Search

Your search keyword '"Makinen K"' showing total 102 results
Start Over Author "Makinen K"
102 results on '"Makinen K"'

1. Insufficient arterial driving pressure turns hypoxic microvascular remodeling into a catastrophe

Author

Korpisalo, P, primary, Tarvainen, S, additional, Wirth, G, additional, Juusola, G, additional, Happonen, K, additional, Frimodig, C, additional, Hytonen, J, additional, Taavitsainen, J, additional, Greco, D, additional, Knuuti, J, additional, Hartikainen, J, additional, Laitinen, T, additional, Yla-Herttuala, S, additional, Hakovirta, H, additional, and Makinen, K, additional

Published
2023
Full Text
View/download PDF

6. Abstracts of presentations on plant protection issues at the xth international congress of virology: August 11–16,1996 Binyanei haOoma, Jerusalem, Israel Part 2 Plenary Lectures

Author

Ramirez, E., Hernádez, A., Ham, E., Barrón, B. L., Ding, S. W., Li, W. X., Shi, B. J., Symons, R. H., Li, Q., Ryu, K. H., Palukaitis, P., Kaplan, I. B., Palukaitis, P., Kaplan, I. B., Palukaitis, P., Gal-On, A., Kunhara, J., Otsubo, T., Tomaru, K., Tsuda, S., Kinta, M., Lin, T., Johnson, J. E., Porta, C., Taylor, K. M., Spall, V. E., Lomonossoff, G. P., Spall, V. E., Porta, C., Lomonossoff, G. P., Gal-On, A., Meiri, E., Raccah, B., Gaba, V., Ikegami, M., Kawashima, H., Murayama, A., Natsuaki, T., Kageyama, Y., Sugimura, N., Thole, V., Bol, J. F., Deiman, B. A. L. M., Koenen, A. K., Pleij, C. W. A., Chaleeprom, W., Bateson, M. F., Dale, J. L., Badge, J. L., Foster, G. D., Brunt, A. A., Robinson, D., Schubert, J., Rabenstein, F., Merits, A., Yeh, Shyi-Dong, Chiang, Chu-Hui, Wang, Ching-Hsien, Chiang, Chu-Hui, Yeh, Shyi-Dong, Golshani, A., Ivanov, I. G., AbouHaidar, M. G., Rodoni, B. C., Harding, R. M., Bateson, M. F., Dale, J. L., Oertel, U., Fuchs, E., Schubert, J., Yang, S. J., Revere, F., Walter, J., Le Gall, O., Dunez, J., Candresse, T., Lot, H., Souche, S., Kasschau, Kristin D., Carrington, James C., Chiang, A. N., Turner, N. E., Hwang, D. J., Chachulska, A. M., Zagórski, W., Robaglia, C., Chrzanowska, M., Truve, E., Tamm, T., Saarma, M., Makinen, K., Wang, Aiming, Carrier, Karma, Wieczorek, Andrew, Huguenot, Claire, Sanfacon, Helene, Wurscher, M. A., Christensen, F. E., Prody, G. A., Sanchez-Navarro, J. A., Pallas, V., Carson, R., Dagless, E., Lock, S., Turner, R., Foster, G. D., Badge, J. L., Adams, M., Antoniw, J., Brunt, A. A., Phillips, S., Kashiwazaki, S., Seal, S., Karamagioli, M., Druka, Amis, Makhdoom, Rahat, Yitang, Yan, Hull, Roger, Kikkert, M., Bodegom, P., Storms, M., van Lent, J., Kormelink, R., Goldbach, R., De Haan, P., De Rover, A. R., Van Schepen, A., Gielen, J. J. L., Van Grinsven, M. Q. J. M., Livneh, O., Vardi, E., Kuznetsova, L., Aliskevicius, E., Stram, Y., Sela, I., Dinant, S., Kusiak, C., Blaise, F., Chupeau, Y., Astier, S., Albouy, J., Clifford, T. B., Taylor, S. C., Stratford, R., Foster, G. D., Xiao, X. W., Frenkel, M. J., Chu, P., Tabe, L., Shukla, D. D., Ward, C. W., Hwang, Duk-Ju, Turner, Nilgun, Taylor, S. C., Mooney, A., MacFarlane, S. A., Twell, D., Foster, G. D., Jacquet, C., Ravelonandro, M., Bachelier, J. C., Dunez, J., Almási, A., Böddi, B., Szigeti, Z., Ekes, M., Gaborianvi, R., Yankulova, Margarita, Ivanova, Lidia, Adam, G., Guelemerov, S., Nikolaeva, Velitchka, Atanassov, A., Prins, Marcel, de Haan, Peter, Goldbach, Rob, Duan, Y. P., Powell, C. A., Purcifull, D. E., Hiebert, E., Levine, B., Faktor, O., Zeituny, Silvy, Edelbaum, Orit, Sela, L., Marano, Maria-Rosa, Ratcliff, Frank, Baulcombe, David C., van Oers, Monique M., Linthorst, Huub J. M., Bol, John F., Schillberg, S., Zimmermann, S., Drossard, J., Schumann, D., Nahring, J., Fischer, R., Lapidot, Moshe, Arce-Johnson, Patricio, Rivera-Bustamante, Rafael, Beachy, Roger N., Cassidy, Brandt G., Flasinski, Stanislaw, Hajimorad, M. R., Wesley, Varsha, Angel-Diaz, J., Mayo, M. A., Hafner, G. J., May, G. D., Becker, D. K., Harding, R. M., Arntzen, C. J., Dale, J. L., Taylor, S. C., Porter, J., Foster, G. D., Palukaitis, P., Hellwald, K. H., Banerjee, N., Zaitlin, M., Gal-On, A., Wolf, D., Faure, J. E., Pilowsky, M., Cohen, S., Zelcer, A., Hardi, V., Tomassoli, L., Kaniewski, W. K., Mitsky, T., Barba, M., Hou, Y. -M., Ursin, V. M., Sanders, R., Gilbertson, R. L., Gruden, Kristina, Štrukelj, Borut, Brzin, Joze, Ravnikar, Maja, Maganja, Darja Barlič, Kregar, Igor, Maki-Valkama, T., Pehu, T., Valkonen, J., Lento, K., Pehu, E., Zaitlin, M., Kaniewski, W. K., Lawson, E. C., Feldman, J., Zalewski, J., Saarma, M., Kuittinen, T., Valkonen, J., Atiri, G. I., Romero, A., Arroyo, R., Soto, M. J., Martínez-Zapater, J. M., Ponz, F., Gilardi, P., López, L., García-Luque, I., Serra, M. T., Pang, Sheng-Zhi, Jan, Fuh-Jyh, Carney, Kim, Tricoli, David M., Quemada, Hector D., Gonsalves, Dennis, Aboul-Ata, A. E., Thouvenel, J. -C., Marshall, D., Abo-El-Saad, Sh., Satour, M., Mazithulela, G., Mehlo, L., Gahakwa, D., Leech, M., Boulton, M. I., Davies, J. W., Christou, P., Huet, H., Sivamani, E., Ong, C. A., Chen, L., de Kochko, A., Beachy, R. N., Fauquet, C. M., Sithisarn-Burns, P., Maugeri, M. M., Dale, J. L., Smith, G. R., Harding, R. M., Handley, J. A., Harding, R. M., Smith, G. R., Dale, J. L., Graichen, K., Peterka, J., Chu, Paul, Larkin, Phil, Higgins, T. J., Wylie, S., Jones, M. G. K., Somsap, V., Loo, H. P., Li, D., Mathews, A., Jones, M. G. K., Dwyer, G. I., Jones, M. G. K., McCarthy, P. L., Hansen, J., Shiel, P. J., Zemetra, R. S., Wyatt, S. D., Berger, P. H., Ford, C., Collins, N., Rathjen, J., Shams-Bakhsh, M., Paltridge, N., Symons, R. H., Aboul-Ata, A. E., Makkouk, K. M., El-Saied, M. A., El-Hariry, M., Salem, G., Soliman, N. H., Rishi, Narayan, Lodhi, G. P., Bishnoi, S. S., Sangwan, R. B., Sijen, Titia, Wellink, Joan, van Kammen, Ab, Ravelonandro, M., Scorza, R., Bachelier, J., Callahan, A., Levy, L., Dunez, J., Polák, J., Oukropec, I., Kominek, P., Bitoova, M., Cardol, Erwin, Prins, Marcel, Kormelink, Richard, Goldbach, Rob, Baulcombe, D. C., English, J. J., Davenport, G., Ruiz-Perez, T., Mueller, E., Truve, E., Nigul, L., Saarma, M., Kelve, M., Fedorkin, O. N., Denisenko, O. N., Zelenina, D. A., Morozov, S. Yu., Atabekov, J. G., Laliberté, J. -F., Wittmann, S., Plante, Daniel, Fortin, Marc G., Chatel, H., Rodriguez-Alvarado, G., Garcia-Arenal, F., Roossinck, M. J., Palukaitis, P., Roossinck, M. J., Palukaitis, P., Gellatly, D. L., AbouHaidar, M. G., Rasochova, L., Aulik, M., Passmore, B., Falk, B., Miller, W. A., Lin, Na-Sheng, Lin, Biing-Yuan, Hsu, Yau-Heiu, Tamada, T., Kiguchi, T., Saito, M., Kusume, T., Uchino, H., Taliansky, M., Robinson, D., DiSerio, F., Daròs, J. A., Ragozzino, A., Floras, R., Hohn, Thomas, Chen, Gang, Rothnie, Helen, Corsten, Sandra, Fütterer, Johannes, Mikhailov, M. V., Bishop, D. H. L., and Roy, P.

Published
1997
Full Text
View/download PDF

8. Abstracts of presentations on plant protection issues at the xth international congress of virology: August 11-16,1996 Binyanei haOoma, Jerusalem, Israel Part 2 Plenary Lectures

Author

Ramirez, E., Hernádez, A., Ham, E., Barrón, B., Ding, S., Li, W., Shi, B., Symons, R., Li, Q., Ryu, K., Palukaitis, P., Kaplan, I., Gal-On, A., Kunhara, J., Otsubo, T., Tomaru, K., Tsuda, S., Kinta, M., Lin, T., Johnson, J., Porta, C., Taylor, K., Spall, V., Lomonossoff, G., Meiri, E., Raccah, B., Gaba, V., Ikegami, M., Kawashima, H., Murayama, A., Natsuaki, T., Kageyama, Y., Sugimura, N., Thole, V., Bol, J., Deiman, B., Koenen, A., Pleij, C., Chaleeprom, W., Bateson, M., Dale, J., Badge, J., Foster, G., Brunt, A., Robinson, D., Schubert, J., Rabenstein, F., Merits, A., Yeh, Shyi-Dong, Chiang, Chu-Hui, Wang, Ching-Hsien, Golshani, A., Ivanov, I., AbouHaidar, M., Rodoni, B., Harding, R., Oertel, U., Fuchs, E., Yang, S., Revere, F., Walter, J., Le Gall, O., Dunez, J., Candresse, T., Lot, H., Souche, S., Kasschau, Kristin, Carrington, James, Chiang, A., Turner, N., Hwang, D., Chachulska, A., Zagórski, W., Robaglia, C., Chrzanowska, M., Truve, E., Tamm, T., Saarma, M., Makinen, K., Wang, Aiming, Carrier, Karma, Wieczorek, Andrew, Huguenot, Claire, Sanfacon, Helene, Wurscher, M., Christensen, F., Prody, G., Sanchez-Navarro, J., Pallas, V., Carson, R., Dagless, E., Lock, S., Turner, R., Adams, M., Antoniw, J., Phillips, S., Kashiwazaki, S., Seal, S., Karamagioli, M., Druka, Amis, Makhdoom, Rahat, Yitang, Yan, Hull, Roger, Kikkert, M., Bodegom, P., Storms, M., van Lent, J., Kormelink, R., Goldbach, R., De Haan, P., De Rover, A., Van Schepen, A., Gielen, J., Van Grinsven, M., Livneh, O., Vardi, E., Kuznetsova, L., Aliskevicius, E., Stram, Y., Sela, I., Dinant, S., Kusiak, C., Blaise, F., Chupeau, Y., Astier, S., Albouy, J., Clifford, T., Taylor, S., Stratford, R., Xiao, X., Frenkel, M., Chu, P., Tabe, L., Shukla, D., Ward, C., Hwang, Duk-Ju, Turner, Nilgun, Mooney, A., MacFarlane, S., Twell, D., Jacquet, C., Ravelonandro, M., Bachelier, J., Almási, A., Böddi, B., Szigeti, Z., Ekes, M., Gaborianvi, R., Yankulova, Margarita, Ivanova, Lidia, Adam, G., Guelemerov, S., Nikolaeva, Velitchka, Atanassov, A., Prins, Marcel, de Haan, Peter, Goldbach, Rob, Duan, Y., Powell, C., Purcifull, D., Hiebert, E., Levine, B., Faktor, O., Zeituny, Silvy, Edelbaum, Orit, Sela, L., Marano, Maria-Rosa, Ratcliff, Frank, Baulcombe, David, van Oers, Monique, Linthorst, Huub, Bol, John, Schillberg, S., Zimmermann, S., Drossard, J., Schumann, D., Nahring, J., Fischer, R., Lapidot, Moshe, Arce-Johnson, Patricio, Rivera-Bustamante, Rafael, Beachy, Roger, Cassidy, Brandt, Flasinski, Stanislaw, Hajimorad, M., Wesley, Varsha, Angel-Diaz, J., Mayo, M., Hafner, G., May, G., Becker, D., Arntzen, C., Porter, J., Hellwald, K., Banerjee, N., Zaitlin, M., Wolf, D., Faure, J., Pilowsky, M., Cohen, S., Zelcer, A., Hardi, V., Tomassoli, L., Kaniewski, W., Mitsky, T., Barba, M., Hou, Y., Ursin, V., Sanders, R., Gilbertson, R., Gruden, Kristina, Štrukelj, Borut, Brzin, Joze, Ravnikar, Maja, Maganja, Darja, Kregar, Igor, Maki-Valkama, T., Pehu, T., Valkonen, J., Lento, K., Pehu, E., Lawson, E., Feldman, J., Zalewski, J., Kuittinen, T., Atiri, G., Romero, A., Arroyo, R., Soto, M., Martínez-Zapater, J., Ponz, F., Gilardi, P., López, L., García-Luque, I., Serra, M., Pang, Sheng-Zhi, Jan, Fuh-Jyh, Carney, Kim, Tricoli, David, Quemada, Hector, Gonsalves, Dennis, Aboul-Ata, A., Thouvenel, J., Marshall, D., Abo-El-Saad, Sh, Satour, M., Mazithulela, G., Mehlo, L., Gahakwa, D., Leech, M., Boulton, M., Davies, J., Christou, P., Huet, H., Sivamani, E., Ong, C., Chen, L., de Kochko, A., Beachy, R., Fauquet, C., Sithisarn-Burns, P., Maugeri, M., Smith, G., Handley, J., Graichen, K., Peterka, J., Chu, Paul, Larkin, Phil, Higgins, T., Wylie, S., Jones, M., Somsap, V., Loo, H., Li, D., Mathews, A., Dwyer, G., McCarthy, P., Hansen, J., Shiel, P., Zemetra, R., Wyatt, S., Berger, P., Ford, C., Collins, N., Rathjen, J., Shams-Bakhsh, M., Paltridge, N., Makkouk, K., El-Saied, M., El-Hariry, M., Salem, G., Soliman, N., Rishi, Narayan, Lodhi, G., Bishnoi, S., Sangwan, R., Sijen, Titia, Wellink, Joan, van Kammen, Ab, Scorza, R., Callahan, A., Levy, L., Polák, J., Oukropec, I., Kominek, P., Bitoova, M., Cardol, Erwin, Kormelink, Richard, Baulcombe, D., English, J., Davenport, G., Ruiz-Perez, T., Mueller, E., Nigul, L., Kelve, M., Fedorkin, O., Denisenko, O., Zelenina, D., Morozov, S., Atabekov, J., Laliberté, J., Wittmann, S., Plante, Daniel, Fortin, Marc, Chatel, H., Rodriguez-Alvarado, G., Garcia-Arenal, F., Roossinck, M., Gellatly, D., Rasochova, L., Aulik, M., Passmore, B., Falk, B., Miller, W., Lin, Na-Sheng, Lin, Biing-Yuan, Hsu, Yau-Heiu, Tamada, T., Kiguchi, T., Saito, M., Kusume, T., Uchino, H., Taliansky, M., DiSerio, F., Daròs, J., Ragozzino, A., Floras, R., Hohn, Thomas, Chen, Gang, Rothnie, Helen, Corsten, Sandra, Fütterer, Johannes, Mikhailov, M., Bishop, D., Roy, P., Ramirez, E., Hernádez, A., Ham, E., Barrón, B., Ding, S., Li, W., Shi, B., Symons, R., Li, Q., Ryu, K., Palukaitis, P., Kaplan, I., Gal-On, A., Kunhara, J., Otsubo, T., Tomaru, K., Tsuda, S., Kinta, M., Lin, T., Johnson, J., Porta, C., Taylor, K., Spall, V., Lomonossoff, G., Meiri, E., Raccah, B., Gaba, V., Ikegami, M., Kawashima, H., Murayama, A., Natsuaki, T., Kageyama, Y., Sugimura, N., Thole, V., Bol, J., Deiman, B., Koenen, A., Pleij, C., Chaleeprom, W., Bateson, M., Dale, J., Badge, J., Foster, G., Brunt, A., Robinson, D., Schubert, J., Rabenstein, F., Merits, A., Yeh, Shyi-Dong, Chiang, Chu-Hui, Wang, Ching-Hsien, Golshani, A., Ivanov, I., AbouHaidar, M., Rodoni, B., Harding, R., Oertel, U., Fuchs, E., Yang, S., Revere, F., Walter, J., Le Gall, O., Dunez, J., Candresse, T., Lot, H., Souche, S., Kasschau, Kristin, Carrington, James, Chiang, A., Turner, N., Hwang, D., Chachulska, A., Zagórski, W., Robaglia, C., Chrzanowska, M., Truve, E., Tamm, T., Saarma, M., Makinen, K., Wang, Aiming, Carrier, Karma, Wieczorek, Andrew, Huguenot, Claire, Sanfacon, Helene, Wurscher, M., Christensen, F., Prody, G., Sanchez-Navarro, J., Pallas, V., Carson, R., Dagless, E., Lock, S., Turner, R., Adams, M., Antoniw, J., Phillips, S., Kashiwazaki, S., Seal, S., Karamagioli, M., Druka, Amis, Makhdoom, Rahat, Yitang, Yan, Hull, Roger, Kikkert, M., Bodegom, P., Storms, M., van Lent, J., Kormelink, R., Goldbach, R., De Haan, P., De Rover, A., Van Schepen, A., Gielen, J., Van Grinsven, M., Livneh, O., Vardi, E., Kuznetsova, L., Aliskevicius, E., Stram, Y., Sela, I., Dinant, S., Kusiak, C., Blaise, F., Chupeau, Y., Astier, S., Albouy, J., Clifford, T., Taylor, S., Stratford, R., Xiao, X., Frenkel, M., Chu, P., Tabe, L., Shukla, D., Ward, C., Hwang, Duk-Ju, Turner, Nilgun, Mooney, A., MacFarlane, S., Twell, D., Jacquet, C., Ravelonandro, M., Bachelier, J., Almási, A., Böddi, B., Szigeti, Z., Ekes, M., Gaborianvi, R., Yankulova, Margarita, Ivanova, Lidia, Adam, G., Guelemerov, S., Nikolaeva, Velitchka, Atanassov, A., Prins, Marcel, de Haan, Peter, Goldbach, Rob, Duan, Y., Powell, C., Purcifull, D., Hiebert, E., Levine, B., Faktor, O., Zeituny, Silvy, Edelbaum, Orit, Sela, L., Marano, Maria-Rosa, Ratcliff, Frank, Baulcombe, David, van Oers, Monique, Linthorst, Huub, Bol, John, Schillberg, S., Zimmermann, S., Drossard, J., Schumann, D., Nahring, J., Fischer, R., Lapidot, Moshe, Arce-Johnson, Patricio, Rivera-Bustamante, Rafael, Beachy, Roger, Cassidy, Brandt, Flasinski, Stanislaw, Hajimorad, M., Wesley, Varsha, Angel-Diaz, J., Mayo, M., Hafner, G., May, G., Becker, D., Arntzen, C., Porter, J., Hellwald, K., Banerjee, N., Zaitlin, M., Wolf, D., Faure, J., Pilowsky, M., Cohen, S., Zelcer, A., Hardi, V., Tomassoli, L., Kaniewski, W., Mitsky, T., Barba, M., Hou, Y., Ursin, V., Sanders, R., Gilbertson, R., Gruden, Kristina, Štrukelj, Borut, Brzin, Joze, Ravnikar, Maja, Maganja, Darja, Kregar, Igor, Maki-Valkama, T., Pehu, T., Valkonen, J., Lento, K., Pehu, E., Lawson, E., Feldman, J., Zalewski, J., Kuittinen, T., Atiri, G., Romero, A., Arroyo, R., Soto, M., Martínez-Zapater, J., Ponz, F., Gilardi, P., López, L., García-Luque, I., Serra, M., Pang, Sheng-Zhi, Jan, Fuh-Jyh, Carney, Kim, Tricoli, David, Quemada, Hector, Gonsalves, Dennis, Aboul-Ata, A., Thouvenel, J., Marshall, D., Abo-El-Saad, Sh, Satour, M., Mazithulela, G., Mehlo, L., Gahakwa, D., Leech, M., Boulton, M., Davies, J., Christou, P., Huet, H., Sivamani, E., Ong, C., Chen, L., de Kochko, A., Beachy, R., Fauquet, C., Sithisarn-Burns, P., Maugeri, M., Smith, G., Handley, J., Graichen, K., Peterka, J., Chu, Paul, Larkin, Phil, Higgins, T., Wylie, S., Jones, M., Somsap, V., Loo, H., Li, D., Mathews, A., Dwyer, G., McCarthy, P., Hansen, J., Shiel, P., Zemetra, R., Wyatt, S., Berger, P., Ford, C., Collins, N., Rathjen, J., Shams-Bakhsh, M., Paltridge, N., Makkouk, K., El-Saied, M., El-Hariry, M., Salem, G., Soliman, N., Rishi, Narayan, Lodhi, G., Bishnoi, S., Sangwan, R., Sijen, Titia, Wellink, Joan, van Kammen, Ab, Scorza, R., Callahan, A., Levy, L., Polák, J., Oukropec, I., Kominek, P., Bitoova, M., Cardol, Erwin, Kormelink, Richard, Baulcombe, D., English, J., Davenport, G., Ruiz-Perez, T., Mueller, E., Nigul, L., Kelve, M., Fedorkin, O., Denisenko, O., Zelenina, D., Morozov, S., Atabekov, J., Laliberté, J., Wittmann, S., Plante, Daniel, Fortin, Marc, Chatel, H., Rodriguez-Alvarado, G., Garcia-Arenal, F., Roossinck, M., Gellatly, D., Rasochova, L., Aulik, M., Passmore, B., Falk, B., Miller, W., Lin, Na-Sheng, Lin, Biing-Yuan, Hsu, Yau-Heiu, Tamada, T., Kiguchi, T., Saito, M., Kusume, T., Uchino, H., Taliansky, M., DiSerio, F., Daròs, J., Ragozzino, A., Floras, R., Hohn, Thomas, Chen, Gang, Rothnie, Helen, Corsten, Sandra, Fütterer, Johannes, Mikhailov, M., Bishop, D., and Roy, P.

Published
2018

12. Fenofibrate intervention and event lowering in diabetes (FIELD) study: baseline characteristics and short-term effects of fenofibrate [ISRCTN64783481]

Author

Scott, R, Best, J, Forder, P, Taskinen, M-R, Simes, J, Barter, P, Keech, A, Colman, P, D'Emden, M, Davis, T, Drury, P, Ehnholm, C, Glasziou, P, Hunt, D, Kesaniemi, YA, Laakso, M, Simes, RJ, Sullivan, D, Whiting, M, Ansquer, J-C, Fraitag, B, Anderson, N, Hankey, G, Lehto, S, Mann, S, Romo, M, Li, LP, Hennekens, C, MacMahon, S, Pocock, S, Tonkin, A, Wilhelmsen, L, Akauola, H, Alford, F, Beinart, I, Bohra, S, Boyages, S, Connor, H, Darnell, D, Davoren, P, Lepre, F, De Looze, F, Duffield, A, Fassett, R, Flack, J, Fulcher, G, Grant, S, Hamwood, S, Harmelin, D, Jackson, R, Jeffries, W, Kamp, M, Kritharides, L, Mahar, L, McCann, V, McIntyre, D, Moses, R, Newnham, H, Nicholson, G, O'Brien, R, Park, K, Petrovsky, N, Phillips, P, Pinn, G, Simmons, D, Stanton, K, Stuckey, B, Sullivan, DR, Suranyi, M, Suthers, M, Tan, Y, Templer, M, Topliss, D, Waites, JH, Watts, G, Welborn, T, Wyndham, R, Haapamaki, H, Kesaniemi, A, Lahtela, J, Levanen, H, Saltevo, J, Sodervik, H, Taskinen, M, Vanhala, M, Baker, J, Burton, A, Dixon, P, Doran, J, Dunn, P, Graham, N, Hamer, A, Hedley, J, Lloyd, J, Manning, P, McPherson, I, Morris, S, Renner, C, Smith, R, Wackrow, M, Young, S, Alard, F, Alcoe, J, Allan, C, Amerena, J, Anderson, R, Arnold, N, Arsov, T, Ashby, D, Atkinson, C, Badhni, L, Balme, M, Barton, D, Batrouney, B, Beare, C, Beattie, T, Beggs, J, Bendall, C, Benz, A, Bond, A, Bradfield, R, Bradshaw, J, Brearley, S, Bruce, D, Burgess, J, Butler, J, Callary, M, Campbell, J, Chambers, K, Chow, J, Chow, S, Ciszek, K, Clifton, P, Clifton-Bligh, P, Clowes, V, Coates, P, Cocks, C, Cole, S, Colquhoun, D, Correcha, M, Costa, B, Coverdale, S, Croft, M, Crowe, J, Dal Sasso, S, Davis, W, Dunn, J, Edwards, S, Elder, R, El-Kaissi, S, Emery, L, England, M, Farouque, O, Fernandez, M, Fitzpatrick, B, Francis, N, Freeman, P, Fuller, A, Gale, D, Gaylard, V, Gillzan, C, Glatthaar, C, Goddard, J, Grange, V, Greenaway, T, Griffin, J, Grogan, A, Guha, S, Gustafson, J, Hamblin, PS, Hannay, T, Hardie, C, Harper, A, Hartl, G, Harvey, A, Havlin, S, Haworth, K, Hay, P, Hay, L, Heenan, B, Hesketh, R, Heyworth, A, Hines, M, Hockings, G, Hodge, A, Hoffman, L, Hoskin, L, Howells, M, Hunt, A, Inder, W, Jackson, D, Jovanovska, A, Kearins, K, Kee, P, Keen, J, Kilpatrick, D, Kindellan, J, Kingston-Ray, M, Kotowicz, M, Lassig, A, Layton, M, Lean, S, Lim, E, Long, F, Lucas, L, Ludeman, D, Ludeman-Robertson, C, Lyall, M, Lynch, L, Maddison, C, Malkus, B, Marangou, A, Margrie, F, Matthiesson, K, Matthiesson, J, Maxwell, S, McCarthy, K, McElduff, A, Mckee, H, McKenzie, J, McLachan, K, McNair, P, Meischke, M, Miller, AMC, Morrison, B, Morton, A, Mossman, W, Mowat, A, Muecke, J, Murie, P, Murray, S, Nadorp, P, Nair, S, Nairn, J, Nankervis, A, Narayan, K, Nattrass, N, Ngui, J, Nicholls, S, Nicholls, V, Nye, JA, Nye, E, O'Neal, D, O'Neill, M, O'Rourke, S, Pearse, J, Pearson, C, Phillips, J, Pittis, L, Playford, D, Porter, L, Portley, R, Powell, M, Preston, C, Pringle, S, Quinn, WA, Raffaele, J, Ramnath, G, Ramsden, J, Richtsteiger, D, Roffe, S, Rosen, S, Ross, G, Ross, Z, Rowe, J, Rumble, D, Ryan, S, Sansom, J, Seymour, C, Shanahan, E, Shelly, S, Shepherd, J, Sherman, G, Siddall, R, Silva, D, Simmons, S, Simpson, R, Sinha, A, Slobodniuk, R, Smith, M, Smith, P, Smith, S, Smith-Orr, V, Snow, J, Socha, L, Stack, T, Steed, K, Steele, K, Stephensen, J, Stevens, P, Stewart, G, Stewart, R, Strakosch, C, Sullivan, M, Sunder, S, Sunderland, J, Tapp, E, Taylor, J, Thorn, D, Tolley, A, Torpy, D, Truran, G, Turner, F, Turner, J, Van de Velde, J, Varley, S, Wallace, J, Walsh, J, Walshe, J, Ward, G, Watson, B, Watson, J, Webb, A, Werner, F, White, E, Whitehouse, A, Whitehouse, N, Wigg, S, Wilkinson, J, Wilmshurst, E, Wilson, D, Wittert, G, Wong, B, Wong, M, Worboys, S, Wright, S, Wu, S, Yarker, J, Yeo, M, Young, K, Youssef, J, Yuen, R, Zeimer, H, Ziffer, RW, Aura, A, Friman, A, Hanninen, J, Henell, J, Hyvarinen, N, Ikonen, M, Itkonen, A, Jappinen, J, Jarva, A, Jerkkola, T, Jokinen, V, Juutilainen, J, Kahkonen, H, Kangas, T, Karttunen, M, Kauranen, P, Kortelainen, S, Koukkunen, H, Kumpulainen, L, Laitinen, T, Laitinen, M, Lehto, R, Leinonen, E, Lindstron-Karjalainen, M, Lumiaho, A, Makela, J, Makinen, K, Mannermaa, L, Mard, T, Miettinen, J, Naatti, V, Paavola, S, Parssinen, N, Ripatti, J, Ruotsalainen, S, Salo, A, Siiskonen, M, Soppela, A, Starck, J, Suonranta, I, Ukkola, L, Valli, K, Virolainen, J, Allan, P, Arnold, W, Bagg, W, Balfour, K, Ball, T, Ballantine, B, Ballantyne, C, Barker, C, Bartley, F, Berry, E, Braatvedt, G, Campbell, A, Clarke, T, Clarke, R, Claydon, A, Clayton, S, Cresswell, P, Cutfield, R, Daffurn, J, Delahunt, J, Dissnayake, A, Eagleton, C, Ferguson, C, Florkowski, C, Fry, D, Giles, P, Gluyas, M, Grant, C, Guile, P, Guolo, M, Hale, P, Hammond, M, Healy, P, Hills, M, Hinge, J, Holland, J, Hyne, B, Ireland, A, Johnstone, A, Jones, S, Kerr, G, Kerr, K, Khant, M, Krebs, J, Law, L, Lydon, B, MacAuley, K, McEwan, R, McGregor, P, McLaren, B, McLeod, L, Medforth, J, Miskimmin, R, Moffat, J, Pickup, M, Prentice, C, Rahman, M, Reda, E, Ross, C, Ryalls, A, Schmid, D, Shergill, N, Snaddon, A, Snell, H, Stevens, L, Waterman, A, Watts, V, Jayne, K, Keirnan, E, Newman, P, Ritchie, G, Rosenfeld, A, Beller, E, Gebski, V, Pillai, A, Anderson, C, Blakesmith, S, Chan, S-Y, Czyniewski, S, Dobbie, A, Doshi, S, Dupuy, A, Eckermann, S, Edwards, M, Fields, N, Flood, K, Ford, S, French, C, Gillies, S, Greig, C, Groshens, M, Gu, J, Guo, Y, Hague, W, Healy, S, Hones, L, Hossain, Z, Howlett, M, Lee, J, Li, L-P, Matthews, T, Micallef, J, Martin, A, Minns, I, Nguyen, A, Papuni, F, Patel, A, Pike, R, Pena, M, Pinto, K, Schipp, D, Schroeder, J, Sim, B, Sodhi, C, Sourjina, T, Sutton, C, Taylor, R, Vlagsma, P, Walder, S, Walker, R, Wong, W, Zhang, J, Zhong, B, Kokkonen, A, Narva, P, Niemi, E-L, Syrjanen, A-M, Lintott, C, Tirimacco, R, Kajosaari, M, Raman, L, Sundvall, J, Tukianen, M, Crimet, D, Sirugue, I, and Aubonnet, P

Subjects
Male, Cardiac & Cardiovascular Systems, Endocrinology, Diabetes and Metabolism, Atorvastatin, Coronary Disease, Fibrate, SECONDARY PREVENTION, ATORVASTATIN, law.invention, Placebos, Randomized controlled trial, Fenofibrate, law, Myocardial infarction, 1102 Cardiorespiratory Medicine and Haematology, Finland, Original Investigation, Hypolipidemic Agents, PLASMA, CHOLESTEROL, Middle Aged, INSULIN, CARDIOVASCULAR-DISEASE, Cardiovascular Diseases, Female, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, medicine.drug, medicine.medical_specialty, medicine.drug_class, Diabetes Complications, Endocrinology & Metabolism, Double-Blind Method, Internal medicine, Diabetes mellitus, Intervention (counseling), medicine, Humans, CORONARY-HEART-DISEASE, Obesity, Triglycerides, Aged, Apolipoproteins B, Bezafibrate, Science & Technology, business.industry, Cholesterol, HDL, Australia, Cholesterol, LDL, medicine.disease, BEZAFIBRATE, FIELD Study Investigators, MYOCARDIAL-INFARCTION, Diabetes Mellitus, Type 2, Cardiovascular System & Hematology, Cardiovascular System & Cardiology, business, HIGH-DENSITY-LIPOPROTEIN, New Zealand
Abstract

Objective The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study is examining the effects of long-term fibrate therapy on coronary heart disease (CHD) event rates in patients with diabetes mellitus. This article describes the trial's run-in phase and patients' baseline characteristics. Research design and methods FIELD is a double-blind, placebo-controlled trial in 63 centres in 3 countries evaluating the effects of fenofibrate versus placebo on CHD morbidity and mortality in 9795 patients with type 2 diabetes mellitus. Patients were to have no indication for lipid-lowering therapy on randomization, but could start these or other drugs at any time after randomization. Follow-up in the study was to be for a median duration of not less than 5 years and until 500 major coronary events (fatal coronary heart disease plus nonfatal myocardial infarction) had occurred. Results About 2100 patients (22%) had some manifestation of cardiovascular disease (CVD) at baseline and thus high risk status. Less than 25% of patients without CVD had a (UKPDS determined) calculated 5-year CHD risk of 30), most were men, two-thirds were aged over 60 years, and substantial proportions had NCEP ATP III features of the metabolic syndrome independent of their diabetes, including low HDL (60%), high blood pressure measurement or treatment for hypertension (84%), high waist measurement (68%), and raised triglycerides (52%). After a 6-week run-in period before randomisation with all participants receiving 200 mg comicronized fenofibrate, there were declines in total and LDL cholesterol (10%) and triglycerides (26%) and an increase in HDL cholesterol (6.5%). Conclusion The study will show the effect of PPAR-alpha agonist action on CHD and other vascular outcomes in patients with type 2 diabetes including substantial numbers with low to moderate CVD risk but with the various components of the metabolic syndrome. The main results of the study will be reported in late 2005.

Published
2005

13. Global DNA methylation analysis of human atherosclerotic plaques reveals extensive genomic hypomethylation and reactivation at imprinted locus 14q32 involving induction of a miRNA cluster

Author

Aavik, E., primary, Lumivuori, H., additional, Leppanen, O., additional, Wirth, T., additional, Hakkinen, S.-K., additional, Brasen, J.-H., additional, Beschorner, U., additional, Zeller, T., additional, Braspenning, M., additional, van Criekinge, W., additional, Makinen, K., additional, and Yla-Herttuala, S., additional

Published
2014
Full Text
View/download PDF

14. Xylitol Chewing Gums and Caries Rates: A 40-month Cohort Study

Author

Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, Michigan 48109-1078, Belize City Hospital, Belize City, Belize, Department of Dental Public Health Sciences, University of Washington, Seattle, Ylivieska Health Center, Ylivieska, Finland, Institute of Dentistry, University of Turku, Turku, Finland, Makinen, K. K., Bennett, C. A., Hujoel, P. P., Isokangas, P. J., Isotupa, K. P., Pape, H. R., Makinen, P. L., Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, Michigan 48109-1078, Belize City Hospital, Belize City, Belize, Department of Dental Public Health Sciences, University of Washington, Seattle, Ylivieska Health Center, Ylivieska, Finland, Institute of Dentistry, University of Turku, Turku, Finland, Makinen, K. K., Bennett, C. A., Hujoel, P. P., Isokangas, P. J., Isotupa, K. P., Pape, H. R., and Makinen, P. L.

Abstract

Dental caries is a pandemic infectious disease which can affect the quality of life and consumes considerable health care resources. The chewing of xylitol, sorbitol, and even sugar gum has been suggested to reduce caries rates. No clinical study has simultaneously investigated the effectiveness of these gums when compared with a group receiving no chewing gum. A 40-month double-blind cohort study on the relationship between the use of chewing gum and dental caries was performed in 1989-1993 in Belize, Central America. One thousand two hundred and seventy-seven subjects (mean age, 10.2 years) were assigned to nine treatment groups: one control group (no supervised gum use), four xylitol groups (range of supervised xylitol consumption: 4.3 to 9.0 g/day), two xylitol-sorbitol groups (range of supervised consumption of total polyols: 8.0 to 9.7 g/day), one sorbitol group (supervised consumption: 9.0 g/day), and one sucrose group (9.0 g/day). The gum use during school hours was supervised. Four calibrated dentists performed the caries registrations by means of a modified WHO procedure. The primary endpoint was the development of an unequivocal caries lesion on a non-cavitated tooth surface. Compared with the no-gum group, sucrose gum usage resulted in a marginal increase in the caries rate (relative risk, 1.20; 95% confidence interval, 0.96 to 1.49; p = 0.1128). Sorbitol gum significantly reduced caries rates (relative risk, 0.74; 95% confidence interval, 0.6 to 0.92; p = 0.0074). The four xylitol gums were most effective in reducing caries rates, the most effective agent being a 100% xylitol pellet gum (relative risk, 0.27; 95% confidence interval, 0.20 to 0.36; p = 0.0001). This gum was superior to any other gum (p < 0.01). The xylitol-sorbitol mixtures were less effective than xylitol, but they still reduced caries rates significantly compared with the no-gum group. DMFS analyses were consistent with these conclusions. The results suggest that systematic usage of pol

Published
2010

15. A Re-analysis of Caries Rates in a Preventive Trial using Poisson Regression Models

Author

Department of Biological and Material Sciences, University of Michigan, Ann Arbor, Michigan 48109, Department of Dental Public Health Sciences, School of Dentistry, SM-35, University of Washington, Seattle, Washington 98195, Department of Epidemiology, School of Public Healthand Community Medicine, Department of Community Dentistry, Institute of Dentistry, University of Turku, Finland, Department of Epidemiology, School of Public Healthand Community Medicine, Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Program in Epidemiology, and University of Washington, Seattle, Department of Oral Biology, University of Washington, Seattle, Department of Dental Public Health Sciences, School of Dentistry, SM-35, University of Washington, Seattle, Washington 98195, Department of Biostatistics, University of Washington, Seattle, Hujoel, P. P., Isokangas, P. J., Tiekso, J., Davis, S., Lamont, R. J., DeRouen, T. A., Makinen, K. K., Department of Biological and Material Sciences, University of Michigan, Ann Arbor, Michigan 48109, Department of Dental Public Health Sciences, School of Dentistry, SM-35, University of Washington, Seattle, Washington 98195, Department of Epidemiology, School of Public Healthand Community Medicine, Department of Community Dentistry, Institute of Dentistry, University of Turku, Finland, Department of Epidemiology, School of Public Healthand Community Medicine, Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Program in Epidemiology, and University of Washington, Seattle, Department of Oral Biology, University of Washington, Seattle, Department of Dental Public Health Sciences, School of Dentistry, SM-35, University of Washington, Seattle, Washington 98195, Department of Biostatistics, University of Washington, Seattle, Hujoel, P. P., Isokangas, P. J., Tiekso, J., Davis, S., Lamont, R. J., DeRouen, T. A., and Makinen, K. K.

Abstract

The analysis of caries incidence in clinical trials has several challenging features: (1) The distribution of the number of caries onsets per patient is skewed, with the majority of patients having few or no cavities; (2) the number of surfaces at risk varies (i) over time and (ii) between patients, due to eruption and exfoliation patterns, dental diseases, and treatments ; (3) surfaces within a patient differ in their caries susceptibility, and (4) caries onsets within a patient are correlated due to shared host factors. Recent statistical developments in the area of correlated data analyses permit incorporation of some of these characteristics into the analyses. With Poisson regression models, the expected number of caries onsets can be related to the number of surfaces at risk, the time they have been at risk, and surface- and subject-specific explanatory variables. The parameter estimated in these models is an epidemiological measure of disease occurrence: the disease incidence rate (caries rate) or the rate of change from healthy (sound) to diseased (carious). Differences and ratios of these rates provide standard epidemiological measures of excess risk. To illustrate, Poisson regression models were used for exploratory analyses of the Ylivieska xylitol study.

Published
2010

18. Dysfunctionality of a tobacco mosaic virus movement protein mutant mimicking threonine 104 phosphorylation.

Author

Karger, E M, Frolova, O Yu, Fedorova, N V, Baratova, L A, Ovchinnikova, T V, Susi, P, Makinen, K, Rönnstrand, Lars, Dorokhov, Yu L, Atabekov, J G, Karger, E M, Frolova, O Yu, Fedorova, N V, Baratova, L A, Ovchinnikova, T V, Susi, P, Makinen, K, Rönnstrand, Lars, Dorokhov, Yu L, and Atabekov, J G

Abstract

Replication of tobacco mosaic virus (TMV) is connected with endoplasmic reticulum (ER)-associated membranes at early stages of infection. This study reports that TMV movement protein (MP)-specific protein kinases (PKs) associated with the ER of tobacco were capable of phosphorylating Thr(104) in TMV MP. The MP-specific PKs with apparent molecular masses of about 45-50 kDa and 38 kDa were revealed by gel PK assays. Two types of mutations were introduced in TMV MP gene of wild-type TMV U1 genome to substitute Thr(104) by neutral Ala or by negatively charged Asp. Mutation of Thr(104) to Ala did not affect the size of necrotic lesions induced by the mutant virus in Nicotiana tabacum Xanthi nc. plants. Conversely, mutation of Thr to Asp mimicking Thr(104) phosphorylation strongly inhibited cell-to-cell movement. The possible role of Thr(104) phosphorylation in TMV MP function is discussed.

Published
2003

19. Sunday, 18 July 2010

Author

Schuchardt, M., primary, Toelle, M., additional, Huang, T., additional, Wiedon, A., additional, Van Der Giet, M., additional, Mill, C., additional, George, S., additional, Jeremy, J., additional, Santulli, G., additional, Illario, M., additional, Cipolletta, E., additional, Sorriento, D., additional, Del Giudice, C., additional, Anastasio, A., additional, Trimarco, B., additional, Iaccarino, G., additional, Jobs, A., additional, Wagner, C., additional, Kurtz, A., additional, De Wit, C., additional, Koller, A., additional, Suvorava, T., additional, Weber, M., additional, Dao, V., additional, Kojda, G., additional, Tsaousi, A., additional, Lyon, C., additional, Williams, H., additional, Barth, N., additional, Loot, A., additional, Fleming, I., additional, Keul, P., additional, Lucke, S., additional, Graeler, M., additional, Heusch, G., additional, Levkau, B., additional, Biessen, E., additional, De Jager, S., additional, Bermudez-Pulgarin, B., additional, Bot, I., additional, Abia, R., additional, Van Berkel, T., additional, Renger, A., additional, Noack, C., additional, Zafiriou, M., additional, Dietz, R., additional, Bergmann, M., additional, Zelarayan, L., additional, Hammond, J., additional, Hamelet, J., additional, Van Assche, T., additional, Belge, C., additional, Vanderper, A., additional, Langin, D., additional, Herijgers, P., additional, Balligand, J., additional, Perrot, A., additional, Neubert, M., additional, Posch, M., additional, Oezcelik, C., additional, Waldmuller, S., additional, Berger, F., additional, Scheffold, T., additional, Bouvagnet, P., additional, Ozcelik, C., additional, Lebreiro, A., additional, Martins, E., additional, Lourenco, P., additional, Cruz, C., additional, Martins, M., additional, Bettencourt, P., additional, Maciel, M., additional, Abreu-Lima, C., additional, Pilichou, K., additional, Bauce, B., additional, Rampazzo, A., additional, Carturan, E., additional, Corrado, D., additional, Thiene, G., additional, Basso, C., additional, Piccini, I., additional, Fortmueller, L., additional, Kuhlmann, M., additional, Schaefers, M., additional, Carmeliet, P., additional, Kirchhof, P., additional, Fabritz, L., additional, Sanchez, J., additional, Rodriguez-Sinovas, A., additional, Agullo, E., additional, Garcia-Dorado, D., additional, Lymperopoulos, A., additional, Rengo, G., additional, Gao, E., additional, Zincarelli, C., additional, Koch, W., additional, Morgan, P., additional, Diez, A., additional, Perez, N., additional, Cingolani, H., additional, Zahradnikova, A., additional, Polakova, E., additional, Zahradnik, I., additional, Fluschnik, N., additional, Sossalla, S., additional, Ort, K., additional, Neef, S., additional, Hasenfuss, G., additional, Maier, L., additional, Weinert, S., additional, Poitz, D., additional, Herold, J., additional, Schmeisser, A., additional, Strasser, J., additional, Braun-Dullaeus, R., additional, Nazari-Jahantigh, M., additional, Weber, C., additional, Schober, A., additional, Leuner, A., additional, Eichhorn, B., additional, Ravens, U., additional, Morawietz, H., additional, Babes, E., additional, Babes, V., additional, Popescu, M., additional, Ardelean, A., additional, Rus, M., additional, Bustea, C., additional, Gwozdz, P., additional, Csanyi, G., additional, Luzak, B., additional, Gajda, M., additional, Mateuszuk, L., additional, Chmura-Skirlinska, A., additional, Watala, C., additional, Chlopicki, S., additional, Kierzkowska, I., additional, Sulicka, J., additional, Kwater, A., additional, Strach, M., additional, Surdacki, A., additional, Siedlar, M., additional, Grodzicki, T., additional, Olieslagers, S., additional, Pardali, L., additional, Tchaikovski, V., additional, Ten Dijke, P., additional, Waltenberger, J., additional, Renner, M., additional, Redwan, B., additional, Winter, M., additional, Panzenboeck, A., additional, Jakowitsch, J., additional, Sadushi-Kolici, R., additional, Bonderman, D., additional, Lang, I., additional, Toso, A., additional, Tanini, L., additional, Pizzetti, T., additional, Leoncini, M., additional, Maioli, M., additional, Tedeschi, D., additional, Oliviero, C., additional, Bellandi, F., additional, Casprini, P., additional, Amato, M., additional, Molins, B., additional, Pena, E., additional, Badimon, L., additional, Ferreiro Gutierrez, J., additional, Ueno, M., additional, Alissa, R., additional, Dharmashankar, K., additional, Capodanno, D., additional, Desai, B., additional, Bass, T., additional, Angiolillo, D., additional, Chabielska, E., additional, Gromotowicz, A., additional, Szemraj, J., additional, Stankiewicz, A., additional, Zakrzeska, A., additional, Mohammed, S., additional, Molla, F., additional, Soldo, A., additional, Russo, I., additional, Germano, G., additional, Balconi, G., additional, Staszewsky, L., additional, Latini, R., additional, Lynch, F., additional, Austin, C., additional, Prendergast, B., additional, Keenan, D., additional, Malik, R., additional, Izzard, A., additional, Heagerty, A., additional, Czikora, A., additional, Lizanecz, E., additional, Rutkai, I., additional, Boczan, J., additional, Porszasz, R., additional, Papp, Z., additional, Edes, I., additional, Toth, A., additional, Colantuoni, A., additional, Vagnani, S., additional, Lapi, D., additional, Maroz-Vadalazhskaya, N., additional, Koslov, I., additional, Shumavetz, V., additional, Glibovskaya, T., additional, Ostrovskiy, Y., additional, Koutsiaris, A., additional, Tachmitzi, S., additional, Kotoula, M., additional, Giannoukas, A., additional, Tsironi, E., additional, Darago, A., additional, Orosz, P., additional, Megyesi, Z., additional, Schudeja, S., additional, Matschke, K., additional, Deussen, A., additional, Castro, M., additional, Cena, J., additional, Walsh, M., additional, Schulz, R., additional, Poddar, K., additional, Rha, S., additional, Ramasamy, S., additional, Park, J., additional, Choi, C., additional, Seo, H., additional, Park, C., additional, Oh, D., additional, Almeida, J., additional, Pimenta, S., additional, Bernardes, J., additional, Machado, J., additional, Sabatasso, S., additional, Laissue, J., additional, Hlushchuk, R., additional, Brauer-Krisch, E., additional, Bravin, A., additional, Blattmann, H., additional, Michaud, K., additional, Djonov, V., additional, Hirschberg, K., additional, Tarcea, V., additional, Pali, S., additional, Korkmaz, S., additional, Loganathan, S., additional, Merkely, B., additional, Karck, M., additional, Szabo, G., additional, Pagliani, L., additional, Faggin, E., additional, Rattazzi, M., additional, Puato, M., additional, Presta, M., additional, Grego, F., additional, Deriu, G., additional, Pauletto, P., additional, Kaiser, R., additional, Albrecht, K., additional, Schgoer, W., additional, Theurl, M., additional, Beer, A., additional, Wiedemann, D., additional, Steger, C., additional, Bonaros, N., additional, Kirchmair, R., additional, Kharlamov, A., additional, Cabaravdic, M., additional, Breuss, J., additional, Uhrin, P., additional, Binder, B., additional, Fiordaliso, F., additional, Maggioni, M., additional, Biondi, A., additional, Masson, S., additional, Cervo, L., additional, Francke, A., additional, Soenke, W., additional, Strasser, R., additional, Hecht, N., additional, Vajkoczy, P., additional, Woitzik, J., additional, Hackbusch, D., additional, Gatzke, N., additional, Duelsner, A., additional, Tsuprykov, O., additional, Slavic, S., additional, Buschmann, I., additional, Kappert, K., additional, Massaro, M., additional, Scoditti, E., additional, Carluccio, M., additional, Storelli, C., additional, Distante, A., additional, De Caterina, R., additional, Barandi, L., additional, Harmati, G., additional, Simko, J., additional, Horvath, B., additional, Szentandrassy, N., additional, Banyasz, T., additional, Magyar, J., additional, Nanasi, P., additional, Kaya, A., additional, Uzunhasan, I., additional, Yildiz, A., additional, Yigit, Z., additional, Turkoglu, C., additional, Doisne, N., additional, Zannad, N., additional, Hivert, B., additional, Cosnay, P., additional, Maupoil, V., additional, Findlay, I., additional, Virag, L., additional, Kristof, A., additional, Koncz, I., additional, Szel, T., additional, Jost, N., additional, Biliczki, P., additional, Papp, J., additional, Varro, A., additional, Bukowska, A., additional, Skopp, K., additional, Hammwoehner, M., additional, Huth, C., additional, Bode-Boeger, S., additional, Goette, A., additional, Workman, A., additional, Dempster, J., additional, Marshall, G., additional, Rankin, A., additional, Revnic, C., additional, Ginghina, C., additional, Revnic, F., additional, Yakushev, S., additional, Petrushanko, I., additional, Makhro, A., additional, Segato Komniski, M., additional, Mitkevich, V., additional, Makarov, A., additional, Gassmann, M., additional, Bogdanova, A., additional, Rutkovskiy, A., additional, Mariero, L., additional, Stenslokken, K., additional, Valen, G., additional, Vaage, J., additional, Dizayee, S., additional, Kaestner, S., additional, Kuck, F., additional, Piekorz, R., additional, Hein, P., additional, Matthes, J., additional, Nurnberg, B., additional, Herzig, S., additional, Hertel, F., additional, Switalski, A., additional, Bender, K., additional, Kienitz, M.-C., additional, Pott, L., additional, Fornai, L., additional, Angelini, A., additional, Erika Amstalden Van Hove, E., additional, Fedrigo, M., additional, Heeren, R., additional, Kruse, M., additional, Pongs, O., additional, Lehmann, H., additional, Martens-Lobenhoffer, J., additional, Roehl, F., additional, Radicke, S., additional, Cotella, C., additional, Sblattero, D., additional, Schaefer, M., additional, Wettwer, E., additional, Santoro, C., additional, Seyler, C., additional, Kulzer, M., additional, Zitron, E., additional, Scholz, E., additional, Welke, F., additional, Thomas, D., additional, Karle, C., additional, Schmidt, K., additional, Dobrev, D., additional, Houshmand, N., additional, Menesi, D., additional, Cotella, D., additional, Szuts, V., additional, Puskas, L., additional, Kiss, I., additional, Deak, F., additional, Tereshchenko, S., additional, Gladyshev, M., additional, Kalachova, G., additional, Syshchik, N., additional, Gogolashvili, N., additional, Dedok, E., additional, Evert, L., additional, Wenzel, J., additional, Brandenburger, M., additional, Bogdan, R., additional, Richardt, D., additional, Reppel, M., additional, Hescheler, J., additional, Dendorfer, A., additional, Terlau, H., additional, Wiegerinck, R., additional, Galvez-Monton, C., additional, Jorge, E., additional, Martinez, R., additional, Ricart, E., additional, Cinca, J., additional, Bagavananthem Andavan, G., additional, Lemmens Gruber, R., additional, Brack, K., additional, Coote, J., additional, Ng, G., additional, Daimi, H., additional, Haj Khelil, A., additional, Neji, A., additional, Ben Hamda, K., additional, Maaoui, S., additional, Aranega, A., additional, Chibani, J., additional, Franco Jaime, D., additional, Tanko, A.-S., additional, Daniel, J.-M., additional, Bielenberg, W., additional, Stieger, P., additional, Tillmanns, H., additional, Sedding, D., additional, Fortini, C., additional, Toffoletto, B., additional, Fucili, A., additional, Beltrami, A., additional, Fiorelli, V., additional, Francolini, G., additional, Ferrari, R., additional, Beltrami, C., additional, Castellani, C., additional, Ravara, B., additional, Tavano, R., additional, Vettor, R., additional, De Coppi, P., additional, Papini, E., additional, Gunetti, M., additional, Fagioli, F., additional, Suffredini, S., additional, Sartiani, L., additional, Stillitano, F., additional, Mugelli, A., additional, Cerbai, E., additional, Krausgrill, B., additional, Halbach, M., additional, Soemantri, S., additional, Schenk, K., additional, Lange, N., additional, Saric, T., additional, Muller-Ehmsen, J., additional, Kavanagh, D., additional, Zhao, Y., additional, Yemm, A., additional, Kalia, N., additional, Wright, E., additional, Farrell, K., additional, Wallrapp, C., additional, Geigle, P., additional, Lewis, A., additional, Stratford, P., additional, Malik, N., additional, Holt, C., additional, Raths, M., additional, Zagallo, M., additional, Luni, C., additional, Serena, E., additional, Cimetta, E., additional, Zatti, S., additional, Giobbe, G., additional, Elvassore, N., additional, Zaglia, T., additional, Zambon, A., additional, Gordon, K., additional, Mioulane, M., additional, Foldes, G., additional, Ali, N., additional, Harding, S., additional, Gorbe, A., additional, Szunyog, A., additional, Varga, Z., additional, Pirity, M., additional, Rungaruniert, S., additional, Dinnyes, A., additional, Csont, T., additional, Ferdinandy, P., additional, Iqbal, A., additional, Schneider, M. D., additional, Khodjaeva, E., additional, Ibadov, R., additional, Khalikulov, K., additional, Mansurov, A., additional, Astvatsatryan, A., additional, Senan, M., additional, Nemeth, A., additional, Lenkey, Z., additional, Ajtay, Z., additional, Cziraki, A., additional, Sulyok, E., additional, Horvath, I., additional, Lobenhoffer, J., additional, Bode-Boger, S., additional, Li, J., additional, He, Y., additional, Yang, X., additional, Wang, F., additional, Xu, H., additional, Li, X., additional, Zhao, X., additional, Lin, Y., additional, Juszynski, M., additional, Ciszek, B., additional, Jablonska, A., additional, Stachurska, E., additional, Ratajska, A., additional, Atkinson, A., additional, Inada, S., additional, Sleiman, R., additional, Zhang, H., additional, Boyett, M., additional, Dobrzynski, H., additional, Fedorenko, O., additional, Hao, G., additional, Yanni, J., additional, Buckley, D., additional, Anderson, R., additional, Ma, Y., additional, Ma, X., additional, Hu, Y., additional, Yang, Y., additional, Huang, D., additional, Liu, F., additional, Huang, Y., additional, Liu, C., additional, Jedrzejczyk, T., additional, Balwicki, L., additional, Wierucki, L., additional, Zdrojewski, T., additional, Agarkova, I., additional, Vogel, J., additional, Korybalska, K., additional, Pyda, M., additional, Witowski, J., additional, Ibatov, A., additional, Sozmen, N., additional, Seymen, A., additional, Tuncay, E., additional, Turan, B., additional, Chen, B., additional, Houston-Feenstra, L., additional, Chiong, J. R., additional, Jutzy, K., additional, Furundzija, V., additional, Kaufmann, J., additional, Meyborg, H., additional, Fleck, E., additional, Stawowy, P., additional, Ksiezycka-Majczynska, E., additional, Lubiszewska, B., additional, Kruk, M., additional, Kurjata, P., additional, Ruzyllo, W., additional, Driesen, R., additional, Coenen, T., additional, Fagard, R., additional, Sipido, K., additional, Petrov, V., additional, Aksentijevic, D., additional, Lygate, C., additional, Makinen, K., additional, Sebag-Montefiore, L., additional, Medway, D., additional, Schneider, J., additional, Neubauer, S., additional, Gasser, R., additional, Holzwart, E., additional, Rainer, P., additional, Von Lewinski, D., additional, Maechler, H., additional, Gasser, S., additional, Roessl, U., additional, Pieske, B., additional, Krueger, J., additional, Kintscher, U., additional, Podramagi, T., additional, Paju, K., additional, Piirsoo, A., additional, Roosimaa, M., additional, Kadaja, L., additional, Orlova, E., additional, Ruusalepp, A., additional, Seppet, E., additional, Auquier, J., additional, Ginion, A., additional, Hue, L., additional, Horman, S., additional, Beauloye, C., additional, Vanoverschelde, J., additional, Bertrand, L., additional, Fekete, V., additional, Zvara, A., additional, Pipis, J., additional, Konya, C., additional, Csonka, C., additional, Kraigher-Krainer, E., additional, Von Lewinksi, D., additional, Gonzalez-Loyola, A., additional, Barba, I., additional, Fernandez-Sanz, C., additional, Ruiz-Meana, M., additional, Forteza, M., additional, Bodi Peris, V., additional, Monleon, D., additional, Mainar, L., additional, Morales, J., additional, Moratal, D., additional, Trapero, I., additional, Chorro, F., additional, Leszek, P., additional, Sochanowicz, B., additional, Szperl, M., additional, Kolsut, P., additional, Piotrowski, W., additional, Rywik, T., additional, Danko, B., additional, Kruszewski, M., additional, Stanley, W., additional, Khairallah, R., additional, Khanna, N., additional, O'shea, K., additional, Kristian, T., additional, Hecker, P., additional, Des Rosiers, R., additional, Fiskum, G., additional, Fernandez-Alfonso, M., additional, Guzman-Ruiz, R., additional, Somoza, B., additional, Gil-Ortega, M., additional, Attane, C., additional, Castan-Laurell, I., additional, Valet, P., additional, Ruiz-Gayo, M., additional, Denissevich, T., additional, Schrepper, A., additional, Schwarzer, M., additional, Amorim, P., additional, Schoepe, M., additional, Mohr, F., additional, Doenst, T., additional, Chiellini, G., additional, Ghelardoni, S., additional, Saba, A., additional, Marchini, M., additional, Frascarelli, S., additional, Raffaelli, A., additional, Scanlan, T., additional, Zucchi, R., additional, Van Den Akker, N., additional, Molin, D., additional, Kolk, F., additional, Jeukens, F., additional, Olde Engberink, R., additional, Post, M., additional, Verbruggen, S., additional, Schulten, H., additional, Rochais, F., additional, Kelly, R., additional, Aberg, M., additional, Johnell, M., additional, Wickstrom, M., additional, Siegbahn, A., additional, Dimitrakis, P., additional, Groppalli, V., additional, Ott, D., additional, Seifriz, F., additional, Suter, T., additional, Zuppinger, C., additional, Kashcheyeu, Y., additional, Mueller, R., additional, Wiesen, M., additional, Gruendemann, D., additional, Falcao-Pires, I., additional, Fontes-Sousa, A., additional, Lopes-Conceicao, L., additional, Bras-Silva, C., additional, Leite-Moreira, A., additional, Bukauskas, F., additional, Palacios-Prado, N., additional, Norheim, F., additional, Raastad, T., additional, Thiede, B., additional, Drevon, C., additional, Haugen, F., additional, Lindner, D., additional, Westermann, D., additional, Zietsch, C., additional, Schultheiss, H.-P., additional, Tschoepe, C., additional, Horn, M., additional, Graham, H., additional, Hall, M., additional, Richards, M., additional, Clarke, J., additional, Dibb, K., additional, Trafford, A., additional, Cheng, C.-F., additional, Lin, H., additional, Eigeldiger-Berthou, S., additional, Buntschu, P., additional, Frobert, A., additional, Flueck, M., additional, Tevaearai, H., additional, Kadner, A., additional, Mikhailov, A., additional, Torrado, M., additional, Centeno, A., additional, Lopez, E., additional, Lourido, L., additional, Castro Beiras, A., additional, Popov, T., additional, Srdanovic, I., additional, Petrovic, M., additional, Canji, T., additional, Kovacevic, M., additional, Jovelic, A., additional, Sladojevic, M., additional, Panic, G., additional, Kararigas, G., additional, Fliegner, D., additional, Regitz-Zagrosek, V., additional, De La Rosa Sanchez, A., additional, Dominguez, J., additional, Sedmera, D., additional, Franco, D., additional, Medunjanin, S., additional, Burgbacher, F., additional, Han, W., additional, Zhang, J., additional, Gao, X., additional, Bayliss, C., additional, Song, W., additional, Stuckey, D., additional, Dyer, E., additional, Leung, M.-C., additional, Monserrat, L., additional, Marston, S., additional, Fusco, A., additional, Paillard, M., additional, Liang, J., additional, Strub, G., additional, Gomez, L., additional, Hait, N., additional, Allegood, J., additional, Lesnefsky, E., additional, Spiegel, S., additional, Zuchi, C., additional, Coiro, S., additional, Bettini, M., additional, Ciliberti, G., additional, Mancini, I., additional, Tritto, I., additional, Becker, L., additional, Ambrosio, G., additional, Adam, T., additional, Sharp, S., additional, Opie, L., additional, Lecour, S., additional, Khaliulin, I., additional, Parker, J., additional, Halestrap, A., additional, Kandasamy, A., additional, Osterholt, M., additional, Miro-Casas, E., additional, Boengler, K., additional, Menazza, S., additional, Canton, M., additional, Sheeran, F., additional, Di Lisa, F., additional, Pepe, S., additional, Borchi, E., additional, Manni, M., additional, Bargelli, V., additional, Giordano, C., additional, D'amati, G., additional, Nediani, C., additional, Raimondi, L., additional, Micova, P., additional, Balkova, P., additional, Kolar, F., additional, Neckar, J., additional, Novak, F., additional, Novakova, O., additional, Schuchardt, M., additional, Pruefer, N., additional, Pruefer, J., additional, Jankowski, V., additional, Jankowski, J., additional, Su, Y., additional, Zervou, S., additional, Seidel, B., additional, Radovits, T., additional, Barnucz, E., additional, Aggeli, I., additional, Kefaloyianni, E., additional, Beis, I., additional, Gaitanaki, C., additional, Lacerda, L., additional, Somers, S., additional, Paur, H., additional, Nikolaev, V., additional, Lyon, A., additional, Silva, S., additional, Gomes, M., additional, Ferreira, P., additional, Capuano, V., additional, Ferron, L., additional, Ruchon, Y., additional, Ben Mohamed, F., additional, Renaud, J.-F., additional, Goncalves, N., additional, Gavina, C., additional, Pinho, S., additional, Moura, C., additional, Amorim, M., additional, Pinho, P., additional, Christ, T., additional, Molenaar, P., additional, Kaumann, A., additional, Kletsiou, E., additional, Giannakopoulou, M., additional, Bozas, E., additional, Iliodromitis, E., additional, Anastasiou-Nana, M., additional, Papathanassoglou, E., additional, Chottova Dvorakova, M., additional, Mistrova, E., additional, Slavikova, J., additional, Hynie, S., additional, Sida, P., additional, Klenerova, V., additional, Zakrzewicz, A., additional, Hoffmann, C., additional, Hohberg, M., additional, Chlench, S., additional, Maroski, J., additional, Drab, M., additional, Siegel, G., additional, Pries, A., additional, Schrot, G., additional, Wilck, N., additional, Fechner, M., additional, Arias, A., additional, Meiners, S., additional, Baumann, G., additional, Stangl, V., additional, Stangl, K., additional, Ludwig, A., additional, Christ, A., additional, Eijgelaar, W., additional, Daemen, M., additional, Penfold, M., additional, Schall, T., additional, Hintenberger, R., additional, Kaun, C., additional, Pfaffenberger, S., additional, Maurer, G., additional, Huber, K., additional, Wojta, J., additional, Demyanets, S., additional, Titov, V., additional, Chin-Dusting, J., additional, Vaisman, B., additional, Khong, S., additional, Remaley, A., additional, Andrews, K., additional, Hoeper, A., additional, Khalid, A., additional, Fuglested, B., additional, Aasum, E., additional, Larsen, T., additional, Diebold, I., additional, Petry, A., additional, Djordjevic, T., additional, Belaiba, R., additional, Fratz, S., additional, Hess, J., additional, Kietzmann, T., additional, Goerlach, A., additional, Chess, D., additional, Walsh, K., additional, Van Der Velden, J., additional, Moreira-Goncalves, D., additional, Paulus, W., additional, Niessen, H., additional, Perlini, S., additional, Azibani, F., additional, Tournoux, F., additional, Fazal, L., additional, Polidano, E., additional, Merval, R., additional, Chatziantoniou, C., additional, Samuel, J., additional, Delcayre, C., additional, Mgandela, P., additional, Brooksbank, R., additional, Maswanganyi, T., additional, Woodiwiss, A., additional, Norton, G., additional, Makaula, S., additional, Bucciantini, M., additional, Spinelli, V., additional, Coppini, R., additional, Russo, E., additional, Stefani, M., additional, Sukumaran, V., additional, Watanabe, K., additional, Ma, M., additional, Thandavarayan, R., additional, Azrozal, W., additional, Sari, F., additional, Shimazaki, H., additional, Kobayashi, Y., additional, Roleder, T., additional, Golba, K., additional, Deja, M., additional, Malinowski, M., additional, Wos, S., additional, Grebe, M., additional, Preissner, K., additional, Ercan, E., additional, Guven, A., additional, Asgun, F., additional, Ickin, M., additional, Ercan, F., additional, Kaplan, A., additional, Yavuz, O., additional, Bagla, S., additional, Kuka, J., additional, Vilskersts, R., additional, Vavers, E., additional, Liepins, E., additional, Dambrova, M., additional, Duerr, G., additional, Suchan, G., additional, Heuft, T., additional, Klaas, T., additional, Zimmer, A., additional, Welz, A., additional, Fleischmann, B., additional, Dewald, O., additional, Voelkl, J., additional, Haubner, B., additional, Kremser, C., additional, Mayr, A., additional, Klug, G., additional, Reiner, M., additional, Pachinger, O., additional, Metzler, B., additional, Pisarenko, O., additional, Shulzhenko, V., additional, Pelogeykina, Y., additional, Khatri, D., additional, Studneva, I., additional, Bencsik, P., additional, Kocsis, G., additional, Shamloo, M., additional, Woodburn, K., additional, Szucs, G., additional, Kupai, K., additional, Csont, C., additional, Kocsisne Fodor, G., additional, Monostori, P., additional, and Turi, S., additional

Published
2010
Full Text
View/download PDF

25. High-energy phosphotransfer in the failing mouse heart: role of adenylate kinase and glycolytic enzymes.

Author

Aksentijevic D, Lygate CA, Makinen K, Zervou S, Sebag-Montefiore L, Medway D, Barnes H, Schneider JE, Neubauer S, Aksentijević, Dunja, Lygate, Craig A, Makinen, Kimmo, Zervou, Sevasti, Sebag-Montefiore, Liam, Medway, Debra, Barnes, Hannah, Schneider, Jurgen E, and Neubauer, Stefan

Abstract

Aims: To measure the activity of the key phosphotransfer enzymes creatine kinase (CK), adenylate kinase (AK), and glycolytic enzymes in two common mouse models of chronic heart failure.Methods and Results: C57BL/6 mice were subjected to transverse aortic constriction (TAC), myocardial infarction induced by coronary artery ligation (CAL), or sham operation. Activities of phosphotransfer enzymes CK, AK, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 3-phosphoglycerate kinase (PGK), and pyruvate kinase were assessed spectrophotometrically. Mice were characterized by echocardiography or magnetic resonance imaging 5- to 8-week post-surgery and selected for the presence of congestive heart failure. All mice had severe left ventricular hypertrophy, impaired systolic function and pulmonary congestion compared with sham controls. A significant decrease in myocardial CK and maximal CK reaction velocity was observed in both experimental models of heart failure. However, the activity of AK and its isoforms remained unchanged, despite a reduction in its protein expression. In contrast, the activities of glycolytic phosphotransfer mediators GAPDH and PGK were 19 and 12% higher in TAC, and 31 and 23% higher in CAL models, respectively.Conclusion: Chronic heart failure in the mouse is characterized by impaired CK function, unaltered AK, and increased activity of glycolytic phosphotransfer enzymes. This pattern of altered phosphotransfer activity was observed independent of the heart failure aetiology. [ABSTRACT FROM AUTHOR]

Published
2010
Full Text
View/download PDF

28. Xylitol-Induced Increase of Lactoperoxidase Activity.

Author

MAKINEN, K. K., TENOVUO, J., and SCHEININ, A.

Subjects
XYLITOL, PEROXIDASE, ENZYMES, SUCROSE, FRUCTOSE, ANTIBACTERIAL agents, INFLAMMATION, AMYLASES, SALIVA, GLUTAMIC acid, LACTOBACILLUS, STREPTOCOCCUS
Abstract

Persons who were fed a strict diet with regard to the type of sweeteners used (sucrose, fructose, and xylitol) displayed differences in salivary peroxidase activity. Xylitol consumption considerably increased the salivary lactoperoxidase activity. Persons habitually consuming a xylitol-containing diet may avoid certain oral inflammatory processes because of the antibacterial properties of the enzyme. [ABSTRACT FROM AUTHOR]

Published
1976

32. Purification and properties of an extracellular collagenolytic protease produced by the human oral bacterium Bacillus cereus (strain Soc 67).

Author

Makinen, K K and Makinen, P L

Abstract

The major collagenolytic proteinase present in the culture filtrate of Bacillus cereus (strain Soc 67, isolated from the human oral cavity) has been purified to homogeneity by a procedure that comprised concentration of ultrafiltered growth medium on a Millipore PTTK00005 membrane, precipitation with ammonium sulfate, gel permeation chromatography, chromatofocusing, fast protein liquid chromatography on an anion-exchange column, and finally fast protein liquid chromatography on a gel column. The enzyme hydrolyzed, with decreasing rates, phenylazobenzyloxy-carbonyl-L-Pro-L-Leu Gly-L-Pro-D-Arg (PZ-PLGPA), furylacrylolyl-L-Leu-Gly-L-Pro-L-Ala, and furylacryloyl-L-Phe-Gly-Gly, while furylacryloyl-Gly-L-Leu-NH2 was not hydrolyzed. The enzyme degraded soluble and insoluble collagens, Azocoll and gelatin. Bradykinin was hydrolyzed at a high rate at the Phe-Ser bond. The enzyme was sensitive to pyrophosphate, L-cysteine, and L-histidine and could be totally inactivated in the presence of metal chelators. The enzyme contains 1 mol of Zn/mol and the hydrolysis of PZ-PLGPA is slightly increased by Ca2+. The enzyme is readily inhibited by heavy metal cations, but Cu2+ and Ni2+ affected the catalysis in opposite ways: increasing levels of Cu2+ decreased the affinity of the enzyme for PZ-PLGPA, whereas Ni2+ had no effect. The effect of Cu2+ also depended on the pH and type of buffer used. Detailed chemical modification experiments suggested that the active site of the enzyme contains at least 1 tyrosyl and 1 lysyl residue, and 1 carboxyl group. The enzyme was not sensitive to sulfhydryl reagents and thiols did not activate the enzyme. The modification studies were unable to reveal active histidyl residues. The ability of the enzyme to hydrolyze PZ-PLGPA, furylacryloyl-L-Leu-Gly-L-Pro-L-Ala, furylacryloyl-L-Phe-Gly-Gly, and various collagenous materials, its inactivity toward furylacryloyl-Gly-L-Leu-NH2, and the results from the chemical modification studies suggest that the B. cereus (Soc 67) collagenolytic enzyme can be regarded as a true collagenase which resembles the Clostridium histolyticum collagenase(s).

Published
1987
Full Text
View/download PDF

33. Purification and characterization of an enzyme produced by Treponema denticola capable of hydrolyzing synthetic trypsin substrates

Author

Ohta, K, Makinen, K K, and Loesche, W J

Abstract

An enzyme from Treponema denticola that hydrolyzes a synthetic trypsin substrate, N-alpha-benzoyl-L-arginine-p-nitroanilide (BAPNA), was purified to near homogeneity, as judged by gel electrophoresis. The molecular weight of the enzyme was estimated to be ca. 69,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and ca. 50,000 by gel filtration on Sephadex G-100. The pH optimum for the hydrolysis of BAPNA was around 8.5. The enzyme was heat labile and irreversibly inactivated at low pH values. Enzyme activity was enhanced by Ca2+, Mg2+, and Ba2+ but inhibited by Mn2+, Hg2+, Co2+, and Zn2+. Metal chelators and sulfhydryl reagents had no effect on this activity. The enzyme was inhibited by certain protease inhibitors such as diisopropyl fluorophosphate, N-alpha-p-tosyl-L-lysine chloromethyl ketone, phenylmethylsulfonyl fluoride, L-1-tosylamide-2-phenylethylchloromethyl ketone, alpha-1-antitrypsin, and soybean trypsin inhibitor. The Km values for BAPNA and N-alpha-benzoyl-L-arginine ethyl ester were 0.05 and 0.12 mM, respectively, and the Vmax values were higher than those observed with trypsin. Although the purified enzyme hydrolyzed some low-molecular-weight synthetic trypsin substrates, it did not hydrolyze casein, hemoglobin, azocasein, azocoll, bovine serum albumin, or gelatin. Thus, this enzyme is probably not a protease but is capable of hydrolyzing ester, amide, and peptide bonds involving the carboxyl group of arginine and lysine.

Published
1986
Full Text
View/download PDF

34. Adenovirus-mediated gene transfer into an experimental pancreatic tumour

Author

Makinen, K., Loimas, S., Kosma, V. M., Wahlfors, J., Seppo Ylä-Herttuala, Alhava, E., and Janne, J.

Subjects
Male, Adenoviruses, Human, Genetic Vectors, Genetic Therapy, beta-Galactosidase, Rats, Gene Expression Regulation, Neoplastic, Pancreatic Neoplasms, Disease Models, Animal, Rats, Inbred Lew, Tumor Cells, Cultured, Animals, Immunocompetence, Carcinoma, Pancreatic Ductal
Abstract

Gene therapy has been suggested as a novel approach against pancreatic cancer, a disease with a grim prognosis with current modes of therapy. Despite recent advances in in vitro and experimental in vivo studies, there is no data available concerning gene transfer efficiency in intrapancreatic tumours in immunocompetent animal models.In in vitro studies rat pancreatic carcinoma cells (DSL-6A/C1) were transduced with replication-deficient adenovirus carrying Escherichia Coli beta-galactosidase (lacZ) gene. Gene transfer efficacy was assessed at different multiplicities of infection (MOIs). Pancreatic tumours were induced by inoculating cultured DSL-6A/C1 cancer cells into Lewis rat pancreases. Established tumours were transduced and three days post-transduction, pancreatic tumours as well as other intra-abdominal organs were harvested and processed for histological analyses, including staining for marker gene expression.In vitro assays showed that DSL-6A/C1 cells were transduced efficiently, even at low MOIs. In vivo gene transfer was successful in all animals, and all pancreatic samples showed reporter gene expression. Positive cells were detected in the peritumoural areas as well as to a lesser extent within the tumours. The transgene activity was not evenly distributed and the gene transfer efficiency varied from a few detectable blue cells to 11% per field. Our studies demonstrated safe in vivo gene transfer into intrapancreatic tumours, suggesting that pancreatic tumours are potential targets for in vivo delivery of therapeutic genes.

35. Tracing of uranium-rich boulders at Pahtavuoma, in northern Finland.

Author

Hirvas H., Makinen K., Hirvas H., and Makinen K.

Abstract

A great number of uranium-rich boulders in a number of separate boulder trains have been found in the area. The most extensive lies to the NE of the known uranium subcrop and is composed of over 400 uranium-bearing surface boulders arranged in a broad but intermittent train along the trend of the youngest glacial transport in the area. A second train of boulders, similarly rich in Mo and Cu, has been identified to the south of the known mineralisation; these are located in discharge sediments laid down as a result of an outflow from a glacial ice lake NW of the mineralisation. A further 120 uranium-bearing boulders discovered about 700 m west of the known uranium subcrop have low Mo and Cu contents and form a train which runs almost exactly N-S. Mineralisation was found at the northern tip of this train., A great number of uranium-rich boulders in a number of separate boulder trains have been found in the area. The most extensive lies to the NE of the known uranium subcrop and is composed of over 400 uranium-bearing surface boulders arranged in a broad but intermittent train along the trend of the youngest glacial transport in the area. A second train of boulders, similarly rich in Mo and Cu, has been identified to the south of the known mineralisation; these are located in discharge sediments laid down as a result of an outflow from a glacial ice lake NW of the mineralisation. A further 120 uranium-bearing boulders discovered about 700 m west of the known uranium subcrop have low Mo and Cu contents and form a train which runs almost exactly N-S. Mineralisation was found at the northern tip of this train.

36. Abstracts of presentations on plant protection issues at the xth international congress of virology: August 11-16,1996 Binyanei haOoma, Jerusalem, Israel Part 2 Plenary Lectures

Author

Ramirez, E., Hernádez, A., Ham, E., Barrón, B., Ding, S., Li, W., Shi, B., Symons, R., Li, Q., Ryu, K., Palukaitis, P., Kaplan, I., Gal-On, A., Kunhara, J., Otsubo, T., Tomaru, K., Tsuda, S., Kinta, M., Lin, T., Johnson, J., Porta, C., Taylor, K., Spall, V., Lomonossoff, G., Meiri, E., Raccah, B., Gaba, V., Ikegami, M., Kawashima, H., Murayama, A., Natsuaki, T., Kageyama, Y., Sugimura, N., Thole, V., Bol, J., Deiman, B., Koenen, A., Pleij, C., Chaleeprom, W., Bateson, M., Dale, J., Badge, J., Foster, G., Brunt, A., Robinson, D., Schubert, J., Rabenstein, F., Merits, A., Yeh, Shyi-Dong, Chiang, Chu-Hui, Wang, Ching-Hsien, Golshani, A., Ivanov, I., AbouHaidar, M., Rodoni, B., Harding, R., Oertel, U., Fuchs, E., Yang, S., Revere, F., Walter, J., Le Gall, O., Dunez, J., Candresse, T., Lot, H., Souche, S., Kasschau, Kristin, Carrington, James, Chiang, A., Turner, N., Hwang, D., Chachulska, A., Zagórski, W., Robaglia, C., Chrzanowska, M., Truve, E., Tamm, T., Saarma, M., Makinen, K., Wang, Aiming, Carrier, Karma, Wieczorek, Andrew, Huguenot, Claire, Sanfacon, Helene, Wurscher, M., Christensen, F., Prody, G., Sanchez-Navarro, J., Pallas, V., Carson, R., Dagless, E., Lock, S., Turner, R., Adams, M., Antoniw, J., Phillips, S., Kashiwazaki, S., Seal, S., Karamagioli, M., Druka, Amis, Makhdoom, Rahat, Yitang, Yan, Hull, Roger, Kikkert, M., Bodegom, P., Storms, M., van Lent, J., Kormelink, R., Goldbach, R., De Haan, P., De Rover, A., Van Schepen, A., Gielen, J., Van Grinsven, M., Livneh, O., Vardi, E., Kuznetsova, L., Aliskevicius, E., Stram, Y., Sela, I., Dinant, S., Kusiak, C., Blaise, F., Chupeau, Y., Astier, S., Albouy, J., Clifford, T., Taylor, S., Stratford, R., Xiao, X., Frenkel, M., Chu, P., Tabe, L., Shukla, D., Ward, C., Hwang, Duk-Ju, Turner, Nilgun, Mooney, A., MacFarlane, S., Twell, D., Jacquet, C., Ravelonandro, M., Bachelier, J., Almási, A., Böddi, B., Szigeti, Z., Ekes, M., Gaborianvi, R., Yankulova, Margarita, Ivanova, Lidia, Adam, G., Guelemerov, S., Nikolaeva, Velitchka, Atanassov, A., Prins, Marcel, de Haan, Peter, Goldbach, Rob, Duan, Y., Powell, C., Purcifull, D., Hiebert, E., Levine, B., Faktor, O., Zeituny, Silvy, Edelbaum, Orit, Sela, L., Marano, Maria-Rosa, Ratcliff, Frank, Baulcombe, David, van Oers, Monique, Linthorst, Huub, Bol, John, Schillberg, S., Zimmermann, S., Drossard, J., Schumann, D., Nahring, J., Fischer, R., Lapidot, Moshe, Arce-Johnson, Patricio, Rivera-Bustamante, Rafael, Beachy, Roger, Cassidy, Brandt, Flasinski, Stanislaw, Hajimorad, M., Wesley, Varsha, Angel-Diaz, J., Mayo, M., Hafner, G., May, G., Becker, D., Arntzen, C., Porter, J., Hellwald, K., Banerjee, N., Zaitlin, M., Wolf, D., Faure, J., Pilowsky, M., Cohen, S., Zelcer, A., Hardi, V., Tomassoli, L., Kaniewski, W., Mitsky, T., Barba, M., Hou, Y., Ursin, V., Sanders, R., Gilbertson, R., Gruden, Kristina, Štrukelj, Borut, Brzin, Joze, Ravnikar, Maja, Maganja, Darja, Kregar, Igor, Maki-Valkama, T., Pehu, T., Valkonen, J., Lento, K., Pehu, E., Lawson, E., Feldman, J., Zalewski, J., Kuittinen, T., Atiri, G., Romero, A., Arroyo, R., Soto, M., Martínez-Zapater, J., Ponz, F., Gilardi, P., López, L., García-Luque, I., Serra, M., Pang, Sheng-Zhi, Jan, Fuh-Jyh, Carney, Kim, Tricoli, David, Quemada, Hector, Gonsalves, Dennis, Aboul-Ata, A., Thouvenel, J., Marshall, D., Abo-El-Saad, Sh, Satour, M., Mazithulela, G., Mehlo, L., Gahakwa, D., Leech, M., Boulton, M., Davies, J., Christou, P., Huet, H., Sivamani, E., Ong, C., Chen, L., de Kochko, A., Beachy, R., Fauquet, C., Sithisarn-Burns, P., Maugeri, M., Smith, G., Handley, J., Graichen, K., Peterka, J., Chu, Paul, Larkin, Phil, Higgins, T., Wylie, S., Jones, M., Somsap, V., Loo, H., Li, D., Mathews, A., Dwyer, G., McCarthy, P., Hansen, J., Shiel, P., Zemetra, R., Wyatt, S., Berger, P., Ford, C., Collins, N., Rathjen, J., Shams-Bakhsh, M., Paltridge, N., Makkouk, K., El-Saied, M., El-Hariry, M., Salem, G., Soliman, N., Rishi, Narayan, Lodhi, G., Bishnoi, S., Sangwan, R., Sijen, Titia, Wellink, Joan, van Kammen, Ab, Scorza, R., Callahan, A., Levy, L., Polák, J., Oukropec, I., Kominek, P., Bitoova, M., Cardol, Erwin, Kormelink, Richard, Baulcombe, D., English, J., Davenport, G., Ruiz-Perez, T., Mueller, E., Nigul, L., Kelve, M., Fedorkin, O., Denisenko, O., Zelenina, D., Morozov, S., Atabekov, J., Laliberté, J., Wittmann, S., Plante, Daniel, Fortin, Marc, Chatel, H., Rodriguez-Alvarado, G., Garcia-Arenal, F., Roossinck, M., Gellatly, D., Rasochova, L., Aulik, M., Passmore, B., Falk, B., Miller, W., Lin, Na-Sheng, Lin, Biing-Yuan, Hsu, Yau-Heiu, Tamada, T., Kiguchi, T., Saito, M., Kusume, T., Uchino, H., Taliansky, M., DiSerio, F., Daròs, J., Ragozzino, A., Floras, R., Hohn, Thomas, Chen, Gang, Rothnie, Helen, Corsten, Sandra, Fütterer, Johannes, Mikhailov, M., Bishop, D., Roy, P., Ramirez, E., Hernádez, A., Ham, E., Barrón, B., Ding, S., Li, W., Shi, B., Symons, R., Li, Q., Ryu, K., Palukaitis, P., Kaplan, I., Gal-On, A., Kunhara, J., Otsubo, T., Tomaru, K., Tsuda, S., Kinta, M., Lin, T., Johnson, J., Porta, C., Taylor, K., Spall, V., Lomonossoff, G., Meiri, E., Raccah, B., Gaba, V., Ikegami, M., Kawashima, H., Murayama, A., Natsuaki, T., Kageyama, Y., Sugimura, N., Thole, V., Bol, J., Deiman, B., Koenen, A., Pleij, C., Chaleeprom, W., Bateson, M., Dale, J., Badge, J., Foster, G., Brunt, A., Robinson, D., Schubert, J., Rabenstein, F., Merits, A., Yeh, Shyi-Dong, Chiang, Chu-Hui, Wang, Ching-Hsien, Golshani, A., Ivanov, I., AbouHaidar, M., Rodoni, B., Harding, R., Oertel, U., Fuchs, E., Yang, S., Revere, F., Walter, J., Le Gall, O., Dunez, J., Candresse, T., Lot, H., Souche, S., Kasschau, Kristin, Carrington, James, Chiang, A., Turner, N., Hwang, D., Chachulska, A., Zagórski, W., Robaglia, C., Chrzanowska, M., Truve, E., Tamm, T., Saarma, M., Makinen, K., Wang, Aiming, Carrier, Karma, Wieczorek, Andrew, Huguenot, Claire, Sanfacon, Helene, Wurscher, M., Christensen, F., Prody, G., Sanchez-Navarro, J., Pallas, V., Carson, R., Dagless, E., Lock, S., Turner, R., Adams, M., Antoniw, J., Phillips, S., Kashiwazaki, S., Seal, S., Karamagioli, M., Druka, Amis, Makhdoom, Rahat, Yitang, Yan, Hull, Roger, Kikkert, M., Bodegom, P., Storms, M., van Lent, J., Kormelink, R., Goldbach, R., De Haan, P., De Rover, A., Van Schepen, A., Gielen, J., Van Grinsven, M., Livneh, O., Vardi, E., Kuznetsova, L., Aliskevicius, E., Stram, Y., Sela, I., Dinant, S., Kusiak, C., Blaise, F., Chupeau, Y., Astier, S., Albouy, J., Clifford, T., Taylor, S., Stratford, R., Xiao, X., Frenkel, M., Chu, P., Tabe, L., Shukla, D., Ward, C., Hwang, Duk-Ju, Turner, Nilgun, Mooney, A., MacFarlane, S., Twell, D., Jacquet, C., Ravelonandro, M., Bachelier, J., Almási, A., Böddi, B., Szigeti, Z., Ekes, M., Gaborianvi, R., Yankulova, Margarita, Ivanova, Lidia, Adam, G., Guelemerov, S., Nikolaeva, Velitchka, Atanassov, A., Prins, Marcel, de Haan, Peter, Goldbach, Rob, Duan, Y., Powell, C., Purcifull, D., Hiebert, E., Levine, B., Faktor, O., Zeituny, Silvy, Edelbaum, Orit, Sela, L., Marano, Maria-Rosa, Ratcliff, Frank, Baulcombe, David, van Oers, Monique, Linthorst, Huub, Bol, John, Schillberg, S., Zimmermann, S., Drossard, J., Schumann, D., Nahring, J., Fischer, R., Lapidot, Moshe, Arce-Johnson, Patricio, Rivera-Bustamante, Rafael, Beachy, Roger, Cassidy, Brandt, Flasinski, Stanislaw, Hajimorad, M., Wesley, Varsha, Angel-Diaz, J., Mayo, M., Hafner, G., May, G., Becker, D., Arntzen, C., Porter, J., Hellwald, K., Banerjee, N., Zaitlin, M., Wolf, D., Faure, J., Pilowsky, M., Cohen, S., Zelcer, A., Hardi, V., Tomassoli, L., Kaniewski, W., Mitsky, T., Barba, M., Hou, Y., Ursin, V., Sanders, R., Gilbertson, R., Gruden, Kristina, Štrukelj, Borut, Brzin, Joze, Ravnikar, Maja, Maganja, Darja, Kregar, Igor, Maki-Valkama, T., Pehu, T., Valkonen, J., Lento, K., Pehu, E., Lawson, E., Feldman, J., Zalewski, J., Kuittinen, T., Atiri, G., Romero, A., Arroyo, R., Soto, M., Martínez-Zapater, J., Ponz, F., Gilardi, P., López, L., García-Luque, I., Serra, M., Pang, Sheng-Zhi, Jan, Fuh-Jyh, Carney, Kim, Tricoli, David, Quemada, Hector, Gonsalves, Dennis, Aboul-Ata, A., Thouvenel, J., Marshall, D., Abo-El-Saad, Sh, Satour, M., Mazithulela, G., Mehlo, L., Gahakwa, D., Leech, M., Boulton, M., Davies, J., Christou, P., Huet, H., Sivamani, E., Ong, C., Chen, L., de Kochko, A., Beachy, R., Fauquet, C., Sithisarn-Burns, P., Maugeri, M., Smith, G., Handley, J., Graichen, K., Peterka, J., Chu, Paul, Larkin, Phil, Higgins, T., Wylie, S., Jones, M., Somsap, V., Loo, H., Li, D., Mathews, A., Dwyer, G., McCarthy, P., Hansen, J., Shiel, P., Zemetra, R., Wyatt, S., Berger, P., Ford, C., Collins, N., Rathjen, J., Shams-Bakhsh, M., Paltridge, N., Makkouk, K., El-Saied, M., El-Hariry, M., Salem, G., Soliman, N., Rishi, Narayan, Lodhi, G., Bishnoi, S., Sangwan, R., Sijen, Titia, Wellink, Joan, van Kammen, Ab, Scorza, R., Callahan, A., Levy, L., Polák, J., Oukropec, I., Kominek, P., Bitoova, M., Cardol, Erwin, Kormelink, Richard, Baulcombe, D., English, J., Davenport, G., Ruiz-Perez, T., Mueller, E., Nigul, L., Kelve, M., Fedorkin, O., Denisenko, O., Zelenina, D., Morozov, S., Atabekov, J., Laliberté, J., Wittmann, S., Plante, Daniel, Fortin, Marc, Chatel, H., Rodriguez-Alvarado, G., Garcia-Arenal, F., Roossinck, M., Gellatly, D., Rasochova, L., Aulik, M., Passmore, B., Falk, B., Miller, W., Lin, Na-Sheng, Lin, Biing-Yuan, Hsu, Yau-Heiu, Tamada, T., Kiguchi, T., Saito, M., Kusume, T., Uchino, H., Taliansky, M., DiSerio, F., Daròs, J., Ragozzino, A., Floras, R., Hohn, Thomas, Chen, Gang, Rothnie, Helen, Corsten, Sandra, Fütterer, Johannes, Mikhailov, M., Bishop, D., and Roy, P.

47. Treatment With FoxP3+ Antigen-Experienced T Regulatory Cells Arrests Progressive Retinal Damage in a Spontaneous Model of Uveitis.

Author

Liu YH, Mölzer C, Makinen K, Kamoi K, Corbett CLC, Klaska IP, Reid DM, Wilson HM, Kuffová L, Cornall RJ, and Forrester JV

Subjects
Animals, Cells, Cultured, Disease Models, Animal, Eye Proteins immunology, Forkhead Transcription Factors metabolism, Humans, Immune Tolerance, Interleukin-2 Receptor alpha Subunit metabolism, Mice, Mice, Transgenic, Retinol-Binding Proteins immunology, T-Lymphocytes, Regulatory transplantation, Autoimmune Diseases immunology, Immunotherapy, Adoptive methods, Retina pathology, T-Lymphocytes, Regulatory immunology, Uveitis immunology
Abstract

We specify the clinical features of a spontaneous experimental autoimmune uveitis (EAU) model, in which foreign hen-egg lysozyme (HEL) is expressed in the retina, controlled by the promoter for interphotoreceptor retinol binding protein (IRBP). We previously reported 100% P21 (post-partum day) IRBP:HEL single transgenic (sTg) mice, when crossed to transgenic T cell receptor mice (3A9) generating the double transgenic (dTg) genotype, develop EAU despite profound lymphopenia (thymic HEL-specific T cell deletion). In this work, we characterized the immune component of this model and found conventional dTg CD4+ T cells were less anergic than those from 3A9 controls. Furthermore, prior in vitro HEL-activation of 3A9 anergic T cells (T an ) rendered them uveitogenic upon adoptive transfer (Tx) to sTg mice, while antigen-experienced (AgX, dTg), but not naïve (3A9) T cells halted disease in P21 dTg mice. Flow cytometric analysis of the AgX cells elucidated the underlying pathology: FoxP3+CD25 hi CD4+ T regulatory cells (T reg ) comprised ∼18%, while FR4+CD73+FoxP3-CD25 lo/- CD4+ T an comprised ∼1.2% of total cells. Further T reg -enrichment (∼80%) of the AgX population indicated FoxP3+CD25 hi CD4+ T reg played a key role in EAU-suppression while FoxP3-CD25 lo/- CD4+ T cells did not. Here we present the novel concept of dual immunological tolerance where spontaneous EAU is due to escape from anergy with consequent failure of T reg induction and subsequent imbalance in the [T reg :T effector ] cell ratio. The reduced numbers of T an , normally sustaining T reg to prevent autoimmunity, are the trigger for disease, while immune homeostasis can be restored by supplementation with AgX, but not naïve, antigen-specific T reg ., (Copyright © 2020 Liu, Mölzer, Makinen, Kamoi, Corbett, Klaska, Reid, Wilson, Kuffová, Cornall and Forrester.)

Published
2020
Full Text
View/download PDF

48. Preterm Birth: A Narrative Review of the Current Evidence on Nutritional and Bioactive Solutions for Risk Reduction.

Author

Samuel TM, Sakwinska O, Makinen K, Burdge GC, Godfrey KM, and Silva-Zolezzi I

Subjects
Female, Humans, Risk Factors, Maternal Nutritional Physiological Phenomena, Nutritional Status, Premature Birth
Abstract

Preterm birth (PTB) (<37 weeks of gestation) is the leading cause of newborn death and a risk factor for short and long-term adverse health outcomes. Most cases are of unknown cause. Although the mechanisms triggering PTB remain unclear, an inappropriate increase in net inflammatory load seems to be key. To date, interventions that reduce the risk of PTB are effective only in specific groups of women, probably due to the heterogeneity of its etiopathogenesis. Use of progesterone is the most effective, but only in singleton pregnancies with history of PTB. Thus, primary prevention is greatly needed and nutritional and bioactive solutions are a promising alternative. Among these, docosahexaenoic acid (DHA) is the most promising to reduce the risk for early PTB. Other potential nutrient interventions include the administration of zinc (possibly limited to populations with low nutritional status or poor zinc status) and vitamin D; additional preliminary evidence exists for vitamin A, calcium, iron, folic acid, combined iron-folate, magnesium, multiple micronutrients, and probiotics. Considering the public health relevance of PTB, promising interventions should be studied in large and well-designed clinical trials. The objective of this review is to describe, summarize, and discuss the existing evidence on nutritional and bioactive solutions for reducing the risk of PTB.

Published
2019
Full Text
View/download PDF

49. Partial retinal photoreceptor loss in a transgenic mouse model associated with reduced levels of interphotoreceptor retinol binding protein (IRBP, RBP3).

Author

Liu YH, Corbett C, Klaska IP, Makinen K, Nickerson JM, Cornall RJ, Kuffova L, and Forrester JV

Subjects
Animals, Blotting, Western, Immunohistochemistry, Mice, Mice, Transgenic, Muramidase genetics, Photoreceptor Cells, Vertebrate metabolism, Polymerase Chain Reaction, Retinal Degeneration genetics, Retinal Degeneration metabolism, Transgenes, Disease Models, Animal, Eye Proteins metabolism, Photoreceptor Cells, Vertebrate pathology, Retinal Degeneration pathology, Retinol-Binding Proteins metabolism
Abstract

Organ-specific transgenic membrane expression of hen egg lysozyme (HEL) as a "neo-self antigen" has been used in several models to study immunological tolerance. In this study we report the changes which occur in the B10.BR mouse retina when membrane-bound HEL is expressed in photoreceptors under the control of the promoter for interphotoreceptor retinoid binding protein (IRBP, RBP3). On direct clinical examination of the single transgenic (sTg-IRBP:HEL) mouse fundus, a low-level increase in retinal degeneration compared to non-transgenic controls was observed, presenting as drusenoid deposits and occasional small patches of atrophy. On histological examination, there was an overall shortening of outer segments and loss of photoreceptor nuclei in sTg-IRBP:HEL mice, which was more pronounced in the retinal periphery, particularly inferiorly. The fundoscopically observed lesions did not correlate with the photoreceptor shortening/loss but appeared to be located at the level of the retinal pigment epithelium/choriocapillaris layer and were an exaggeration in size and number of similar age-related changes found in wild type (WT) mice. In addition, neither the atrophic lesions nor the photoreceptor shortening were associated with common retinal degeneration genes, nor were they caused by exposure to light damage since mice housed at both high and low ambient light levels had similar degrees of retinal degeneration. Instead, sTg-IRBP:HEL mice expressed reduced levels of soluble retinal IRBP compared to WT mice which were present from postnatal day16 (P16) and preceded development of photoreceptor shortening (onset P21). We propose that insertion of the HEL transgene in the photoreceptor membrane disrupted normal photoreceptor function and led to reduced levels of soluble IRBP and retinal thinning. A similar phenotype has been observed in IRBP deficient mice. Despite the retinal thinning, the amount of HEL expressed in the retina was sufficient to act as an autoantigenic target when the mice were crossed to the HEL T cell receptor Tg mouse, since double transgenic (dTg-IRBP:HEL) mice spontaneously developed a severe uveoretinitis with onset at weaning. We suggest that, although membrane expression of foreign transgene products is likely to modify the structure and function of tissues and cells, the technology provides useful models to investigate mechanisms of antigen-specific immunological tolerance., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Published
2018
Full Text
View/download PDF

50. Ocular antigen does not cause disease unless presented in the context of inflammation.

Author

Voigt V, Wikstrom ME, Kezic JM, Schuster IS, Fleming P, Makinen K, Daley SR, Andoniou CE, Degli-Esposti MA, and Forrester JV

Subjects
Animals, Antigen Presentation, Autoimmunity, CD4-Positive T-Lymphocytes cytology, Cell Proliferation, Cross Reactions, Inflammation immunology, Mice, Muramidase immunology, Risk, Autoantigens immunology, Retina immunology
Abstract

Ocular antigens are sequestered behind the blood-retina barrier and the ocular environment protects ocular tissues from autoimmune attack. The signals required to activate autoreactive T cells and allow them to cause disease in the eye remain in part unclear. In particular, the consequences of peripheral presentation of ocular antigens are not fully understood. We examined peripheral expression and presentation of ocular neo-self-antigen in transgenic mice expressing hen egg lysozyme (HEL) under a retina-specific promoter. High levels of HEL were expressed in the eye compared to low expression throughout the lymphoid system. Adoptively transferred naïve HEL-specific CD4 + T cells proliferated in the eye draining lymph nodes, but did not induce uveitis. By contrast, systemic infection with a murine cytomegalovirus (MCMV) engineered to express HEL induced extensive proliferation of transferred naïve CD4 + T cells, and significant uveoretinitis. In this model, wild-type MCMV, lacking HEL, did not induce overt uveitis, suggesting that disease is mediated by antigen-specific peripherally activated CD4 + T cells that infiltrate the retina. Our results demonstrate that retinal antigen is presented to T cells in the periphery under physiological conditions. However, when the same antigen is presented during viral infection, antigen-specific T cells access the retina and autoimmune uveitis ensues.

Published
2017
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results