182 results on '"Obana M"'
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2. Characteristics of subsurface water flow influenced by formation process of gravel bar
- Author
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Obana, M, primary, Chibana, T, additional, and Tsujimoto, T, additional
- Published
- 2014
- Full Text
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3. Efectividad de la simvastatina tópica e inyectable contra hidrocoloide en la epitelización de heridas de espesor parcial en un modelo animal
- Author
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Murakami-Morishige, Pablo D., Erazo-Franco, Mauricio A., Zozaya-Mininchini, Ximena, López-Silva, Felipe A., Barreda-Gaxiola, Marco A., Bernal-Obana, M. Teresa, and Watanabe, Shoko
- Subjects
Simvastatin ,Heridas espesor parcial ,Split thickness wounds ,Epitelización ,Statins ,Simvastatina ,Estatinas ,Re-epithelialization - Abstract
Introducción y Objetivos. En la actualidad existen una gran cantidad de apósitos y coberturas para el tratamiento de las heridas de espesor parcial; la elección depende de la experiencia del cirujano y sobre todo de la disponibilidad y recursos existentes. Las estatinas (inhibidores de la Hidroxi-Metil-CoA reductasa) se usan en el tratamiento de la hipercolesterolemia, aunque recientemente se han encontrado propiedades antinflamatorias, estimulantes de la angiogénesis y linfangiogénesis, antifibróticas, y especialmente estimuladoras de los queratinocitos. Nos proponemos comparar la epitelización e inflamación de las heridas en un modelo animal con la aplicación de simvastatina tópica, inyectable y apósito de hidrocoloide. Material y método. Empleamos 20 ratas Wistar en 4 grupos, cada uno con 5 ratas, a las que practicamos heridas de espesor parcial por dermoabrasión en el dorso. A cada grupo se le aplicó gasa de organza, apósito de hidrocoloide, simvastatina tópica y simvastatina inyectada, respectivamente. Descubrimos las heridas a los 7 días y sacrificamos a los animales. Tomamos biopsias de las heridas y comparamos el grado de epitelización de cada grupo. Resultados. Al comparar la simvastatina en preparación tópica con el grupo de gasa de organza y el grupo de apósito de hidrocoloide, encontramos un mayor porcentaje de epitelización en el grupo tratado con simvastatina tópica, con una diferencia estadísticamente significativa (p < 0.05). Las heridas tratadas con simvastatina tópica demostraron menor inflamación, menor fibrosis, mayor epitelización (queratinocitos), mayor cantidad de fibroblastos y no presentaron costra, de forma estadísticamente significativa. Conclusiones. La cobertura de heridas de espesor parcial con simvastatina tópica es más efectiva en epitelización y efecto antinflamatorio, en comparación con la simvastatina inyectable, los apósitos de hidrocoloide y las gasas de organza. Background and Objective. There are various alternatives and dressings for split thickness skin wounds, the choice depends on the experience and training of each surgeon. Statins, which are normally used for the treatment of hypercholesterolemia, have proven to induce and antinflammatory effect on wound keratinocytes, which provokes a faster re-epithelialization on in vitro studies. Our aim was to compare epithelialization and anti-inflammatory properties in split thickness wounds of rats, using hydrocolloid dressings versus a simvastatin based emulsion or simvastatin injected. Methods. We used 20 Wistar rats divided in 4 groups in which split thickness wounds were induced in the dorsum by dermoabrasion. Each group was treated with organza gauze, hydrolloid dressings, simvastatin cream and injectable simvastatin in the wound, respectively. Seven days later, the wounds were exposed and the animals where sacrificed. The wounds were analyzed with digital photographs and biopsies where taken in order to compare the epithelization percentage in each group. Results. There was a statistically significant improvement (p < 0.05) in wound rate epithelialization in the rats treated with topic simvastatin. The wounds treated with topic simvastatin had less inflammation, less fibrosis, no evidence of crusting and a higher number of fibroblast. Conclusions. Split thickness skin wounds coverage with topical simvastatin is most effective in epithelialization and antinflamatory effect compared with injectable simvastatin, organza gauze dressings and hydrocolloid dressings.
- Published
- 2016
4. Integrated modeling for eco-compatible management of river basin complex around Ise bay, Japan
- Author
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Tsujimoto, T., primary, Toda, Y., additional, Tashiro, T., additional, Takaoka, H., additional, Anbutsu, K., additional, and Obana, M., additional
- Published
- 2012
- Full Text
- View/download PDF
5. Abstracts
- Author
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Dunet, V., primary, Dabiri, A., additional, Allenbach, G., additional, Goyeneche Achigar, A., additional, Waeber, B., additional, Feihl, F., additional, Heinzer, R., additional, Prior, J. O., additional, Van Velzen, J. E., additional, Schuijf, J. D., additional, De Graaf, F. R., additional, De Graaf, M. A., additional, Schalij, M. J., additional, Kroft, L. J., additional, De Roos, A., additional, Jukema, J. W., additional, Van Der Wall, E. E., additional, Bax, J. J., additional, Lankinen, E., additional, Saraste, A., additional, Noponen, T., additional, Klen, R., additional, Teras, M., additional, Kokki, T., additional, Kajander, S., additional, Pietila, M., additional, Ukkonen, H., additional, Knuuti, J., additional, Pazhenkottil, A. P., additional, Nkoulou, R. N., additional, Ghadri, J. R., additional, Herzog, B. A., additional, Buechel, R. R., additional, Kuest, S. M., additional, Wolfrum, M., additional, Gaemperli, O., additional, Husmann, L., additional, Kaufmann, P. A., additional, Andreini, D., additional, Pontone, G., additional, Mushtaq, S., additional, Antonioli, L., additional, Bertella, E., additional, Formenti, A., additional, Cortinovis, S., additional, Ballerini, G., additional, Fiorentini, C., additional, Pepi, M., additional, Koh, A. S., additional, Flores, J. S., additional, Keng, F. Y. J., additional, Tan, R. S., additional, Chua, T. S. J., additional, Annoni, A. D., additional, Tamborini, G., additional, Fusari, M., additional, Bartorelli, A. L., additional, Ewe, S. H., additional, Ng, A. C. T., additional, Delgado, V., additional, Schuijf, J., additional, Van Der Kley, F., additional, Colli, A., additional, De Weger, A., additional, Marsan, N. A., additional, Yiu, K. H., additional, Ng, A. C., additional, Timmer, S. A. J., additional, Knaapen, P., additional, Germans, T., additional, Dijkmans, P. A., additional, Lubberink, M., additional, Ten Berg, J. M., additional, Ten Cate, F. J., additional, Russel, I. K., additional, Lammertsma, A. A., additional, Van Rossum, A. C., additional, Wong, Y. Y., additional, Ruiter, G., additional, Raijmakers, P., additional, Van Der Laarse, W. J., additional, Westerhof, N., additional, Vonk-Noordegraaf, A., additional, Youssef, G., additional, Leung, E., additional, Wisenberg, G., additional, Marriot, C., additional, Williams, K., additional, Etele, J., additional, Dekemp, R. A., additional, Dasilva, J., additional, Birnie, D., additional, Beanlands, R. S. B., additional, Thompson, R. C., additional, Allam, A. H., additional, Wann, L. S., additional, Nureldin, A. H., additional, Adelmaksoub, G., additional, Badr, I., additional, Sutherland, M. L., additional, Sutherland, J. D., additional, Miyamoto, M. I., additional, Thomas, G. S., additional, Harms, H. J., additional, De Haan, S., additional, Huisman, M. C., additional, Schuit, R. C., additional, Windhorst, A. D., additional, Allaart, C., additional, Einstein, A. J., additional, Khawaja, T., additional, Greer, C., additional, Chokshi, A., additional, Jones, M., additional, Schaefle, K., additional, Bhatia, K., additional, Shimbo, D., additional, Schulze, P. C., additional, Srivastava, A., additional, Chettiar, R., additional, Moody, J., additional, Weyman, C., additional, Natale, D., additional, Bruni, W., additional, Liu, Y., additional, Ficaro, E., additional, Sinusas, A. J., additional, Peix, A., additional, Batista, E., additional, Cabrera, L. O., additional, Padron, K., additional, Rodriguez, L., additional, Sainz, B., additional, Mendoza, V., additional, Carrillo, R., additional, Fernandez, Y., additional, Mena, E., additional, Naum, A., additional, Bach-Gansmo, T., additional, Kleven-Madsen, N., additional, Biermann, M., additional, Johnsen, B., additional, Aase Husby, J., additional, Rotevatn, S., additional, Nordrehaug, J. E., additional, Schaap, J., additional, Kauling, R. M., additional, Post, M. C., additional, Rensing, B. J. W. M., additional, Verzijlbergen, J. F., additional, Sanchez, J., additional, Giamouzis, G., additional, Tziolas, N., additional, Georgoulias, P., additional, Karayannis, G., additional, Chamaidi, A., additional, Zavos, N., additional, Koutrakis, K., additional, Sitafidis, G., additional, Skoularigis, J., additional, Triposkiadis, F., additional, Radovanovic, S., additional, Djokovic, A., additional, Simic, D. V., additional, Krotin, M., additional, Savic-Radojevic, A., additional, Pljesa-Ercegovac, M., additional, Zdravkovic, M., additional, Saponjski, J., additional, Jelic, S., additional, Simic, T., additional, Eckardt, R., additional, Kjeldsen, B. J., additional, Andersen, L. I., additional, Haghfelt, T., additional, Grupe, P., additional, Johansen, A., additional, Hesse, B., additional, Pena, H., additional, Cantinho, G., additional, Wilk, M., additional, Srour, Y., additional, Godinho, F., additional, Zafrir, N., additional, Gutstein, A., additional, Mats, I., additional, Battler, A., additional, Solodky, A., additional, Sari, E., additional, Singh, N., additional, Vara, A., additional, Peters, A. M., additional, De Belder, A., additional, Nair, S., additional, Ryan, N., additional, James, R., additional, Dizdarevic, S., additional, Depuey, G., additional, Friedman, M., additional, Wray, R., additional, Old, R., additional, Babla, H., additional, Chuanyong, B., additional, Maddahi, J., additional, Tragardh Johansson, E., additional, Sjostrand, K., additional, Edenbrandt, L., additional, Aguade-Bruix, S., additional, Cuberas-Borros, G., additional, Pizzi, M. N., additional, Sabate-Fernandez, M., additional, De Leon, G., additional, Garcia-Dorado, D., additional, Castell-Conesa, J., additional, Candell-Riera, J., additional, Casset-Senon, D., additional, Edjlali-Goujon, M., additional, Alison, D., additional, Delhommais, A., additional, Cosnay, P., additional, Low, C. S., additional, Notghi, A., additional, O'brien, J., additional, Tweddel, A. C., additional, Bingham, N., additional, O Neil, P., additional, Harbinson, M., additional, Lindner, O., additional, Burchert, W., additional, Schaefers, M., additional, Marcassa, C., additional, Campini, R., additional, Calza, P., additional, Zoccarato, O., additional, Kisko, A., additional, Kmec, J., additional, Babcak, M., additional, Vereb, M., additional, Vytykacova, M., additional, Cencarik, J., additional, Gazdic, P., additional, Stasko, J., additional, Abreu, A., additional, Pereira, E., additional, Oliveira, L., additional, Colarinha, P., additional, Veloso, V., additional, Enriksson, I., additional, Proenca, G., additional, Delgado, P., additional, Rosario, L., additional, Sequeira, J., additional, Kosa, I., additional, Vassanyi, I., additional, Egyed, C. S., additional, Kozmann, G. Y., additional, Morita, S., additional, Nanasato, M., additional, Nanbu, I., additional, Yoshida, Y., additional, Hirayama, H., additional, Allam, A., additional, Sharef, A., additional, Shawky, I., additional, Farid, M., additional, Mouden, M., additional, Ottervanger, J. P., additional, Timmer, J. R., additional, De Boer, M. J., additional, Reiffers, S., additional, Jager, P. L., additional, Knollema, S., additional, Nasr, G. M., additional, Mohy Eldin, M., additional, Ragheb, M., additional, Casans-Tormo, I., additional, Diaz-Exposito, R., additional, Hurtado-Mauricio, F. J., additional, Ruano, R., additional, Diego, M., additional, Gomez-Caminero, F., additional, Albarran, C., additional, Martin De Arriba, A., additional, Rosero, A., additional, Lopez, R., additional, Martin Luengo, C., additional, Garcia-Talavera, J. R., additional, Laitinen, I. E. K., additional, Rudelius, M., additional, Weidl, E., additional, Henriksen, G., additional, Wester, H. J., additional, Schwaiger, M., additional, Pan, X. B., additional, Schindler, T., additional, Quercioli, A., additional, Zaidi, H., additional, Ratib, O., additional, Declerck, J. M., additional, Alexanderson Rosas, E., additional, Jacome, R., additional, Jimenez-Santos, M., additional, Romero, E., additional, Pena-Cabral, M. A., additional, Meave, A., additional, Gonzalez, J., additional, Rouzet, F., additional, Bachelet, L., additional, Alsac, J. M., additional, Suzuki, M., additional, Louedec, L., additional, Petiet, A., additional, Chaubet, F., additional, Letourneur, D., additional, Michel, J. B., additional, Le Guludec, D., additional, Aktas, A., additional, Cinar, A., additional, Yaman, G., additional, Bahceci, T., additional, Kavak, K., additional, Gencoglu, A., additional, Jimenez-Heffernan, A., additional, Sanchez De Mora, E., additional, Lopez-Martin, J., additional, Lopez-Aguilar, R., additional, Ramos, C., additional, Salgado, C., additional, Ortega, A., additional, Sanchez-Gonzalez, C., additional, Roa, J., additional, Tobaruela, A., additional, Nesterov, S. V., additional, Turta, O., additional, Maki, M., additional, Han, C., additional, Daou, D., additional, Tawileh, M., additional, Chamouine, S. O., additional, Coaguila, C., additional, Mariscal-Labrador, E., additional, Kisiel-Gonzalez, N., additional, De Araujo Goncalves, P., additional, Sousa, P. J., additional, Marques, H., additional, O'neill, J., additional, Pisco, J., additional, Cale, R., additional, Brito, J., additional, Gaspar, A., additional, Machado, F. P., additional, Roquette, J., additional, Martinez, M., additional, Melendez, G., additional, Kimura, E., additional, Ochoa, J. M., additional, Alessio, A. M., additional, Patel, A., additional, Lautamaki, R., additional, Bengel, F. M., additional, Bassingthwaighte, J. B., additional, Caldwell, J. H., additional, Rahbar, K., additional, Seifarth, H., additional, Schafers, M., additional, Stegger, L., additional, Spieker, T., additional, Hoffmeier, A., additional, Maintz, D., additional, Scheld, H., additional, Schober, O., additional, Weckesser, M., additional, Aoki, H., additional, Matsunari, I., additional, Kajinami, K., additional, Martin Fernandez, M., additional, Barreiro Perez, M., additional, Fernandez Cimadevilla, O. V., additional, Leon Duran, D., additional, Velasco Alonso, E., additional, Florez Munoz, J. P., additional, Luyando, L. H., additional, Templin, C., additional, Veltman, C. E., additional, Reiber, J. H. C., additional, Venuraju, S., additional, Yerramasu, A., additional, Atwal, S., additional, Lahiri, A., additional, Kunimasa, T., additional, Shiba, M., additional, Ishii, K., additional, Aikawa, J., additional, Kroner, E. S. J., additional, Ho, K. T., additional, Yong, Q. W., additional, Chua, K. C., additional, Panknin, C., additional, Roos, C. J., additional, Van Werkhoven, J. M., additional, Witkowska-Grzeslo, A. J., additional, Boogers, M. J., additional, Anand, D. V., additional, Dey, D., additional, Berman, D., additional, Mut, F., additional, Giubbini, R., additional, Lusa, L., additional, Massardo, T., additional, Iskandrian, A., additional, Dondi, M., additional, Sato, A., additional, Kakefuda, Y., additional, Ojima, E., additional, Adachi, T., additional, Atsumi, A., additional, Ishizu, T., additional, Seo, Y., additional, Hiroe, M., additional, Aonuma, K., additional, Kruk, M., additional, Pracon, R., additional, Kepka, C., additional, Pregowski, J., additional, Kowalewska, A., additional, Pilka, M., additional, Opolski, M., additional, Michalowska, I., additional, Dzielinska, Z., additional, Demkow, M., additional, Stoll, V., additional, Sabharwal, N., additional, Chakera, A., additional, Ormerod, O., additional, Fernandes, H., additional, Bernardes, M., additional, Martins, E., additional, Oliveira, P., additional, Vieira, T., additional, Terroso, G., additional, Oliveira, A., additional, Faria, T., additional, Ventura, F., additional, Pereira, J., additional, Fukuzawa, S., additional, Inagaki, M., additional, Sugioka, J., additional, Ikeda, A., additional, Okino, S., additional, Maekawa, J., additional, Uchiyama, T., additional, Kamioka, N., additional, Ichikawa, S., additional, Afshar, M., additional, Alvi, R., additional, Aguilar, N., additional, Ippili, R., additional, Shaqra, H., additional, Bella, J., additional, Bhalodkar, N., additional, Dos Santos, A., additional, Daicz, M., additional, Cendoya, L. O., additional, Marrero, H. G., additional, Casuscelli, J., additional, Embon, M., additional, Vera Janavel, G., additional, Duronto, E., additional, Gurfinkel, E. P., additional, Cortes, C. M., additional, Takeishi, Y., additional, Nakajima, K., additional, Yamasaki, Y., additional, Nishimura, T., additional, Hayes Brown, K., additional, Collado, F., additional, Alhaji, M., additional, Green, J., additional, Alexander, S., additional, Vashistha, R., additional, Jain, S., additional, Aldaas, F., additional, Shanes, J., additional, Doukky, R., additional, Ashikaga, K., additional, Akashi, Y. J., additional, Uemarsu, M., additional, Kamijima, R., additional, Yoneyama, K., additional, Omiya, K., additional, Miyake, Y., additional, Brodov, Y., additional, Raval, U., additional, Berezin, A., additional, Seden, V., additional, Koretskaya, E., additional, Panasenko, T. A., additional, Matsuo, S., additional, Kinuya, S., additional, Chen, J., additional, Van Bommel, R. J., additional, Van Der Hiel, B., additional, Dibbets-Schneider, P., additional, Garcia, E. V., additional, Rutten-Vermeltfoort, I., additional, Gevers, M. M. J., additional, Verhoeven, B., additional, Dijk Van, A. B., additional, Raaijmakers, E., additional, Raijmakers, P. G. H. M., additional, Engvall, J. E., additional, Gjerde, M., additional, De Geer, J., additional, Olsson, E., additional, Quick, P., additional, Persson, A., additional, Mazzanti, M., additional, Marini, M., additional, Pimpini, L., additional, Perna, G. P., additional, Marciano, C., additional, Gargiulo, P., additional, Galderisi, M., additional, D'amore, C., additional, Savarese, G., additional, Casaretti, L., additional, Paolillo, S., additional, Cuocolo, A., additional, Perrone Filardi, P., additional, Al-Amoodi, M., additional, Thompson, E. C., additional, Kennedy, K., additional, Bybee, K. A., additional, Mcghie, A. I., additional, O'keefe, J. H., additional, Bateman, T. M., additional, Van Der Palen, R. L. F., additional, Mavinkurve-Groothuis, A. M., additional, Bulten, B., additional, Bellersen, L., additional, Van Laarhoven, H. W. M., additional, Kapusta, L., additional, De Geus-Oei, L. F., additional, Pollice, P. P., additional, Bonifazi, M. B., additional, Pollice, F. P., additional, Clements, I. P., additional, Hodge, D. O., additional, Scott, C. G., additional, De Ville De Goyet, M., additional, Brichard, B., additional, Pirotte, T., additional, Moniotte, S., additional, Tio, R. A., additional, Elvan, A., additional, Dierckx, R. A. I. O., additional, Slart, R. H. J. A., additional, Furuhashi, T., additional, Moroi, M., additional, Hase, H., additional, Joki, N., additional, Masai, H., additional, Nakazato, R., additional, Fukuda, H., additional, Sugi, K., additional, Kryczka, K., additional, Kaczmarska, E., additional, Petryka, J., additional, Mazurkiewicz, L., additional, Ruzyllo, W., additional, Smanio, P., additional, Vieira Segundo, E., additional, Siqueira, M., additional, Kelendjian, J., additional, Ribeiro, J., additional, Alaca, J., additional, Oliveira, M., additional, Alves, F., additional, Peovska, I., additional, Maksimovic, J., additional, Vavlukis, M., additional, Kostova, N., additional, Pop Gorceva, D., additional, Majstorov, V., additional, Zdraveska, M., additional, Hussain, S., additional, Djearaman, M., additional, Hoey, E., additional, Morus, L., additional, Erinfolami, O., additional, Macnamara, A., additional, Opolski, M. P., additional, Witkowski, A., additional, Berti, V., additional, Ricci, F., additional, Gallicchio, R., additional, Acampa, W., additional, Cerisano, G., additional, Vigorito, C., additional, Sciagra', R., additional, Pupi, A., additional, Sliem, H., additional, Collado, F. M., additional, Schmidt, S., additional, Maheshwari, A., additional, Kiriakos, R., additional, Mwansa, V., additional, Ljubojevic, S., additional, Sedej, S., additional, Holzer, M., additional, Marsche, G., additional, Marijanski, V., additional, Kockskaemper, J., additional, Pieske, B., additional, Ricalde, A., additional, Alexanderson, G., additional, Mohani, A., additional, Khanna, P., additional, Sinusas, A., additional, Lee, F., additional, Pinas, V. A., additional, Van Eck-Smit, B. L. F., additional, Verberne, H. J., additional, De Bruin, C. M., additional, Guilhermina, G., additional, Jimenez-Angeles, L., additional, Ruiz De Jesus, O., additional, Yanez-Suarez, O., additional, Vallejo, E., additional, Reyes, E., additional, Chan, M., additional, Hossen, M. L., additional, Underwood, S. R., additional, Karu, A., additional, Bokhari, S., additional, Pineda, V., additional, Gracia-Sanchez, L. M., additional, Garcia-Burillo, A., additional, Zavadovskiy, K., additional, Lishmanov, Y. U., additional, Saushkin, W., additional, Kovalev, I., additional, Chernishov, A., additional, Annoni, A., additional, Tarkia, M., additional, Saanijoki, T., additional, Oikonen, V., additional, Savunen, T., additional, Green, M. A., additional, Strandberg, M., additional, Roivainen, A., additional, Gaeta, M. C., additional, Artigas, C., additional, Deportos, J., additional, Geraldo, L., additional, Flotats, A., additional, La Delfa, V., additional, Carrio, I., additional, Laarse, W. J., additional, Izquierdo Gomez, M. M., additional, Lacalzada Almeida, J., additional, Barragan Acea, A., additional, De La Rosa Hernandez, A., additional, Juarez Prera, R., additional, Blanco Palacios, G., additional, Bonilla Arjona, J. A., additional, Jimenez Rivera, J. J., additional, Iribarren Sarrias, J. L., additional, Laynez Cerdena, I., additional, Dedic, A., additional, Rossi, A., additional, Ten Kate, G. J. R., additional, Dharampal, A., additional, Moelker, A., additional, Galema, T. W., additional, Mollet, N., additional, De Feyter, P. J., additional, Nieman, K., additional, Trabattoni, D., additional, Broersen, A., additional, Frenay, M., additional, Boogers, M. M., additional, Kitslaar, P. H., additional, Dijkstra, J., additional, Annoni, D. A., additional, Muratori, M., additional, Johki, N., additional, Tokue, M., additional, Dharampal, A. S., additional, Weustink, A. C., additional, Neefjes, L. A. E., additional, Papadopoulou, S. L., additional, Chen, C., additional, Mollet, N. R. A., additional, Boersma, E. H., additional, Krestin, G. P., additional, Purvis, J. A., additional, Sharma, D., additional, Hughes, S. M., additional, Berman, D. S., additional, Taillefer, R., additional, Udelson, J., additional, Devine, M., additional, Lazewatsky, J., additional, Bhat, G., additional, Washburn, D., additional, Patel, D., additional, Mazurek, T., additional, Tandon, S., additional, Bansal, S., additional, Inzucchi, S., additional, Staib, L., additional, Davey, J., additional, Chyun, D., additional, Young, L., additional, Wackers, F., additional, Harbinson, M. T., additional, Wells, G., additional, Dougan, J., additional, Borges-Neto, S., additional, Phillips, H., additional, Farzaneh-Far, A., additional, Starr, Z., additional, Shaw, L. K., additional, Fiuzat, M., additional, O'connor, C., additional, Henzlova, M., additional, Duvall, W. L., additional, Levine, A., additional, Baber, U., additional, Croft, L., additional, Sahni, S., additional, Sethi, S., additional, Hermann, L., additional, Nureldin, A., additional, Gomaa, A., additional, Soliman, M. A. T., additional, Hany, H. A. R., additional, De Graaf, F., additional, Pazhenkottil, A., additional, Siebelink, H. M. J., additional, Reiber, J. H., additional, Ayub, M., additional, Naveed, T., additional, Azhar, M., additional, Van Tosh, A., additional, Faber, T. L., additional, Votaw, J. R., additional, Reichek, N., additional, Pulipati, B., additional, Palestro, C., additional, Nichols, K. J., additional, Okuda, K., additional, Kirihara, Y., additional, Ishikawa, T., additional, Taki, J., additional, Yoshita, M., additional, Yamada, M., additional, Salacata, A., additional, Keavey, S., additional, Chavarri, V., additional, Mills, J., additional, Nagaraj, H., additional, Bhambhani, P., additional, Kliner, D. E., additional, Soman, P., additional, Heo, J., additional, Iskandrian, A. E., additional, Jain, M., additional, Lin, B., additional, Walker, A., additional, Nkonde, C., additional, Bond, S., additional, Baskin, A., additional, Declerck, J., additional, Soto, M. E., additional, Mendoza, G., additional, Aguilar, M., additional, Williams, S. P., additional, Colice, G., additional, Mcardle, J. R., additional, Lankford, A., additional, Kajdasz, D. K., additional, Reed, C. R., additional, Angelini, L., additional, Angelozzi, F., additional, Ascoli, G., additional, Jacobson, A., additional, Lessig, H. J., additional, Gerson, M. C., additional, Cerqueira, M. D., additional, Narula, J., additional, Uematsu, M., additional, Kida, K., additional, Suzuki, K., additional, Bravo, P. E., additional, Fukushima, K., additional, Chaudhry, M., additional, Merrill, J., additional, Alonso Tello, A., additional, Rodriguez Palomares, J. F., additional, Marti Aguasca, G., additional, Aguade Bruix, S., additional, Aliaga, V., additional, Mahia, P., additional, Gonzalez-Alujas, T., additional, Candell, J., additional, Evangelista, A., additional, Mlynarski, R., additional, Mlynarska, A., additional, Sosnowski, M., additional, Zerahn, B., additional, Hasbak, P., additional, Mortensen, C. E., additional, Mathiesen, H. F., additional, Andersson, M., additional, Nielsen, D., additional, Ferreira Santos, L., additional, Ferreira, M. J., additional, Ramos, D., additional, Moreira, D., additional, Cunha, M. J., additional, Albuquerque, A., additional, Moreira, A., additional, Oliveira Santos, J., additional, Costa, G., additional, Providencia, L. A., additional, Arita, Y., additional, Kihara, S., additional, Mitsusada, N., additional, Miyawaki, M., additional, Ueda, H., additional, Hiraoka, H., additional, Matsuzawa, Y., additional, Askew, J., additional, O'connor, M., additional, Jordan, L., additional, Ruter, R., additional, Gibbons, R., additional, Miller, T., additional, Emmett, L., additional, Ng, A., additional, Sorensen, N., additional, Mansberg, R., additional, Kritharides, L., additional, Gonzalez, T., additional, Majmundar, H., additional, Coats, N. P., additional, Vernotico, S., additional, Doan, J. H., additional, Hernandez, T. M., additional, Evini, M., additional, Hepner, A. D., additional, Ip, T. K., additional, Chalela, W. A., additional, Falcao, A. M., additional, Azouri, L. O., additional, Ramires, J. A. F., additional, Meneghetti, J. C., additional, Manganelli, F., additional, Spadafora, M., additional, Varrella, P., additional, Peluso, G., additional, Sauro, R., additional, Di Lorenzo, E., additional, Rotondi, F., additional, Daniele, S., additional, Miletto, P., additional, Rijnders, A. J. M., additional, Hendrickx, B. W., additional, Van Der Bruggen, W., additional, America, Y. G. C. J., additional, Thorley, P. J., additional, Chowdhury, F. U., additional, Dickinson, C. J., additional, Sazonova, S. I., additional, Proskokova, I. Y. U., additional, Gusakova, A. M., additional, Minin, S. M., additional, Lishmanov, Y. U. B., additional, Saushkin, V. V., additional, Rodriguez, G., additional, Roffe, F., additional, Ilarraza, H., additional, Bialostozky, D., additional, Kitsiou, A. N., additional, Arsenos, P., additional, Tsiantis, I., additional, Charizopoulos, S., additional, Karas, S., additional, Vidal Perez, R. C., additional, Garrido, M., additional, Pubul, V., additional, Argibay, S., additional, Pena, C., additional, Pombo, M., additional, Ciobotaru, A. B., additional, Sanchez-Salmon, A., additional, Ruibal Morell, A., additional, Gonzalez-Juanatey, J. R., additional, Rodriguez-Gomez, E., additional, Martinez, B., additional, Pontillo, D., additional, Benvissuto, F., additional, Fiore Melacrinis, F., additional, Maccafeo, S., additional, Scabbia, E. V., additional, Schiavo, R., additional, Golzar, Y., additional, Gidea, C., additional, Golzar, J., additional, Pop-Gorceva, D., additional, Zdravkovska, M., additional, Stojanovski, S., additional, Georgievska-Ismail, L. 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W., additional, Verdes, L., additional, Campos, L., additional, Gulyaev, V., additional, Pankova, A., additional, Santos, J., additional, Carmona, S., additional, Henriksson, I., additional, Prata, A., additional, Carrageta, M., additional, Santos, A. I., additional, Yoshinaga, K., additional, Naya, M., additional, Katoh, C., additional, Manabe, O., additional, Yamada, S., additional, Iwano, H., additional, Chiba, S., additional, Tsutsui, H., additional, Tamaki, N., additional, Vassiliadis, I., additional, Despotopoulos, E., additional, Kaitozis, O., additional, Hatzistamatiou, E., additional, Thompson, R., additional, Hatch, J., additional, Zink, M., additional, Gu, B. S., additional, Bae, G. D., additional, Dae, C. M., additional, Min, G. H., additional, Chun, E. J., additional, Choi, S. I., additional, Al-Mallah, M., additional, Kassem, K., additional, Khawaja, O., additional, Goodman, D., additional, Lipkin, D., additional, Christiaens, L., additional, Bonnet, B., additional, Mergy, J., additional, Coisne, D., additional, Allal, J., additional, Dias Ferreira, N., additional, Leite, D., additional, Rocha, J., additional, Carvalho, M., additional, Caeiro, D., additional, Bettencourt, N., additional, Braga, P., additional, Gama Ribeiro, V., additional, Kristoffersen, U. S., additional, Lebech, A. M., additional, Gutte, H., additional, Ripa, R. S., additional, Wiinberg, N., additional, Petersen, C. L., additional, Jensen, G., additional, Kjaer, A., additional, Bai, C., additional, Conwell, R., additional, Folks, R. D., additional, Verdes-Moreiras, L., additional, Manatunga, D., additional, Jacobson, A. F., additional, Belzer, D., additional, Hasid, Y., additional, Rehling, M., additional, Poulsen, R. H., additional, Falborg, L., additional, Rasmussen, J. T., additional, Waehrens, L. N., additional, Heegaard, C. W., additional, Silvola, J. M. U., additional, Forsback, S., additional, Laine, J. O., additional, Heinonen, S., additional, Ylaherttuala, S., additional, Broisat, A., additional, Ruiz, M., additional, Goodman, N. C., additional, Dimastromatteo, J., additional, Glover, D. K., additional, Hyafil, F., additional, Blackwell, F., additional, Pavon-Djavid, G., additional, Sarda-Mantel, L., additional, Feldman, L. J., additional, Meddahi-Pelle, A., additional, Tsatkin, V., additional, Liu, Y.- H., additional, De Kemp, R., additional, Slomka, P. J., additional, Klein, R., additional, Germano, G., additional, Beanlands, R. S., additional, Rohani, A., additional, Akbari, V., additional, Groothuis, J. G. J., additional, Fransen, M., additional, Beek, A. M., additional, Brinckman, S. L., additional, Meijerink, M. R., additional, Hofman, M. B. M., additional, Van Kuijk, C., additional, Kogure, S., additional, Yamashita, E., additional, Murakami, J., additional, Kawaguchi, R., additional, Adachi, H., additional, Oshima, S., additional, Minin, S., additional, Popov, S., additional, Saushkina, Y. U., additional, Savenkova, G., additional, Lebedev, D., additional, Alexandridis, E., additional, Rovithis, D., additional, Parisis, C., additional, Sazonova, I., additional, Saushkin, V., additional, Chernov, V., additional, Zaabar, L., additional, Bahri, H., additional, Hadj Ali, S., additional, Sellem, A., additional, Slim, I., additional, El Kadri, N., additional, Slimen, H., additional, Hammami, H., additional, Lucic, S., additional, Peter, A., additional, Tadic, S., additional, Nikoletic, K., additional, Jung, R., additional, Lucic, M., additional, Tagil, K., additional, Jakobsson, D., additional, Svensson, S.- E., additional, Wollmer, P., additional, Leccisotti, L., additional, Indovina, L., additional, Paraggio, L., additional, Calcagni, M. L., additional, Giordano, A., additional, Kapitan, M., additional, Paolino, A., additional, Nunez, M., additional, Sweeny, J., additional, Kulkarni, N., additional, Guma, K., additional, Akashi, Y., additional, Takano, M., additional, Takai, M., additional, Koh, S., additional, Miyake, F., additional, Torun, N., additional, Durmus Altun, G., additional, Altun, A., additional, Kaya, E., additional, Saglam, H., additional, Matsuoka, D. T., additional, Sanchez, A., additional, Bartolozzi, C., additional, Padua, D., additional, Ponta, G., additional, Ponte, A., additional, Carneiro, A., additional, Thom, A., additional, Ashrafi, R., additional, Garg, P., additional, Davis, G., additional, Falcao, A., additional, Costa, M., additional, Bussolini, F., additional, Meneghetti, J. A. C., additional, Tobisaka, M., additional, Correia, E., additional, Jansen, J. W., additional, Van Der Vleuten, P. A., additional, Willems, T. P., additional, Zijlstra, F., additional, Sato, M., additional, Taniguchi, K., additional, Kurabayashi, M., additional, Pop Gjorcheva, D., additional, Zdraveska-Kochovska, M., additional, Moriwaki, K., additional, Kawamura, A., additional, Watanabe, K., additional, Omura, T., additional, Sakabe, S., additional, Seko, T., additional, Kasai, A., additional, Ito, M., additional, Obana, M., additional, Akasaka, T., additional, Hruska, C., additional, Truong, D., additional, Pletta, C., additional, Collins, D., additional, Tortorelli, C., additional, Rhodes, D., additional, El-Prince, M., additional, Martinez-Moeller, A., additional, Marinelli, M., additional, Weismueller, S., additional, Hillerer, C., additional, Jensen, B., additional, Nekolla, S. G., additional, Wakabayashi, H., additional, Tsukamoto, K., additional, Baker, S. M. E. A., additional, Sirajul Haque, K. M. H. S., additional, Siddique, A., additional, Krishna Banarjee, S., additional, Ahsan, A., additional, Rahman, F., additional, Mukhlesur Rahman, M., additional, Parveen, T., additional, Lutfinnessa, M., additional, Nasreen, F., additional, Sano, H., additional, Naito, S., additional, De Rimini, M. L., additional, Borrelli, G., additional, Baldascino, F., additional, Calabro, P., additional, Maiello, C., additional, Russo, A., additional, Amarelli, C., additional, Muto, P., additional, Danad, I., additional, Raijmakers, P. G., additional, Appelman, Y. E., additional, Hoekstra, O. S., additional, Marcus, J. T., additional, Boonstra, A., additional, Ryzhkova, D. V., additional, Kuzmina, T. V., additional, Borodina, O. S., additional, Trukshina, M. A., additional, Kostina, I. S., additional, Hommel, H., additional, Feuchtner, G., additional, Pachinger, O., additional, Friedrich, G., additional, Stel, A. M., additional, Deckers, J. W., additional, Gama, V., additional, Ciarka, A., additional, Neefjes, L. A., additional, Mollet, N. R., additional, Sijbrands, E. J., additional, Wilczek, J., additional, Llibre Pallares, C., additional, Abdul-Jawad Altisent, O., additional, Cuellar Calabria, H., additional, Mahia Casado, P., additional, Gonzalez-Alujas, M. T., additional, Evangelista Masip, A., additional, Garcia-Dorado Garcia, D., additional, Tekabe, Y., additional, Shen, X., additional, Li, Q., additional, Luma, J., additional, Weisenberger, D., additional, Schmidt, A. M., additional, Haubner, R., additional, Johnson, L., additional, Sleiman, L., additional, Thorn, S., additional, Hasu, M., additional, Thabet, M., additional, Dasilva, J. N., additional, Whitman, S. C., additional, Genovesi, D., additional, Giorgetti, A., additional, Gimelli, A., additional, Cannizzaro, G., additional, Bertagna, F., additional, Fagioli, G., additional, Rossi, M., additional, Bonini, R., additional, Marzullo, P., additional, Paterson, C. A., additional, Smith, S. A., additional, Small, A. D., additional, Goodfield, N. E. R., additional, Martin, W., additional, Nekolla, S., additional, Sherif, H., additional, Reder, S., additional, Yu, M., additional, Kusch, A., additional, Li, D., additional, Zou, J., additional, Lloyd, M. S., additional, Cao, K., additional, Motherwell, D. W., additional, Rice, A., additional, Mccurrach, G. M., additional, Cobbe, S. M., additional, Petrie, M. C., additional, Al Younis, I., additional, Van Der Wall, E., additional, Mirza, T., additional, Raza, M., additional, Hashemizadeh, H., additional, Santos, L., additional, Krishna, B. A., additional, Perna, F., additional, Lago, M., additional, Leo, M., additional, Pelargonio, G., additional, Bencardino, G., additional, Narducci, M. L., additional, Casella, M., additional, Bellocci, F., additional, Kirac, S., additional, Yaylali, O., additional, Serteser, M., additional, Yaylali, T., additional, Okizaki, A., additional, Urano, Y., additional, Nakayama, M., additional, Ishitoya, S., additional, Sato, J., additional, Ishikawa, Y., additional, Sakaguchi, M., additional, Nakagami, N., additional, Aburano, T., additional, Solav, S. V., additional, Bhandari, R., additional, Burrell, S., additional, Dorbala, S., additional, Bruno, I., additional, Caldarella, C., additional, Collarino, A., additional, Mattoli, M. V., additional, Stefanelli, A., additional, Cannarile, A., additional, Maggi, F., additional, Soukhov, V., additional, Bondarev, S., additional, Yalfimov, A., additional, Khan, M., additional, Priyadharshan, P. P., additional, Chandok, G., additional, Aziz, T., additional, Avison, M., additional, Smith, R. A., additional, Bulugahapitya, D. S., additional, Vakhtangadze, T., additional, Todua, F., additional, Baramia, M., additional, Antelava, G., additional, Roche, N.- C., additional, Paule, P., additional, Kerebel, S., additional, Gil, J.- M., additional, Fourcade, L., additional, Tzonevska, A., additional, Tzvetkov, K., additional, Atanasova, M., additional, Parvanova, V., additional, Chakarova, A., additional, Piperkova, E., additional, Kocabas, B., additional, Muderrisoglu, H., additional, Allaart, C. P., additional, Entok, E., additional, Simsek, S., additional, Akcay, B., additional, Ak, I., additional, Vardareli, E., additional, Stachura, M., additional, Kwasiborski, P. J., additional, Horszczaruk, G. J., additional, Komar, E., additional, Cwetsch, A., additional, Zraik, B., additional, Morales Demori, R., additional, Almeida, A. D. J., additional, Siqueira, M. E., additional, Vieira, E., additional, Balogh, I., additional, Kerecsen, G., additional, Marosi, E., additional, Szelid, Z. S., additional, Sattar, A., additional, Swadia, T., additional, Chattahi, J., additional, Qureshi, W., additional, Khalid, F., additional, Gonzalez, A., additional, Hechavarria, S., additional, Takamura, K., additional, Fujimoto, S., additional, Nakanishi, R., additional, Yamashina, S., additional, Namiki, A., additional, Yamazaki, J., additional, Koshino, K., additional, Hashikawa, Y., additional, Teramoto, N., additional, Hikake, M., additional, Ishikane, S., additional, Ikeda, T., additional, Iida, H., additional, Takahashi, Y., additional, Oriuchi, N., additional, Higashino, H., additional, Endo, K., additional, Mochizuki, T., additional, Murase, K., additional, Baali, A., additional, Moreno, R., additional, Chau, M., additional, Rousseau, H., additional, Nicoud, F., additional, Dolliner, P., additional, Brammen, L., additional, Steurer, G., additional, Traub-Weidinger, T., additional, Ubl, P., additional, Schaffarich, P., additional, Dobrozemsky, G., additional, Staudenherz, A., additional, Ozgen Kiratli, M., additional, Temelli, B., additional, Kanat, N. B., additional, Aksoy, T., additional, Slavich, G. A., additional, Piccoli, G., additional, Puppato, M., additional, Grillone, S., additional, Gasparini, D., additional, Dunet, V., additional, Perruchoud, S., additional, Poitry-Yamate, C., additional, Lepore, M., additional, Gruetter, R., additional, Pedrazzini, T., additional, Anselm, D., additional, Anselm, A., additional, Atkins, H., additional, Renaud, J., additional, Dekemp, R., additional, Burwash, I., additional, Guo, A., additional, Beanlands, R., additional, Glover, C., additional, Vilardi, I., additional, Zangheri, B., additional, Calabrese, L., additional, Romano, P., additional, Bruno, A., additional, Fernandez Cimadevilla, O. C., additional, Uusitalo, V. A., additional, Luotolahti, M., additional, Wendelin-Saarenhovi, M., additional, Sundell, J., additional, Raitakari, O., additional, Huidu, S., additional, Gadiraju, R., additional, Ghesani, M., additional, Uddin, Q., additional, Wosnitzer, B., additional, Takahashi, N., additional, Alhaj, E., additional, Legasto, A., additional, Abiri, B., additional, Elsaban, K., additional, El Khouly, T., additional, El Kammash, T., additional, Al Ghamdi, A., additional, Kyung Deok, B., additional, Bon Seung, K., additional, Sang Geun, Y., additional, Chang Min, D., additional, and Gwan Hong, M., additional
- Published
- 2011
- Full Text
- View/download PDF
6. Mobile Game Terminal based Interactive Education Environment for Large-Scale Lectures
- Author
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Hanakawa, N., primary and Obana, M., additional
- Published
- 2010
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- View/download PDF
7. Segmental vs global membranous glomerulonephritis in children: segmental membranous glomerulonephritis in children: comparison with global membranous glomerulonephritis
- Author
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Obana, M., Nakanishi, K., and Sako, M.
- Subjects
Glomerulonephritis -- Comparative analysis ,Children -- Diagnosis ,Health - Published
- 2006
8. Orientation of one-dimensional silicon backbones in ternary Si : C : H films prepared by evaporation of organopolysilane
- Author
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Furukawa, S, primary, Obana, M, additional, Tamura, M, additional, and Fujishiro, H, additional
- Published
- 1992
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9. Structure and optical properties of ternary Si:C:H films prepared by evaporation of organo-polysilane
- Author
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Furukawa, S, primary, Obana, M, additional, Nakamine, T, additional, Shirakawa, Y, additional, Sorai, A, additional, and Tamura, M, additional
- Published
- 1992
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- View/download PDF
10. Therapeutic activation of signal transducer and activator of transcription 3 by interleukin-11 ameliorates cardiac fibrosis after myocardial infarction.
- Author
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Obana M, Maeda M, Takeda K, Hayama A, Mohri T, Yamashita T, Nakaoka Y, Komuro I, Matsumiya G, Azuma J, and Fujio Y
- Published
- 2010
- Full Text
- View/download PDF
11. Rat peritoneal macrophages express endothelin ET~B but not endothelin ET~A receptors
- Author
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Sakurai-Yamashita, Y., Yamashita, K., Yoshida, A., Obana, M., Takada, K., Shibaguchi, H., Shigematsu, K., Niwa, M., and Taniyama, K.
- Published
- 1997
- Full Text
- View/download PDF
12. Inhibition of M-type K^+ current by linopirdine, a neurotransmitter-release enhancer, in NG108-15 neuronal cells and rat cerebral neurons in culture
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Noda, M., Obana, M., and Akaike, N.
- Published
- 1998
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- View/download PDF
13. ChemInform Abstract: CATALYTIC ASYMMETRIC HYDROGENATION OF CYCLIC ANHYDRIDES USING RUTHENIUM(II) CHIRAL PHOSPHINE COMPLEX
- Author
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OSAKADA, K., primary, OBANA, M., additional, IKARIYA, T., additional, SABURI, M., additional, and YOSHIKAWA, S., additional
- Published
- 1982
- Full Text
- View/download PDF
14. Surface acoustic wave sensor for sensing acoustic properties of liquid
- Author
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Nomura, T., primary, Takebayashi, M., additional, Furukawa, S., additional, and Obana, M., additional
- Full Text
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15. New SAW humidity sensor using double-coated hygroscopic film
- Author
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Furukawa, S., primary, Obana, M., additional, and Nomura, T., additional
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16. Effects of ions in liquid on leaky SAW character propagating along liquid/layered-substrate structures.
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Furukawa, S., Obana, M., and Nomura, T.
- Published
- 1996
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- View/download PDF
17. Surface acoustic wave sensor for sensing acoustic properties of liquid.
- Author
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Nomura, T., Takebayashi, M., Furukawa, S., and Obana, M.
- Published
- 1995
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18. New SAW humidity sensor using double-coated hygroscopic film.
- Author
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Furukawa, S., Obana, M., and Nomura, T.
- Published
- 1995
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19. Characteristic of leaky surface acoustic wave propagating along liquid/SiO/sub 2LiNbO/sub 3/ and its application to liquid sensor.
- Author
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Furukawa, S., Nishimura, R., Obana, M., Nomura, T., and Yasuda, T.
- Published
- 1994
- Full Text
- View/download PDF
20. Metabolite phosphatase from anhydrobiotic tardigrades.
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Kato S, Deguchi K, Obana M, Fujio Y, Fukuda Y, and Inoue T
- Abstract
Terrestrial organisms have systems to escape from desiccation stresses. For example, tardigrades (also known as water bears) can survive severe dried and other extreme environments by anhydrobiosis. Although their extraordinary ability has enchanted people, little is known about the detailed molecular mechanisms of anhydrobiosis. Here, we focused on the tardigrade Ramazzottius varieornatus, one of the toughest animals on Earth. A transcriptome database of R. varieornatus shows that genes encoding a Ferritin-like protein are upregulated during desiccation or ultraviolet radiation. This protein shows sequence similarity to enigmatic proteins in desiccation-tolerant bacteria and plants, which are hypothesized to be desiccation-related. However, because these proteins lack detailed biological information, their functions are relatively unknown. We determined an atomic (1.05 Å) resolution crystal structure of a Ferritin-like protein from R. varieornatus. The structure revealed a dinuclear metal binding site, and we showed that this Ferritin-like protein has phosphatase activity toward several metabolite compounds including unusual nucleotide phosphates produced by oxidative or radiation damage. We also found that a homologous protein from a desiccation- and ultraviolet-tolerant bacterium Deinococcus radiodurans is a metabolite phosphatase. Our results indicate that through cleaning up damaged metabolites or regulation of metabolite levels, this phosphatase family can contribute to stress tolerances. This study provides a clue to one of the universal molecular bases of desiccation-stress tolerance., (© 2024 The Author(s). The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
- Published
- 2024
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21. JAK inhibition during the early phase of SARS-CoV-2 infection worsens kidney injury by suppressing endogenous antiviral activity in mice.
- Author
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Sakai H, Kamuro H, Tokunoh N, Izawa T, Tamiya S, Yamamoto A, Tanaka S, Okuzaki D, Ono C, Matsuura Y, Okada Y, Yoshioka Y, Fujio Y, and Obana M
- Subjects
- Animals, Mice, Disease Models, Animal, Acute Kidney Injury virology, Acute Kidney Injury etiology, Acute Kidney Injury metabolism, Azetidines pharmacology, Azetidines therapeutic use, Janus Kinases metabolism, Janus Kinases antagonists & inhibitors, Kidney pathology, Kidney virology, Kidney metabolism, Kidney drug effects, COVID-19 Drug Treatment, Antiviral Agents pharmacology, Antiviral Agents therapeutic use, Male, Mice, Inbred C57BL, COVID-19 complications, Janus Kinase Inhibitors pharmacology, Janus Kinase Inhibitors therapeutic use, SARS-CoV-2, Sulfonamides pharmacology, Purines pharmacology, Pyrazoles pharmacology
- Abstract
Coronavirus disease 2019 (COVID-19) induces respiratory dysfunction as well as kidney injury. Although the kidney is considered a target organ of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and affected by the COVID-19-induced cytokine storm, the mechanisms of renal reaction in SARS-CoV-2 infection are unknown. In this study, a murine COVID-19 model was induced by nasal infection with mouse-adapted SARS-CoV-2 (MA10). MA10 infection induced body weight loss along with lung inflammation in mice 4 days after infection. Serum creatinine levels and the urinary albumin/creatinine ratio increased on day 4 after MA10 infection. Measurement of the urinary neutrophil gelatinase-associated lipocalin/creatinine ratio and hematoxylin and eosin staining revealed tubular damage in MA10-infected murine kidneys, indicating kidney injury in the murine COVID-19 model. Interferon (IFN)-γ and interleukin-6 upregulation in the sera of MA10-infected mice, along with the absence of MA10 in the kidneys, implied that the kidneys were affected by the MA10 infection-induced cytokine storm rather than by direct MA10 infection of the kidneys. RNA-sequencing analysis revealed that antiviral genes, such as the IFN/Janus kinase (JAK) pathway, were upregulated in MA10-infected kidneys. Upon administration of the JAK inhibitor baricitinib on days 1 - 3 after MA10 infection, an antiviral pathway was suppressed, and MA10 was detected more frequently in the kidneys. Notably, JAK inhibition upregulated the hypoxia response and exaggerated kidney injury. These results suggest that endogenous antiviral activity protects against SARS-CoV-2-induced kidney injury in the early phase of infection, providing valuable insights into the pathogenesis of COVID-19-associated nephropathy. NEW & NOTEWORTHY Patients frequently present with acute kidney injury or abnormal urinary findings after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we investigated how the kidneys respond during SARS-CoV-2 infection using a murine coronavirus disease 2019 (COVID-19) model and showed that Janus kinase-mediated endogenous antiviral activity protects against kidney injury in the early phase of SARS-CoV-2 infection. These findings provide valuable insights into the renal pathophysiology of COVID-19.
- Published
- 2024
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22. Endothelial ROBO4 suppresses PTGS2/COX-2 expression and inflammatory diseases.
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Tanaka M, Shirakura K, Takayama Y, Μatsui M, Watanabe Y, Yamamoto T, Takahashi J, Tanaka S, Hino N, Doi T, Obana M, Fujio Y, Takayama K, and Okada Y
- Subjects
- Animals, Mice, Humans, Mice, Knockout, Mice, Inbred C57BL, Male, Endothelial Cells metabolism, Roundabout Proteins, Cyclooxygenase 2 metabolism, Cyclooxygenase 2 genetics, Inflammation metabolism, Inflammation genetics, Receptors, Cell Surface metabolism, Receptors, Cell Surface genetics
- Abstract
Accumulating evidence suggests that endothelial cells can be useful therapeutic targets. One of the potential targets is an endothelial cell-specific protein, Roundabout4 (ROBO4). ROBO4 has been shown to ameliorate multiple diseases in mice, including infectious diseases and sepsis. However, its mechanisms are not fully understood. In this study, using RNA-seq analysis, we found that ROBO4 downregulates prostaglandin-endoperoxide synthase 2 (PTGS2), which encodes cyclooxygenase-2. Mechanistic analysis reveals that ROBO4 interacts with IQ motif-containing GTPase-activating protein 1 (IQGAP1) and TNF receptor-associated factor 7 (TRAF7), a ubiquitin E3 ligase. In this complex, ROBO4 enhances IQGAP1 ubiquitination through TRAF7, inhibits prolonged RAC1 activation, and decreases PTGS2 expression in inflammatory endothelial cells. In addition, Robo4-deficiency in mice exacerbates PTGS2-associated inflammatory diseases, including arthritis, edema, and pain. Thus, we reveal the molecular mechanism by which ROBO4 suppresses the inflammatory response and vascular hyperpermeability, highlighting its potential as a promising therapeutic target for inflammatory diseases., (© 2024. The Author(s).)
- Published
- 2024
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23. Cardioprotective effect of Interleukin-11 against warm ischemia-reperfusion injury in a rat heart donor model.
- Author
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Sakata T, Kohno H, Inui T, Ikeuchi H, Shiko Y, Kawasaki Y, Suzuki S, Tanaka S, Obana M, Ishikawa K, Fujio Y, and Matsumiya G
- Subjects
- Rats, Male, Animals, Humans, Interleukin-11 pharmacology, Brain Death, Rats, Sprague-Dawley, Tissue Donors, Reperfusion Injury drug therapy, Reperfusion Injury prevention & control, Heart Transplantation
- Abstract
Shortage of donor organs for heart transplantation is a worldwide problem. Donation after circulatory death (DCD) has been proposed to expand the donor pool. However, in contrast to the donation after brain death that undergoes immediate cold preservation, warm ischemia and subsequent reperfusion injury are inevitable in DCD. It has been reported that interleukin-11 (IL-11) mitigates ischemia-reperfusion injury in rodent models of myocardial infarction and donation after brain death heart transplantation. We hypothesized that IL-11 also offers benefit to warm ischemia in an experimental model of cardiac transplantation that resembles DCD. The hearts of naïve male Sprague Dawley rats (n = 15/group) were procured, subjected to 25-min warm ischemia, and reperfused for 60 min using Langendorff apparatus. IL-11 or saline was administered intravenously before the procurement, added to maintenance buffer, and infused via perfusion during reperfusion. IL-11 group exhibited significantly better cardiac function post-reperfusion. Severely damaged mitochondria was found in the electron microscopic analysis of control hearts whereas the mitochondrial structure was better preserved in the IL-11 treated hearts. Immunoblot analysis using neonatal rat cardiomyocytes revealed increased signal transducer and activator of transcription 3 (STAT3) phosphorylation at Ser727 after IL-11 treatment, suggesting its role in mitochondrial protection. Consistent with expected activation of mitochondrial respiration by mitochondrial STAT3, immunohistochemical staining demonstrated a higher mitochondrial cytochrome c oxidase subunit 2 expression. In summary, IL-11 protects the heart from warm ischemia reperfusion injury by alleviating mitochondrial injury and could be a viable therapeutic option for DCD heart transplantation., Competing Interests: Declaration of competing interest K.H., T.I. and G.M. received research funding from Edwards Lifesciences Corporation and Medtronic Japan Co, Ltd. These are not related to this study., (Copyright © 2023 Elsevier B.V. All rights reserved.)
- Published
- 2023
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24. Runx1 is upregulated by STAT3 and promotes proliferation of neonatal rat cardiomyocytes.
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Suzuki S, Tanaka S, Kametani Y, Umeda A, Nishinaka K, Egawa K, Okada Y, Obana M, and Fujio Y
- Subjects
- Animals, Rats, Animals, Newborn, Cell Cycle, Cell Proliferation, Cells, Cultured, Mammals, Myocytes, Cardiac metabolism
- Abstract
Though it is well known that mammalian cardiomyocytes exit cell cycle soon after birth, the mechanisms that regulate proliferation remain to be fully elucidated. Recent studies reported that cardiomyocytes undergo dedifferentiation before proliferation, indicating the importance of dedifferentiation in cardiomyocyte proliferation. Since Runx1 is expressed in dedifferentiated cardiomyocytes, Runx1 is widely used as a dedifferentiation marker of cardiomyocytes; however, little is known about the role of Runx1 in the proliferation of cardiomyocytes. The purpose of this study was to clarify the functional significance of Runx1 in cardiomyocyte proliferation. qRT-PCR analysis and immunoblot analysis demonstrated that Runx1 expression was upregulated in neonatal rat cardiomyocytes when cultured in the presence of FBS. Similarly, STAT3 was activated in the presence of FBS. Interestingly, knockdown of STAT3 significantly decreased Runx1 expression, indicating Runx1 is regulated by STAT3. We next investigated the effect of Runx1 on proliferation. Immunofluorescence microscopic analysis using an anti-Ki-67 antibody revealed that knockdown of Runx1 decreased the ratio of proliferating cardiomyocytes. Conversely, Runx1 overexpression using adenovirus vector induced cardiomyocyte proliferation in the absence of FBS. Finally, RNA-sequencing analysis revealed that Runx1 overexpression induced upregulation of cardiac fetal genes and downregulation of genes associated with fatty acid oxidation. Collectively, Runx1 is regulated by STAT3 and induces cardiomyocyte proliferation by juvenilizing cardiomyocytes., (© 2023 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)
- Published
- 2023
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25. Myeloid-derived suppressor cells exacerbate poly(I:C)-induced lung inflammation in mice with renal injury and older mice.
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Xie Z, Zhou H, Obana M, Fujio Y, Okada N, and Tachibana M
- Subjects
- Humans, Mice, Animals, Aged, Poly I-C, Kidney, Disease Models, Animal, Myeloid-Derived Suppressor Cells, Pneumonia, Viral
- Abstract
Viral pneumonia is a global health burden with a high mortality rate, especially in the elderly and in patients with underlying diseases. Recent studies have found that myeloid-derived suppressor cells (MDSCs) are abundant in these patient groups; however, their roles in the progression of viral pneumonia remain unclear. In this study, we observed a substantial increase in MDSCs in a mouse model of renal ischemia/reperfusion (I/R) injury and in older mice. When intranasal polyinosinic-polycytidylic acid (poly(I:C)) administration was used to mimic viral pneumonia, mice with renal I/R injury exhibited more severe lung inflammation than sham mice challenged with poly(I:C). In addition, MDSC depletion attenuated lung inflammation in mice with I/R injury. Similar results were obtained in older mice compared with those in young mice. Furthermore, adoptive transfer of in vitro -differentiated MDSCs exacerbated poly(I:C)-induced lung inflammation. Taken together, these experimental results suggest that the increased proportion of MDSCs in mice with renal I/R injury and in older mice exacerbates poly(I:C)-induced lung inflammation. These findings have important implications for the treatment and prevention of severe lung inflammation caused by viral pneumonia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xie, Zhou, Obana, Fujio, Okada and Tachibana.)
- Published
- 2023
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26. Upregulation of Robo4 expression by SMAD signaling suppresses vascular permeability and mortality in endotoxemia and COVID-19 models.
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Morita M, Yoneda A, Tokunoh N, Masaki T, Shirakura K, Kinoshita M, Hashimoto R, Shigesada N, Takahashi J, Tachibana M, Tanaka S, Obana M, Hino N, Ikawa M, Tsujikawa K, Ono C, Matsuura Y, Kidoya H, Takakura N, Kubota Y, Doi T, Takayama K, Yoshioka Y, Fujio Y, and Okada Y
- Subjects
- Animals, Mice, Receptors, Cell Surface metabolism, Capillary Permeability, Endothelial Cells metabolism, Signal Transduction, Up-Regulation, Lipopolysaccharides pharmacology, Lipopolysaccharides metabolism, SARS-CoV-2 metabolism, Endotoxemia metabolism, COVID-19 metabolism
- Abstract
There is an urgent need to develop novel drugs to reduce the mortality from severe infectious diseases with the emergence of new pathogens, including Coronavirus disease 2019 (COVID-19). Although current drugs effectively suppress the proliferation of pathogens, immune cell activation, and inflammatory cytokine functions, they cannot completely reduce mortality from severe infections and sepsis. In this study, we focused on the endothelial cell-specific protein, Roundabout 4 (Robo4), which suppresses vascular permeability by stabilizing endothelial cells, and investigated whether enhanced Robo4 expression could be a novel therapeutic strategy against severe infectious diseases. Endothelial-specific overexpression of Robo4 suppresses vascular permeability and reduces mortality in lipopolysaccharide (LPS)-treated mice. Screening of small molecules that regulate Robo4 expression and subsequent analysis revealed that two competitive small mothers against decapentaplegic (SMAD) signaling pathways, activin receptor-like kinase 5 (ALK5)-SMAD2/3 and ALK1-SMAD1/5, positively and negatively regulate Robo4 expression, respectively. An ALK1 inhibitor was found to increase Robo4 expression in mouse lungs, suppress vascular permeability, prevent extravasation of melanoma cells, and decrease mortality in LPS-treated mice. The inhibitor suppressed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced endothelial barrier disruption and decreased mortality in mice infected with SARS-CoV-2. These results indicate that enhancing Robo4 expression is an efficient strategy to suppress vascular permeability and mortality in severe infectious diseases, including COVID-19, and that small molecules that upregulate Robo4 can be potential therapeutic agents against these diseases.
- Published
- 2023
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27. Arid5a/IL-6/PAI-1 Signaling Is Involved in the Pathogenesis of Lipopolysaccharide-Induced Kidney Injury.
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Tanaka K, Harada H, Kamuro H, Sakai H, Yamamoto A, Tomimatsu M, Ikeda A, Chosokabe R, Tanaka S, Okada Y, Fujio Y, and Obana M
- Subjects
- Humans, Mice, Animals, Plasminogen Activator Inhibitor 1 genetics, Mice, Inbred C57BL, Human Umbilical Vein Endothelial Cells metabolism, Kidney metabolism, RNA, Messenger metabolism, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Transcription Factors metabolism, Interleukin-6, Lipopolysaccharides pharmacology
- Abstract
A systemic inflammatory response leads to widespread organ dysfunction, such as kidney dysfunction. Plasminogen activator inhibitor-1 (PAI-1) is involved in the pathogenesis of inflammatory kidney injury; however, the regulatory mechanism of PAI-1 in injured kidneys remains unclear. PAI-1 is induced by interleukin (IL)-6 in patients with sepsis. In addition, the stabilization of IL-6 is regulated by the adenine-thymine-rich interactive domain-containing protein 5a (Arid5a). Therefore, the aim of the present study was to examine the involvement of Arid5a/IL-6/PAI-1 signaling in lipopolysaccharide (LPS)-induced inflammatory kidney injury. LPS treatment to C57BL/6J mice upregulated Pai-1 mRNA in the kidneys. Enzyme-linked immunosorbent assay (ELISA) revealed that PAI-1 expression was induced in the culture supernatants of LPS-treated human umbilical vein endothelial cells, but not in those of LPS-treated human kidney 2 (HK-2) cells, a tubular cell line. Combined with single-cell analysis, endothelial cells were found to be responsible for PAI-1 elevation in LPS-treated kidneys. Administration of TM5441, a PAI-1 inhibitor, reduced the urinary albumin/creatinine ratio, concomitant with downregulation of Il-6 and Arid5a mRNA expressions. IL-6 treatment in LPS model mice further upregulated Pai-1 mRNA expression compared with LPS alone, accompanied by renal impairment. Furthermore, the expression of Il-6 and Pai-1 mRNA was lower in Arid5a knockout mice than in wild-type mice after LPS treatment. Taken together, the vicious cycle of Arid5a/IL-6/PAI-1 signaling is involved in LPS-induced kidney injury.
- Published
- 2023
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28. Myeloid cell-specific ablation of Runx2 gene exacerbates post-infarct cardiac remodeling.
- Author
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Tomimatsu M, Matsumoto K, Ashizuka M, Kumagai S, Tanaka S, Nakae T, Yokota K, Kominami S, Kajiura R, Okuzaki D, Motooka D, Shiraishi A, Abe T, Matsuda H, Okada Y, Maeda M, Seno S, Obana M, and Fujio Y
- Subjects
- Animals, Collagen metabolism, Core Binding Factor Alpha 1 Subunit genetics, Core Binding Factor Alpha 1 Subunit metabolism, Culture Media, Conditioned metabolism, Disease Models, Animal, Endothelial Cells metabolism, Macrophages metabolism, Mice, Mice, Inbred C57BL, Myocardium metabolism, RNA metabolism, RNA, Messenger metabolism, Myocardial Infarction metabolism, Ventricular Remodeling genetics
- Abstract
Runt-related transcription factor 2 (Runx2), a regulator of osteoblast differentiation, is pathologically involved in vascular calcification; however, the significance of Runx2 in cardiac homeostasis remains unclear. Here, we investigated the roles of Runx2 in cardiac remodeling after myocardial infarction (MI). The expression of Runx2 mRNA and protein was upregulated in murine hearts after MI. Runx2 was expressed in heart-infiltrating myeloid cells, especially in macrophages, at the border zone of post-infarct myocardium. To analyze the biological functions of Runx2 in cardiac remodeling, myeloid cell-specific Runx2 deficient (CKO) mice were exposed to MI. After MI, ventricular weight/tibia length ratio was increased in CKO mice, concomitant with severe cardiac dysfunction. Cardiac fibrosis was exacerbated in CKO mice, consistent with the upregulation of collagen 1a1 expression. Mechanistically, immunohistochemical analysis using anti-CD31 antibody showed that capillary density was decreased in CKO mice. Additionally, conditioned culture media of myeloid cells from Runx2 deficient mice exposed to MI induced the tube formation of vascular endothelial cells to a lesser extent than those from control mice. RNA-sequence showed that the expression of pro-angiogenic or anti-angiogenic factors was altered in macrophages from Runx2-deficient mice. Collectively, Runx2
+ myeloid cells infiltrate into post-infarct myocardium and prevent adverse cardiac remodeling, at least partially, by regulating endothelial cell function., (© 2022. The Author(s).)- Published
- 2022
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29. SARS-CoV-2 disrupts respiratory vascular barriers by suppressing Claudin-5 expression.
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Hashimoto R, Takahashi J, Shirakura K, Funatsu R, Kosugi K, Deguchi S, Yamamoto M, Tsunoda Y, Morita M, Muraoka K, Tanaka M, Kanbara T, Tanaka S, Tamiya S, Tokunoh N, Kawai A, Ikawa M, Ono C, Tachibana K, Kondoh M, Obana M, Matsuura Y, Ohsumi A, Noda T, Yamamoto T, Yoshioka Y, Torisawa YS, Date H, Fujio Y, Nagao M, Takayama K, and Okada Y
- Subjects
- Claudin-5 genetics, Endothelial Cells metabolism, Fluvastatin metabolism, Fluvastatin pharmacology, Humans, Tight Junction Proteins metabolism, COVID-19, Claudin-5 metabolism, SARS-CoV-2
- Abstract
In the initial process of coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects respiratory epithelial cells and then transfers to other organs the blood vessels. It is believed that SARS-CoV-2 can pass the vascular wall by altering the endothelial barrier using an unknown mechanism. In this study, we investigated the effect of SARS-CoV-2 on the endothelial barrier using an airway-on-a-chip that mimics respiratory organs and found that SARS-CoV-2 produced from infected epithelial cells disrupts the barrier by decreasing Claudin-5 (CLDN5), a tight junction protein, and disrupting vascular endothelial cadherin-mediated adherens junctions. Consistently, the gene and protein expression levels of CLDN5 in the lungs of a patient with COVID-19 were decreased. CLDN5 overexpression or Fluvastatin treatment rescued the SARS-CoV-2-induced respiratory endothelial barrier disruption. We concluded that the down-regulation of CLDN5 expression is a pivotal mechanism for SARS-CoV-2-induced endothelial barrier disruption in respiratory organs and that inducing CLDN5 expression is a therapeutic strategy against COVID-19.
- Published
- 2022
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30. Upregulation of OASIS/CREB3L1 in podocytes contributes to the disturbance of kidney homeostasis.
- Author
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Miyake Y, Obana M, Yamamoto A, Noda S, Tanaka K, Sakai H, Tatsumoto N, Makino C, Kanemoto S, Shioi G, Tanaka S, Maeda M, Okada Y, Imaizumi K, Asanuma K, and Fujio Y
- Subjects
- Albuminuria genetics, Albuminuria metabolism, Animals, Cyclic AMP Response Element-Binding Protein metabolism, Fibrosis, Homeostasis, Kidney metabolism, Lipopolysaccharides metabolism, Mice, Nerve Tissue Proteins metabolism, Up-Regulation, Diabetes Mellitus, Experimental pathology, Diabetic Nephropathies metabolism, Podocytes
- Abstract
Podocyte injury is involved in the onset and progression of various kidney diseases. We previously demonstrated that the transcription factor, old astrocyte specifically induced substance (OASIS) in myofibroblasts, contributes to kidney fibrosis, as a novel role of OASIS in the kidneys. Importantly, we found that OASIS is also expressed in podocytes; however, the pathophysiological significance of OASIS in podocytes remains unknown. Upon lipopolysaccharide (LPS) treatment, there is an increase in OASIS in murine podocytes. Enhanced serum creatinine levels and tubular injury, but not albuminuria and podocyte injury, are attenuated upon podocyte-restricted OASIS knockout in LPS-treated mice, as well as diabetic mice. The protective effects of podocyte-specific OASIS deficiency on tubular injury are mediated by protein kinase C iota (PRKCI/PKCι), which is negatively regulated by OASIS in podocytes. Furthermore, podocyte-restricted OASIS transgenic mice show tubular injury and tubulointerstitial fibrosis, with severe albuminuria and podocyte degeneration. Finally, there is an increase in OASIS-positive podocytes in the glomeruli of patients with minimal change nephrotic syndrome and diabetic nephropathy. Taken together, OASIS in podocytes contributes to podocyte and/or tubular injury, in part through decreased PRKCI. The induction of OASIS in podocytes is a critical event for the disturbance of kidney homeostasis., (© 2022. The Author(s).)
- Published
- 2022
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31. Glycoprotein 130 orchestrates signal transduction network to promote cardiomyocyte proliferation for normal growth.
- Author
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Obana M, Maeda M, and Fujio Y
- Subjects
- Cell Proliferation physiology, Cytokine Receptor gp130, Glycoproteins, Signal Transduction, Heart growth & development, Myocytes, Cardiac
- Published
- 2022
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32. Yes-associated protein activation potentiates glycogen synthase kinase-3 inhibitor-induced proliferation of neonatal cardiomyocytes and iPS cell-derived cardiomyocytes.
- Author
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Kametani Y, Tanaka S, Wada Y, Suzuki S, Umeda A, Nishinaka K, Okada Y, Maeda M, Miyagawa S, Sawa Y, Obana M, and Fujio Y
- Subjects
- Animals, Cell Proliferation, Glycogen Synthase Kinase 3 metabolism, Glycogen Synthase Kinase 3 beta metabolism, Mammals metabolism, Rats, YAP-Signaling Proteins, beta Catenin metabolism, Induced Pluripotent Stem Cells metabolism, Myocytes, Cardiac metabolism
- Abstract
Because mammalian cardiomyocytes largely cease to proliferate immediately after birth, the regenerative activity of the heart is limited. To date, much effort has been made to clarify the regulatory mechanism of cardiomyocyte proliferation because the amplification of cardiomyocytes could be a promising strategy for heart regenerative therapy. Recently, it was reported that the inhibition of glycogen synthase kinase (GSK)-3 promotes the proliferation of neonatal rat cardiomyocytes (NRCMs) and human iPS cell-derived cardiomyocytes (hiPSC-CMs). Additionally, Yes-associated protein (YAP) induces cardiomyocyte proliferation. The purpose of this study was to address the importance of YAP activity in cardiomyocyte proliferation induced by GSK-3 inhibitors (GSK-3Is) to develop a novel strategy for cardiomyocyte amplification. Immunofluorescent microscopic analysis using an anti-Ki-67 antibody demonstrated that the treatment of NRCMs with GSK-3Is, such as BIO and CHIR99021, increased the ratio of proliferative cardiomyocytes. YAP was localized in the nuclei of more than 95% of cardiomyocytes, either in the presence or absence of GSK-3Is, indicating that YAP was endogenously activated. GSK-3Is increased the expression of β-catenin and promoted its translocation into the nucleus without influencing YAP activity. The knockdown of YAP using siRNA or pharmacological inhibition of YAP using verteporfin or CIL56 dramatically reduced GSK-3I-induced cardiomyocyte proliferation without suppressing β-catenin activation. Interestingly, the inhibition of GSK-3 also induced the proliferation of hiPSC-CMs under sparse culture conditions, where YAP was constitutively activated. In contrast, under dense culture conditions, in which YAP activity was suppressed, the proliferative effects of GSK-3Is on hiPSC-CMs were not detected. Importantly, the activation of YAP by the knockdown of α-catenin restored the proproliferative activity of GSK-3Is. Collectively, YAP activation potentiates the GSK-3I-induced proliferation of cardiomyocytes. The blockade of GSK-3 in combination with YAP activation resulted in remarkable amplification of cardiomyocytes., (© 2022 The Authors. Journal of Cellular Physiology published by Wiley Periodicals LLC.)
- Published
- 2022
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33. CXCL10 is a novel anti-angiogenic factor downstream of p53 in cardiomyocytes.
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Wahyuni T, Tanaka S, Igarashi R, Miyake Y, Yamamoto A, Mori S, Kametani Y, Tomimatsu M, Suzuki S, Yokota K, Okada Y, Maeda M, Obana M, and Fujio Y
- Subjects
- Animals, Cell Hypoxia, Doxorubicin pharmacology, Endothelial Cells, Neovascularization, Pathologic metabolism, Rats, Chemokine CXCL10 genetics, Chemokine CXCL10 metabolism, Myocytes, Cardiac metabolism, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 metabolism
- Abstract
Tumor suppressor protein p53 plays crucial roles in the onset of heart failure. p53 activation results in cardiac dysfunction, at least partially by suppressing angiogenesis. Though p53 has been reported to reduce VEGF production by inhibiting hypoxia-inducible factor, the anti-angiogenic property of p53 remains to be fully elucidated in cardiomyocytes. To explore the molecular signals downstream of p53 that regulate vascular function, especially under normoxic conditions, DNA microarray was performed using p53-overexpressing rat neonatal cardiomyocytes. Among genes induced by more than 2-fold, we focused on CXCL10, an anti-angiogenic chemokine. Real-time PCR revealed that p53 upregulated the CXCL10 expression as well as p21, a well-known downstream target of p53. Since p53 is known to be activated by doxorubicin (Doxo), we examined the effects of Doxo on the expression of CXCL10 and found that Doxo enhanced the CXCL10 expression, accompanied by p53 induction. Importantly, Doxo-induced CXCL10 was abrogated by siRNA knockdown of p53, indicating that p53 activation is necessary for Doxo-induced CXCL10. Next, we examined the effect of hypoxic condition on p53-mediated induction of CXCL10. Interestingly, CXCL10 was induced by hypoxia and its induction was potentiated by the overexpression of p53. Finally, the conditioned media from cultured cardiomyocytes expressing p53 decreased the tube formation of endothelial cells compared with control, analyzed by angiogenesis assay. However, the inhibition of CXCR3, the receptor of CXCL10, restored the tube formation. These data indicate that CXCL10 is a novel anti-angiogenic factor downstream of p53 in cardiomyocytes and could contribute to the suppression of vascular function by p53., (© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)
- Published
- 2022
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34. The antiplatelet effect of mirtazapine is mediated by co-blocking 5-HT 2A and α 2 -adrenergic receptors on platelets: An in vitro human plasma-based study.
- Author
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Kawano Y, Obana M, Nagata M, Mano Y, Katsuyama M, Yamamoto Y, Maeda-Minami A, Negishi K, Takagi M, Shimada S, and Aoyama T
- Subjects
- Humans, Male, Animals, Adult, Adenosine Diphosphate pharmacology, Mice, Epinephrine pharmacology, Serotonin metabolism, Female, Adrenergic alpha-2 Receptor Antagonists pharmacology, Platelet Aggregation drug effects, Blood Platelets drug effects, Blood Platelets metabolism, Receptors, Adrenergic, alpha-2 metabolism, Receptor, Serotonin, 5-HT2A metabolism, Mirtazapine pharmacology, Platelet Aggregation Inhibitors pharmacology, Serotonin 5-HT2 Receptor Antagonists pharmacology
- Abstract
Mirtazapine (MTZ) is a noradrenergic and specific serotonergic antidepressant that has been associated with an increased risk of bleeding. However, there is insufficient evidence confirming this association. We hypothesised that 5-HT
2A and α2 receptor-mediated inhibitory effects of MTZ on platelets suppress platelet aggregation and increase the risk of bleeding. In this study, we examined the antiplatelet effect of MTZ on human platelets to test our hypothesis. Blood samples for platelet aggregation tests were obtained from 14 healthy volunteers. The antiplatelet effect of MTZ was evaluated using light transmission aggregometry. MTZ significantly suppressed platelet aggregation mediated both by the synergistic interaction of serotonin (5-HT) and adrenaline and the synergistic interaction of ADP and 5-HT or adrenaline. In conclusion, MTZ exerts its antiplatelet effects by co-blocking the 5-HT2A and α2 -adrenergic receptors on platelets and also suppresses platelet aggregation induced by ADP and 5-HT or adrenaline. Therefore, when MTZ is used, especially for patients with a high risk of bleeding, the significance of its use must be considered carefully. In addition, the platelet aggregation pattern by adrenaline + 5-HT, ADP + adrenaline, and ADP + 5-HT was similar between humans and mice; however, this study did not directly compare the effects of MTZ on human and murine platelets. Therefore, under the conditions for inducing platelet aggregation using adrenaline + 5-HT, ADP + adrenaline, and ADP + 5-HT, mouse platelets can be used in the evaluation of the efficacy of antiplatelet drugs in humans., (Copyright © 2021 Elsevier B.V. All rights reserved.)- Published
- 2022
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35. A Case of Iliopsoas Hematoma Caused by Prophylactic Anticoagulation against COVID-19.
- Author
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Masaki S, Takahashi T, Sahara T, Endo R, and Obana M
- Abstract
Background: COVID-19 is associated with an increased risk of venous thromboembolism (VTE), and prophylactic anticoagulation is recommended for the prevention of VTE in COVID-19 patients. We encountered a patient with COVID-19 who developed iliopsoas hematoma (IPH) that was likely caused by prophylactic anticoagulation against VTE; we report the case here because IPH is an important risk in rehabilitation treatment., Case: The patient was a 73-year-old man with severe COVID-19 who received anticoagulation therapy from the time of admission (day 0). On day 22, decreased hemoglobin levels, muscle weakness in the left lower extremity, and pain on passive movement of the left hip joint were noted. On day 29, computed tomography (CT) was performed and revealed a mass lesion suspicious of a hematoma in the left iliopsoas muscle. On day 36, magnetic resonance imaging (MRI) was carried out to re-evaluate the mass lesion and revealed a multicystic lesion that could also have been an abscess. CT-guided puncture drainage was performed, but no pus-like material was collected; this finding led to a diagnosis of IPH. Subsequent exercise loads were gradually increased while the status of the hematoma was assessed., Discussion: The prevalence of IPH in COVID-19 patients has been reported to be 7.6 cases per 1000 admissions, and the use of anticoagulation is likely to increase the risk of IPH. Because rehabilitative interventions can lead to the discovery or aggravation of IPH, the possibility of IPH should be kept in mind when providing rehabilitation treatment for COVID-19 patients., Competing Interests: CONFLICTS OF INTEREST: The authors declare that there are no conflict of interests., (2022 The Japanese Association of Rehabilitation Medicine.)
- Published
- 2022
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36. Identification of biomarkers of chronic kidney disease among kidney-derived proteins.
- Author
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Higashisaka K, Takeya S, Kamada H, Obana M, Maeda M, Kabayama M, Yamamoto K, Ishida N, Isaka R, Tsujino H, Nagano K, Tomiyama N, Rakugi H, Fujio Y, Kamide K, and Tsutsumi Y
- Abstract
Background: Chronic kidney disease (CKD) has few objective symptoms, and it is difficult to make an early diagnosis by using existing methods. Therefore, new biomarkers enabling diagnosis of renal dysfunction at an early stage need to be developed. Here, we searched for new biomarkers of CKD by focusing on kidney-derived proteins that could sensitively reflect that organ's disease state., Methods: To identify candidate marker proteins, we performed a proteomics analysis on renal influx and efflux blood collected from the same individual., Results: Proteomics analysis revealed 662 proteins in influx blood and 809 in efflux. From these identified proteins, we selected complement C1q as a candidate; the plasma C1q level was significantly elevated in the renal efflux of donors. Moreover, the plasma concentration of C1q in a mouse model of diabetic nephropathy was significantly increased, in association with increases in blood glucose concentration and urinary protein content. Importantly, we demonstrated that the tendency of C1q to increase in the plasma of CKD patients was correlated with a decrease in their estimated glomerular filtration rate., Conclusion: Overall, our results indicate that our approach of focusing on kidney-derived proteins is useful for identifying new CKD biomarkers and that C1q has potential as a biomarker of renal function., (© 2022. The Author(s).)
- Published
- 2022
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37. Effects of 1-year treatment with canagliflozin on body composition and total body water in patients with type 2 diabetes.
- Author
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Matsuba I, Takihata M, Takai M, Maeda H, Kubota A, Iemitsu K, Umezawa S, Obana M, Kaneshiro M, Kawata T, Takuma T, Takeda H, Machimura H, Mokubo A, Motomiya T, Asakura T, Kikuchi T, Matsuzawa Y, Ito S, Miyakawa M, Terauchi Y, and Kanamori A
- Subjects
- Body Composition, Body Water, Canagliflozin therapeutic use, Humans, Hypoglycemic Agents therapeutic use, Diabetes Mellitus, Type 2 drug therapy, Sodium-Glucose Transporter 2 Inhibitors therapeutic use
- Abstract
Aim: To characterize the long-term changes in body composition associated with sodium-glucose cotransporter-2 (SGLT2) inhibitors., Materials and Methods: In this multicentre, single-arm, open-label study, 107 patients with type 2 diabetes were treated with canagliflozin 100 mg, as add-on therapy, for 12 months. Body composition was measured with a body composition analyser (T-SCAN PLUS) using the impedance method to prospectively analyse changes in body components, including percentage of body fat, body fat mass, total body water, muscle mass and mineral mass. Estimated plasma volume (PV) was calculated using the Kaplan formula., Results: Body weight showed a significant decrease from 1 month to 12 months of treatment with canagliflozin, with a higher rate of decrease in body fat in body composition. A significant decrease in mineral mass was also observed, but its rate was low. Following treatment with canagliflozin, changes in total body water did not affect intracellular water, and a significant decrease in extracellular water, including plasma components, was observed early and was sustained up to 12 months. Protein mass, a component of muscle mass, was not affected, with only a slight decrease in water volume observed., Conclusions: Canagliflozin decreased extracellular fluid and PV in addition to decreasing fat in the body via calorie loss resulting from urinary glucose excretion. This study suggested that SGLT2 inhibitors might reduce body weight by regulating fat mass or water distribution in the body and might have cardiac and renal protective effects by resetting the homeostasis of fluid balance., (© 2021 John Wiley & Sons Ltd.)
- Published
- 2021
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38. PKNOX2 regulates myofibroblast functions and tubular cell survival during kidney fibrosis.
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Miyake Y, Obana M, Nakae T, Yamamoto A, Tanaka S, Maeda M, Okada Y, and Fujio Y
- Subjects
- Animals, Cell Survival, Cells, Cultured, Fibrosis pathology, Homeodomain Proteins genetics, Kidney Tubules pathology, Male, Mice, Mice, Inbred C57BL, Myofibroblasts pathology, Transcription Factors genetics, Ureteral Obstruction pathology, Fibrosis metabolism, Homeodomain Proteins metabolism, Kidney Tubules metabolism, Myofibroblasts metabolism, Transcription Factors metabolism, Ureteral Obstruction metabolism
- Abstract
The number of patients with chronic kidney disease (CKD) is increasing worldwide. When kidneys are exposed to severe injury, tubular cell death occurs and kidney fibrosis progresses by activating fibroblasts and myofibroblasts (referred to as (myo)fibroblasts), leading to CKD; however, the pathological and molecular mechanisms underlying CKD, including kidney fibrosis, remain obscure. In the present study, we focused on a transcription factor PBX/Knotted Homeobox 2 (PKNOX2) in kidney fibrosis. The transcript and protein expression of PKNOX2 was upregulated in fibrotic kidneys after unilateral ureteral obstruction (UUO). Importantly, immunofluorescence microscopic analysis revealed that the number of PKNOX2-expressing myofibroblasts was increased, whereas the expression of PKNOX2 was decreased in proximal tubular epithelial cells after UUO. In (myo)fibroblasts, PKNOX2 was induced by TGF-β1. Knockdown of PKNOX2 using shRNA lentiviral system reduced the viability of (myo)fibroblasts either in the presence or absence of TGF-β1, accompanied by increased apoptosis. Moreover, PKNOX2 knockdown decreased TGF-β1-induced migration of myofibroblasts and differentiation of fibroblasts into myofibroblasts. Significantly, knockdown of PKNOX2 also decreased the viability and increased apoptosis of tubular epithelial cells. Collectively, PKNOX2 regulates the function of (myo)fibroblasts and the viability of proximal tubular epithelial cells in progression of kidney fibrosis., Competing Interests: Declaration of competing interest The authors have declared that no conflict of interest exists., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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39. Title: Gene transfer by pyro-drive jet injector is a novel therapeutic approach for muscle diseases.
- Author
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Nakae T, Obana M, Maeda T, Ikeda A, Miyazaki H, Tanaka S, Maeda M, Yamashita K, Terai K, Obika S, and Fujio Y
- Subjects
- Animals, Cell Line, Fibroblast Growth Factor 2 genetics, Fibroblast Growth Factor 2 metabolism, Genetic Therapy instrumentation, Genetic Vectors administration & dosage, Genetic Vectors pharmacology, Hindlimb, Humans, Male, Mice, Mice, Inbred C57BL, Muscular Diseases genetics, Muscular Diseases metabolism, Muscular Diseases therapy, Plasmids genetics, Fibroblast Growth Factor 2 administration & dosage, Gene Transfer Techniques instrumentation, Muscle, Skeletal metabolism, Myocardium metabolism
- Abstract
The angiogenic gene therapy is an attractive approach for the treatment of ischemic muscle diseases, including peripheral arterial disease and ischemic heart diseases. Although a variety of gene transfer methods have been developed, the efficiency of gene transfer is still limited. We have been developing the needleless high-energy bioinjector device, Pyro-drive Jet Injector (PJI), based on pyrotechnics using a combination of ignition powder and gunpowder, however, the utility of PJI in gene transfer into muscle tissues remains unclear. pcDNA3.1 plasmid containing Flag was injected to the thigh muscles of C57BL/6J mice using PJI or needle, as a control. Histological analysis demonstrated that the protein expression of Flag was observed in a wider range in PJI group than in needle group. To assess the validity of PJI for gene therapy, pcDNA3.1-human fibroblast growth factor 2 (FGF2), which has angiogenic activity and tissue protective properties, was injected into the ischemic thigh muscles with PJI or needle. ELISA assay revealed that the protein expression of FGF2 was increased in the thigh muscle tissues by PJI-mediated gene delivery. Significantly, histological analyses revealed that muscle fiber cross-sectional area and the number of endothelial marker CD31 (+) cells was increased in ischemic hind-limb tissues of the PJI-FGF2 group but not in those of needle-FGF2 group. To expand the applicability of the PJI-mediated gene transfer, pcDNA3.1-venus plasmid was injected into murine hearts with PJI or needle. PJI method was successful in gene transfer into murine hearts, especially into cardiomyocytes, with high efficiency when compared to needle method. Collectively, the non-needle, non-liposomal and non-viral gene transfer by PJI could be a novel therapeutic approach for muscle diseases., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Published
- 2021
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40. Maresin-1 induces cardiomyocyte hypertrophy through IGF-1 paracrine pathway.
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Wahyuni T, Kobayashi A, Tanaka S, Miyake Y, Yamamoto A, Bahtiar A, Mori S, Kametani Y, Tomimatsu M, Matsumoto K, Maeda M, Obana M, and Fujio Y
- Subjects
- Animals, Cardiomegaly chemically induced, Cardiomegaly pathology, Cardiomegaly prevention & control, Disease Models, Animal, Docosahexaenoic Acids antagonists & inhibitors, Gene Expression Regulation, Insulin-Like Growth Factor I antagonists & inhibitors, Insulin-Like Growth Factor I metabolism, Male, Mice, Mice, Inbred C57BL, Myocardial Infarction chemically induced, Myocardial Infarction pathology, Myocardial Infarction prevention & control, Myocytes, Cardiac metabolism, Myocytes, Cardiac pathology, Nuclear Receptor Subfamily 1, Group F, Member 1 antagonists & inhibitors, Nuclear Receptor Subfamily 1, Group F, Member 1 genetics, Nuclear Receptor Subfamily 1, Group F, Member 1 metabolism, Paracrine Communication drug effects, Phosphatidylinositol 3-Kinases genetics, Phosphatidylinositol 3-Kinases metabolism, Primary Cell Culture, Proto-Oncogene Proteins c-akt antagonists & inhibitors, Proto-Oncogene Proteins c-akt genetics, Proto-Oncogene Proteins c-akt metabolism, Pyrimidines pharmacology, Pyrroles pharmacology, Rats, Ribonucleosides pharmacology, Signal Transduction, Sulfonamides pharmacology, Thiophenes pharmacology, Wortmannin pharmacology, Cardiomegaly genetics, Cardiotonic Agents pharmacology, Docosahexaenoic Acids adverse effects, Insulin-Like Growth Factor I genetics, Myocardial Infarction genetics, Myocytes, Cardiac drug effects, Paracrine Communication genetics
- Abstract
The resolution of inflammation is closely linked with tissue repair. Recent studies have revealed that macrophages suppress inflammatory reactions by producing lipid mediators, called specialized proresolving mediators (SPMs); however, the biological significance of SPMs in tissue repair remains to be fully elucidated in the heart. In this study, we focused on maresin-1 (MaR1) and examined the reparative effects of MaR1 in cardiomyocytes. The treatment with MaR1 increased cell size in cultured neonatal rat cardiomyocytes. Since the expression of fetal cardiac genes was unchanged by MaR1, physiological hypertrophy was induced by MaR1. SR3335, an inhibitor of retinoic acid-related orphan receptor α (RORα), mitigated MaR1-induced cardiomyocyte hypertrophy, consistent with the recent report that RORα is one of MaR1 receptors. Importantly, in response to MaR1, cardiomyocytes produced IGF-1 via RORα. Moreover, MaR1 activated phosphoinositide 3-kinase (PI3K)/Akt signaling pathway and wortmannin, a PI3K inhibitor, or triciribine, an Akt inhibitor, abrogated MaR1-induced cardiomyocyte hypertrophy. Finally, the blockade of IGF-1 receptor by NVP-AEW541 inhibited MaR-1-induced cardiomyocyte hypertrophy as well as the activation of PI3K/Akt pathway. These data indicate that MaR1 induces cardiomyocyte hypertrophy through RORα/IGF-1/PI3K/Akt pathway. Considering that MaR1 is a potent resolving factor, MaR1 could be a key mediator that orchestrates the resolution of inflammation with myocardial repair.
- Published
- 2021
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41. [Mitral Valve Repair via Right Thoracotomy Thirty-seven Years after Right Pneumonectomy:Report of a Case].
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Shimada N, Arimoto M, Ohba M, Obana M, Yamamoto T, and Tanaka M
- Subjects
- Humans, Male, Middle Aged, Mitral Valve diagnostic imaging, Mitral Valve surgery, Pneumonectomy, Thoracotomy, Cardiac Surgical Procedures, Mitral Valve Insufficiency diagnostic imaging, Mitral Valve Insufficiency surgery
- Abstract
A 57-year-old man was referred to our hospital due to dyspnea on exertion with severe mitral regurgitation. Because he had underdone right pneumonectomy 37 years earlier due to congenital defect of the right pulmonary artery, his mediastinum was severely shifted to the right, and his pulmonary function was poor. Mitral valve repair was successfully performed with right thoracotomy approach, which made excellent exposure of the mitral valve. The patient was extubated three hours after the surgery. He was discharged on the 30th postoperative day without postoperative respiratory complications. With an appropriate plan of the surgery and postoperative optimal management, cardiac surgery can be performed on patients with a single lung.
- Published
- 2021
42. Clinical Features of Venous Thromboembolism in Patients With Coronavirus Disease 2019 (COVID-19) in Japan - A Case Series Study.
- Author
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Yamashita Y, Hara N, Obana M, Ikeda S, Furuichi M, Ishiguro S, Iwai T, Kobayashi T, Mo M, and Yamada N
- Subjects
- Adult, Aged, COVID-19 blood, Fibrin Fibrinogen Degradation Products analysis, Humans, Intensive Care Units, Japan epidemiology, Male, Middle Aged, Obesity complications, Oxygen blood, Patients' Rooms, Pulmonary Embolism epidemiology, Pulmonary Embolism etiology, Respiration, Artificial, Respiratory Distress Syndrome diagnostic imaging, Respiratory Distress Syndrome etiology, Respiratory Distress Syndrome therapy, Thrombophilia blood, Thrombophilia etiology, Tomography, X-Ray Computed, Venous Thromboembolism epidemiology, Venous Thrombosis epidemiology, Venous Thrombosis etiology, COVID-19 complications, SARS-CoV-2, Venous Thromboembolism etiology
- Abstract
Background: Suspicion that the coronavirus disease 2019 (COVID-19) caused venous thromboembolism (VTE)., Methods and results: We conducted a case series study of 5 VTE patients with COVID-19 in Japan. The median body mass index was 27.7 kg/m
2 , and all patients required mechanical ventilation during hospitalization. Patients were diagnosed as VTE in the intensive care unit (ICU), general ward, and outpatient ward., Conclusions: The current case series study revealed some clinical features of VTE patients with COVID-19 in Japan, including obese patients and those requiring mechanical ventilation during hospitalization, who should be followed closely for VTE, even after leaving the ICU.- Published
- 2021
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43. Transcription factor old astrocyte specifically induced substance is a novel regulator of kidney fibrosis.
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Yamamoto A, Morioki H, Nakae T, Miyake Y, Harada T, Noda S, Mitsuoka S, Matsumoto K, Tomimatsu M, Kanemoto S, Tanaka S, Maeda M, Conway SJ, Imaizumi K, Fujio Y, and Obana M
- Subjects
- Animals, Antigens, CD metabolism, Cyclic AMP Response Element-Binding Protein genetics, Disease Models, Animal, Fibrosis, GPI-Linked Proteins metabolism, HEK293 Cells, Humans, Male, Membrane Glycoproteins metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Myofibroblasts metabolism, Nerve Tissue Proteins genetics, Signal Transduction genetics, Transfection, Up-Regulation genetics, Cyclic AMP Response Element-Binding Protein metabolism, Kidney metabolism, Kidney pathology, Nerve Tissue Proteins metabolism, Renal Insufficiency, Chronic metabolism
- Abstract
Prevention of kidney fibrosis is an essential requisite for effective therapy in preventing chronic kidney disease (CKD). Here, we identify Old astrocyte specifically induced substance (OASIS)/cAMP responsive element-binding protein 3-like 1 (CREB3l1), a CREB/ATF family transcription factor, as a candidate profibrotic gene that drives the final common pathological step along the fibrotic pathway in CKD. Although microarray data from diseased patient kidneys and fibrotic mouse model kidneys both exhibit OASIS/Creb3l1 upregulation, the pathophysiological roles of OASIS in CKD remains unknown. Immunohistochemistry revealed that OASIS protein was overexpressed in human fibrotic kidney compared with normal kidney. Moreover, OASIS was upregulated in murine fibrotic kidneys, following unilateral ureteral obstruction (UUO), resulting in an increase in the number of OASIS-expressing pathological myofibroblasts. In vitro assays revealed exogenous TGF-β1 increased OASIS expression coincident with fibroblast-to-myofibroblast transition and OASIS contributed to TGF-β1-mediated myofibroblast migration and increased proliferation. Significantly, in vivo kidney fibrosis induced via UUO or ischemia/reperfusion injury was ameliorated by systemic genetic knockout of OASIS, accompanied by reduced myofibroblast proliferation. Microarrays revealed that the transmembrane glycoprotein Bone marrow stromal antigen 2 (Bst2) expression was reduced in OASIS knockout myofibroblasts. Interestingly, a systemic anti-Bst2 blocking antibody approach attenuated kidney fibrosis in normal mice but not in OASIS knockout mice after UUO, signifying Bst2 functions downstream of OASIS. Finally, myofibroblast-restricted OASIS conditional knockouts resulted in resistance to kidney fibrosis. Taken together, OASIS in myofibroblasts promotes kidney fibrosis, at least in part, via increased Bst2 expression. Thus, we have identified and demonstrated that OASIS signaling is a novel regulator of kidney fibrosis., (© 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)
- Published
- 2021
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44. Antiplatelet Effect of Mirtazapine via Co-blocking of the 5-HT 2A and α 2 -Adrenergic Receptors on Platelets.
- Author
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Kawano Y, Katsuyama M, Nagata M, Obana M, Nakamatsu S, Mori A, Sakamoto N, Mano Y, Negishi K, Shimada S, and Aoyama T
- Subjects
- Administration, Oral, Adrenergic alpha-2 Receptor Antagonists administration & dosage, Animals, Blood Platelets drug effects, Blood Platelets metabolism, Epinephrine metabolism, Male, Mice, Mirtazapine administration & dosage, Models, Animal, Receptor, Serotonin, 5-HT2A metabolism, Serotonin metabolism, Serotonin 5-HT2 Receptor Antagonists administration & dosage, Succinates administration & dosage, Yohimbine administration & dosage, Adrenergic alpha-2 Receptor Antagonists adverse effects, Mirtazapine adverse effects, Platelet Aggregation drug effects, Serotonin 5-HT2 Receptor Antagonists adverse effects
- Abstract
Mirtazapine (MTZ) is a noradrenergic and specific serotonergic antidepressant. MTZ is reportedly associated with an increased risk of bleeding. However, the underlying mechanism remains unclear. In this study, we investigated the antiplatelet effect of MTZ in mice via light transmission aggregometry to elucidate the mechanism of MTZ-induced bleeding. The results of the ex vivo study showed that the oral administration of MTZ (20 or 100 mg/kg) significantly suppressed platelet aggregation mediated by the synergic interaction of 5-hydroxytryptamine (5-HT) and adrenaline. Additionally, MTZ significantly suppressed platelet aggregation, mediated by the synergic interaction of ADP and 5-HT or adrenaline. Similar results were obtained in vitro, under the condition of 5-HT- and adrenaline-induced platelet aggregation. Overall, the results suggest that MTZ exerts antiplatelet effect by co-blocking 5-HT
2A and α2 -adrenergic receptors on platelets and suppresses platelet aggregation mediated by ADP, increased by either 5-HT or adrenaline. Thus, a detailed monitoring of bleeding is recommended for patients taking MTZ.- Published
- 2021
- Full Text
- View/download PDF
45. Factors associated with the number of microorganisms on the tongue surface in patients following acute stroke.
- Author
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Furuya J, Beniya A, Suzuki H, Hidaka R, Matsubara C, Obana M, Yoshimi K, Yamaguchi K, Hara K, Nakagawa K, Nakane A, Tohara H, and Minakuchi S
- Subjects
- Aged, Cross-Sectional Studies, Humans, Oral Hygiene, Saliva, Stroke, Tongue
- Abstract
Background: Oral hygiene management of patients with acute stroke is important for preventing aspiration pneumonia and ensuring oral intake. The tongue coating score can be useful for evaluating the oral hygiene level since it reflects the microorganism number on the tongue surface in elderly patients. However, the relationship between the number of oral microorganisms and the tongue coating score in patients with acute stroke remains unclear., Objectives: We aimed to investigate the relationships between the microorganism number on the tongue surface and oral factors, including tongue coating score, tongue surface moisture level and tongue function., Methods: This cross-sectional study enrolled 73 patients with acute stroke who were hospitalised at an acute care hospital and underwent dental intervention. Potential explanatory factors, including sex, age, Glasgow Coma Scale score, tongue coating score, tongue surface moisture level, nutrition intake method, number of functional teeth and tongue function, were evaluated. Logistic regression analysis determined their association with the microorganism number on the tongue surface., Results: The tongue coating score (odds ratio: 1.31) and tongue surface moisture level (odds ratio: 1.10) were significantly associated with increased microorganism numbers on the tongue surface., Conclusion: The tongue coating score, which reflects the actual number of microorganisms on the tongue surface, could be an effective tool for evaluating oral hygiene level in patients with stroke. Moreover, reducing oral microorganisms in saliva through oral hygiene management, including removing the tongue coating, could contribute towards the prevention of aspiration pneumonia., (© 2020 John Wiley & Sons Ltd.)
- Published
- 2020
- Full Text
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46. Cross-sectional study of age-specific differences in salivary occult blood test results in older adults.
- Author
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Matsubara C, Furuya J, Watanabe Y, Obana M, Shirobe M, Ohara Y, Edahiro A, Nakajima J, Motokawa K, Inagaki H, Hirano H, Minakuchi S, Shinkai S, and Awata S
- Subjects
- Cross-Sectional Studies, Smoking, Surveys and Questionnaires, Occult Blood, Oral Health
- Abstract
This study aimed to identify factors associated with poor oral health status, as indicated by salivary occult blood (SOB) level, in community-dwelling older adults. A total of 592 community-dwelling participants aged 70 to 84 years with 20 to 28 teeth participated in the survey and SOB evaluation. Survey items included behaviors during dental visits, systemic diseases, smoking habit, cognitive function, and findings of intraoral examination. To identify factors associated with high SOB levels, binomial logistic regression analysis was performed after classifying participants as having high and low SOB on the basis of 75th-percentile SOB measurements. Presence of dental plaque (odds ratio [OR]: 2.26), poor subjective oral health (OR: 2.99) (for the age group 70 to 74 years), fewer remaining teeth (OR: 0.80), no dental visits during the previous year (OR: 2.80) (for the age group 75 to 79 years), and no dental visits during the previous year (OR: 3.93) (for the age group 80 to 84 years) were significantly associated with high SOB levels. The factors associated with high SOB, which indicates poor oral health status, differed by age group in community-dwelling older adults. Therefore, oral health management may improve oral health by providing different age groups with care that accounts for their physical and social functional abilities.
- Published
- 2020
- Full Text
- View/download PDF
47. The current status of bereavement follow-up in Japanese emergency departments: A cross-sectional nationwide survey.
- Author
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Ito Y, Obana M, Kawakami D, Murakami N, and Sakaguchi Y
- Subjects
- Adult, Cross-Sectional Studies, Female, Humans, Japan, Male, Surveys and Questionnaires, Bereavement, Emergency Service, Hospital, Nurse's Role, Professional-Family Relations
- Abstract
Introduction: The aim of this study was to investigate the current status of bereavement follow-up in Japanese emergency departments., Methods: This study employed a cross-sectional design and conducted a nationwide survey of all emergency departments in Japan. Self-reported questionnaires were sent to the nurse leaders of each emergency department., Results: Of 289 nurse leaders approached, 145 (50.2%) responded. Only 17.9% emergency departments provided bereavement follow-up strategies, and the most frequent strategy was referral to a specialist for psychological treatment. Most nurse leaders perceived that bereavement follow-up is necessary, and the greatest need of the bereaved as perceived by the nurse leaders was explanation of the patient's death. However, 60% of the nurse leaders perceived bereavement follow-up to be necessary but difficult, and the major challenges in bereavement follow-up were lack of time, knowledge, and skill., Conclusion: In contemporary Japan, the prevalence of bereavement follow-up strategies offered by emergency departments was low, and although most nurse leaders perceived follow-up as necessary, it could not be provided because of limitations in human resources and staff training., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2020
- Full Text
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48. β2-adrenergic stimulation induces interleukin-6 by increasing Arid5a, a stabilizer of mRNA, through cAMP/PKA/CREB pathway in cardiac fibroblasts.
- Author
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Tanaka S, Imaeda A, Matsumoto K, Maeda M, Obana M, and Fujio Y
- Subjects
- Adrenergic beta-Agonists pharmacology, Animals, Female, Isoproterenol pharmacology, Male, Mice, Inbred C57BL, Mice, Knockout, Myocardium cytology, RNA, Messenger metabolism, Signal Transduction, Transcription Factor RelA metabolism, Cyclic AMP metabolism, Cyclic AMP Response Element-Binding Protein metabolism, Cyclic AMP-Dependent Protein Kinases metabolism, DNA-Binding Proteins genetics, Fibroblasts metabolism, Interleukin-6 genetics, Receptors, Adrenergic, beta-2 metabolism, Transcription Factors genetics
- Abstract
Background and Purpose: In cardiovascular diseases, cardiac fibroblasts (CFs) participate in the myocardial inflammation by producing pro-inflammatory cytokines, worsening the prognosis. β2-adrenergic receptor (AR) and β3AR are expressed in CFs, and β-adrenergic stimulation promotes CFs to produce pro-inflammatory cytokines. However, the mechanism of the expression of pro-inflammatory cytokines in response to β-adrenergic stimulation remains to be fully elucidated., Experimental Approach: CFs were isolated from adult wild-type or AT-rich interactive domain-containing protein 5A (Arid5a) knockout mice. The expression of mRNA was measured by real-time RT-PCR. Interleukin (IL)-6 protein was measured by ELISA. The activity of nuclear factor-κB (NF-κB) and cyclic AMP (cAMP) response element binding protein (CREB) was assessed by ELISA-like assay or Western blotting., Key Results: The β-adrenergic stimulation remarkably induced IL-6 mRNA and protein through β2AR in CFs. The activation of adenylate cyclase and the enhancement of intracellular cAMP resulted in the upregulation of IL-6 mRNA expression. The induction of IL-6 transcript by β2AR signaling was independent of NF-κB. Concomitant with IL-6, the expression of Arid5a, an IL-6 mRNA stabilizing factor, was enhanced by β2-adrenergic stimulation and by cAMP increase. Importantly, β2AR signaling-mediated IL-6 induction was suppressed in Arid5a knockout CFs. Finally, β2AR stimulation phosphorylated CREB via PKA pathway, and the activation of CREB was essential for the induction of Arid5a and IL-6 mRNA., Conclusion and Implications: β2-adrenergic stimulation post-transcriptionally upregulates the expression of IL-6 by the induction of Arid5a through cAMP/PKA/CREB pathway in adult CFs. β2AR/Arid5a/IL-6 axis could be a therapeutic target against cardiac inflammation., (© 2020 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.)
- Published
- 2020
- Full Text
- View/download PDF
49. Survey on the oral health status of community-dwelling older people with visual impairment.
- Author
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Hidaka R, Furuya J, Suzuki H, Matsubara C, Obana M, Tokunaga J, and Endo K
- Subjects
- Aged, Aged, 80 and over, Health Status, Humans, Japan, Oral Health, Surveys and Questionnaires, Independent Living, Vision, Low
- Abstract
Aims: Little is known about the impact of low vision (LV) on dental care in the elderly population. The present study aimed to clarify the oral health status and oral health behavior of older people with LV., Methods and Results: We surveyed community-dwelling older people (age ≥ 65 years, non-LV = 35, LV = 23); and collected data on sex, age, systemic diseases, oral health status, and oral health behavior. Although there was no difference in dental clinic visits within one year, the LV group received significantly lesser oral health instructions by dental hygienists and dentists than the non-LV (60.9% vs 85.7%, P < 0.05) group. Additionally, the LV group was more than twice as aware of the "8020 Campaign," written by the Ministry of Health, Labor and Welfare in Japan than the non-LV group. The non-LV group had higher awareness of thickening agents and denture cleaners, both of which may require visual input. Although we had assumed that LV would lead to poor results for the oral health status, there were no demonstrable differences between both groups., Conclusion: Older individuals with LV require suitable forms of nonvisual communication to receive oral health instruction and literacy., (© 2019 Special Care Dentistry Association and Wiley Periodicals, Inc.)
- Published
- 2020
- Full Text
- View/download PDF
50. Canagliflozin Increases Calorie Intake in Type 2 Diabetes Without Changing the Energy Ratio of the Three Macronutrients: CANA-K Study.
- Author
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Matsuba I, Kanamori A, Takihata M, Takai M, Maeda H, Kubota A, Iemitsu K, Umezawa S, Obana M, Kaneshiro M, Kawata T, Takuma T, Takeda H, Machimura H, Mokubo A, Motomiya T, Asakura T, Kikuchi T, Matsuzawa Y, Ito S, Miyakawa M, Terauchi Y, and Tanaka Y
- Subjects
- Aged, Diabetes Mellitus, Type 2 blood, Diet Surveys, Dietary Carbohydrates blood, Dietary Fats blood, Dietary Proteins blood, Female, Glycated Hemoglobin analysis, Humans, Hypoglycemic Agents therapeutic use, Insulin therapeutic use, Male, Middle Aged, Prospective Studies, Weight Loss drug effects, Canagliflozin pharmacology, Diabetes Mellitus, Type 2 drug therapy, Energy Intake drug effects, Energy Metabolism drug effects, Nutrients blood, Sodium-Glucose Transporter 2 Inhibitors pharmacology
- Abstract
Background: Sodium/glucose cotransporter-2 (SGLT2) inhibitors improve glycemic control and reduce body weight by increasing glycosuria. Although a compensatory increase of food intake has been reported, the long-term effect of SGLT2 inhibitors on food intake remains unclear. This study investigated the influence of canagliflozin on calorie and nutrient intake over 1 year. Materials and Methods: Patients with type 2 diabetes ( n = 107) were enrolled and followed prospectively while receiving canagliflozin at 100 mg/day for 12 months. Intake of nutrients was investigated by using the food frequency questionnaire. Hemoglobin A1c, body weight, and satisfaction with diabetes treatment (assessed by the Diabetes Treatment Satisfaction Questionnaire: DTSQ) were also investigated. Results: The baseline total energy intake was 1723 ± 525 kcal/day and it showed a persistent increase during treatment with canagliflozin, being 132 kcal higher at 6 months ( P = 0.0058) and 113 kcal higher at 12 months ( P = 0.0516). Intake of all three macronutrients (carbohydrate, protein, and fat) was significantly increased after 6 months of canagliflozin treatment ( P = 0.0129, P = 0.0160, and P = 0.0314, respectively), but their ratio was unchanged. The DTSQ score improved significantly and both hemoglobin A1c and body weight showed a significant decrease throughout treatment (all P < 0.0001). Conclusions: After patients with type 2 diabetes commenced canagliflozin, their calorie intake increased without changing the ratio of the three macronutrients. Despite elevation of the calorie intake, glycemic control improved and weight loss was achieved. Satisfaction with treatment of diabetes also increased.
- Published
- 2020
- Full Text
- View/download PDF
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