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5. Secretion-mediated STAT3 activation promotes self-renewal of glioma stem-like cells during hypoxia

Author

Almiron Bonnin, D A, Havrda, M C, Lee, M C, Liu, H, Zhang, Z, Nguyen, L N, Harrington, L X, Hassanpour, S, Cheng, C, and Israel, M A

Abstract

High-grade gliomas (HGGs) include the most common and the most aggressive primary brain tumor of adults and children. Despite multimodality treatment, most high-grade gliomas eventually recur and are ultimately incurable. Several studies suggest that the initiation, progression, and recurrence of gliomas are driven, at least partly, by cancer stem-like cells. A defining characteristic of these cancer stem-like cells is their capacity to self-renew. We have identified a hypoxia-induced pathway that utilizes the Hypoxia Inducible Factor 1a (HIF-1a) transcription factor and the JAK1/2-STAT3 (Janus Kinase 1/2 - Signal Transducer and Activator of Transcription 3) axis to enhance the self-renewal of glioma stem-like cells. Hypoxia is a commonly found pathologic feature of HGGs. Under hypoxic conditions, HIF-1a levels are greatly increased in glioma stem-like cells. Increased HIF-1a activates the JAK1/2-STAT3 axis and enhances tumor stem-like cell self-renewal. Our data further demonstrate the importance of Vascular Endothelial Growth Factor (VEGF) secretion for this pathway of hypoxia-mediated self-renewal. Brefeldin A and EHT-1864, agents that significantly inhibit VEGF secretion, decreased stem cell self-renewal, inhibited tumor growth, and increased the survival of mice allografted with S100ß-v-erbB/p53-/-glioma stem-like cells. These agents also inhibit the expression of a hypoxia gene expression signature that is associated with decreased survival of HGG patients. These findings suggest that targeting the secretion of extracellular, autocrine/paracrine mediators of glioma stem-like cell self-renewal could potentially contribute to the treatment of HGGs.

Published
2018
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6. Extended follow-up of the CYCLOFA-LUNE trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide or on cyclosporine A

Author

Závada, J, primary, Pešičková, S Sinikka, additional, Ryšavá, R, additional, Horák, P, additional, Hrnčíř, Z, additional, Lukáč, J, additional, Rovenský, J, additional, Vítová, J, additional, Havrda, M, additional, Rychlík, I, additional, Böhmova, J, additional, Vlasáková, V, additional, Slatinská, J, additional, Zadražil, J, additional, Olejárová, M, additional, Tegzova, D, additional, and Tesar, V, additional

Published
2013
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7. THU0280 Extended Follow-Up of the Cyclofa-Lune Trial Comparing Two Sequential Induction and Maintenance Treatment Regimens for Proliferative Lupus Nephritis Based Either on Cyclophosphamide or Cyclosporine a

Author

Zavada, J., primary, Pesickova, S. S., additional, Rysava, R., additional, Horak, P., additional, Hrncir, Z., additional, Lukac, J., additional, Rovensky, J., additional, Vitova, J., additional, Bohmova, J., additional, Havrda, M., additional, Tegzova, D., additional, Olejarova, M., additional, and Tesar, V., additional

Published
2013
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8. Lab methods / biomarkers

Author

Borras, M., primary, Roig, J., additional, Betriu, A., additional, Vilar, A., additional, Hernandez, M., additional, Martin, M., additional, Fernandez, E. D., additional, Dounousi, E., additional, Kiatou, V., additional, Papagianni, A., additional, Zikou, X., additional, Pappas, K., additional, Pappas, E., additional, Tatsioni, A., additional, Tsakiris, D., additional, Siamopoulos, K. C., additional, Kim, J.-K., additional, Kim, Y., additional, Kim, S. G., additional, Kim, H. J., additional, Ahn, S. Y., additional, Chin, H. J., additional, Oh, K.-H., additional, Ahn, C., additional, Chae, D.-W., additional, Yazici, R., additional, Altintepe, L., additional, Bakdik, S., additional, Guney, I., additional, Arslan, S., additional, Topal, M., additional, Karagoz, A., additional, Stefan, G., additional, Mircescu, G., additional, Capusa, C., additional, Stancu, S., additional, Petrescu, L., additional, Alecu, S., additional, Nedelcu, D., additional, Bennett, A. H. L., additional, Pham, H., additional, Garrity, M., additional, Magdeleyns, E., additional, Vermeer, C., additional, Zhang, M., additional, Ni, Z., additional, Zhu, M., additional, Yan, J., additional, Mou, S., additional, Wang, Q., additional, Qian, J., additional, Saade, A., additional, Karavetian, M., additional, ElZein, H., additional, de Vries, N., additional, de Haseth, D. E., additional, Lay Penne, E., additional, van Dam, B., additional, Bax, W. A., additional, Bots, M. L., additional, Grooteman, M. P. C., additional, van den Dorpel, R. A., additional, Blankenstijn, P. J., additional, Nube, M. J., additional, Wee, P. M., additional, Park, J. H., additional, Jo, Y.-I., additional, Lee, J. H., additional, Cianfrone, P., additional, Comi, N., additional, Lucisano, G., additional, Piraina, V., additional, Talarico, R., additional, Fuiano, G., additional, Toyonaga, M., additional, Fukami, K., additional, Yamagishi, S.-i., additional, Kaida, Y., additional, Nakayama, Y., additional, Ando, R., additional, Obara, N., additional, Ueda, S., additional, Okuda, S., additional, Granatova, J., additional, Havrda, M., additional, Hruskova, Z., additional, Tesar, V., additional, Viklicky, O., additional, Rysava, R., additional, Rychlik, I., additional, Kratka, K., additional, Honsova, E., additional, Vernerova, Z., additional, Maluskova, J., additional, Vranova, J., additional, Bolkova, M., additional, Borecka, K., additional, Benakova, H., additional, Zima, T., additional, Lu, K.-C., additional, Yang, H.-Y., additional, Su, S.-L., additional, Cao, Y.-H., additional, Lv, L.-L., additional, Liu, B.-C., additional, Zeng, R., additional, Gao, X.-F., additional, Deng, Y.-Y., additional, Boelaert, J., additional, t' Kindt, R., additional, Glorieux, G., additional, Schepers, E., additional, Jorge, L., additional, Neirynck, N., additional, Lynen, F., additional, Sandra, P., additional, Sandra, K., additional, Vanholder, R., additional, Yamamoto, T., additional, Nameta, M., additional, Yoshida, Y., additional, Uhlen, M., additional, Shi, Y., additional, Tang, J., additional, Zhang, J., additional, An, Y., additional, Liao, Y., additional, Li, Y., additional, Tao, Y., additional, Wang, L., additional, Koibuchi, K., additional, Tanaka, K., additional, Aoki, T., additional, Miyagi, M., additional, Sakai, K., additional, Aikawa, A., additional, Martins, A. R., additional, Branco, P. Q., additional, Serra, F. M., additional, Matias, P. J., additional, Lucas, C. P., additional, Adragao, T., additional, Duarte, J., additional, Oliveira, M. M., additional, Saraiva, A. M., additional, Barata, J. D., additional, Masola, V., additional, Zaza, G., additional, Granata, S., additional, Proglio, M., additional, Pontrelli, P., additional, Abaterusso, C., additional, Schena, F., additional, Gesualdo, L., additional, Gambaro, G., additional, Lupo, A., additional, Pruijm, M., additional, Hofmann, L., additional, Stuber, M., additional, Zweiacker, C., additional, Piskunowicz, M., additional, Muller, M.-E., additional, Vogt, B., additional, Burnier, M., additional, Togashi, N., additional, Yamashita, T., additional, Mita, T., additional, Ohnuma, Y., additional, Hasegawa, T., additional, Endo, T., additional, Tsuchida, A., additional, Ando, T., additional, Yoshida, H., additional, Miura, T., additional, Bevins, A., additional, Assi, L., additional, Ritchie, J., additional, Jesky, M., additional, Stringer, S., additional, Kalra, P., additional, Hutchison, C., additional, Harding, S., additional, Cockwell, P., additional, Viccica, G., additional, Cupisti, A., additional, Chiavistelli, S., additional, Borsari, S., additional, Pardi, E., additional, Centoni, R., additional, Fumagalli, G., additional, Cetani, F., additional, Marcocci, C., additional, Scully, P., additional, O'Flaherty, D., additional, Sankaralingam, A., additional, Hampson, G., additional, Goldsmith, D. J., additional, Pallet, N., additional, Chauvet, S., additional, Beaune, P., additional, Nochy, D., additional, Thervet, E., additional, Karras, A., additional, Bertho, G., additional, Gallyamov, M. G., additional, Saginova, E. A., additional, Severova, M. M., additional, Krasnova, T. N., additional, Kopylova, A. A., additional, Cho, E., additional, Jo, S.-K., additional, Kim, M.-G., additional, Cho, W.-Y., additional, kim, H. K., additional, Trivin, C., additional, Metzger, M., additional, Boffa, J.-J., additional, Vrtovsnik, F., additional, Houiller, P., additional, Haymann, J.-P., additional, Flamant, M., additional, Stengel, B., additional, Roozbeh, J., additional, Yavari, V., additional, Pakfetrat, M., additional, Zolghadr, A. A., additional, Kim, C. S., additional, Kim, M. J., additional, Kang, Y. U., additional, Choi, J. S., additional, Bae, E. H., additional, Ma, S. K., additional, Kim, S. W., additional, Lemoine, S., additional, Guebre-Egziabher, F., additional, Dubourg, L., additional, Hadj-Aissa, A., additional, Blumberg, S., additional, Katzir, Z., additional, Biro, A., additional, Cernes, R., additional, Barnea, Z., additional, Vasquez, D., additional, Gordillo, R., additional, Aller, C., additional, Fernandez, B., additional, Jabary, N., additional, Perez, V., additional, Mendiluce, A., additional, Bustamante, J., additional, Coca, A., additional, Goek, O.-N., additional, Sekula, P., additional, Prehn, C., additional, Meisinger, C., additional, Gieger, C., additional, Suhre, K., additional, Adamski, J., additional, Kastenmuller, G., additional, Kottgen, A., additional, Kuzniewski, M., additional, Fedak, D., additional, Dumnicka, P., additional, Solnica, B., additional, Kusnierz-Cabala, B., additional, Kapusta, M., additional, Sulowicz, W., additional, Drozdz, R., additional, Zawada, A. M., additional, Rogacev, K. S., additional, Hummel, B., additional, Fliser, D., additional, Geisel, J., additional, Heine, G. H., additional, Kretschmer, A., additional, Volsek, M., additional, Krahn, T., additional, Kolkhof, P., additional, Kribben, A., additional, Bruck, H., additional, Koh, E. S., additional, Chung, S., additional, Yoon, H. E., additional, Park, C. W., additional, Chang, Y. S., additional, Shin, S. J., additional, Deagostini, M. C., additional, Vigotti, F. N., additional, Ferraresi, M., additional, Consiglio, V., additional, Scognamiglio, S., additional, Moro, I., additional, Clari, R., additional, Daidola, G., additional, Versino, E., additional, Piccoli, G. B., additional, Mammadrahim Agayev, M., additional, Mehrali Mammadova, I., additional, Qarib Ismayilova, S., additional, Anguiano, L., additional, Riera, M., additional, Pascual, J., additional, Barrios, C., additional, Valdivielso, J. M., additional, Fernandez, E., additional, Soler, M. J., additional, Tsarpali, V., additional, Liakopoulos, V., additional, Panagopoulou, E., additional, Kapoukranidou, D., additional, Spaia, S., additional, Kostopoulou, M., additional, Michalaki, A., additional, Nikitidou, O., additional, Dombros, N., additional, Zhu, F., additional, Abba, S., additional, Flores-Gama, C., additional, Williams, C., additional, Cartagena, C., additional, Carter, M., additional, Kotanko, P., additional, Levin, N. W., additional, Kolesnyk, M., additional, Stepanova, N., additional, Driyanska, V., additional, Stashevska, N., additional, Kundin, V., additional, Shifris, I., additional, Dudar, I., additional, Zaporozhets, O., additional, Keda, T., additional, Ishchenko, M., additional, Khil, M., additional, Choe, J.-Y., additional, Nam, S.-A., additional, Kim, J., additional, Cha, J.-H., additional, Gliga, M. L., additional, Irimescu, C. G., additional, Caldararu, C. D., additional, Gliga, M. G., additional, Toma, L. V., additional, Gomotarceanu, A., additional, Park, Y., additional, Jeon, J., additional, Kwon, S. K., additional, Kim, S. J., additional, Kim, S. M., additional, Kim, H.-Y., additional, Montero, N., additional, Marquez, E., additional, Berrada, A., additional, Arias, C., additional, Prada, J. A., additional, Orfila, M. A., additional, Mojal, S., additional, Vilaplana, C., additional, Attini, R., additional, Parisi, S., additional, Fassio, F., additional, Ghiotto, S., additional, Biolcati, M., additional, Todros, T., additional, Jin, K., additional, Vaziri, N. D., additional, Tramonti, G., additional, Romiti, N., additional, Chieli, E., additional, Maksudova, A. N., additional, Khusnutdinova, L. A., additional, Reque, J. E., additional, Quiroga, B., additional, Lopez, J. M., additional, Verdallez, U. G., additional, Garcia de Vinuesa, M., additional, Goicoechea, M., additional, Nayara, P. G., additional, Arroyo, D. R., additional, Luno, J., additional, Tanaka, H., additional, Abbas, S. R., additional, Thijssen, S., additional, Berthoux, F. C., additional, Azzouz, L., additional, Afiani, A., additional, Ziane, A., additional, Mariat, C., additional, Fournier, H., additional, Kusztal, M., additional, Dzierzek, P., additional, Witkowski, G., additional, Nurzynski, M., additional, Golebiowski, T., additional, Weyde, W., additional, Klinger, M., additional, Altiparmak, M. R., additional, Seyahi, N., additional, Trabulus, S., additional, Bolayirli, M., additional, Andican, Z. G., additional, Suleymanlar, G., additional, Serdengecti, K., additional, Niculae, A., additional, Checherita, I.-A., additional, Neagoe, D.-N., additional, Ciocalteu, A., additional, Seiler, S., additional, Pickering, J. W., additional, Emrich, I., additional, Heine, G., additional, Bargnoux, A.-S., additional, Obiols, J., additional, Kuster, N., additional, Fessler, P., additional, Badiou, S., additional, Dupuy, A.-M., additional, Ribstein, J., additional, Cristol, J.-P., additional, Yanagisawa, N., additional, Ando, M., additional, Ajisawa, A., additional, Tsuchiya, K., additional, Nitta, K., additional, Bouquegneau, A., additional, Cavalier, E., additional, Krzesinski, J.-M., additional, Delanaye, P., additional, Tominaga, N., additional, Shibagaki, Y., additional, Kida, K., additional, Miyake, F., additional, Kimura, K., additional, Ayvazyan, A., additional, Rameev, V., additional, Kozlovskaya, L., additional, Simonyan, A., additional, Scholze, A., additional, Marckmann, P., additional, Tepel, M., additional, Rasmussen, L. M., additional, Hara, M., additional, Kanai, H., additional, Harada, K., additional, Tamura, Y., additional, Kawai, Y., additional, Al-Jebouri, M. M., additional, Madash, S. A., additional, Leonidovna Berezinets, O., additional, and Nicolaevich Rossolovskiy, A., additional

Published
2013
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9. AKI - Clinical

Author

Gok Oguz, E., primary, Olmaz, R., additional, Turgutalp, K., additional, Muslu, N., additional, Sungur, M. A., additional, Kiykim, A., additional, Van Biesen, W., additional, Vanmassenhove, J., additional, Glorieux, G., additional, Vanholder, R., additional, Chew, S., additional, Forster, K., additional, Kaufeld, T., additional, Kielstein, J., additional, Schilling, T., additional, Haverich, A., additional, Haller, H., additional, Schmidt, B., additional, Hu, P., additional, Liang, X., additional, Chen, Y., additional, LI, R., additional, Jiang, F., additional, LI, Z., additional, Shi, W., additional, Lim, C. C. W., additional, Chia, C. M. L., additional, Tan, A. K., additional, Tan, C. S., additional, Ng, R., additional, Subramani, S., additional, Perez de Jose, A., additional, Bernis Carro, C., additional, Madero Jarabo, R., additional, Bustamante, J., additional, Sanchez Tomero, J. A., additional, Chung, W., additional, Ro, H., additional, Chang, J. H., additional, Lee, H. H., additional, Jung, J. Y., additional, Fazzari, L., additional, Giuliani, A., additional, Scrivano, J., additional, Pettorini, L., additional, Benedetto, U., additional, Luciani, R., additional, Roscitano, A., additional, Napoletano, A., additional, Coclite, D., additional, Cordova, E., additional, Punzo, G., additional, Sinatra, R., additional, Mene, P., additional, Pirozzi, N., additional, Shavit, L., additional, Manilov, R., additional, Algur, N., additional, Wiener-Well, Y., additional, Slotki, I., additional, Pipili, C., additional, Vrettou, C. S., additional, Avrami, K., additional, Economidou, F., additional, Glynos, K., additional, Ioannidou, S., additional, Markaki, V., additional, Douka, E., additional, Nanas, S., additional, De Pascalis, A., additional, Cofano, P., additional, Proia, S., additional, Valletta, A., additional, Vitale, O., additional, Russo, F., additional, Buongiorno, E., additional, Filiopoulos, V., additional, Biblaki, D., additional, Lazarou, D., additional, Chrysis, D., additional, Fatourou, M., additional, Lafoyianni, S., additional, Vlassopoulos, D., additional, Zakiyanov, O., additional, Kriha, V., additional, Vachek, J., additional, Svarcova, J., additional, Zima, T., additional, Tesar, V., additional, Kalousova, M., additional, Kaushik, M., additional, Ronco, C., additional, Cruz, D., additional, Zhang, L., additional, Zhang, W., additional, Chen, N., additional, Ejaz, A. A., additional, Kambhampati, G., additional, Ejaz, N., additional, Dass, B., additional, Lapsia, V., additional, Arif, A. A., additional, Asmar, A., additional, Shimada, M., additional, Alsabbagh, M., additional, Aiyer, R., additional, Johnson, R., additional, Chen, T.-H., additional, Chang, C.-H., additional, Chang, M.-Y., additional, Tian, Y.-C., additional, Hung, C.-C., additional, Fang, J.-T., additional, Yang, C.-W., additional, Chen, Y.-C., additional, Cantaluppi, V., additional, Quercia, A. D., additional, Figliolini, F., additional, Giacalone, S., additional, Pacitti, A., additional, Gai, M., additional, Guarena, C., additional, Leonardi, G., additional, Biancone, L., additional, Camussi, G., additional, Segoloni, G. P., additional, De Cal, M., additional, Lentini, P., additional, Clementi, A., additional, Virzi, G. M., additional, Scalzotto, E., additional, Lacquaniti, A., additional, Donato, V., additional, Fazio, M. R., additional, Lucisano, S., additional, Cernaro, V., additional, Lupica, R., additional, Buemi, M., additional, Helvaci, I., additional, Anik, E., additional, Wani, M., additional, Wani, D. I., additional, Bhat, D. M. A., additional, Banday, D. K., additional, Najar, D. M. S., additional, Reshi, D. A. R., additional, Palla, D. N. A., additional, Iglesias, P., additional, Olea, T., additional, Vega-Cabrera, C., additional, Heras, M., additional, Bajo, M. A., additional, Del Peso, G., additional, Arias, M. J., additional, Selgas, R., additional, Diez, J. J., additional, Daher, E., additional, Costa, P. L., additional, Pereira, E. N. S., additional, Santos, R. D. P., additional, Abreu, K. L., additional, Silva Junior, G., additional, Pereira, E. D. B., additional, Raimundo, M., additional, Crichton, S., additional, Syed, Y., additional, Martin, J., additional, Whiteley, C., additional, Bennett, D., additional, Ostermann, M., additional, Gjyzari, A., additional, Thereska, N., additional, Koroshi, A., additional, Barbullushi, M., additional, Kodra, S., additional, Idrizi, A., additional, Strakosha, A., additional, Petrela, E., additional, Lemmich Smith, J., additional, Klimenko, A., additional, Tuykhmenev, E., additional, Villevalde, S., additional, Kobalava, Z., additional, Avdoshina, S., additional, Tyukhmenev, E., additional, Efremovtseva, M., additional, Hayashi, H., additional, Suzuki, S., additional, Kataoka, K., additional, Kondoh, Y., additional, Taniguchi, H., additional, Sugiyama, D., additional, Nishimura, K., additional, Sato, W., additional, Maruyama, S., additional, Matsuo, S., additional, Yuzawa, Y., additional, Geraldine, D., additional, Muriel, F., additional, Alexandre, H., additional, Eric, R., additional, Fu, P., additional, Pozzato, M., additional, Ferrari, F., additional, Cecere, P., additional, Mesiano, P., additional, Vallero, A., additional, Livigni, S., additional, Quarello, F., additional, Hudier, L., additional, Decaux, O., additional, Haddj-Elmrabet, A., additional, Mandart, L., additional, Lino-Daniel, M., additional, Bridoux, F., additional, Renaudineau, E., additional, Sawadogo, T., additional, Le Pogamp, P., additional, Vigneau, C., additional, Famee, D., additional, Koo, H. M., additional, Oh, H. J., additional, Han, S. H., additional, Choi, K. H., additional, Kang, S.-W., additional, Mehdi, M., additional, Nicolas, M., additional, Mariat, C., additional, Shah, P., additional, Kute, V. B., additional, Vanikar, A., additional, Gumber, M., additional, Patel, H., additional, Trivedi, H., additional, Manetos, C., additional, Poulaki, S., additional, Tripodaki, E.-S., additional, Papastylianou, A., additional, Routsi, C., additional, Uchida, K., additional, Kensuke, U., additional, Yamagata, K., additional, Saitou, C., additional, Okada, M., additional, Chita, G., additional, Davies, M., additional, Veriawa, Y., additional, Naicker, S., additional, Mukhopadhyay, P., additional, Mukherjee, D., additional, Mishra, R., additional, Kar, M., additional, Zickler, D., additional, Wesselmann, H., additional, Schindler, R., additional, Gutierrez*, E., additional, Egido, J., additional, Rubio-Navarro, A., additional, Buendia, I., additional, Blanco-Colio, L. M., additional, Toldos, O., additional, Manzarbeitia, F., additional, De Lorenzo, A., additional, Sanchez, R., additional, Praga^, M., additional, Moreno^, J. A., additional, Kim, M. Y., additional, Kang, N. R., additional, Jang, H. R., additional, Lee, J. E., additional, Huh, W., additional, Kim, Y.-G., additional, Kim, D. J., additional, Hong, S.-C., additional, Kim, J.-S., additional, Oh, H. Y., additional, Okamoto, T., additional, Kamata, K., additional, Naito, S., additional, Tazaki, H., additional, Kan, S., additional, Anne-Kathrin, L.-G., additional, Matthias, K., additional, Speer, T., additional, Andreas, L., additional, Heinrich, G., additional, Thomas, V., additional, Poppleton, A., additional, Danilo, F., additional, Lai, C.-F., additional, Wu, V.-C., additional, Shiao, C.-C., additional, Huang, T.-M., additional, Wu, K.-D., additional, Bedford, M., additional, Farmer, C., additional, Irving, J., additional, Stevens, P., additional, Patera, F., additional, Mattozzi, F., additional, Battistoni, S., additional, Fagugli, R. M., additional, Park, M. Y., additional, Choi, S. J., additional, Kim, J. G., additional, Hwang, S. D., additional, Xie, H., additional, Chen, H., additional, Xu, S., additional, He, Q., additional, Liu, J., additional, Hu, W., additional, Liu, Z., additional, Dalboni, M., additional, Blaya, R., additional, Quinto, B. M., additional, Narciso, R., additional, Oliveira, M., additional, Monte, J., additional, Durao, M., additional, Cendoroglo, M., additional, Batista, M., additional, Hanemann, A. L., additional, Liborio, A., additional, Martins, A., additional, Pinheiro, M. C. C., additional, Meneses, G., additional, De Paula Pessoa, R., additional, Sousa, M., additional, Bezerra, F. S. M., additional, Albuquerque, P. L. M. M., additional, Lima, J. B., additional, Lima, C. B., additional, Veras, M. D. S. B., additional, Nemoto Matsui, T., additional, Totoli, C., additional, Cruz Andreoli, M. C., additional, Vilela Coelho, M. P., additional, Guimaraes de Souza, N. K., additional, Ammirati, A. L., additional, De Carvalho Barreto, F., additional, Ferraz Neto, B.-H., additional, Fortunato Cardoso Dos Santos, B., additional, Abraham, A., additional, Abraham, G., additional, Mathew, M., additional, Duarte, P. M. A., additional, Duarte, F. B., additional, Barros, E. M., additional, Castro, F. Q. S., additional, Palomba, H., additional, Castro, I., additional, Sousa, S. R., additional, Jesus, A. N., additional, Romano, T., additional, Burdmann, E., additional, Yu, L., additional, Kwon, S. H., additional, You, J. Y., additional, Hyun, Y. K., additional, Woo, S. A., additional, Jeon, J. S., additional, Noh, H. J., additional, Han, D. C., additional, Tozija, L., additional, Petronievic, Z., additional, Selim, G., additional, Nikolov, I., additional, Stojceva-Taneva, O., additional, Cakalaroski, K., additional, Lukasz, A., additional, Beneke, J., additional, Menne, J., additional, Schiffer, M., additional, Polanco, N., additional, Hernandez, E., additional, Gutierrez, E., additional, Gutierrez Millet, V., additional, Gonzalez Monte, E., additional, Morales, E., additional, Praga, M., additional, Francisco Javier, L., additional, Nuria, G.-F., additional, Jose Maria, M.-G., additional, Bes Rastrollo, M., additional, Angioi, A., additional, Conti, M., additional, Cao, R., additional, Atzeni, A., additional, Pili, G., additional, Matta, V., additional, Murgia, E., additional, Melis, P., additional, Binda, V., additional, Pani, A., additional, Thome*, F., additional, Leusin, F., additional, Barros, E., additional, Morsch, C., additional, Balbinotto, A., additional, Pilla, C., additional, Premru, V., additional, Buturovic-Ponikvar, J., additional, Ponikvar, R., additional, Marn-Pernat, A., additional, Knap, B., additional, Kovac, J., additional, Gubensek, J., additional, Kersnic, B., additional, Krnjak, L., additional, Prezelj, M., additional, Granatova, J., additional, Havrda, M., additional, Hruskova, Z., additional, Kratka, K., additional, Remes, O., additional, Mokrejsova, M., additional, Bolkova, M., additional, Lanska, V., additional, Rychlik, I., additional, Uniacke, M. D., additional, Lewis, R. J., additional, Harris, S., additional, Roderick, P., additional, Martin, N., additional, Ulrich, K., additional, Jan, B., additional, Jorn, B., additional, Reinhard, B., additional, Jan, K., additional, Hermann, H., additional, Meyer Tobias, F., additional, Leyla, R., additional, Schmidt Bernhard, M. W., additional, Harald, S., additional, Jurgen, S., additional, Tanja, K., additional, Mario, S., additional, Sang Hi, E., additional, Claus, M., additional, Frank, V., additional, Aleksej, S., additional, Sengul, S., additional, Robert, S., additional, Karin, W., additional, Feikah, G., additional, Menne Tobias, F., additional, Meyer Tobias, N., additional, Beutel, G., additional, Fleig, S., additional, Steinhoff, J., additional, Meyer, T., additional, Hafer, C., additional, Bramstedt, J., additional, Busch, V., additional, Vischedyk, M., additional, Kuhlmann, U., additional, Ries, W., additional, Mitzner, S., additional, Mees, S., additional, Stracke, S., additional, Nurnberger, J., additional, Gerke, P., additional, Wiesner, M., additional, Sucke, B., additional, Abu-Tair, M., additional, Kribben, A., additional, Klause, N., additional, Merkel, F., additional, Schnatter, S., additional, Dorresteijn, E., additional, Samuelsson, O., additional, Brunkhorst, R., additional, Stec-Hus Registry, G., additional, Reising, A., additional, Bange, F.-C., additional, Hiss, M., additional, Vetter, F., additional, Bode-Boger, S. M., additional, Martens-Lobenhoffer, J., additional, Schmidt, B. M. W., additional, Kielstein, J. T., additional, Shin, H. S., additional, Jung, Y. S., additional, and Rim, H., additional

Published
2012
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10. Cyclosporine A or intravenous cyclophosphamide for lupus nephritis: the Cyclofa-Lune study

Author

Zavada, J., primary, Pešickova, SS, additional, Ryšava, R., additional, Olejarova, M., additional, Horák, P., additional, Hrnčíř, Z., additional, Rychlík, I., additional, Havrda, M., additional, Vítova, J., additional, Lukáč, J., additional, Rovensky, J., additional, Tegzova, D., additional, Böhmova, J., additional, Zadražil, J., additional, Hána, J., additional, Dostál, C., additional, and Tesar, V., additional

Published
2010
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12. Extended follow-up of the CYCLOFA-LUNE trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide or on cyclosporine A.

Author

Závada, J, Pešičková, S Sinikka, Ryšavá, R, Horák, P, Hrnčíř, Z, Lukáč, J, Rovenský, J, Vítová, J, Havrda, M, Rychlík, I, Böhmova, J, Vlasáková, V, Slatinská, J, Zadražil, J, Olejárová, M, Tegzova, D, and Tesar, V

Subjects
LUPUS nephritis, RENAL manifestations of general diseases, CYCLOSPORINE, CYCLOPHOSPHAMIDE, KIDNEY diseases, CLINICAL trials, THERAPEUTICS
Abstract

The article examines the extended follow-up of the CYLOFA-LUNE randomized controlled trial that compares two sequential proliferative lupus nephritis induction and maintenance treatments based on cyclosporine A (CyA) or cyclophosphamide (CPH). The study shows no difference on the end-stage renal disease and renal impairment rates between CyA and CPH. The similar long term clinical results between CPH and CyA are also noted.

Published
2014
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13. Improvement of the Combustion Chamber

Author

Novosád Jan, Peukert Pavel, and Havrda Marcel

Subjects
Engineering (General). Civil engineering (General), TA1-2040
Abstract

The subject of this work is the analysis of an independent heater combustion chamber. The main goals are the analysis of the current state and modification of the combustion chamber design, while the CFD methods are applied. The standard methodology considering the model and grid preparation and the ANSYS Fluent solver setup were provided to obtain the velocity, thermal and species concentration fields as results. These results were used for the analysis of the flame stability as well as the heat load of the individual component of the combustion chamber. The initial results leads to the identification of areas for possible improvement due to the uneven thermal fields and high thermal stress. Then, several modifications were designed and tested. Finally, the results for modified design were analysed to evaluate the variant suitable for future experimental testing.

Published
2020
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14. Osteopontin, a novel substrate for matrix metalloproteinase-3 (stromelysin-1) and matrix metalloproteinase-7 (matrilysin).

Author

Agnihotri, R, Crawford, H C, Haro, H, Matrisian, L M, Havrda, M C, and Liaw, L

Abstract

Osteopontin (OPN) is a secreted phosphoprotein shown to function in wound healing, inflammation, and tumor progression. Expression of OPN is often co-localized with members of the matrix metalloproteinase (MMP) family. We report that OPN is a novel substrate for two MMPs, MMP-3 (stromelysin-1) and MMP-7 (matrilysin). Three cleavage sites were identified for MMP-3 in human OPN, and two of those sites were also cleaved by MMP-7. These include hydrolysis of the human Gly166-Leu167, Ala201-Tyr202 (MMP-3 only), and Asp210-Leu211 peptide bonds. Only the N-terminal Gly-Leu cleavage site is conserved in rat OPN (Gly151-Leu152). These sites are distinct from previously reported cleavage sites in OPN for the proteases thrombin or enterokinase. We found evidence for the predicted MMP cleavage fragments of OPN in vitro in tumor cell lines, and in vivo in remodeling tissues such as the postpartum uterus, where OPN and MMPs are co-expressed. Furthermore, cleavage of OPN by MMP-3 or MMP-7 potentiated the function of OPN as an adhesive and migratory stimulus in vitro through cell surface integrins. We predict that interaction of MMPs with OPN at tumor and wound healing sites in vivo may be a mechanism of regulation of OPN bioactivity.

Published
2001
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19. Immunological shifts during early-stage Parkinson's disease identified with DNA methylation data on longitudinally collected blood samples.

Author

Pike SC, Havrda M, Gilli F, Zhang Z, and Salas LA

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease in the United States. Decades before motor symptoms manifest, non-motor symptoms such as hyposmia and rapid eye movement (REM) sleep behavior disorder are highly predictive of PD. Previous immune profiling studies have identified alterations to the proportions of immune cells in the blood of clinically defined PD patients. However, it remains unclear if these phenotypes manifest before the clinical diagnosis of PD. We utilized longitudinal DNA methylation (DNAm) microarray data from the Parkinson's Progression Marker's Initiative (PPMI) to perform immune profiling in clinically defined PD and prodromal PD patients (Prod). We identified previously reported changes in neutrophil, monocyte, and T cell numbers in PD patients. Additionally, we noted previously unrecognized decreases in the naive B cell compartment in the defined PD and Prod patient group. Over time, we observed the proportion of innate immune cells in PD blood increased, but the proportion of adaptive immune cells decreased. We identified decreases in T and B cell subsets associated with REM sleep disturbances and early cognitive decline. Lastly, we identified increases in B memory cells associated with both genetic (LRRK2 genotype) and infectious (cytomegalovirus seropositivity) risk factors of PD. Our analysis shows that the peripheral immune system is dynamic as the disease progresses. The study provides a platform to understand how and when peripheral immune alterations occur in PD and whether intervention at particular stages may be therapeutically advantageous., (© 2024. The Author(s).)

Published
2024
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20. The most common founder pathogenic variant c.868G > A (p.Val290Met) in the NPHS2 gene in a representative adult Czech cohort with focal segmental glomerulosclerosis is associated with a milder disease and its underdiagnosis in childhood.

Author

Thomasová D, Zelinová M, Libik M, Geryk J, Votýpka P, Rajnochová Bloudíčková S, Krejčí K, Reiterová J, Jančová E, Machová J, Kollárová M, Rychík I, Havrda M, Horáčková M, Putzová M, Šafránek R, Kollár M, and Macek M Jr

Abstract

Background: Genetic focal segmental glomerulosclerosis (FSGS) is caused by pathogenic variants in a broad spectrum of genes that have a variable representation based on subjects' ethnicity and/or age. The most frequently mutated autosomal recessive gene in FSGS is NPHS2 . In this study, we analyzed the spectrum of NPHS2 variants and their associated phenotype in Czech adult FSGS patients., Methods: A representative cohort of 234 adult patients with FSGS, derived from 225 families originating from all regions of Czechia, was analyzed by massively parallel sequencing. In this study, we focused on the comprehensive analysis of the NPHS2 gene. The histological classification of FSGS followed the Columbia classification., Results: We detected seven (3%) cases bearing homozygous or compound heterozygous pathogenic NPHS2 variants. A single pathogenic variant c.868G > A (p.Val290Met) was found in the majority of NPHS2 -positive cases (86%; 6 out of 7) in histologically confirmed instances of FSGS. Its allele frequency among unrelated NPHS2 -associated FSGS patients was 50% (6/12), and Haplotype analysis predicted its origin to be a result of a founder effect. There is an identical V290M-related haplotype on all V290M alleles spanning a 0,7 Mb region flanking NPHS2 in Central European FSGS populations. The phenotype of the p.Val290Met NPHS2 -associated FSGS demonstrated a later onset and a much milder course of the disease compared to other NPHS2 pathogenic variants associated with FSGS. The mean age of the FSGS diagnosis based on kidney biopsy evaluation was 31.2 ± 7.46 years. In 50% of all cases, the initial disease manifestation of proteinuria occurred only in adulthood, with 83% of these cases not presenting with edemas. One-third (33%) of the studied subjects progressed to ESRD (2 out of 6) at the mean age of 35.0 ± 2.82 years., Conclusions: We identified the most prevalent pathogenic variant, p.Val290Met, in the NPHS2 gene among Czech adult FSGS patients, which has arisen due to a founder effect in Central Europe. The documented milder course of the disease associated with this variant leads to the underdiagnosis in childhood. We established the histopathological features of the NPHS2 -associated adult FSGS cases based on the Columbia classification. This might improve patient stratification and optimize their treatment., Competing Interests: MP was employed by Biopticka Laboratory. The remaining 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 Thomasová, Zelinová, Libik, Geryk, Votýpka, Rajnochová Bloudíčková, Krejčí, Reiterová, Jančová, Machová, Kollárová, Rychík, Havrda, Horáčková, Putzová, Šafránek, Kollár and Macek.)

Published
2023
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21. Well-being impact assessment of artificial intelligence - A search for causality and proposal for an open platform for well-being impact assessment of AI systems.

Author

Havrda M and Klocek A

Subjects
Humans, Program Evaluation, Causality, Artificial Intelligence, Technology
Abstract

In recent years, the well-being impact assessment approach has been applied in the area of Artificial Intelligence (AI). Existing well-being frameworks and tools provide a relevant starting point. Taking into account its multidimensional nature, well-being assessment is well suited to assess both the expected positive effects of the technology as well as unintended negative consequences. To-date the establishment of causal links mostly stems from intuitive causal models. Such approaches neglect the fact that to prove causal links between the operation of an AI system and observed effects is difficult due to the immense complexity of the socio-technical context. This article aims at providing a framework for ascertaining the attribution of effects of observed impact of AI on well-being. An elaborated approach to impact assessment potentially enabling causal inferences is demonstrated. Furthermore, a new Open Platform for Well-Being Impact Assessment of AI systems (OPIA) is introduced, which is based on a distributed community to build reproducible evidence through effective identification, refinement, iterative testing, and cross-validation of expected causal structures., (Copyright © 2023. Published by Elsevier Ltd.)

Published
2023
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22. A case report: Acute kidney injury with progression to chronicity in an eldery woman.

Author

Snížková O, Krátká K, Havrda M, Rychlík I, Bonatto MEK, and Honsová E

Subjects
Female, Humans, Aged, Kidney pathology, Acute Kidney Injury chemically induced, Acute Kidney Injury therapy
Abstract

Acute renal failure in elderly patients can be caused by a wide spectrum of diseases that usually have a cause outside the kidney. The most common causes include renal impairment as part of ANCA vasculitis, another category includes clonal plasmatic cell disease with light chain cast nephropathy; and there also exists an increasing number of drug-induced tubulointerstial damage. We present a case of iatrogenic less common form of acute failure in a 73-year-old woman, who did not suffer from any serious disease until then. Although the biopsy helped to determine the cause of the failure and thus affect subsequent therapy, the function did not return to the previous state and the patient progressed to CKD G3bA1 with serum creatinine values of around 170-140 μmol/l.

Published
2023

23. Unveiling the Unexpected: Why Doctors Should Look beyond the Lungs when Predicting COVID-19 Mortality.

Author

Zolotov E, Sigal A, Havrda M, Raskova M, Girsa D, Hochfeld U, Krátká K, and Rychlík I

Subjects
Humans, Prognosis, Retrospective Studies, Lung diagnostic imaging, Risk Factors, Hospital Mortality, COVID-19, Acute Kidney Injury, Renal Insufficiency, Chronic
Abstract

Introduction: The main objective of this study was to identify the best combination of admission day parameters for predicting COVID-19 mortality in hospitalized patients. Furthermore, we sought to compare the predictive capacity of pulmonary parameters to that of renal parameters for mortality from COVID-19., Methods: In this retrospective study, all patients admitted to a tertiary hospital between September 1st, 2020, and December 31st, 2020, who were clinically symptomatic and tested positive for COVID-19, were included. We gathered extensive data on patient admissions, including laboratory results, comorbidities, chest X-ray (CXR) images, and SpO2 levels, to determine their role in predicting mortality. Experienced radiologists evaluated the CXR images and assigned a score from 0 to 18 based on the severity of COVID-19 pneumonia. Further, we categorized patients into two independent groups based on their renal function using the RIFLE and KDIGO criteria to define the acute kidney injury (AKI) and chronic kidney disease (CKD) groups. The first group ("AKI&CKD") was subdivided into six subgroups: normal renal function (A); CKD grade 2+3a (B); AKI-DROP (C); CKD grade 3b (D); AKI-RISE (E); and grade 4 + 5 CKD (F). The second group was based only on estimated glomerular filtration rate (eGFR) at the admission, and thus it was divided into four grades: grade 1, grade 2+3a, grade 3b, and grade 4 + 5., Results: The cohort comprised 619 patients. Patients who died during hospitalization had a significantly higher mean radiological score compared to those who survived, with a p value <0.01. Moreover, we observed that the risk for mortality was significantly increased as renal function deteriorated, as evidenced by the AKI&CKD and eGFR groups (p < 0.001 for each group). Regarding mortality prediction, the area under the curve (AUC) for renal parameters (AKI&CKD group, eGFR group, and age) was found to be superior to that of pulmonary parameters (age, radiological score, SpO2, CRP, and D-dimer) with an AUC of 0.8068 versus 0.7667. However, when renal and pulmonary parameters were combined, the AUC increased to 0.8813. Optimal parameter combinations for predicting mortality from COVID-19 were identified for three medical settings: Emergency Medical Service (EMS), the Emergency Department, and the Internal Medicine Floor. The AUC for these settings was 0.7874, 0.8614, and 0.8813, respectively., Conclusions: Our study demonstrated that selected renal parameters are superior to pulmonary parameters in predicting COVID-19 mortality for patients requiring hospitalization. When combining both renal and pulmonary factors, the predictive ability of mortality significantly improved. Additionally, we identified the optimal combination of factors for mortality prediction in three distinct settings: EMS, Emergency Department, and Internal Medicine Floor., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Published
2023
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24. Glomerulonephritides associated with infections.

Author

Havrda M

Subjects
Child, Humans, Aged, Adolescent, Hepatitis B virus, Acute Disease, COVID-19, Glomerulonephritis complications, Glomerulonephritis diagnosis, Endocarditis, Bacterial
Abstract

Glomerulonephritides associated with infections constitute an important group of diseases. Their occurrence is shifting from children and young people to elderly people. The rates of acute post-streptococcal glomerulonephritis, a condition with a good prognosis, are decreasing, and the rates of glomerulonephritides associated with various bacterial, viral, or parasitic infections, often with a poor prognosis, are increasing. Renal biopsy plays an important role in the diagnostic process. Manifestations of glomerulonephritis can be the initial sign of an occult infection. When evaluating renal biopsy specimens, certain signs may suggest this option, but it cannot be relied on completely. The search for an active infection is warranted in every patient with newly diagnosed glomerulonephritis. Hepatitis B and C serology is always performed, with other investigations depending on individual risk factors, clinical manifestations, and laboratory and histological findings. Failure to follow this rule may have serious consequences, in part because immunosuppressive therapy for glomerulonephritis can worsen the underlying infection and also because the progressive nature of parainfective glomerulonephritis cannot be reversed without eliminating the causative infection. Distinguishing between parainfective and autoimmune glomerulonephritis can be difficult, as there are no major differences in clinical manifestations, laboratory, and sometimes even histological findings. In the setting of the Czech Republic, important diseases include, in particular, staphylococcus infection-associated glomerulonephritis (SAGN) and, in general, infective endocarditis-associated glomerulonephritis, shunt nephritis, and other cases associated with foreign-material infection, such as catheters or electrodes. Among viral diseases, glomerulonephritides associated with the hepatitis B virus, hepatitis C virus, and the SARS CoV-2 virus are of major significance. The treatment of parainfectious glomerulonephritides involves elimination of the causative infection; only in rare cases, a combination of anti-infective treatment and mild immunosuppression can be indicated.

Published
2022
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25. Can Renal Parameters Predict the Mortality of Hospitalized COVID-19 Patients?

Author

Zolotov E, Sigal A, Havrda M, Jeřábková K, Krátká K, Uzlová N, and Rychlík I

Subjects
Adult, Female, Hospital Mortality, Humans, Kidney physiology, Male, Retrospective Studies, Risk Factors, Acute Kidney Injury, COVID-19, Renal Insufficiency, Chronic
Abstract

Introduction: Our study aimed to analyze whether renal parameters can predict mortality from COVID-19 disease in hospitalized patients., Methods: This retrospective cohort includes all adult patients with confirmed COVID-19 disease who were consecutively admitted to the tertiary hospital during the 4-month period (September 1 to December 31, 2020). We analyzed their basic laboratory values, urinalysis, comorbidities, length of hospitalization, and survival. The RIFLE and KDIGO criteria were used for AKI and CKD grading, respectively. To display renal function evolution and the severity of renal damage, we subdivided patients further into 6 groups as follows: group 1 (normal renal function), group 2 (CKD grades 2 + 3a), group 3 (AKI-DROP defined as whose s-Cr level dropped by >33.3% during the hospitalization), group 4 (CKD 3b), group 5 (CKD 4 + 5), and group 6 (AKI-RISE defined as whose s-Cr level was elevated by ≥50% within 7 days or by ≥26.5 μmol/L within 48 h during hospitalization). Then, we used eGFR on admission independently of renal damage to check whether it can predict mortality. Only 4 groups were used: group I - normal renal function (eGFR > 1.5 mL/s), group II - mild renal involvement (eGFR 0.75-1.5), group III - moderate (eGFR 0.5-0.75), and group IV - severe (GFR <0.5)., Results: A total of 680 patients were included in our cohort; among them, 244 patients displayed normal renal function, 207 patients fulfilled AKI, and 229 patients suffered from CKD. In total, a significantly higher mortality rate was found in the AKI and the CKD groups versus normal renal function - 37.2% and 32.3% versus 9.4%, respectively (p < 0.001). In addition, the groups 1-6 divided by severity of renal damage reported mortality of 9.4%, 21.2%, 24.1%, 48.7%, 62.8%, and 55.1%, respectively (p < 0.001). The mean hospitalization duration of alive patients with normal renal findings was 9.5 days, while it was 12.1 days in patients with any renal damage (p < 0.001). When all patients were compared according to eGFR on admission, the mortality was as follows: group I (normal) 9.8%, group II (mild) 22.1%, group III (moderate) 40.9%, and group IV (severe) 50.5%, respectively (p < 0.001). It was a significantly better mortality predictor than CRP on admission (AUC 0.7053 vs. 0.6053)., Conclusions: Mortality in patients with abnormal renal function was 3 times higher compared to patients with normal renal function. Also, patients with renal damage had a worse and longer hospitalization course. Lastly, eGFR on admission, independently of renal damage type, was an excellent tool for predicting mortality. Further, the change in s-Cr levels during hospitalization reflected the mortality prognosis., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Published
2022
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26. Bioptically Proven "Anticoagulation-Related Nephropathy" Induced by Dual Antiplatelet Therapy.

Author

Krátká K, Havrda M, Honsová E, and Rychlík I

Abstract

Anticoagulation-related nephropathy (ARN) is a significant and underdiagnosed complication in patients who receive anticoagulation therapy. It is characterized by acute kidney injury in the setting of excessive anticoagulation defined as an international normalized ratio > 3.0 in patients treated with warfarin. A definitive diagnosis is made by renal biopsy showing acute tubular necrosis with obstruction of the tubuli by red blood cell casts. However, the evidence shows that ARN can occur during treatment with novel oral anticoagulants as well. Although it has been suggested that antiplatelet therapy, such as aspirin, might contribute to coagulopathy (and therefore the hypothetical risk of ARN), there are no reports of ARN induced by antiplatelet therapy according to our knowledge. It is also reported that glomerular lesions (i.e., kidney disease) represent a risk factor for ARN. We present a case of an 82-year-old man who developed biopsy-proven ARN after the administration of dual antiplatelet therapy with no previous anticoagulation treatment and normal coagulation tests.

Published
2018
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27. [More safe anticoagulant treatment - use of idarucizumab (Praxbind®): case reports from RE-VERSE AD study and clinical practice].

Author

Tuček D, Veleta T, and Havrda M

Subjects
Cohort Studies, Dabigatran therapeutic use, Humans, Prospective Studies, Antibodies, Monoclonal, Humanized therapeutic use, Anticoagulants therapeutic use
Abstract

RE-VERSE AD, a prospective multicentric cohort study, examined the effect of idarucizumab on 2 cohorts of patients anticoagulated with dabigatran - in cohort A in patients with uncontrollable or life threatening bleeding, in cohort B in patients who undergo acute surgery. Within the study patients were intravenously administered 5 g antidote divided into 2 doses per 2.5 g within 15 min to eliminate the anticoagulation effect of dabigatran. A series of case studies is presented to describe the use of idarucizumab within the RE-VERSE AD study and in clinical practice in the period of 2015-2016 at the University Hospital Hradec Králové. The included examples illustrate the benefit of dabigatran as the only drug so far from the group of direct oral anticoagulants which has an antidote.Key words: antidote - bleeding - dabigatran - direct oral anticoagulants - DOAC - high risk of bleeding - idarucizumab - intervention.

Published
2018

28. Clinical case: idelalisib-induced immunoglobulin flare.

Author

Novak J, Havrda M, Gaherova L, Spicka J, and Kozak T

Subjects
Aged, Cladribine adverse effects, Female, Humans, Rituximab adverse effects, Waldenstrom Macroglobulinemia drug therapy, Waldenstrom Macroglobulinemia immunology, Cladribine immunology, Immunoglobulin M immunology, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Leukemia, Lymphocytic, Chronic, B-Cell immunology, Purines adverse effects, Quinazolinones adverse effects
Abstract

IgM flare is a transient, treatment-induced, increase of monoclonal IgM levels in lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) patients. Until recently this phenomenon was observed in patients treated with Cladribine and Rituximab. Here we report a case of a heavily pretreated chronic lymphocytic leukemia patient with an atypically high immunoglobulin production who developed clinically significant immunoglobulin flare following Idelalisib treatment.

Published
2017
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29. The Purpose of Galen's Treatise On Demonstration.

Author

Havrda M

Subjects
Education, Medical, History, Ancient, Physicians, Dissent and Disputes, Judgment, Manuscripts, Medical as Topic history
Abstract

This paper concerns the lost treatise On Demonstration (DD) written by Galen of Pergamum (129 - ca. 215 AD). Its aim is to reconstruct the purpose of this treatise, especially the question of how, in Galen's view, it was supposed to be useful for doctors. While showing that the methods described in DD were designed to settle disagreements among doctors, the paper argues that the choice of topics discussed there was partly determined by Galen's worry about a mode of reasoning, exemplified by scepticism, that leads people into believing that plain phenomena, such as those on which both medical practice and theory are based, do not exist.

Published
2015
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30. Short-term effect of evidence-based medicine heart failure therapy on glomerular filtration rate in elderly patients with chronic cardiorenal syndrome.

Author

Málek F, Havrda M, Fruhaufová Z, and Vránová J

Subjects
Aged, 80 and over, Chronic Disease, Female, Humans, Male, Syndrome, Time Factors, Evidence-Based Medicine, Glomerular Filtration Rate drug effects, Heart Failure drug therapy, Heart Failure physiopathology, Kidney Failure, Chronic drug therapy, Kidney Failure, Chronic physiopathology
Published
2009
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31. Variable recombination efficiency in responder transgenes activated by Cre recombinase in the vasculature.

Author

Hara-Kaonga B, Gao YA, Havrda M, Harrington A, Bergquist I, and Liaw L

Subjects
Animals, Cell Line, Female, Genes, Reporter, Male, Mice, Mice, Transgenic, Myocytes, Smooth Muscle enzymology, Receptors, Notch antagonists & inhibitors, Signal Transduction physiology, Integrases, Myocytes, Smooth Muscle metabolism, Recombination, Genetic, Transgenes
Abstract

Cre recombinase has become a ubiquitous tool in transgenic strategies for regulation of transgene expression in a tissue-specific manner. We report analysis of two SM22alphaCre lines and their ability to mediate genomic recombination in five independent Cre-responsive transgenic lines. One of the SM22alphaCre lines developed was a tet-on system based on the reverse tetracycline transactivator. Our goal was to use this strategy to inhibit the Notch signaling pathway specifically in smooth muscle cells. Our responder transgenes contained a constitutively expressed marker gene (chloramphenicol acetyltransferase, CAT), flanked by loxP sites in direct orientation, upstream of Notch-related transgenes. We developed two dominant negative Notch transgenic responder lines activated by Cre-mediated DNA recombination. The first is the extracellular domain of human Jagged1, and the second is the extracellular domain of the human Notch2 receptor. Despite high expression of the marker gene in all responder lines, we found that Cre-mediated genomic recombination between these five lines was highly variable, ranging from 46 to 93% of individuals using an SM22alphaCre activating strain, or 8-58% of individuals using an inducible SM22alphartTACre. In all cases examined, detection of recombination by PCR correlated with expression of the transgene as determined by Western blot analysis. Our studies reflect the variability in recombination success based on the responder strain, presumably due to inaccessibility of the locus of integration of the responder allele.

Published
2006
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32. [Vasoactive factors in chronic glomerulonephritis].

Author

Knotková V, Havrda M, Jáchymová M, and Jindra V

Subjects
Adaptation, Physiological, Adult, Atrial Natriuretic Factor blood, Atrial Natriuretic Factor physiology, Chronic Disease, Endothelins blood, Endothelins physiology, Glomerular Filtration Rate, Glomerulonephritis metabolism, Humans, Middle Aged, Prostaglandins physiology, Prostaglandins urine, Proteinuria, Renin blood, Renin physiology, Glomerulonephritis physiopathology, Renal Circulation, Vasomotor System physiopathology
Abstract

Background: The kidney damage in chronic glomerulonephritis develops not only as a result of causal immunopathological evens, but also due to chronic adaptation changes. The study was aimed at identification of active agents, which can serve as markers of proceeding adaptation changes and to determine, if these changes may be determined in patients undergoing the stage of remission of chronic glomerulonephritis., Methods and Results: The authors determined renin activity, concentration of atrium natriuretic peptide and endothelin in plasma and elimination of some prostanoids in urine in 33 patients with chronic stabilized glomerulonephritis with normal glomerular filtration and with normal blood pressure and in 21 healthy subjects. Seventeen patients without proteinuria did not receive therapy, 16 patients with minute proteinuria received 100 mg of acetylosalicylic acid daily. In the untreated patients without proteinuria, the elimination of thromboxane in urine was significantly higher than in both other groups. The plasma level of atrium natriuretic peptide in all 33 patients was significantly lower than in the healthy persons., Conclusions: Based on this study the authors believe that adaptation changes proceed even in patients with chronic glomerulonephritis in clinical remission. The increased production of renal thromboxane, which can be successfully blocked by acetylosalicylic acid may be the marker of glomerular changes. A decreased level of atrium natriuretic peptide could reflect tubulointerstitial changes.

Published
1996

33. [Microalbuminuria in patients with glomerulonephritis in remission].

Author

Havrda M, Knotková V, and Pospísilová B

Subjects
Creatinine urine, Female, Humans, Male, Remission Induction, Albuminuria, Glomerulonephritis urine
Abstract

The authors focused their attention on residual changes in patients with glomerulonephritis who have a zero or only "physiological" proteinuria (under 0.15 g/24 hours), normal or slightly elevated s-creatinine and who do not suffer from hypertension. In these patients microalbuminuria in urine per 24 hours was assessed. Patients with albuminuria under 20 micrograms/min were included in the group with normal albuminuria (13 patients) and patients with albuminuria of more than 20 micrograms/min in the microalbuminuric group (11 patients). The two groups did not differ significantly as to age, sex, duration of the disease, maximum levels of proteinuria and s-creatinine values at the onset of the disease. S-creatinine and blood pressure values at the time of investigation were also comparable. The groups differed, however, significantly as to the period of "absolute" remission which the authors defined as the period during which proteinuria did not exceed the "physiological" limit. This period was in the normoalbuminuric group significantly longer--on average 5.1 years--while in the microalbuminuric group it was 2.1 years (difference at the 1% level of significance).

Published
1996

34. [Successful completion of pregnancy in a dialyzed patient].

Author

Fialová J, Havrda M, Nĕmecek K, Umnerová V, Golán L, Kulovaný E, Rezácová J, Sucharová E, and Tocík J

Subjects
Adult, Female, Humans, Peritoneal Dialysis, Continuous Ambulatory, Pregnancy, Kidney Failure, Chronic therapy, Pregnancy Complications therapy
Abstract

The authors describe the first case of a successful pregnancy in the Czech Republic in a patient treated by continuous ambulatory peritoneal dialysis. The 22-year-old patient became pregnant ten months after the onset of treatment by peritoneal dialysis. During pregnancy deterioration of arterial hypertension occurred, deterioration of anaemia and from the 29th week onwards cholestasis gravidarum developed. The development of the foetus was within normal limits. Because of suspected preeclampsia the pregnancy was terminated during the 35th week by Caesarean section. The patient was delivered of a healthy eutrophic boy without any congenital abnormalities.

Published
1995

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