Abeta(1-42)-induced phagocytosis was reduced by butaprost but not by 17-phenyl trinor PGE(2), sulprostone, or PGE(1) alcohol. The reduction effect of PGE(2) on phagocytosis was reversed by AH6809, an E-prostanoid receptor 2 (EP2) antagonist, which inhibited cyclic adenosine monophosphate (AMP) accumulation induced by PGE(2). Butaprost, but not 17-phenyl trinor PGE(2), sulprostone, or PGE(1) alcohol increased intracellular cyclic AMP accumulation. In western blotting analysis, EP2-like immunoreactivity was detected in the crude membrane fraction of microglia. On the other hand, Abeta(1-42)-induced phagocytosis was not affected by SC-560, a cyclooxygenase-1 (COX-1) inhibitor, NS-398, a COX-2 inhibitor, or ibuprofen, a non-specific COX inhibitor. Abeta(1-42) or PGE(2) had little effect on the expression levels of COX-1 or COX-2. These results indicate that Abeta(1-42)-induced microglial phagocytosis is reduced by PGE(2) through EP2.

Published
2009

14. Prostaglandin E2 reduces extracellular ATP-induced migration in cultured rat microglia

Author

Shinya H. Kimura, Motohiko Takemura, and Takayuki Nagano

Subjects
Agonist, medicine.medical_specialty, medicine.drug_class, Cell Survival, Prostaglandin E2 receptor, medicine.medical_treatment, Adenylate kinase, Biology, Cyclase, Dinoprostone, chemistry.chemical_compound, Adenosine Triphosphate, Cell Movement, Internal medicine, medicine, Animals, Receptors, Prostaglandin E, Prostaglandin E2, Alprostadil, Enzyme Inhibitors, Rats, Wistar, Molecular Biology, Cells, Cultured, Forskolin, General Neuroscience, Colforsin, Extracellular Fluid, Receptors, Prostaglandin E, EP2 Subtype, Rats, Endocrinology, chemistry, Animals, Newborn, lipids (amino acids, peptides, and proteins), Neurology (clinical), Microglia, Adenosine triphosphate, Developmental Biology, Prostaglandin E, medicine.drug, Adenylyl Cyclases
Abstract

Treatment with 100 microM adenosine triphosphate (ATP) for 120 min augmented migration of cultured rat microglia by about 4-fold. This augmentation was effectively reduced by 0.1-10 microM prostaglandin E(2) (PGE(2)). PGE(2)-mediated reduction was reversed by the EP2 antagonist AH6809 at 10 microM. The EP2 agonist butaprost also reduced ATP-induced migration at 10 microM, whereas the EP1 agonist 17-phenyl trinor PGE(2), the EP3 agonist sulprostone, and the EP4 agonist PGE(1) alcohol all had no effect at 10 microM. In addition, ATP-induced migration was reduced by the adenylate cyclase activator forskolin at 100 microM, whereas the adenylate cyclase inhibitor SQ22536 reversed the effect of PGE(2) on ATP-induced migration at 100 microM. Over the same experimental duration, PGE(2), butaprost, and forskolin had little effect on cell viability. These findings indicate that ATP-induced microglial migration is reduced by PGE(2) through EP2 and adenylate cyclase.

Published
2008

15. RECS1 deficiency in mice induces susceptibility to cystic medial degeneration

Author

Hanjun Zhao, Yuji Matsuzawa, Hiroshi Nojima, Naohiko Sakai, Shizuya Yamashita, Akihiko Ito, Shinya H. Kimura, Norikazu Yabuta, Masaru Okabe, and Masahito Ikawa

Subjects
Molecular Sequence Data, Endosomes, Muscle, Smooth, Vascular, Cell Line, PEST sequence, Mice, Western blot, Cell Line, Tumor, Genetics, medicine, Animals, Humans, Genetic Predisposition to Disease, Northern blot, Amino Acid Sequence, Molecular Biology, Mice, Knockout, Messenger RNA, medicine.diagnostic_test, biology, Membrane Proteins, General Medicine, Intracellular Membranes, Fusion protein, Molecular biology, Aortic Aneurysm, Transmembrane domain, Polyclonal antibodies, Cytoplasm, biology.protein, Stress, Mechanical, Lysosomes, HeLa Cells
Abstract

RECS1 is a novel shear stress-responsive gene that encodes a protein putatively forming seven-span transmembrane domains. We reports here that mouse RECS1 (mRECS1) transcripts is detected in most tissues except for thymus, spleen and testis. The putative cytoplasmic N-terminus of mRECS1 has a high content of proline (23%) and glycine (12%) residues, contains one PPXY motif, multiple PXXP motifs and one overlapping P(T/S)AP and PPXY motif (P(T/S)APPXY). The PPXY motif lies within one potential PEST sequence (PEST score: +7.65). We prepared anti-RECS1 polyclonal antibody and found by western blot analysis that the mRECS1 protein in the lung and aorta was detected as a 34.4 kDa band. However, one shifted 58 kDa band or three shifted bands (48, 69, 82 kDa) were detected in the heart or the liver, respectively. Since northern blot detected only one species of mRECS1 mRNA in heart and liver tissues, as well as other tissues (approximately 2.2 kb), these differences in molecular weight seem to be due to posttranslational modification. Biochemical fractionation and RECS1-GFP fusion protein revealed that RECS1 localizes at the endosomal/lysosomal membranes in the cytoplasm. To understand the function of RECS1 in the body, we made RECS1 knockout (KO) mice and found that RECS1 KO mice (older than 14 months) are prone to cystic medial degeneration (CMD). Taken together, we conclude that RECS1 is an endosomal/lysosomal membrane protein which plays protective roles in vascular remodeling.

Published
2006

16. Lipopolysaccharide sensitizes microglia toward Ca(2+)-induced cell death: mode of cell death shifts from apoptosis to necrosis

Author

Takayuki Nagano, Motohiko Takemura, Eri Takai, Shinya H. Kimura, and Toshio Matsuda

Subjects
Intracellular Fluid, Lipopolysaccharides, Programmed cell death, Necrosis, Thapsigargin, Apoptosis, Biology, S-Nitroso-N-Acetylpenicillamine, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Interferon-gamma, medicine, Animals, Drug Interactions, Viability assay, Calcium Signaling, Gliosis, Rats, Wistar, Egtazic Acid, Cells, Cultured, Ionomycin, Cell biology, Rats, medicine.anatomical_structure, Neurology, chemistry, Animals, Newborn, Astrocytes, Neuroglia, Encephalitis, lipids (amino acids, peptides, and proteins), Calcium, Microglia, medicine.symptom, Inflammation Mediators, Intracellular
Abstract

Little is known about the effect of microglial activation on cell death. This study examines the effects of lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma), triggers of microglial activation, on cell death induced by several agents in cultured rat microglia. For comparison, the effect of LPS on cell death is also examined in cultured astrocytes. LPS or IFN-gamma enhanced cell death induced by thapsigargin or ionomycin, an agent that increases intracellular Ca2+ concentration, although LPS or IFN-gamma alone did not affect cell viability. Thapsigargin or ionomycin induced apoptosis in LPS-untreated microglia, while they induced necrosis in LPS-treated microglia, which were partially reversed by O,O'-bis(2-aminophenyl)ethyleneglycol-N,N,N',N'-tetraacetic acid tetraacetoxymethyl ester (BAPTA-AM, an intracellular Ca2+ chelator). In contrast, LPS treatment did not affect tunicamycin- or staurosporine-induced apoptosis, while it inhibited S-nitroso-N-acetylpenicillamine-induced apoptosis. The effect of LPS on thapsigargin or ionomycin-induced apoptosis was not observed in astrocytes. These results indicate that microglial activation sensitizes the cells toward cell death induced by the change in intracellular Ca2+ concentration and shifts the mode of cell death from apoptosis to necrosis.

Published
2005

17. Cyclin G1 associates with MDM2 and regulates accumulation and degradation of p53 protein

Author

Shinya H, Kimura and Hiroshi, Nojima

Subjects
Cyclin G1, Hydrolysis, Tumor Suppressor Proteins, Nuclear Proteins, Cell Cycle Proteins, Proto-Oncogene Proteins c-mdm2, Ataxia Telangiectasia Mutated Proteins, Protein Serine-Threonine Kinases, Cyclin G, DNA-Binding Proteins, Mice, Cyclins, Proto-Oncogene Proteins, Animals, Tumor Suppressor Protein p53, DNA Damage, Protein Binding
Abstract

Cyclin G1 is a transcriptional target of p53 and is induced by DNA damage in a p53 dependent manner. Analysis of cyclin G1 disrupted mice demonstrated that cyclin G1 is involved in many of the functions regulated by p53 such as apoptosis, growth control and check point regulation in response to DNA damage. The results suggest that the main role of cyclin G1 is to mediate or regulate the function of p53.Western blot analysis revealed that the accumulation of p53 protein during the initial 24 h period following DNA damage is reduced in cyclin G1-/- cells compared to wild-type cells. This decrease in p53 accumulation could be recovered by introducing a cDNA expressing cyclin G1. Cyclin G1 interacted directly with MDM2 and promoted the formation of the ARF/MDM2 complex within the initial 24 h period following DNA damage. Furthermore, 48 h after irradiation, accumulation of p53 protein was enhanced in cyclin G1-/- cells compared to wild-type cells. In contrast, in 48 h postirradiated wild-type cells, the cyclin G1-MDM2 complex was found not to be associated with ARF but with the B'alpha subunit of protein phosphatase A.These results suggest that cyclin G1 stabilizes and promotes the degradation of p53 protein by associating, respectively, with MDM2 complexes containing ARF and PP2A.

Published
2002

18. Genomic structure and chromosomal localization of mouse cyclin G1 gene

Author

Hiroshi Nojima, Shinya H. Kimura, Tatsuki R. Kataoka, and Yuichi Endo

Subjects
Genetics, DNA, Complementary, Base Sequence, Cyclin G1, Pseudogene, Molecular Sequence Data, Chromosome Mapping, Biology, Molecular biology, Cyclin G, genomic DNA, Exon, Mice, Chromosome 4, Gene mapping, Cyclins, Sequence Homology, Nucleic Acid, Coding region, Animals, Humans, Human genome, Gene, In Situ Hybridization, Fluorescence
Abstract

Mouse genomic DNA harboring the full coding sequence of cyclin G1 was cloned and analyzed. The locations of five coding exons and the intron-exon boundary sequences were found to be conserved between the mouse and the human genes. Two putative binding sites for the p53 tumor suppressor gene product were found around the first exon: one was located in the 5' regulatory region, and the other was in the first intron. The mouse cyclin G1 gene was mapped to bands A5 to B1 of chromosomes 11 (11A5-B1) by FISH using genomic DNA clone as a biotinylated probe. The location of mouse cyclin G1 is syntenic to that of its human homologue, which we previously mapped to 5q32-q34 of chromosome 5. An additional faint signal was detected on chromosome 4 (4B1-C2), probably indicating the presence of a cyclin G1-related gene or pseudogene in the mouse genome.

Published
1998

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