97 results on '"Cernadas M"'
Search Results
2. Temporary immersion systems to improve alder micropropagation
- Author
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San José, M. C., Blázquez, N., Cernadas, M. J., Janeiro, L. V., Cuenca, B., Sánchez, C., and Vidal, N.
- Published
- 2020
- Full Text
- View/download PDF
3. Dental Health and Mortality in People With End-Stage Kidney Disease Treated With Hemodialysis: A Multinational Cohort Study
- Author
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Raña, S., Serrano, M., Claros, S., Arias, M., Petracci, L., Arana, M., De Rosa, P., Gutierrez, A., Simon, M., Vergara, V., Tosi, M., Cernadas, M., Vilamajó, I., Gravac, D., Paulón, M., Penayo, L., Carrizo, G., Ghiani, M., Perez, G., Da Cruz, O., Galarce, D., Gravielle, M., Vescovo, E., Paparone, R., Mato Mira, C., Mojico, E., Hermida, O., Florio, D., Yucoswky, M., Labonia, W., Rubio, D., Di Napoli, G., Fernandez, A., Altman, H., Rodriguez, J., Serrano, S., Valle, G., Lobos, M., Acosta, V., Corpacci, G., Jofre, M., Gianoni, L., Chiesura, G., Capdevila, M., Montenegro, J., Bequi, J., Dayer, J., Gómez, A., Calderón, C., Abrego, E., Cechín, C., García, J., Corral, J., Natiello, M., Coronel, A., Muñiz, M., Muñiz, V., Bonelli, A., Sanchez, F., Maestre, S., Olivera, S., Camargo, M., Avalos, V., Geandet, E., Canteli, M., Escobar, A., Sena, E., Tirado, S., Peñalba, A., Neme, G., Cisneros, M., Oliszewski, R., Nascar, V., Daud, M., Mansilla, S., Paredes Álvarez, A., Gamín, L., Arijón, M., Coombes, M., Zapata, M., Boriceanu, C., Frantzen-Trendel, S., Albert, K., Csaszar, I., Kiss, E., Kosa, D., Orosz, A., Redl, J., Kovacs, L., Varga, E., Szabo, M., Magyar, K., Kriza, G., Zajko, E., Bereczki, A., Csikos, J., Kuti, A., Mike, A., Steiner, K., Nemeth, E., Tolnai, K., Toth, A., Vinczene, J., Szummer, Sz., Tanyi, E., Toth, R., Szilvia, M., Dambrosio, N., Paparella, G., Sambati, M., Donatelli, C., Pedone, F., Cagnazzo, V.A., Antinoro, R., Torsello, F., Saturno, C., Giannoccaro, G., Maldera, S., Boccia, E., Mantuano, M., Di Toro Mammarella, R., Meconizzi, M., Steri, P.F., Riccardi, C., Flammini, A., Moscardelli, L., Murgo, M., San Filippo, N., Pagano, S., Marino, G., Montalto, G., Cantarella, S., Salamone, B., Randazzo, G., Rallo, D., Maniscalco, A., Fici, M., Lupo, A., Pellegrino, P., Fichera, R., D’Angelo, A., Falsitta, N., Bochenska-Nowacka, E., Jaroszynski, A., Drabik, J., Birecka, M., Daniewska, D., Drobisz, M., Doskocz, K., Wyrwicz, G., Inchaustegui, L., Outerelo, C., Sousa Mendes, D., Mendes, A., Lopes, J., Barbas, J., Madeira, C., Fortes, A., Vizinho, R., Cortesão, A., Almeida, E., Bernat, A., De la Torre, B., Lopez, A., Martín, J., Cuesta, G., Rodriguez, R.M., Ros, F., Garcia, M., Orero, E., Ros, E., Caetano, A., MacGregor, K., Santos, M., Silva Pinheiro, S., Martins, L., Leitão, D., Izidoro, C., Bava, G., Bora, A., Gorena, H., Calderón, T., Dupuy, R., Alonso, N., Siciliano, V., Nagy, K., Bajusz, Ö., Pinke, I., Decsi, G., Gyergyoi, L., Jobba, Zs., Zalai, Zs., Zsedenyi, Á., Kiss, G., Pinter, M., Kereszturi, M., Petruzzi, M., De Benedittis, M., Szkutnik, J., Sieczkarek, J., Capelo, A., Garcia Gallart, M., Mendieta, C., Palmer, Suetonia C., Ruospo, Marinella, Wong, Germaine, Craig, Jonathan C., Petruzzi, Massimo, De Benedittis, Michele, Ford, Pauline, Johnson, David W., Tonelli, Marcello, Natale, Patrizia, Saglimbene, Valeria, Pellegrini, Fabio, Celia, Eduardo, Gelfman, Ruben, Leal, Miguel R., Torok, Marietta, Stroumza, Paul, Bednarek-Skublewska, Anna, Dulawa, Jan, Frantzen, Luc, Ferrari, Juan Nin, del Castillo, Domingo, Bernat, Amparo G., Hegbrant, Jorgen, Wollheim, Charlotta, Gargano, Letizia, Bots, Casper P., and Strippoli, Giovanni F.M.
- Published
- 2015
- Full Text
- View/download PDF
4. Biotechnological efforts for the propagation of Quercus lusitanica Lam., an endangered species
- Author
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José, M. C. San, Martínez, M. T., Cernadas, M. J., Montenegro, R., Mosteiro, F., and Corredoira, E.
- Published
- 2017
- Full Text
- View/download PDF
5. Micropropagation of mature Quercus ilex L. trees by axillary budding
- Author
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Martínez, M. T., Corredoira, E., Vieitez, A. M., Cernadas, M. J., Montenegro, R., Ballester, A., Vieitez, F. J., and San José, M. C.
- Published
- 2017
- Full Text
- View/download PDF
6. Propagation of mature Quercus ilex L. (holm oak) trees by somatic embryogenesis
- Author
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Martínez, M. T., San José, M. C., Vieitez, A. M., Cernadas, M. J., Ballester, A., and Corredoira, E.
- Published
- 2017
- Full Text
- View/download PDF
7. 310: Physically distant but virtually together: CF community-based webcasts during the COVID-19 pandemic
- Author
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Uluer, A., primary, Rits, S., additional, Snell, C., additional, Alao, M., additional, Bailey, I., additional, Huysman, C., additional, Ratner, L., additional, Nash, J., additional, Becker, A., additional, Cardoni, L., additional, Janes, A., additional, Shin, K., additional, McMahon, L., additional, Kennedy, J., additional, Cernadas, M., additional, and Cagnina, R., additional
- Published
- 2021
- Full Text
- View/download PDF
8. 4: The effect of elexacaftor/tezacaftor/ivacaftor on glycemia in adults with cystic fibrosis: A prospective continuous glucose monitoring study
- Author
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Scully, K., primary, Marchetti, P., additional, Sawicki, G., additional, Uluer, A., additional, Cernadas, M., additional, Cagnina, R., additional, Kennedy, J., additional, and Putman, M., additional
- Published
- 2021
- Full Text
- View/download PDF
9. La Sed y Otros Síntomas Orales en Pacientes en HD en Argentina: Un Estudio Multinacional Prospectivo de Cohorte (ORAL-D): 0067
- Author
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Celia, E., Gelfman, R., Bava, G., Raña, S., Serrano, M., Claros, S., Arias, M., Petracci, L., Arana, M., De Rosa, P., Gutierrez, A., Simon, M., Vergara, V., Tosi, M., Cernadas, M., Vilamajó, I., Gravac, D., Paulón, M., Penayo, L., Carrizo, G., Bora, A., Ghiani, M., Perez, G, Da Cruz, O., Ruospo, M., Hegbrant, J., and Strippoli, G.
- Published
- 2014
10. Dietary Patterns and Mortality in a Multinational Cohort of Adults Receiving Hemodialysis
- Author
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Saglimbene, Valeria M., primary, Wong, Germaine, additional, Teixeira-Pinto, Armando, additional, Ruospo, Marinella, additional, Garcia-Larsen, Vanessa, additional, Palmer, Suetonia C., additional, Natale, Patrizia, additional, Campbell, Katrina, additional, Carrero, Juan-Jesus, additional, Stenvinkel, Peter, additional, Gargano, Letizia, additional, Murgo, Angelo M., additional, Johnson, David W., additional, Tonelli, Marcello, additional, Gelfman, Rubén, additional, Celia, Eduardo, additional, Ecder, Tevfik, additional, Bernat, Amparo G., additional, Del Castillo, Domingo, additional, Timofte, Delia, additional, Török, Marietta, additional, Bednarek-Skublewska, Anna, additional, Duława, Jan, additional, Stroumza, Paul, additional, Hansis, Martin, additional, Fabricius, Elisabeth, additional, Felaco, Paolo, additional, Wollheim, Charlotta, additional, Hegbrant, Jörgen, additional, Craig, Jonathan C., additional, Strippoli, Giovanni F.M., additional, Badino, A., additional, Petracci, L., additional, Villareal, C., additional, Soto, M., additional, Arias, M., additional, Vera, F., additional, Quispe, V., additional, Morales, S., additional, Bueno, D., additional, Bargna, R., additional, Peñaloza, G., additional, Alcalde, L., additional, Dayer, J., additional, Milán, A., additional, Centurión, N., additional, Ramos, A., additional, De Orta, E., additional, Menardi, S., additional, Austa Bel, N., additional, Marileo, E., additional, Junqueras, N., additional, Favalli, C., additional, Trioni, R., additional, Valle, G., additional, López, M., additional, Marinaro, C., additional, Fernandez, A., additional, Corral, J., additional, Nattiello, E., additional, Marone, S., additional, García, J., additional, Carrizo, G., additional, González, P., additional, Delicia, O., additional, Maza, M., additional, Chauque, M., additional, Mora, J., additional, Grbavac, D., additional, López, L., additional, Alonso, M., additional, Villalba, C., additional, Simon, M., additional, Cernadas, M., additional, Moscatelli, C., additional, Vilamajó, I., additional, Tursky, C., additional, Martínez, M., additional, Villalba, F., additional, Pereira, D., additional, Araujo, S., additional, López, H., additional, Alonso, V., additional, Vázquez, B., additional, Rapetti, M., additional, Raña, S., additional, Capdevila, M., additional, Ljubich, C., additional, Acosta, M., additional, Coombes, M., additional, Doria, V., additional, Ávila, M., additional, Cáceres, D., additional, Geandet, E., additional, Romero, C., additional, Morales, E., additional, Recalde, C., additional, Casanú, M., additional, Lococo, B., additional, Da Cruz, O., additional, Focsaner, C., additional, Galarce, D., additional, Albarracín, L., additional, Vescovo, E., additional, Gravielle, M., additional, Florio, D., additional, Baumgart, L., additional, Corbalán, M., additional, Aguilera, V., additional, Hermida, O., additional, Galli, C., additional, Ziombra, L., additional, Gutierrez, A., additional, Frydelund, S., additional, Hardaman, A., additional, Maciel, A., additional, Arrigo, M., additional, Mato Mira, C., additional, Leibovich, J., additional, Paparone, R., additional, Muller, E., additional, Malimar, A., additional, Leocadio, I., additional, Cruz, W., additional, Tirado, S., additional, Peñalba, A., additional, Cejas, R., additional, Mansilla, S., additional, Campos, C., additional, Abrego, E., additional, Chávez, P., additional, Corpacci, G., additional, Echavarría, A., additional, Engler, C., additional, Vergara, P., additional, Hubeli, M., additional, Redondo, G., additional, Noroña, B., additional, Boriceanu, C., additional, Lankester, M., additional, Poignet, J.L., additional, Saingra, Y., additional, Indreies, M., additional, Santini, J., additional, Mahi, A., additional, Robert, A., additional, Bouvier, P., additional, Merzouk, T., additional, Villemain, F., additional, Pajot, A., additional, Tollis, F., additional, Brahim-Bounab, M., additional, Benmoussa, A., additional, Albitar, S., additional, Guimont, M.C., additional, Ciobotaru, P., additional, Guerin, A., additional, Diaconita, M., additional, Hoischen, S.H., additional, Saupe, J., additional, Ullmann, I., additional, Grosser, S., additional, Kunow, J., additional, Grueger, S., additional, Bischoff, D., additional, Benders, J., additional, Worch, P., additional, Pfab, T., additional, Kamin, N., additional, Roesch, M., additional, May, M., additional, Albert, K., additional, Csaszar, I., additional, Kiss, E., additional, Kosa, D., additional, Orosz, A., additional, Redl, J., additional, Kovacs, L., additional, Varga, E., additional, Szabo, M., additional, Magyar, K., additional, Zajko, E., additional, Bereczki, A., additional, Csikos, J., additional, Kerekes, E., additional, Mike, A., additional, Steiner, K., additional, Nemeth, E., additional, Tolnai, K., additional, Toth, A., additional, Vinczene, J., additional, Szummer, S.z., additional, Tanyi, E., additional, Szilvia, M., additional, Murgo, A.M., additional, Sanfilippo, N., additional, Dambrosio, N., additional, Saturno, C., additional, Matera, G., additional, Benevento, M., additional, Greco, V., additional, di Leo, G., additional, Papagni, S., additional, Alicino, F., additional, Marangelli, A., additional, Pedone, F., additional, Cagnazzo, A.V., additional, Antinoro, R., additional, Sambati, M.L., additional, Donatelli, C., additional, Ranieri, F., additional, Torsello, F., additional, Steri, P., additional, Riccardi, C., additional, Flammini, A., additional, Moscardelli, L., additional, Boccia, E., additional, Mantuano, M., additional, Di Toro Mammarella, R., additional, Meconizzi, M., additional, Fichera, R., additional, D’Angelo, A., additional, Latassa, G., additional, Molino, A., additional, Fici, M., additional, Lupo, A., additional, Montalto, G., additional, Messina, S., additional, Capostagno, C., additional, Randazzo, G., additional, Pagano, S., additional, Marino, G., additional, Rallo, D., additional, Maniscalco, A., additional, Trovato, O.M., additional, Strano, C., additional, Failla, A., additional, Bua, A., additional, Campo, S., additional, Nasisi, P., additional, Salerno, A., additional, Laudani, S., additional, Grippaldi, F., additional, Bertino, D., additional, Di Benedetto, D.V., additional, Puglisi, A., additional, Chiarenza, S., additional, Lentini Deuscit, M., additional, Incardona, C.M., additional, Scuto, G., additional, Todaro, C., additional, Dino, A., additional, Novello, D., additional, Coco, A., additional, Bocheńska-Nowacka, E., additional, Jaroszyński, A., additional, Drabik, J., additional, Wypych-Birecka, M., additional, Daniewska, D., additional, Drobisz, M., additional, Doskocz, K., additional, Wyrwicz-Zielińska, G., additional, Kosicki, A., additional, Ślizień, W., additional, Rutkowski, P., additional, Arentowicz, S., additional, Dzimira, S., additional, Grabowska, M., additional, Ostrowski, J., additional, Całka, A., additional, Grzegorczyk, T., additional, Dżugan, W., additional, Mazur, M., additional, Myślicki, M., additional, Piechowska, M., additional, Kozicka, D., additional, de Sá Martins, V., additional, Aguiar, L., additional, Mira, A.R., additional, Velez, B., additional, Pinheiro, T., additional, Agapi, E., additional, Ardelean, C.L., additional, Baidog, A., additional, Bako, G., additional, Barb, M., additional, Blaga, A., additional, Bodurian, E., additional, Bumbea, V., additional, Dragan, E., additional, Dumitrache, D., additional, Florescu, L., additional, Havasi, N., additional, Hint, S., additional, Ilies, R., additional, Mandita, A.G.M., additional, Marian, R.I., additional, Medrihan, S.L., additional, Mitea, L., additional, Mitea, S., additional, Mocanu, R., additional, Moro, D.C., additional, Nitu, M., additional, Popa, M.L., additional, Popa, M., additional, Railean, E., additional, Scuturdean, A.R., additional, Szentendrey, K., additional, Teodoru, C.L., additional, Varga, A., additional, García, M., additional, Olaya, M., additional, Abujder, V., additional, Carreras, J., additional, López, A., additional, Ros, F., additional, Cuesta, G., additional, García, A., additional, Orero, E., additional, Ros, E., additional, Bea, S., additional, Pizarro, J.L., additional, Luengo, S., additional, Romero, A., additional, Navarro, M., additional, Cermeño, L., additional, Rodriguez, A., additional, Lopez, D., additional, Barrera, A., additional, Montoya, F., additional, Tajahuerce, J., additional, Carro, M., additional, Cunill, M.Q., additional, Narci, S., additional, Ballester, T., additional, Soler, M.J., additional, Traver, S., additional, Buta, P.P., additional, Cucuiat, L., additional, Rosu, L., additional, Garcia, I., additional, Gavra, C.M., additional, Gonzalez, R., additional, Filimon, S., additional, Peñalver, M., additional, Benages, V., additional, Cardo, M.I., additional, García, E., additional, Soler, P., additional, Fernnandez, E., additional, Popescu, F., additional, Munteanu, R., additional, Tanase, E., additional, Sagau, F., additional, Prades, D., additional, Esteller, S., additional, Gonzalez, E., additional, Martinez, R., additional, Diago, A., additional, Torres, J., additional, Perez, E., additional, Garcia, C., additional, Lluch, I., additional, Forcano, J., additional, Fóns, M., additional, Rodríguez, A., additional, Millán, N.A., additional, Fernández, J., additional, Ferreiro, B., additional, Otero, M., additional, Pesqueira, V., additional, Abal, S., additional, Álvarez, R., additional, Jorge, C., additional, Rico, I., additional, de Dios Ramiro, J., additional, Duzy, L., additional, Soto, A., additional, Lopez, J.L., additional, Diaz, Y., additional, Herrero, I., additional, Farré, M., additional, Blasco, C., additional, Ferrás, S., additional, Agost, M.J., additional, Miracle, C., additional, Farto, J., additional, Goch, J., additional, Katzarski, K.S., additional, Wulcan, A., additional, Akbiber, H., additional, Arslan, H., additional, Bicen, L., additional, Buyukkiraz, A., additional, Celik, R., additional, Dogan, I.S., additional, Erkalkan, S., additional, Ertas, A., additional, Hark, U., additional, Iravul, E., additional, Karakaya, M., additional, Mengu, K., additional, Ongun, S., additional, Ozkan, Z., additional, Ozlu, A., additional, Ozveren, N., additional, Sifil, H.M., additional, Sonmez Turksoz, N., additional, and Yilmaz, Z., additional
- Published
- 2020
- Full Text
- View/download PDF
11. 1369 Cost and Outcomes Analysis of Robotic, Laparoscopic, and Abdominal Hysterectomy for Benign Disease in a Community Hospital Setting
- Author
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Yoo, N, primary, Cernadas, M, additional, and Perisic, D, additional
- Published
- 2019
- Full Text
- View/download PDF
12. CD1a expression defines an interleukin-12 producing population of human dendritic cells
- Author
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Cernadas, M., Lu, J., Watts, G., and Brenner, M. B.
- Published
- 2009
- Full Text
- View/download PDF
13. Nutrition and dietary intake and their association with mortality and hospitalisation in adults with chronic kidney disease treated with haemodialysis: protocol for DIET-HD, a prospective multinational cohort study
- Author
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Palmer, Sc, Ruospo, M, Campbell, Kl, Garcia Larsen, V, Saglimbene, V, Natale, P, Gargano, L, Craig, Jc, Johnson, Dw, Tonelli, M, Knight, J, Bednarek Skublewska, A, Celia, E, Del Castillo, D, Dulawa, J, Ecder, T, Fabricius, E, Frazão, Jm, Gelfman, R, Hoischen, Sh, Schön, S, Stroumza, P, Timofte, D, Török, M, Hegbrant, J, Wollheim, C, Frantzen, L, Strippoli, Gf, Raña, S, Serrano, M, Claros, S, Arias, M, Petracci, L, Arana, M, De Rosa, P, Gutierrez, A, Simon, M, Vergara, V, Tosi, M, Cernadas, M, Vilamajó, I, Gravac, D, Paulón, M, Penayo, L, Carrizo, G, Ghiani, M, Perez, G, Da Cruz, O, Galarce, D, Gravielle, M, Vescovo, E, Paparone, R, Mato Mira, C, Mojico, E, Hermida, O, Florio, D, Yucoswky, M, Labonia, W, Rubio, D, Di Napoli, G, Fernandez, A, Altman, H, Rodriguez, J, Serrano, S, Valle, G, Lobos, M, Acosta, V, Corpacci, G, Jofre, M, Gianoni, L, Chiesura, G, Capdevila, M, Montenegro, J, Bequi, J, Dayer, J, Gómez, A, Calderón, C, Abrego, E, Cechín, C, García, J, Corral, J, Natiello, M, Coronel, A, Muñiz, M, Muñiz, V, Bonelli, A, Sanchez, F, Maestre, S, Olivera, S, Camargo, M, Avalos, V, Geandet, E, Canteli, M, Escobar, A, Sena, E, Tirado, S, Peñalba, A, Neme, G, Cisneros, M, Oliszewski, R, Nascar, V, Daud, M, Mansilla, S, Paredes Álvarez, A, Gamín, L, Arijón, M, Coombes, M, Zapata, M, Boriceanu, C, Lankester, M, Poignet, Jl, Saingra, Y, Indreies, M, Santini, J, Amar, M, Robert, A, Bouvier, P, Merzouk, T, Villemain, F, Pajot, A, Tollis, F, Brahim Bounab, M, Benmoussa, A, Albitar, S, Guimont, Mc, Ciobotaru, P, Guerin, A, Diaconita, M, Shh, Saupe, J, Ullmann, I, Grosser, S, Kunow, J, Grueger, S, Bischoff, D, Benders, J, Worch, P, Pfab, T, Kamin, N, Roesch, M, Albert, K, Csaszar, I, Kiss, E, Kosa, D, Orosz, A, Redl, J, Kovacs, L, Varga, E, Szabo, M, Magyar, K, Zajko, E, Bereczki, A, Csikos, J, Kerekes, E, Mike, A, Steiner, K, Nemeth, E, Tolnai, K, Toth, A, Vinczene, J, Szummer, S, Tanyi, E, Szilvia, M, Murgo, Am, Sanfilippo, N, Dambrosio, N, Saturno, C, Matera, G, Benevento, M, Greco, V, di Leo, G, Papagni, S, Alicino, F, Marangelli, A, Pedone, F, Cagnazzo, Av, Antinoro, R, Sambati, Ml, Donatelli, C, Ranieri, F, Torsello, F, Steri, P, Riccardi, C, Flammini, A, Moscardelli, L, Boccia, E, Mantuano, M, Di Toro Mammarella, R, Meconizzi, M, Fichera, R, D'Angelo, A, Latassa, G, Molino, A, Fici, M, Lupo, Antonio, Montalto, G, Messina, S, Capostagno, C, Randazzo, G, Pagano, S, Marino, G, Rallo, D, Maniscalco, A, Trovato, Om, Strano, C, Failla, A, Bua, A, Campo, S, Nasisi, P, Salerno, A, Laudani, S, Grippaldi, F, Bertino, D, Di Benedetto, Dv, Puglisi, A, Chiarenza, S, Lentini Deuscit, M, Incardona, Cm, Scuto, G, Todaro, C, Dino, A, Novello, D, Coco, A, Bocheńska Nowacka, E, Jaroszyński, A, Drabik, J, Wypych Birecka, M, Daniewska, D, Drobisz, M, Doskocz, K, Wyrwicz Zielińska, G, Kosicki, A, Ślizień, Ws, Rutkowski, P, Arentowicz, S, Dzimira, S, Grabowska, M, Ostrowski, J, Całka, A, Grzegorczyk, T, Dżugan, W, Mazur, M, Myślicki, M, Piechowska, M, Kozicka, D, Mira, Ar, Martins, V, Velez, B, Pinheiro, T, Agapi, E, Ardelean, Cl, Baidog, A, Bako, G, Barb, M, Blaga, A, Bodurian, E, Bumbea, V, Dragan, E, Dumitrache, D, Florescu, L, Havasi, N, Hint, S, Ilies, R, Mandita, Ag, Marian, Ri, Medrihan, Sl, Mitea, L, Mitea, S, Mocanu, R, Moro, Dc, Nitu, M, Popa, Ml, Popa, M, Railean, E, Scuturdean, Ar, Szentendrey, K, Teodoru, Cl, Varga, A, Bernat, A, De la Torre, B, Lopez, A, Martin, J, Cuesta, G, Rodriguez, Rm, Ros, F, Garcia, M, Orero, E, Ros, E, Goch, J, Katzarski, Ks, Wulcan, A, Akbiber, H, Arslan, H, Bicen, L, Buyukkiraz, A, Celik, R, Dogan, Is, Erkalkan, S, Ertas, A, Hark, U, Iravul, E, Karakaya, M, Mengu, K, Ongun, S, Ozkan, Z, Ozlu, A, Ozveren, N, Sifil, Hm, Sonmez Turksoz, N, and Yilmaz, Z.
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pediatrics ,Adolescent ,Turkey ,medicine.medical_treatment ,Argentina ,NUTRITION & DIETETICS ,Nutritional Status ,Infections ,Young Adult ,Informed consent ,Renal Dialysis ,Cause of Death ,Fatty Acids, Omega-6 ,Epidemiology ,Fatty Acids, Omega-3 ,medicine ,Protocol ,Humans ,EPIDEMIOLOGY ,Social determinants of health ,hemodialysis ,Prospective Studies ,Prospective cohort study ,Dialysis ,Renal Medicine ,business.industry ,Other Research Radboud Institute for Health Sciences [Radboudumc 0] ,General Medicine ,medicine.disease ,Europe ,Hospitalization ,Cardiovascular Diseases ,Food ,Research Design ,Emergency medicine ,Kidney Failure, Chronic ,Female ,Hemodialysis ,business ,Energy Intake ,Kidney disease ,Cohort study - Abstract
Contains fulltext : 153534.pdf (Publisher’s version ) (Open Access) INTRODUCTION: Adults with end-stage kidney disease (ESKD) treated with haemodialysis experience mortality of between 15% and 20% each year. Effective interventions that improve health outcomes for long-term dialysis patients remain unproven. Novel and testable determinants of health in dialysis are needed. Nutrition and dietary patterns are potential factors influencing health in other health settings that warrant exploration in multinational studies in men and women treated with dialysis. We report the protocol of the "DIETary intake, death and hospitalisation in adults with end-stage kidney disease treated with HaemoDialysis (DIET-HD) study," a multinational prospective cohort study. DIET-HD will describe associations of nutrition and dietary patterns with major health outcomes for adults treated with dialysis in several countries. METHODS AND ANALYSIS: DIET-HD will recruit approximately 10,000 adults who have ESKD treated by clinics administered by a single dialysis provider in Argentina, France, Germany, Hungary, Italy, Poland, Portugal, Romania, Spain, Sweden and Turkey. Recruitment will take place between March 2014 and June 2015. The study has currently recruited 8000 participants who have completed baseline data. Nutritional intake and dietary patterns will be measured using the Global Allergy and Asthma European Network (GA(2)LEN) food frequency questionnaire. The primary dietary exposures will be n-3 and n-6 polyunsaturated fatty acid consumption. The primary outcome will be cardiovascular mortality and secondary outcomes will be all-cause mortality, infection-related mortality and hospitalisation. ETHICS AND DISSEMINATION: The study is approved by the relevant Ethics Committees in participating countries. All participants will provide written informed consent and be free to withdraw their data at any time. The findings of the study will be disseminated through peer-reviewed journals, conference presentations and to participants via regular newsletters. We expect that the DIET-HD study will inform large pragmatic trials of nutrition or dietary interventions in the setting of advanced kidney disease.
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- 2015
14. Dental Health and Mortality in People With End-Stage Kidney Disease Treated With Hemodialysis: A Multinational Cohort Study
- Author
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Palmer, Suetonia C., primary, Ruospo, Marinella, additional, Wong, Germaine, additional, Craig, Jonathan C., additional, Petruzzi, Massimo, additional, De Benedittis, Michele, additional, Ford, Pauline, additional, Johnson, David W., additional, Tonelli, Marcello, additional, Natale, Patrizia, additional, Saglimbene, Valeria, additional, Pellegrini, Fabio, additional, Celia, Eduardo, additional, Gelfman, Ruben, additional, Leal, Miguel R., additional, Torok, Marietta, additional, Stroumza, Paul, additional, Bednarek-Skublewska, Anna, additional, Dulawa, Jan, additional, Frantzen, Luc, additional, Ferrari, Juan Nin, additional, del Castillo, Domingo, additional, Bernat, Amparo G., additional, Hegbrant, Jorgen, additional, Wollheim, Charlotta, additional, Gargano, Letizia, additional, Bots, Casper P., additional, Strippoli, Giovanni F.M., additional, Raña, S., additional, Serrano, M., additional, Claros, S., additional, Arias, M., additional, Petracci, L., additional, Arana, M., additional, De Rosa, P., additional, Gutierrez, A., additional, Simon, M., additional, Vergara, V., additional, Tosi, M., additional, Cernadas, M., additional, Vilamajó, I., additional, Gravac, D., additional, Paulón, M., additional, Penayo, L., additional, Carrizo, G., additional, Ghiani, M., additional, Perez, G., additional, Da Cruz, O., additional, Galarce, D., additional, Gravielle, M., additional, Vescovo, E., additional, Paparone, R., additional, Mato Mira, C., additional, Mojico, E., additional, Hermida, O., additional, Florio, D., additional, Yucoswky, M., additional, Labonia, W., additional, Rubio, D., additional, Di Napoli, G., additional, Fernandez, A., additional, Altman, H., additional, Rodriguez, J., additional, Serrano, S., additional, Valle, G., additional, Lobos, M., additional, Acosta, V., additional, Corpacci, G., additional, Jofre, M., additional, Gianoni, L., additional, Chiesura, G., additional, Capdevila, M., additional, Montenegro, J., additional, Bequi, J., additional, Dayer, J., additional, Gómez, A., additional, Calderón, C., additional, Abrego, E., additional, Cechín, C., additional, García, J., additional, Corral, J., additional, Natiello, M., additional, Coronel, A., additional, Muñiz, M., additional, Muñiz, V., additional, Bonelli, A., additional, Sanchez, F., additional, Maestre, S., additional, Olivera, S., additional, Camargo, M., additional, Avalos, V., additional, Geandet, E., additional, Canteli, M., additional, Escobar, A., additional, Sena, E., additional, Tirado, S., additional, Peñalba, A., additional, Neme, G., additional, Cisneros, M., additional, Oliszewski, R., additional, Nascar, V., additional, Daud, M., additional, Mansilla, S., additional, Paredes Álvarez, A., additional, Gamín, L., additional, Arijón, M., additional, Coombes, M., additional, Zapata, M., additional, Boriceanu, C., additional, Frantzen-Trendel, S., additional, Albert, K., additional, Csaszar, I., additional, Kiss, E., additional, Kosa, D., additional, Orosz, A., additional, Redl, J., additional, Kovacs, L., additional, Varga, E., additional, Szabo, M., additional, Magyar, K., additional, Kriza, G., additional, Zajko, E., additional, Bereczki, A., additional, Csikos, J., additional, Kuti, A., additional, Mike, A., additional, Steiner, K., additional, Nemeth, E., additional, Tolnai, K., additional, Toth, A., additional, Vinczene, J., additional, Szummer, Sz., additional, Tanyi, E., additional, Toth, R., additional, Szilvia, M., additional, Dambrosio, N., additional, Paparella, G., additional, Sambati, M., additional, Donatelli, C., additional, Pedone, F., additional, Cagnazzo, V.A., additional, Antinoro, R., additional, Torsello, F., additional, Saturno, C., additional, Giannoccaro, G., additional, Maldera, S., additional, Boccia, E., additional, Mantuano, M., additional, Di Toro Mammarella, R., additional, Meconizzi, M., additional, Steri, P.F., additional, Riccardi, C., additional, Flammini, A., additional, Moscardelli, L., additional, Murgo, M., additional, San Filippo, N., additional, Pagano, S., additional, Marino, G., additional, Montalto, G., additional, Cantarella, S., additional, Salamone, B., additional, Randazzo, G., additional, Rallo, D., additional, Maniscalco, A., additional, Fici, M., additional, Lupo, A., additional, Pellegrino, P., additional, Fichera, R., additional, D’Angelo, A., additional, Falsitta, N., additional, Bochenska-Nowacka, E., additional, Jaroszynski, A., additional, Drabik, J., additional, Birecka, M., additional, Daniewska, D., additional, Drobisz, M., additional, Doskocz, K., additional, Wyrwicz, G., additional, Inchaustegui, L., additional, Outerelo, C., additional, Sousa Mendes, D., additional, Mendes, A., additional, Lopes, J., additional, Barbas, J., additional, Madeira, C., additional, Fortes, A., additional, Vizinho, R., additional, Cortesão, A., additional, Almeida, E., additional, Bernat, A., additional, De la Torre, B., additional, Lopez, A., additional, Martín, J., additional, Cuesta, G., additional, Rodriguez, R.M., additional, Ros, F., additional, Garcia, M., additional, Orero, E., additional, Ros, E., additional, Caetano, A., additional, MacGregor, K., additional, Santos, M., additional, Silva Pinheiro, S., additional, Martins, L., additional, Leitão, D., additional, Izidoro, C., additional, Bava, G., additional, Bora, A., additional, Gorena, H., additional, Calderón, T., additional, Dupuy, R., additional, Alonso, N., additional, Siciliano, V., additional, Nagy, K., additional, Bajusz, Ö., additional, Pinke, I., additional, Decsi, G., additional, Gyergyoi, L., additional, Jobba, Zs., additional, Zalai, Zs., additional, Zsedenyi, Á., additional, Kiss, G., additional, Pinter, M., additional, Kereszturi, M., additional, Petruzzi, M., additional, De Benedittis, M., additional, Szkutnik, J., additional, Sieczkarek, J., additional, Capelo, A., additional, Garcia Gallart, M., additional, and Mendieta, C., additional
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- 2015
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15. Integrating Murine Gene Expression Studies to Understand Obstructive Lung Disease Due to Chronic Inhaled Endotoxin
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Lenburg, M, Lai, PS, Hofmann, O, Baron, RM, Cernadas, M, Meng, QR, Bresler, HS, Brass, DM, Yang, IV, Schwartz, DA, Christiani, DC, Hide, W, Lenburg, M, Lai, PS, Hofmann, O, Baron, RM, Cernadas, M, Meng, QR, Bresler, HS, Brass, DM, Yang, IV, Schwartz, DA, Christiani, DC, and Hide, W
- Abstract
RATIONALE: Endotoxin is a near ubiquitous environmental exposure that that has been associated with both asthma and chronic obstructive pulmonary disease (COPD). These obstructive lung diseases have a complex pathophysiology, making them difficult to study comprehensively in the context of endotoxin. Genome-wide gene expression studies have been used to identify a molecular snapshot of the response to environmental exposures. Identification of differentially expressed genes shared across all published murine models of chronic inhaled endotoxin will provide insight into the biology underlying endotoxin-associated lung disease. METHODS: We identified three published murine models with gene expression profiling after repeated low-dose inhaled endotoxin. All array data from these experiments were re-analyzed, annotated consistently, and tested for shared genes found to be differentially expressed. Additional functional comparison was conducted by testing for significant enrichment of differentially expressed genes in known pathways. The importance of this gene signature in smoking-related lung disease was assessed using hierarchical clustering in an independent experiment where mice were exposed to endotoxin, smoke, and endotoxin plus smoke. RESULTS: A 101-gene signature was detected in three murine models, more than expected by chance. The three model systems exhibit additional similarity beyond shared genes when compared at the pathway level, with increasing enrichment of inflammatory pathways associated with longer duration of endotoxin exposure. Genes and pathways important in both asthma and COPD were shared across all endotoxin models. Mice exposed to endotoxin, smoke, and smoke plus endotoxin were accurately classified with the endotoxin gene signature. CONCLUSIONS: Despite the differences in laboratory, duration of exposure, and strain of mouse used in three experimental models of chronic inhaled endotoxin, surprising similarities in gene expression were observe
- Published
- 2013
16. CD1a expression defines an interleukin-12 producing population of human dendritic cells
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Cernadas, M, primary, Lu, J, additional, Watts, G, additional, and Brenner, M B, additional
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- 2008
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17. Role of nitric oxide-related mechanisms in renal function in ageing rats
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Tan, D., primary, Cernadas, M., additional, Aragoncillo, P., additional, Castilla, M., additional, Arroyo, M., additional, Farre, A., additional, Casad, S., additional, and Caramelo, C., additional
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- 1998
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18. Inhibition of T cell costimulation abrogates airway hyperresponsiveness in a murine model.
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Krinzman, S J, primary, De Sanctis, G T, additional, Cernadas, M, additional, Mark, D, additional, Wang, Y, additional, Listman, J, additional, Kobzik, L, additional, Donovan, C, additional, Nassr, K, additional, Katona, I, additional, Christiani, D C, additional, Perkins, D L, additional, and Finn, P W, additional
- Published
- 1996
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19. T cell activation in a murine model of asthma
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Krinzman, S. J., primary, De Sanctis, G. T., additional, Cernadas, M., additional, Kobzik, L., additional, Listman, J. A., additional, Christiani, D. C., additional, Perkins, D. L., additional, and Finn, P. W., additional
- Published
- 1996
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20. Comparison of the effects of meperidine and nalbuphine on intrapartum fetal heart rate tracings
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GIANNINA, G, primary, GUZMAN, E, additional, LAI, Y, additional, LAKE, M, additional, CERNADAS, M, additional, and VINTZILEOS, A, additional
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- 1995
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21. Effect of endothelin-1 on neutrophil adhesion to endothelial cells and perfused heart.
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López Farré, A, primary, Riesco, A, additional, Espinosa, G, additional, Digiuni, E, additional, Cernadas, M R, additional, Alvarez, V, additional, Montón, M, additional, Rivas, F, additional, Gallego, M J, additional, and Egido, J, additional
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- 1993
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22. Renal and systemic effects of aminoacids administered separately: comparison between L-arginine and non-nitric oxide donor aminoacids.
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Cernadas, M R, López-Farré, A, Riesco, A, Gallego, M J, Espinosa, G, Digiuni, E, Hernando, L, Casado, S, and Caramelo, C
- Abstract
The present study examined the mechanisms of the renal effect of the NO-donor aminoacid, L-Arg and different non-NO-donor aminoacids, namely L-Asn, L-Ala, L-Gly L-Gln administered separately. In conscious, unrestricted Wistar rats, a bolus of L-Arg produced a short-lasting decrease in mean arterial pressure. No variations in mean arterial pressure were found with either L-Gly, L-Asn, L-Ala or L-Gln. This effect of L-Arg was inhibited by NwNLA, methylene blue and atropine and not affected by meclofenamate. Simultaneously, a dose-response diuretic and natriuretic effect was observed with all the aminoacids. In further experiments with L-Arg and L-Gly, this effect was associated with increased glomerular filtration rate, renal plasma flow, fractional sodium and free water excretion and urinary cyclic guanosine monophosphate. These effects of L-Arg and L-Gly were inhibited by NwNLA. On the contrary, no inhibition by NwNLA was detected on the diuretic, natriuretic and renal hemodynamic effects of L-Gln, and the diuretic and natriuretic effects of L-Asn or L-Ala. Our results show that all the assayed aminoacids were endowed of diuretic and natriuretic capabilities. Such effects were apparently related with a NO-mediated mechanism in the case of L-Arg and L-Gly, but not in the case of L-Gln, L-Asn or L-Ala, therefore suggesting that more than one mechanism is involved in the renal effect of the different aminoacids. Simultaneously, only L-Arg produced a NO-, cyclic guanosine monophosphate-dependent hypotensive effect, which was not shared by the other assayed aminoacids.
- Published
- 1992
23. It takes a microbiome: commensals, immune regulation, and allergy.
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Cernadas M
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- 2011
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24. SARS-CoV-2 viral clearance and evolution varies by type and severity of immunodeficiency.
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Li Y, Choudhary MC, Regan J, Boucau J, Nathan A, Speidel T, Liew MY, Edelstein GE, Kawano Y, Uddin R, Deo R, Marino C, Getz MA, Reynolds Z, Barry M, Gilbert RF, Tien D, Sagar S, Vyas TD, Flynn JP, Hammond SP, Novack LA, Choi B, Cernadas M, Wallace ZS, Sparks JA, Vyas JM, Seaman MS, Gaiha GD, Siedner MJ, Barczak AK, Lemieux JE, and Li JZ
- Subjects
- Humans, Prospective Studies, Kinetics, Immunosuppression Therapy, SARS-CoV-2, COVID-19
- Abstract
Despite vaccination and antiviral therapies, immunocompromised individuals are at risk for prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but the immune defects that predispose an individual to persistent coronavirus disease 2019 (COVID-19) remain incompletely understood. In this study, we performed detailed viro-immunologic analyses of a prospective cohort of participants with COVID-19. The median times to nasal viral RNA and culture clearance in individuals with severe immunosuppression due to hematologic malignancy or transplant (S-HT) were 72 and 40 days, respectively, both of which were significantly longer than clearance rates in individuals with severe immunosuppression due to autoimmunity or B cell deficiency (S-A), individuals with nonsevere immunodeficiency, and nonimmunocompromised groups ( P < 0.01). Participants who were severely immunocompromised had greater SARS-CoV-2 evolution and a higher risk of developing resistance against therapeutic monoclonal antibodies. Both S-HT and S-A participants had diminished SARS-CoV-2-specific humoral responses, whereas only the S-HT group had reduced T cell-mediated responses. This highlights the varied risk of persistent COVID-19 across distinct immunosuppressive conditions and suggests that suppression of both B and T cell responses results in the highest contributing risk of persistent infection.
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- 2024
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25. SARS-CoV-2 Viral Clearance and Evolution Varies by Extent of Immunodeficiency.
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Li Y, Choudhary MC, Regan J, Boucau J, Nathan A, Speidel T, Liew MY, Edelstein GE, Kawano Y, Uddin R, Deo R, Marino C, Getz MA, Reynold Z, Barry M, Gilbert RF, Tien D, Sagar S, Vyas TD, Flynn JP, Hammond SP, Novack LA, Choi B, Cernadas M, Wallace ZS, Sparks JA, Vyas JM, Seaman MS, Gaiha GD, Siedner MJ, Barczak AK, Lemieux JE, and Li JZ
- Abstract
Despite vaccination and antiviral therapies, immunocompromised individuals are at risk for prolonged SARS-CoV-2 infection, but the immune defects that predispose to persistent COVID-19 remain incompletely understood. In this study, we performed detailed viro-immunologic analyses of a prospective cohort of participants with COVID-19. The median time to nasal viral RNA and culture clearance in the severe hematologic malignancy/transplant group (S-HT) were 72 and 40 days, respectively, which were significantly longer than clearance rates in the severe autoimmune/B-cell deficient (S-A), non-severe, and non-immunocompromised groups (P<0.001). Participants who were severely immunocompromised had greater SARS-CoV-2 evolution and a higher risk of developing antiviral treatment resistance. Both S-HT and S-A participants had diminished SARS-CoV-2-specific humoral, while only the S-HT group had reduced T cell-mediated responses. This highlights the varied risk of persistent COVID-19 across immunosuppressive conditions and suggests that suppression of both B and T cell responses results in the highest contributing risk of persistent infection.
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- 2023
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26. Diagnostic Aspirations.
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Chen HX, Cernadas M, Vargas SO, Levy BD, and Loscalzo J
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- 2022
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27. Surfactant Protein D Influences Mortality During Abdominal Sepsis by Facilitating Escherichia coli Colonization in the Gut.
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Varon J, Arciniegas Rubio A, Amador-Munoz D, Corcoran A, DeCorte JA, Isabelle C, Pinilla Vera M, Walker K, Brown L, Cernadas M, Bry L, Yang H, Kitsios GD, McVerry BJ, Morris A, Lee H, Howrylak J, Englert JA, and Baron RM
- Abstract
Determine the role of surfactant protein D (SPD) in sepsis., Design: Murine in vivo study., Setting: Research laboratory at an academic medical center., Patients: SPD knockout (SPD
-/- ) and wild-type (SPD+/+ ) mice., Interventions: SPD-/- and SPD+/+ mice were subjected to cecal ligation and puncture (CLP). After CLP, Escherichia coli bacteremia was assessed in both groups. Cecal contents from both groups were cultured to assess for colonization by E. coli . To control for parental effects on the microbiome, SPD-/- and SPD+/+ mice were bred from heterozygous parents, and levels of E. coli in their ceca were measured. Gut segments were harvested from mice, and SPD protein expression was measured by Western blot. SPD-/- mice were gavaged with green fluorescent protein, expressing E. coli and recombinant SPD (rSPD)., Measurements and Main Results: SPD-/- mice had decreased mortality and decreased E. coli bacteremia compared with SPD+/+ mice following CLP. At baseline, SPD-/- mice had decreased E. coli in their cecal flora. When SPD-/- and SPD+/+ mice were bred from heterozygous parents and then separated after weaning, less E. coli was cultured from the ceca of SPD-/- mice. E. coli gut colonization was increased by gavage of rSPD in SPD-/- mice. The source of enteric SPD in SPD+/+ mice was the gallbladder., Conclusions: Enteral SPD exacerbates mortality after CLP by facilitating colonization of the mouse gut with E. coli ., Competing Interests: Dr. Baron reports serving on Advisory Boards for Merck and Genentech. Dr. Kitsios has received research funding from Karius. Dr. McVerry receives research funding from Bayer Pharmaceuticals. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)- Published
- 2022
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28. The effect of elexacaftor/tezacaftor/ivacaftor (ETI) on glycemia in adults with cystic fibrosis.
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Scully KJ, Marchetti P, Sawicki GS, Uluer A, Cernadas M, Cagnina RE, Kennedy JC, and Putman MS
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- Adult, Aminophenols adverse effects, Benzodioxoles adverse effects, Blood Glucose, Blood Glucose Self-Monitoring, Cystic Fibrosis Transmembrane Conductance Regulator genetics, Humans, Indoles, Pyrazoles, Pyridines, Pyrrolidines, Quinolones, Cystic Fibrosis complications, Cystic Fibrosis diagnosis, Cystic Fibrosis drug therapy, Hypoglycemia
- Abstract
Background: Cystic fibrosis related diabetes (CFRD) is associated with pulmonary decline and compromised nutritional status. Emerging data suggest that CFTR dysfunction may play a direct role in the pathogenesis of CFRD; however, studies investigating the effect of CFTR modulators on glycemic outcomes in patients with cystic fibrosis (CF) have shown mixed results. The impact of elexacaftor-tezacaftor-ivacaftor (ETI) on glycemic control is currently unknown. Our objective was to investigate the effect of ETI initiation on glycemia in adults with CF using continuous glucose monitoring (CGM)., Methods: In this prospective observational study, 34 adults with CF and at least one F508del CFTR mutation wore CGM sensors for 14 days prior to starting ETI and again 3-12 months after ETI initiation. Hypoglycemia symptoms were queried at each visit, and most recent anthropometric measures and spirometry data were obtained by chart review., Results: Twenty-three participants completed the study. Compared to baseline, average glucose (AG), standard deviation (SD), % time >200 mg/dL, and peak sensor glucose decreased with ETI treatment, and % time in target range 70-180 mg/dL increased. Improvements in glycemic parameters were most notable in individuals with CFRD. There was no significant change in CGM-measured or self-reported hypoglycemia before and after ETI initiation., Conclusion: Initiation of ETI in adults with CF was associated with improvement CGM-derived measures of hyperglycemia and glycemic variability with no effect on hypoglycemia. Further studies are needed to investigate underlying etiology of these changes and the long-term impact of ETI on glycemic control in patients with CF., Competing Interests: Declaration of Competing Interest Dr. Putman reports grants from Vertex Pharmaceuticals and the Cystic Fibrosis Foundation, outside the submitted work. Dr. Sawicki reports personal fees from Vertex Pharmaceuticals, outside the submitted work. Dr. Uluer reports grants from the Cystic Fibrosis Foundation and serves an advisory board for Vertex Pharmaceuticals and as an unpaid board member for the Cystic Fibrosis Research Institute. Dr. Kennedy reports grants from the Cystic Fibrosis Foundation. The other authors have nothing to disclose., (Copyright © 2021. Published by Elsevier B.V.)
- Published
- 2022
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29. Atypical presentation of subdural block resulting in Horner's syndrome and loss of consciousness.
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Chua KJ and Cernadas M
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- Adult, Cesarean Section, Female, Humans, Lidocaine adverse effects, Pregnancy, Unconsciousness, Anesthesia, Epidural adverse effects, Horner Syndrome chemically induced, Horner Syndrome diagnosis
- Abstract
Horner's syndrome is a rare side effect for patients receiving epidural anaesthesia. Studies described Horner's syndrome due to cephalic spread of injected anaesthetics, a high spinal anaesthesia, or a sign of an inadvertent subdural block. A 31-year-old woman (Gravida 1 Para 0) at 40 weeks and 2 days had a caesarean section secondary to second stage arrest. Fourteen minutes after she received the lidocaine bolus, she became unresponsive with nystagmus, unequal pupils and no pupillary reflex. Head CT and MRI showed no intracranial haemorrhage and 2 hours later, she had spontaneous resolution of neurological symptoms with no further sequelae. Although Horner's syndrome is a benign, transient process, clinicians should be mindful regarding epidural catheter placement causing subdural blocks resulting in spontaneous, reversible neurological deficits., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2021
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30. [Home births in Spain].
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Sánchez Redondo MD, Cernadas M, and Couce ML
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- Female, Humans, Pregnancy, Spain, Home Childbirth, Midwifery
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- 2021
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31. Persistence and Evolution of SARS-CoV-2 in an Immunocompromised Host.
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Choi B, Choudhary MC, Regan J, Sparks JA, Padera RF, Qiu X, Solomon IH, Kuo HH, Boucau J, Bowman K, Adhikari UD, Winkler ML, Mueller AA, Hsu TY, Desjardins M, Baden LR, Chan BT, Walker BD, Lichterfeld M, Brigl M, Kwon DS, Kanjilal S, Richardson ET, Jonsson AH, Alter G, Barczak AK, Hanage WP, Yu XG, Gaiha GD, Seaman MS, Cernadas M, and Li JZ
- Subjects
- COVID-19 diagnosis, Fatal Outcome, Humans, Male, Middle Aged, SARS-CoV-2 isolation & purification, Viral Load, Antiphospholipid Syndrome complications, COVID-19 complications, Immunocompromised Host
- Published
- 2020
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32. CFTR regulates B cell activation and lymphoid follicle development.
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Polverino F, Lu B, Quintero JR, Vargas SO, Patel AS, Owen CA, Gerard NP, Gerard C, and Cernadas M
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- Adolescent, Animals, Cystic Fibrosis pathology, Female, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, B-Lymphocytes metabolism, Cystic Fibrosis metabolism, Cystic Fibrosis Transmembrane Conductance Regulator physiology, Tertiary Lymphoid Structures metabolism
- Abstract
Background: Cystic fibrosis (CF) is an inherited disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene that promotes persistent lung infection and inflammation and progressive loss of lung function. Patients with CF have increased lung lymphoid follicles (LFs) and B cell-activating factor of tumor necrosis factor family (BAFF) that regulates B cell survival and maturation. A direct role for CFTR in B cell activation and disease pathogenesis in CF remains unclear., Methods: The number of LFs, BAFF
+ , TLR4+ and proliferation marker Ki67+ B cells in lung explants or resections from subjects with CF and normal controls was quantified by immunostaining. The role of CFTR in B cell activation and LF development was then examined in two independent cohorts of uninfected CFTR-deficient mice (Cftr-/- ) and wild type controls. The number of lung LFs, B cells and BAFF+ , CXCR4+ , immunoglobulin G+ B cells was examined by immunostaining. Lung and splenocyte B cell activation marker and major histocompatibility complex class II (MHC class II) expression was quantified by flow cytometry. Inflammatory cytokine levels were measured in supernatants from isolated B cells from Cftr-/- and wild type mice stimulated in vitro with Pseudomonas aeruginosa lipopolysaccharide (LPS)., Results: There was a significant increase in well-formed LFs in subjects with CF compared to normal controls. Increased B cell activation and proliferation was observed in lung LFs from CF subjects as was quantified by a significant increase in B cell BAFF, TLR4 and Ki67 expression. Uninfected Cftr-/- mice had increased lung LFs and BAFF+ and CXCR4+ B cells compared to wild type controls. Lung B cells isolated from uninfected Cftr-/- mice demonstrated increased MHC class II expression. In vitro, isolated B cells from Cftr-/- mice produced increased IL-6 when stimulated with LPS compared to wild type controls., Conclusions: These data support a direct role for CFTR in B cell activation, proliferation and inflammatory cytokine production that promotes lung LF follicle development in cystic fibrosis.- Published
- 2019
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33. Macrophage FABP4 is required for neutrophil recruitment and bacterial clearance in Pseudomonas aeruginosa pneumonia.
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Liang X, Gupta K, Quintero JR, Cernadas M, Kobzik L, Christou H, Pier GB, Owen CA, and Çataltepe S
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- Acute Lung Injury immunology, Animals, Bone Marrow immunology, Chemokine CXCL1 immunology, Inflammation immunology, Lung immunology, Mice, Mice, Inbred C57BL, Neutrophil Infiltration immunology, Pseudomonas Infections immunology, Fatty Acid-Binding Proteins immunology, Macrophages, Alveolar immunology, Neutrophils immunology, Pneumonia immunology, Pseudomonas aeruginosa immunology
- Abstract
Fatty acid binding protein 4 (FABP4), an intracellular lipid chaperone and adipokine, is expressed by lung macrophages, but the function of macrophage-FABP4 remains elusive. We investigated the role of FABP4 in host defense in a murine model of Pseudomonas aeruginosa pneumonia. Compared with wild-type (WT) mice, FABP4-deficient (FABP4
-/- ) mice exhibited decreased bacterial clearance and increased mortality when challenged intranasally with P. aeruginosa. These findings in FABP4-/- mice were associated with a delayed neutrophil recruitment into the lungs and were followed by greater acute lung injury and inflammation. Among leukocytes, only macrophages expressed FABP4 in WT mice with P. aeruginosa pneumonia. Chimeric FABP4-/- mice with WT bone marrow were protected from increased mortality seen in chimeric WT mice with FABP4-/- bone marrow during P. aeruginosa pneumonia, thus confirming the role of macrophages as the main source of protective FABP4 against that infection. There was less production of C-X-C motif chemokine ligand 1 (CXCL1) in FABP4-/- alveolar macrophages and lower airway CXCL1 levels in FABP4-/- mice. Delivering recombinant CXCL1 to the airways protected FABP4-/- mice from increased susceptibility to P. aeruginosa pneumonia. Thus, macrophage-FABP4 has a novel role in pulmonary host defense against P. aeruginosa infection by facilitating crosstalk between macrophages and neutrophils via regulation of macrophage CXCL1 production.-Liang, X., Gupta, K., Rojas Quintero, J., Cernadas, M., Kobzik, L., Christou, H., Pier, G. B., Owen, C. A., Çataltepe, S. Macrophage FABP4 is required for neutrophil recruitment and bacterial clearance in Pseudomonas aeruginosa pneumonia.- Published
- 2019
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34. Neutrophil cytoplasts induce T H 17 differentiation and skew inflammation toward neutrophilia in severe asthma.
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Krishnamoorthy N, Douda DN, Brüggemann TR, Ricklefs I, Duvall MG, Abdulnour RE, Martinod K, Tavares L, Wang X, Cernadas M, Israel E, Mauger DT, Bleecker ER, Castro M, Erzurum SC, Gaston BM, Jarjour NN, Wenzel S, Dunican E, Fahy JV, Irimia D, Wagner DD, and Levy BD
- Abstract
Severe asthma is a debilitating and treatment refractory disease. As many as half of these patients have complex neutrophil-predominant lung inflammation that is distinct from milder asthma with type 2 eosinophilic inflammation. New insights into severe asthma pathogenesis are needed. Concomitant exposure of mice to an aeroallergen and endotoxin during sensitization resulted in complex neutrophilic immune responses to allergen alone during later airway challenge. Unlike allergen alone, sensitization with allergen and endotoxin led to NETosis. In addition to neutrophil extracellular traps (NETs), enucleated neutrophil cytoplasts were evident in the lungs. Surprisingly, allergen-driven airway neutrophilia was decreased in peptidyl arginine deiminase 4-deficient mice with defective NETosis but not by deoxyribonuclease treatment, implicating the cytoplasts for the non-type 2 immune responses to allergen. Neutrophil cytoplasts were also present in mediastinal lymph nodes, and the cytoplasts activated lung dendritic cells in vitro to trigger antigen-specific interleukin-17 (IL-17) production from naïve CD4
+ T cells. Bronchoalveolar lavage fluid from patients with severe asthma and high neutrophil counts had detectable NETs and cytoplasts that were positively correlated with IL-17 levels. Together, these translational findings have identified neutrophil cytoplast formation in asthmatic lung inflammation and linked the cytoplasts to T helper 17-mediated neutrophilic inflammation in severe asthma., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)- Published
- 2018
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35. ALX receptor ligands define a biochemical endotype for severe asthma.
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Ricklefs I, Barkas I, Duvall MG, Cernadas M, Grossman NL, Israel E, Bleecker ER, Castro M, Erzurum SC, Fahy JV, Gaston BM, Denlinger LC, Mauger DT, Wenzel SE, Comhair SA, Coverstone AM, Fajt ML, Hastie AT, Johansson MW, Peters MC, Phillips BR, and Levy BD
- Published
- 2018
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36. ALX receptor ligands define a biochemical endotype for severe asthma.
- Author
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Ricklefs I, Barkas I, Duvall MG, Cernadas M, Grossman NL, Israel E, Bleecker ER, Castro M, Erzurum SC, Fahy JV, Gaston BM, Denlinger LC, Mauger DT, Wenzel SE, Comhair SA, Coverstone AM, Fajt ML, Hastie AT, Johansson MW, Peters MC, Phillips BR, and Levy BD
- Abstract
Background: In health, inflammation resolution is an active process governed by specialized proresolving mediators and receptors. ALX/FPR2 receptors (ALX) are targeted by both proresolving and proinflammatory ligands for opposing signaling events, suggesting pivotal roles for ALX in the fate of inflammatory responses. Here, we determined if ALX expression and ligands were linked to severe asthma (SA)., Methods: ALX expression and levels of proresolving ligands (lipoxin A4 [LXA4], 15-epi-LXA4, and annexin A1 [ANXA1]), and a proinflammatory ligand (serum amyloid A [SAA]) were measured in bronchoscopy samples collected in Severe Asthma Research Program-3 (SA [n = 69], non-SA [NSA, n = 51] or healthy donors [HDs, n = 47])., Results: Bronchoalveolar lavage (BAL) fluid LXA4 and 15-epi-LXA4 were decreased and SAA was increased in SA relative to NSA. BAL macrophage ALX expression was increased in SA. Subjects with LXA4loSAAhi levels had increased BAL neutrophils, more asthma symptoms, lower lung function, increased relative risk for asthma exacerbation, sinusitis, and gastroesophageal reflux disease, and were assigned more frequently to SA clinical clusters. SAA and aliquots of LXA4loSAAhi BAL fluid induced IL-8 production by lung epithelial cells expressing ALX receptors, which was inhibited by coincubation with 15-epi-LXA4., Conclusions: Together, these findings have established an association between select ALX receptor ligands and asthma severity that define a potentially new biochemical endotype for asthma and support a pivotal functional role for ALX signaling in the fate of lung inflammation., Trial Registration: Severe Asthma Research Program-3 (SARP-3; ClinicalTrials.gov NCT01606826)FUNDING Sources. National Heart, Lung and Blood Institute, the NIH, and the German Society of Pediatric Pneumology.
- Published
- 2017
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37. Natural killer cell-mediated inflammation resolution is disabled in severe asthma.
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Duvall MG, Barnig C, Cernadas M, Ricklefs I, Krishnamoorthy N, Grossman NL, Bhakta NR, Fahy JV, Bleecker ER, Castro M, Erzurum SC, Gaston BM, Jarjour NN, Mauger DT, Wenzel SE, Comhair SA, Coverstone AM, Fajt ML, Hastie AT, Johansson MW, Peters MC, Phillips BR, Israel E, and Levy BD
- Abstract
Severe asthma is typically characterized by chronic airway inflammation that is refractory to corticosteroids and associated with excess morbidity. Patients were recruited into the National Heart, Lung, and Blood Institute-sponsored Severe Asthma Research Program and comprehensively phenotyped by bronchoscopy. Bronchoalveolar lavage (BAL) cells were analyzed by flow cytometry. Compared with healthy individuals ( n = 21), patients with asthma ( n = 53) had fewer BAL natural killer (NK) cells. Patients with severe asthma ( n = 29) had a marked increase in the ratios of CD4
+ T cells to NK cells and neutrophils to NK cells. BAL NK cells in severe asthma were skewed toward the cytotoxic CD56dim subset, with significantly increased BAL fluid levels of the cytotoxic mediator granzyme A. The numbers of BAL CD56dim NK cells and CCR6- CCR4- T helper 1-enriched CD4+ T cells correlated inversely with lung function [forced expiratory volume in 1 s (FEV1 ) % predicted] in asthma. Relative to cells from healthy controls, peripheral blood NK cells from asthmatic patients had impaired killing of K562 myeloid target cells despite releasing more cytotoxic mediators. Ex vivo exposure to dexamethasone markedly decreased blood NK cell lysis of target cells and cytotoxic mediator release. NK cells expressed airway lipoxin A4 /formyl peptide receptor 2 receptors, and in contrast to dexamethasone, lipoxin A4 -exposed NK cells had preserved functional responses. Together, our findings indicate that the immunology of the severe asthma airway is characterized by decreased NK cell cytotoxicity with increased numbers of target leukocytes, which is exacerbated by corticosteroids that further disable NK cell function. These failed resolution mechanisms likely contribute to persistent airway inflammation in severe asthma., (Copyright © 2017, American Association for the Advancement of Science.)- Published
- 2017
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38. Alternative Macrophage Activation Is Increased in Asthma.
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Girodet PO, Nguyen D, Mancini JD, Hundal M, Zhou X, Israel E, and Cernadas M
- Abstract
The immune responses of type 2 T helper cells (Th2) play an important role in asthma and promote the differentiation of alternatively activated (M2) macrophages. M2 macrophages have been increasingly understood to contribute to Th2 immunity. We hypothesized that M2 macrophages are altered in asthma and modulate Th2 responses. The aim of this study was to characterize the phenotype and function of human monocyte-derived M2 and bronchoalveolar lavage fluid (BALF) macrophages from healthy control subjects and subjects with asthma. Phenotypic characteristics and effector function of M2 macrophages were examined using monocyte-derived and BALF macrophages obtained from subjects with asthma (n = 28) and healthy volunteers (n = 9) by flow cytometry and quantitative PCR. Resting monocyte-derived (M0) and M2 macrophages were generated by the addition of macrophage colony-stimulating factor or macrophage colony-stimulating factor plus IL-4, respectively. M2 macrophage cytokine expression and their impact on dendritic and CD4
+ T cell activation were examined in vitro. High levels of CD206 and major histocompatibility complex class II expression identify macrophages with an M2 phenotype that are increased 2.9-fold in the BALF of subjects with asthma compared with control subjects. M2 macrophages have elevated IL-6, IL-10, and IL-12p40 production compared with conventional macrophages and modulate dendritic and CD4+ T cell interactions. Histamine receptor 1 and E-cadherin expression identify M2 macrophage subsets associated with increased airflow obstruction. M2 macrophages have a distinct cell surface and effector phenotype and are found in increased numbers in subjects with asthma. These findings suggest that M2 macrophages may play an important role in allergic asthma through their bidirectional interactions with immune and structural cells, and inflammatory mediators.- Published
- 2016
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39. Vitamin D3 treatment of vitamin D-insufficient asthmatic patients does not alter immune cell function.
- Author
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Reid B, Girodet PO, Boomer JS, Abdel-Gadir A, Zheng K, Wechsler ME, Bacharier LB, Kunselman SJ, King TS, Israel E, Castro M, Cernadas M, and Green JM
- Subjects
- Asthma complications, Asthma immunology, Asthma metabolism, CD4-Positive T-Lymphocytes drug effects, CD4-Positive T-Lymphocytes immunology, Dendritic Cells drug effects, Dendritic Cells immunology, Gene Expression, Humans, Interferon-gamma genetics, Interferon-gamma immunology, Interleukins genetics, Interleukins immunology, Monocytes drug effects, Monocytes immunology, Transforming Growth Factor beta genetics, Transforming Growth Factor beta immunology, Tumor Necrosis Factor-alpha genetics, Tumor Necrosis Factor-alpha immunology, Vitamin D Deficiency complications, Vitamin D Deficiency immunology, Vitamin D Deficiency metabolism, Adrenal Cortex Hormones therapeutic use, Asthma drug therapy, Cholecalciferol therapeutic use, Vitamin D Deficiency drug therapy
- Published
- 2016
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40. Circadian rhythm reprogramming during lung inflammation.
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Haspel JA, Chettimada S, Shaik RS, Chu JH, Raby BA, Cernadas M, Carey V, Process V, Hunninghake GM, Ifedigbo E, Lederer JA, Englert J, Pelton A, Coronata A, Fredenburgh LE, and Choi AM
- Subjects
- Animals, CLOCK Proteins immunology, CLOCK Proteins metabolism, Circadian Rhythm immunology, Circadian Rhythm Signaling Peptides and Proteins genetics, Circadian Rhythm Signaling Peptides and Proteins immunology, Circadian Rhythm Signaling Peptides and Proteins metabolism, Endotoxins toxicity, Gene Expression Regulation, Granulocytes immunology, Leukocyte Count, Lung immunology, Lymphocytes immunology, Mice, Pneumonia chemically induced, Pneumonia metabolism, CLOCK Proteins genetics, Circadian Rhythm genetics, Lung metabolism, Pneumonia genetics, RNA, Messenger metabolism
- Abstract
Circadian rhythms are known to regulate immune responses in healthy animals, but it is unclear whether they persist during acute illnesses where clock gene expression is disrupted by systemic inflammation. Here we use a genome-wide approach to investigate circadian gene and metabolite expression in the lungs of endotoxemic mice and find that novel cellular and molecular circadian rhythms are elicited in this setting. The endotoxin-specific circadian programme exhibits unique features, including a divergent group of rhythmic genes and metabolites compared with the basal state and a distinct periodicity and phase distribution. At the cellular level, endotoxin treatment also alters circadian rhythms of leukocyte counts within the lung in a bmal1-dependent manner, such that granulocytes rather than lymphocytes become the dominant oscillating cell type. Our results show that inflammation produces a complex re-organization of cellular and molecular circadian rhythms that are relevant to early events in lung injury.
- Published
- 2014
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41. Adam8 limits the development of allergic airway inflammation in mice.
- Author
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Knolle MD, Nakajima T, Hergrueter A, Gupta K, Polverino F, Craig VJ, Fyfe SE, Zahid M, Permaul P, Cernadas M, Montano G, Tesfaigzi Y, Sholl L, Kobzik L, Israel E, and Owen CA
- Subjects
- ADAM Proteins metabolism, Adult, Animals, Antigens, CD metabolism, Apoptosis immunology, Asthma metabolism, Asthma pathology, Bronchial Hyperreactivity metabolism, Bronchial Hyperreactivity pathology, Disease Models, Animal, Eosinophils immunology, Eosinophils metabolism, Fluorescent Antibody Technique, Humans, Macrophages immunology, Macrophages metabolism, Membrane Proteins metabolism, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, ADAM Proteins immunology, Antigens, CD immunology, Asthma immunology, Bronchial Hyperreactivity immunology, Membrane Proteins immunology
- Abstract
To determine whether a disintegrin and metalloproteinase-8 (Adam8) regulates allergic airway inflammation (AAI) and airway hyperresponsiveness (AHR), we compared AAI and AHR in wild-type (WT) versus Adam8(-/-) mice in different genetic backgrounds sensitized and challenged with OVA or house dust mite protein extract. OVA- and house dust mite-treated Adam8(-/-) mice had higher lung leukocyte counts, more airway mucus metaplasia, greater lung levels of some Th2 cytokines, and higher methacholine-induced increases in central airway resistance than allergen-treated WT mice. Studies of OVA-treated Adam8 bone marrow chimeric mice confirmed that leukocyte-derived Adam8 predominantly mediated Adam8's anti-inflammatory activities in murine airways. Airway eosinophils and macrophages both expressed Adam8 in WT mice with AAI. Adam8 limited AAI and AHR in mice by reducing leukocyte survival because: 1) Adam8(-/-) mice with AAI had fewer apoptotic eosinophils and macrophages in their airways than WT mice with AAI; and 2) Adam8(-/-) macrophages and eosinophils had reduced rates of apoptosis compared with WT leukocytes when the intrinsic (but not the extrinsic) apoptosis pathway was triggered in the cells in vitro. ADAM8 was robustly expressed by airway granulocytes in lung sections from human asthma patients, but, surprisingly, airway macrophages had less ADAM8 staining than airway eosinophils. Thus, ADAM8 has anti-inflammatory activities during AAI in mice by activating the intrinsic apoptosis pathway in myeloid leukocytes. Strategies that increase ADAM8 levels in myeloid leukocytes may have therapeutic efficacy in asthma.
- Published
- 2013
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42. Integrating murine gene expression studies to understand obstructive lung disease due to chronic inhaled endotoxin.
- Author
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Lai PS, Hofmann O, Baron RM, Cernadas M, Meng QR, Bresler HS, Brass DM, Yang IV, Schwartz DA, Christiani DC, and Hide W
- Subjects
- Administration, Inhalation, Algorithms, Animals, Asthma chemically induced, Asthma physiopathology, Gene Expression Profiling, Lung physiopathology, Mice, Multigene Family, Pulmonary Disease, Chronic Obstructive chemically induced, Pulmonary Disease, Chronic Obstructive physiopathology, Smoking, Transcriptome, Asthma genetics, Endotoxins pharmacology, Gene Expression, Lung metabolism, Pulmonary Disease, Chronic Obstructive genetics, Nicotiana chemistry
- Abstract
Rationale: Endotoxin is a near ubiquitous environmental exposure that that has been associated with both asthma and chronic obstructive pulmonary disease (COPD). These obstructive lung diseases have a complex pathophysiology, making them difficult to study comprehensively in the context of endotoxin. Genome-wide gene expression studies have been used to identify a molecular snapshot of the response to environmental exposures. Identification of differentially expressed genes shared across all published murine models of chronic inhaled endotoxin will provide insight into the biology underlying endotoxin-associated lung disease., Methods: We identified three published murine models with gene expression profiling after repeated low-dose inhaled endotoxin. All array data from these experiments were re-analyzed, annotated consistently, and tested for shared genes found to be differentially expressed. Additional functional comparison was conducted by testing for significant enrichment of differentially expressed genes in known pathways. The importance of this gene signature in smoking-related lung disease was assessed using hierarchical clustering in an independent experiment where mice were exposed to endotoxin, smoke, and endotoxin plus smoke., Results: A 101-gene signature was detected in three murine models, more than expected by chance. The three model systems exhibit additional similarity beyond shared genes when compared at the pathway level, with increasing enrichment of inflammatory pathways associated with longer duration of endotoxin exposure. Genes and pathways important in both asthma and COPD were shared across all endotoxin models. Mice exposed to endotoxin, smoke, and smoke plus endotoxin were accurately classified with the endotoxin gene signature., Conclusions: Despite the differences in laboratory, duration of exposure, and strain of mouse used in three experimental models of chronic inhaled endotoxin, surprising similarities in gene expression were observed. The endotoxin component of tobacco smoke may play an important role in disease development.
- Published
- 2013
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43. Lipoxin A4 regulates natural killer cell and type 2 innate lymphoid cell activation in asthma.
- Author
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Barnig C, Cernadas M, Dutile S, Liu X, Perrella MA, Kazani S, Wechsler ME, Israel E, and Levy BD
- Subjects
- Animals, Humans, Asthma immunology, Asthma pathology, Lymphocytes immunology
- Abstract
Asthma is a prevalent disease of chronic inflammation in which endogenous counterregulatory signaling pathways are dysregulated. Recent evidence suggests that innate lymphoid cells (ILCs), including natural killer (NK) cells and type 2 ILCs (ILC2s), can participate in the regulation of allergic airway responses, in particular airway mucosal inflammation. We have identified both NK cells and ILC2s in human lung and peripheral blood in healthy and asthmatic subjects. NK cells were highly activated in severe asthma, were linked to eosinophilia, and interacted with autologous eosinophils to promote their apoptosis. ILC2s generated antigen-independent interleukin-13 (IL-13) in response to the mast cell product prostaglandin D2 alone and in a synergistic manner with the airway epithelial cytokines IL-25 and IL-33. Both NK cells and ILC2s expressed the pro-resolving ALX/FPR2 receptors. Lipoxin A4, a natural pro-resolving ligand for ALX/FPR2 receptors, significantly increased NK cell-mediated eosinophil apoptosis and decreased IL-13 release by ILC2s. Together, these findings indicate that ILCs are targets for lipoxin A4 to decrease airway inflammation and mediate the catabasis of eosinophilic inflammation. Because lipoxin A4 generation is decreased in severe asthma, these findings also implicate unrestrained ILC activation in asthma pathobiology.
- Published
- 2013
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44. Endothelial cell-fatty acid binding protein 4 promotes angiogenesis: role of stem cell factor/c-kit pathway.
- Author
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Elmasri H, Ghelfi E, Yu CW, Traphagen S, Cernadas M, Cao H, Shi GP, Plutzky J, Sahin M, Hotamisligil G, and Cataltepe S
- Subjects
- Animals, Apoptosis, Blotting, Western, Cell Survival, Cells, Cultured, Chemotaxis, Endothelial Cells metabolism, Endothelium, Vascular cytology, Fatty Acid-Binding Proteins genetics, Gene Expression Regulation physiology, Humans, Mice, Mice, Knockout, RNA Interference, Endothelium, Vascular metabolism, Fatty Acid-Binding Proteins physiology, Neovascularization, Physiologic genetics, Stem Cell Factor physiology
- Abstract
Fatty acid binding protein 4 (FABP4) plays an important role in regulation of glucose and lipid homeostasis as well as inflammation through its actions in adipocytes and macrophages. FABP4 is also expressed in a subset of endothelial cells, but its role in this cell type is not known. We found that FABP4-deficient human umbilical vein endothelial cells (HUVECs) demonstrate a markedly increased susceptibility to apoptosis as well as decreased migration and capillary network formation. Aortic rings from FABP4(-/-) mice demonstrated decreased angiogenic sprouting, which was recovered by reconstitution of FABP4. FABP4 was strongly regulated by mTORC1 and inhibited by Rapamycin. FABP4 modulated activation of several important signaling pathways in HUVECs, including downregulation of P38, eNOS, and stem cell factor (SCF)/c-kit signaling. Of these, the SCF/c-kit pathway was found to have a major role in attenuated angiogenic activity of FABP4-deficient ECs as provision of exogenous SCF resulted in a significant recovery in cell proliferation, survival, morphogenesis, and aortic ring sprouting. These data unravel a novel pro-angiogenic role for endothelial cell-FABP4 and suggest that it could be exploited as a potential target for diseases associated with pathological angiogenesis.
- Published
- 2012
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45. Chronic endotoxin exposure produces airflow obstruction and lung dendritic cell expansion.
- Author
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Lai PS, Fresco JM, Pinilla MA, Macias AA, Brown RD, Englert JA, Hofmann O, Lederer JA, Hide W, Christiani DC, Cernadas M, and Baron RM
- Subjects
- Airway Resistance drug effects, Airway Resistance genetics, Airway Resistance immunology, Animals, Antigen-Presenting Cells immunology, Antigen-Presenting Cells metabolism, Antigen-Presenting Cells pathology, Bronchial Hyperreactivity genetics, Bronchial Hyperreactivity immunology, Bronchial Hyperreactivity metabolism, Bronchial Hyperreactivity pathology, Bronchoalveolar Lavage Fluid immunology, Dendritic Cells immunology, Dendritic Cells metabolism, Dendritic Cells pathology, Endotoxins immunology, Gene Expression, Interleukin-10 genetics, Interleukin-10 immunology, Interleukin-10 metabolism, Interleukin-6 genetics, Interleukin-6 immunology, Interleukin-6 metabolism, Leukocytes, Mononuclear drug effects, Leukocytes, Mononuclear immunology, Leukocytes, Mononuclear metabolism, Leukocytes, Mononuclear pathology, Lipopolysaccharides immunology, Lipopolysaccharides pharmacology, Lung immunology, Lung metabolism, Lung pathology, Macrophages immunology, Macrophages metabolism, Macrophages pathology, Male, Mice, Mice, Inbred C57BL, Models, Animal, Myeloid Cells drug effects, Myeloid Cells immunology, Myeloid Cells metabolism, Myeloid Cells pathology, Neutrophils drug effects, Neutrophils immunology, Neutrophils metabolism, Neutrophils pathology, Occupational Exposure, Pneumonia genetics, Pneumonia immunology, Pneumonia metabolism, Pneumonia pathology, Pulmonary Disease, Chronic Obstructive genetics, Pulmonary Disease, Chronic Obstructive metabolism, Pulmonary Disease, Chronic Obstructive pathology, Up-Regulation, Dendritic Cells drug effects, Endotoxins pharmacology, Lung drug effects, Pulmonary Disease, Chronic Obstructive immunology
- Abstract
Little is known about the mechanisms of persistent airflow obstruction that result from chronic occupational endotoxin exposure. We sought to analyze the inflammatory response underlying persistent airflow obstruction as a result of chronic occupational endotoxin exposure. We developed a murine model of daily inhaled endotoxin for periods of 5 days to 8 weeks. We analyzed physiologic lung dysfunction, lung histology, bronchoalveolar lavage fluid and total lung homogenate inflammatory cell and cytokine profiles, and pulmonary gene expression profiles. We observed an increase in airway hyperresponsiveness as a result of chronic endotoxin exposure. After 8 weeks, the mice exhibited an increase in bronchoalveolar lavage and lung neutrophils that correlated with an increase in proinflammatory cytokines. Detailed analyses of inflammatory cell subsets revealed an expansion of dendritic cells (DCs), and in particular, proinflammatory DCs, with a reduced percentage of macrophages. Gene expression profiling revealed the up-regulation of a panel of genes that was consistent with DC recruitment, and lung histology revealed an accumulation of DCs in inflammatory aggregates around the airways in 8-week-exposed animals. Repeated, low-dose LPS inhalation, which mirrors occupational exposure, resulted in airway hyperresponsiveness, associated with a failure to resolve the proinflammatory response, an inverted macrophage to DC ratio, and a significant rise in the inflammatory DC population. These findings point to a novel underlying mechanism of airflow obstruction as a result of occupational LPS exposure, and suggest molecular and cellular targets for therapeutic development.
- Published
- 2012
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46. PTPN22.6, a dominant negative isoform of PTPN22 and potential biomarker of rheumatoid arthritis.
- Author
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Chang HH, Tai TS, Lu B, Iannaccone C, Cernadas M, Weinblatt M, Shadick N, Miaw SC, and Ho IC
- Subjects
- Arthritis, Rheumatoid genetics, Blotting, Western, Cell Line, Tumor, DNA Primers genetics, DNA, Complementary genetics, Enzyme-Linked Immunosorbent Assay, Humans, Immunoprecipitation, Leukocytes, Mononuclear, Linear Models, Luciferases, Lymphocyte Activation genetics, Mutation, Missense genetics, Polymorphism, Single Nucleotide genetics, Protein Isoforms blood, Protein Isoforms genetics, Real-Time Polymerase Chain Reaction, Alternative Splicing genetics, Arthritis, Rheumatoid blood, Biomarkers blood, Models, Biological, Protein Tyrosine Phosphatase, Non-Receptor Type 22 blood, Protein Tyrosine Phosphatase, Non-Receptor Type 22 genetics, T-Lymphocytes immunology
- Abstract
PTPN22 is a tyrosine phosphatase and functions as a damper of TCR signals. A C-to-T single nucleotide polymorphism (SNP) located at position 1858 of human PTPN22 cDNA and converting an arginine (R620) to tryptophan (W620) confers the highest risk of rheumatoid arthritis among non-HLA genetic variations that are known to be associated with this disease. The effect of the R-to-W conversion on the phosphatase activity of PTPN22 protein and the impact of the minor T allele of the C1858T SNP on the activation of T cells has remained controversial. In addition, how the overall activity of PTPN22 is regulated and how the R-to-W conversion contributes to rheumatoid arthritis is still poorly understood. Here we report the identification of an alternative splice form of human PTPN22, namely PTPN22.6. It lacks the nearly entire phosphatase domain and can function as a dominant negative isoform of the full length PTPN22. Although conversion of R620 to W620 in the context of PTPN22.1 attenuated T cell activation, expression of the tryptophan variant of PTPN22.6 reciprocally led to hyperactivation of human T cells. More importantly, the level of PTPN22.6 in peripheral blood correlates with disease activity of rheumatoid arthritis. Our data depict a model that can reconcile the conflicting observations on the functional impact of the C1858T SNP and also suggest that PTPN22.6 is a novel biomarker of rheumatoid arthritis.
- Published
- 2012
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47. Cyclooxygenase-2 deficiency leads to intestinal barrier dysfunction and increased mortality during polymicrobial sepsis.
- Author
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Fredenburgh LE, Velandia MM, Ma J, Olszak T, Cernadas M, Englert JA, Chung SW, Liu X, Begay C, Padera RF, Blumberg RS, Walsh SR, Baron RM, and Perrella MA
- Subjects
- Animals, Bacteremia enzymology, Bacteremia immunology, Bacteremia mortality, Caco-2 Cells, Cell Membrane Permeability genetics, Cell Membrane Permeability immunology, Cyclooxygenase 2 biosynthesis, Female, Humans, Ileum enzymology, Ileum immunology, Ileum microbiology, Intestinal Mucosa microbiology, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Peritonitis enzymology, Peritonitis immunology, Peritonitis mortality, Sepsis enzymology, Cyclooxygenase 2 deficiency, Cyclooxygenase 2 genetics, Intestinal Mucosa enzymology, Intestinal Mucosa immunology, Sepsis immunology, Sepsis mortality
- Abstract
Sepsis remains the leading cause of death in critically ill patients, despite modern advances in critical care. Intestinal barrier dysfunction may lead to secondary bacterial translocation and the development of the multiple organ dysfunction syndrome during sepsis. Cyclooxygenase (COX)-2 is highly upregulated in the intestine during sepsis, and we hypothesized that it may be critical in the maintenance of intestinal epithelial barrier function during peritonitis-induced polymicrobial sepsis. COX-2(-/-) and COX-2(+/+) BALB/c mice underwent cecal ligation and puncture (CLP) or sham surgery. Mice chimeric for COX-2 were derived by bone marrow transplantation and underwent CLP. C2BBe1 cells, an intestinal epithelial cell line, were treated with the COX-2 inhibitor NS-398, PGD(2), or vehicle and stimulated with cytokines. COX-2(-/-) mice developed exaggerated bacteremia and increased mortality compared with COX-2(+/+) mice following CLP. Mice chimeric for COX-2 exhibited the recipient phenotype, suggesting that epithelial COX-2 expression in the ileum attenuates bacteremia following CLP. Absence of COX-2 significantly increased epithelial permeability of the ileum and reduced expression of the tight junction proteins zonula occludens-1, occludin, and claudin-1 in the ileum following CLP. Furthermore, PGD(2) attenuated cytokine-induced hyperpermeability and zonula occludens-1 downregulation in NS-398-treated C2BBe1 cells. Our findings reveal that absence of COX-2 is associated with enhanced intestinal epithelial permeability and leads to exaggerated bacterial translocation and increased mortality during peritonitis-induced sepsis. Taken together, our results suggest that epithelial expression of COX-2 in the ileum is a critical modulator of tight junction protein expression and intestinal barrier function during sepsis.
- Published
- 2011
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48. NK cells are effectors for resolvin E1 in the timely resolution of allergic airway inflammation.
- Author
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Haworth O, Cernadas M, and Levy BD
- Subjects
- Adaptive Immunity immunology, Adoptive Transfer, Animals, Bronchoalveolar Lavage Fluid cytology, Bronchoalveolar Lavage Fluid immunology, CD11b Antigen immunology, CD11b Antigen metabolism, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes metabolism, Eicosapentaenoic Acid metabolism, Eicosapentaenoic Acid pharmacology, Eosinophils immunology, Eosinophils metabolism, Flow Cytometry, Inflammation metabolism, Killer Cells, Natural metabolism, Killer Cells, Natural transplantation, Lung drug effects, Lung immunology, Lung pathology, Lymph Nodes immunology, Lymph Nodes metabolism, Lymph Nodes pathology, Mice, Mice, Inbred BALB C, Respiratory Hypersensitivity metabolism, Respiratory Mucosa immunology, Respiratory Mucosa metabolism, Respiratory Mucosa pathology, Time Factors, Tumor Necrosis Factor Receptor Superfamily, Member 7 immunology, Tumor Necrosis Factor Receptor Superfamily, Member 7 metabolism, Eicosapentaenoic Acid analogs & derivatives, Inflammation immunology, Killer Cells, Natural immunology, Respiratory Hypersensitivity immunology
- Abstract
Immune responses are pathologically sustained in several common diseases, including asthma. To determine endogenous proresolving mechanisms for adaptive immune responses, we used a murine model of self-limited allergic airway inflammation. After cessation of allergen exposure, eosinophils and T cells were cleared concomitant with the appearance of increased numbers of NK cells in the lung and mediastinal lymph nodes. The mediastinal lymph node NK cells were activated, expressing CD27, CD11b, CD69, CD107a, and IFN-γ. NK cell depletion disrupted the endogenous resolution program, leading to delayed clearance of airway eosinophils and Ag-specific CD4(+) T cells. NK cell trafficking to inflamed tissues for resolution was dependent upon CXCR3 and CD62L. During resolution, eosinophils and Ag-specific CD4(+) T cells expressed NKG2D ligands, and a blocking Ab for the NKG2D receptor delayed clearance of these leukocytes. Of interest, NK cells expressed CMKLR1, a receptor for the proresolving mediator resolvin E1, and depletion of NK cells decreased resolvin E1-mediated resolution of allergic inflammation. Resolvin E1 regulated NK cell migration in vivo and NK cell cytotoxicity in vitro. Together, these findings indicate new functions in catabasis for NK cells that can also serve as targets for proresolving mediators in the resolution of adaptive immunity.
- Published
- 2011
- Full Text
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49. Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome.
- Author
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Nakahira K, Haspel JA, Rathinam VA, Lee SJ, Dolinay T, Lam HC, Englert JA, Rabinovitch M, Cernadas M, Kim HP, Fitzgerald KA, Ryter SW, and Choi AM
- Subjects
- Animals, Caspase 1 immunology, Flow Cytometry, Mice, NLR Family, Pyrin Domain-Containing 3 Protein, Autophagy, Carrier Proteins immunology, DNA, Mitochondrial, Immunity, Innate, Inflammasomes immunology
- Abstract
Autophagy, a cellular process for organelle and protein turnover, regulates innate immune responses. Here we demonstrate that depletion of the autophagic proteins LC3B and beclin 1 enhanced the activation of caspase-1 and secretion of interleukin 1β (IL-1β) and IL-18. Depletion of autophagic proteins promoted the accumulation of dysfunctional mitochondria and cytosolic translocation of mitochondrial DNA (mtDNA) in response to lipopolysaccharide (LPS) and ATP in macrophages. Release of mtDNA into the cytosol depended on the NALP3 inflammasome and mitochondrial reactive oxygen species (ROS). Cytosolic mtDNA contributed to the secretion of IL-1β and IL-18 in response to LPS and ATP. LC3B-deficient mice produced more caspase-1-dependent cytokines in two sepsis models and were susceptible to LPS-induced mortality. Our study suggests that autophagic proteins regulate NALP3-dependent inflammation by preserving mitochondrial integrity.
- Published
- 2011
- Full Text
- View/download PDF
50. Synovial fibroblasts self-direct multicellular lining architecture and synthetic function in three-dimensional organ culture.
- Author
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Kiener HP, Watts GF, Cui Y, Wright J, Thornhill TS, Sköld M, Behar SM, Niederreiter B, Lu J, Cernadas M, Coyle AJ, Sims GP, Smolen J, Warman ML, Brenner MB, and Lee DM
- Subjects
- Animals, Extracellular Matrix ultrastructure, Glycoproteins biosynthesis, Humans, Inflammation physiopathology, Macrophages cytology, Mice, Organ Culture Techniques, Synovial Membrane anatomy & histology, Fibroblasts physiology, Synovial Fluid chemistry, Synovial Membrane cytology
- Abstract
Objective: To define the intrinsic capacity of fibroblast-like synoviocytes (FLS) to establish a 3-dimensional (3-D) complex synovial lining architecture characterized by the multicellular organization of the compacted synovial lining and the elaboration of synovial fluid constituents., Methods: FLS were cultured in spherical extracellular matrix (ECM) micromasses for 3 weeks. The FLS micromass architecture was assessed histologically and compared with that of dermal fibroblast controls. Lubricin synthesis was measured via immunodetection. Basement membrane matrix and reticular fiber stains were performed to examine ECM organization. Primary human and mouse monocytes were prepared and cocultured with FLS in micromass to investigate cocompaction in the lining architecture. Cytokine stimuli were applied to determine the capacity for inflammatory architecture rearrangement., Results: FLS, but not dermal fibroblasts, spontaneously formed a compacted lining architecture over 3 weeks in the 3-D ECM micromass organ cultures. These lining cells produced lubricin. FLS rearranged their surrounding ECM into a complex architecture resembling the synovial lining and supported the survival and cocompaction of monocyte/macrophages in the neo-lining structure. Furthermore, when stimulated by cytokines, FLS lining structures displayed features of the hyperplastic rheumatoid arthritis synovial lining., Conclusion: This 3-D micromass organ culture method demonstrates that many of the phenotypic characteristics of the normal and the hyperplastic synovial lining in vivo are intrinsic functions of FLS. Moreover, FLS promote survival and cocompaction of primary monocytes in a manner remarkably similar to that of synovial lining macrophages. These findings provide new insight into inherent functions of the FLS lineage and establish a powerful in vitro method for further investigation of this lineage.
- Published
- 2010
- Full Text
- View/download PDF
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