93 results on '"Zemel, D."'
Search Results
2. The capability set for work – correlates of sustainable employability in workers with multiple sclerosis
- Author
-
van Gorp, D. A. M., van der Klink, J. J. L., Abma, F. I., Jongen, P. J., van Lieshout, I., Arnoldus, E. P. J., Beenakker, E. A. C., Bos, H. M., van Eijk, J. J. J., Fermont, J., Frequin, S. T. F. M., de Gans, K., Hengstman, G. J. D., Hupperts, R. M. M., Mostert, J. P., Pop, P. H. M., Verhagen, W. I. M., Zemel, D., Heerings, M. A. P., Reneman, M. F., Middelkoop, H. A. M., Visser, L. H., and van der Hiele, K.
- Published
- 2018
- Full Text
- View/download PDF
3. Diffuse alveolar hemorrhage as an early complication of alemtuzumab treatment: A case report of a multiple sclerosis patient and an overview of 14 cases
- Author
-
Drop, B.R.H., Zemel, D., Wokke, B.H.A., van Oosten, B.W., Dik, S., Martins Jarnalo, C.O., Westerweel, P.E., and de Beukelaar, J.W.K.
- Published
- 2021
- Full Text
- View/download PDF
4. Cognitive functioning and employment status in relapsing remitting multiple sclerosis: a 2-year longitudinal study
- Author
-
Gorp, D.A.M. van, Hiele, K. van der, Heerings, M.A.P., Jongen, P.J., Van der Klink, J.J.L., Reneman, M.F., Arnoldus, E.P.J., Beenakker, E.A.C., Van Eijk, J.J.J., Frequin, S.T.F.M., De Gans, K., Hoitsma, E., Mostert, J.P., Verhagen, W.I.M., Zemel, D., Visser, L.H., and Middelkoop, H.A.M.
- Published
- 2019
5. Relationship between personality traits and work functioning in people with multiple sclerosis
- Author
-
van Gorp, D. A. M., van der Hiele, K., van Egmond, E. E. A., Heerings, M. A. P., Jongen, P. J., van der Klink, J. J. L., Reneman, M. F., Arnoldus, E. P. J., Beenakker, E. A. C., Bos, H. M., van Eijk, J. J. J., Fermont, J., Frequin, S. T. F. M., de Gans, K., van Geel, B. M., Hengstman, G. J. D., Hoitsma, E., Hupperts, R. M. M., Moll, J. W. B., Mostert, J. P., Pop, P. H. M., Verhagen, W. I. M., Zemel, D., Middelkoop, H. A. M., Visser, L. H., and Extremities Pain and Disability (EXPAND)
- Published
- 2019
6. The MS@Work study after two years-factors related to (successful) work participation in patients with relapsing-remitting multiple sclerosis
- Author
-
van Gorp, D. A. M., van der Hiele, K., van Egmond, E. E. A., Heerings, M. A. P., Jongen, P. J., van der Klink, J. J. L., Reneman, M. F., Arnoldus, E. P. J., Beenakker, E. A. C., Bos, H. M., van Eijk, J. J. J., Fermont, J., Frequin, S. T. F. M., de Gans, K., van Geel, B. M., Hengstman, G. J. D., Hoitsma, E., Hupperts, R. M. M., Moll, J. W. B., Mostert, J. P., Pop, P. H. M., Verhagen, W. I. M., Zemel, D., Middelkoop, H. A. M., Visser, L. H., and Extremities Pain and Disability (EXPAND)
- Published
- 2019
7. A validation study of the Dutch Multiple Sclerosis Work Difficulties Questionnaire in relapsing-remitting multiple sclerosis
- Author
-
van Egmond, E. E. A., van Gorp, D. A. M., Honan, C. A., Heerings, M. A. P., Jongen, P. J., van der Klink, J. J. L., Reneman, M. F., Beenakker, E. A. C., Frequin, S. T. F. M., de Gans, K., Hengstman, G. J. D., Hoitsma, E., Mostert, J. P., Verhagen, W. I. M., Zemel, D., Middelkoop, H. A. M., Visser, L. H., van der Hiele, K., and Extremities Pain and Disability (EXPAND)
- Published
- 2019
8. Caregiver strain among life partners of individuals with relapsing-remitting multiple sclerosis
- Author
-
Hiele, van der K., Gorp, D.A.M. van, Heerings, M., Jongen, P.J., Lieshout, I., Klink, van der J.J.L., Reneman, M.F., Arnoldus, E.P.J., Beenakker, E.A.C., Bos, H.M., Eijk, van J.J.J., Fermont, J., Frequin, S.T.F.M., Geel, van B., Hengstman, G.J.D., Hoitsma, E., Hupperts, R.M.M., Moll, J.W.B., Mostert, J.P., Pop, P., Verhagen, W., Gans, de K., Zemel, D., Middelkoop, H.A.M., Visser, L. H., A just and caring society, University of Humanistic Studies, and Care Ethics
- Published
- 2019
9. Cognitive functioning as a determinant of employment outcomes in patients with multiple sclerosis; a one-year longitudinal study
- Author
-
van Gorp, D. A. M., van der Hiele, K., Heerings, M. A. P., Jongen, P. J., van Lieshout, I., van der Klink, J. J. L., Reneman, M. F., Arnoldus, E. P. J., Beenakker, E. A. C., Bos, H. M., van Eijk, J. J. J., Fermont, J., Frequin, S. T. F. M., van Geel, B. M., de Gans, K., Hengstman, G. J. D., Hoitsma, E., Hupperts, R. M. M., Moll, J. W. B., Mostert, J. P., Pop, P. H. M., Verhagen, W. I. M., Zemel, D., Visser, L. H., Middelkoop, H. A. M., and Extremities Pain and Disability (EXPAND)
- Published
- 2018
10. Disease modifying drug treatment and work functioning in patients with multiple sclerosis
- Author
-
van der Hiele, K., van Gorp, D. A. M., Jongen, P. J., Reneman, M. F., van der Klink, J. J. L., Arnoldus, E. P. J., Beenakker, E. A. C., Bos, H. M., van Eijk, J. J. J., Frequin, S. T. F. M., Hengstman, G. J. D., Hoitsma, E., Mostert, J. P., Poe, P. H. M., Verhagen, W. I. M., Verheul, G. A. M., Zemel, D., Heerings, M. A. P., Middelkoop, H. A. M., Hupperts, R. M. M., Visser, L. H., and Extremities Pain and Disability (EXPAND)
- Published
- 2018
11. Personality differences in employed and unemployed patients with Multiple Sclerosis (MS)
- Author
-
Gorp, D.A.M. van, Hiele, van der K., Heerings, M., Jongen, P.J., Lieshout, I., Arnoldus, E., Beenakker, E.A.C., Bos, M., van Eijk, J.J.J., Fermont, J., Frequin, S., van Geel, B.M., Hoitsma, E., Hupperts, R., Moll, J.W.B., Mostert, J.P., Pop, P., Verhagen, P.J., Verheul, F., Zemel, D., Visser, L. H., Middelkoop, H.A.M., A just and caring society, University of Humanistic Studies, and Care Ethics
- Published
- 2017
12. The value of work-correlates of sustained employability in workers with Multiple Sclerosis (MS)
- Author
-
van Gorp, D. A. M., van der Klink, J. J. L., Abma, F. I., Jongen, P. J., van Lieshout, I., Arnoldus, E. P. J., Beenakker, E. A. C., Bos, H. M., van Eijk, J. J. J., Fermont, J., Frequin, S. T. F. M., van Geel, B. M., Hoitsma, E., Hupperts, R. M. M., Moll, J. W. B., Mostert, J. P., Pop, P. H. M., Verhagen, W. I. M., Verheul, G. A. M., Zemel, D., Heerings, M. A. P., Reneman, M. F., Middelkoop, H. A. M., Visser, L. H., van der Hiele, K., and Extremities Pain and Disability (EXPAND)
- Published
- 2017
13. Are coping strategies related to negative work events in multiple sclerosis patients?
- Author
-
Hiele, van der K., Gorp, van D, Benedict, R.H.B., Jongen, P.J., Arnoldus, E., Beenakker, E.A.C., Bos, M., van Eijk, J.J.J., Fermont, J., Frequin, S., van Geel, B.M., Hengstman, G.J.D., Hoitsma, E., Hupperts, R., Moll, J.W.B., Mostert, J.P., Pop, P., Verhagen, P.J., Verheul, F., Zemel, D., Frndak, S.E., Heerings, M., Middelkoop, H.A.M., Visser, L. H., A just and caring society, University of Humanistic Studies, and Care Ethics
- Published
- 2016
14. Coping strategies in relation to negative work events and accommodations in employed multiple sclerosis patients
- Author
-
van der Hiele, K, primary, van Gorp, DAM, additional, Benedict, RHB, additional, Jongen, PJ, additional, Arnoldus, EPJ, additional, Beenakker, EAC, additional, Bos, HM, additional, van Eijk, JJJ, additional, Fermont, J, additional, Frequin, STFM, additional, van Geel, BM, additional, Hengstman, GJD, additional, Hoitsma, E, additional, Hupperts, RMM, additional, Mostert, JP, additional, Pop, PHM, additional, Verhagen, WIM, additional, Zemel, D, additional, Frndak, SE, additional, Heerings, MAP, additional, Middelkoop, HAM, additional, and Visser, LH, additional
- Published
- 2016
- Full Text
- View/download PDF
15. Health-related quality of life in multiple sclerosis: Effects of natalizumab
- Author
-
Rudick, R. A., Miller, D., Hass, S., Hutchinson, M, Calabresi, P. A., Confavreux, C., Galetta, S. L., Giovannoni, G., Havrdova, E., Kappos, L., Lublin, F. D., Miller, D. H., O'Connor, P. W., Phillips, J. T., Polman, C. H., Radue, Ew, Stuart, W. H., Wajgt, A., Weinstock Guttman, B., Wynn, D. R., Lynn, F., Panzara, M. A., Affirm, Macdonell, SENTINEL Investigators including: R., Hughes, A., Taylor, I., Lee, Y. C., Ma, H., King, J., Kilpatrick, T., Butzkueven, H., Marriott, M., Pollard, J., Spring, P., Spies, J., Barnett, M., Dehaene, I., Vanopdenbosch, L., D’Hooghe, M., Van Zandijcke, M., Derijck, O., Seeldrayers, P., Jacquy, J., Piette, T., De Cock, C., Medaer, R., Soors, P., Vanroose, E., Vanderhoven, L., Nagels, G., Dubois, B., Deville, M. C., D’Haene, R., Jacques, F., Hallé, D., Gagnon, S., Likavcan, E., Murray, T. J., Bhan, V., Mackelvey, R., Maxner, C. E., Christie, S., Giaccone, R., Guzman, D. A., Melanson, M., Esfahani, F., Gomori, A. J., Nagaria, M. H., Grand’Maison, F., Berger, L., Nasreddine, Z., Duplessis, M., Brunet, D., Jackson, A., Pari, G., O’Connor, P., Gray, T., Hohol, M., Marchetti, P., Lee, L., Murray, B., Sahlas, J., Perry, J., Devonshire, V., Hooge, J., Hashimoto, S., Oger, J., Smyth, P., Rice, G., Kremenchutzky, M., Stourac, P., Kadanka, Z., Benesova, Y., Niedermayerova, I., Meluzinova, E., Marusic, P., M, Bojar, Zarubova, K., Houzvicková, E., Piková, J., Talab, R., Faculty, Hospital Olomouc, Olomouc, B. Muchova, Urbánek, K, Kettnerova, Z., Mares, J., Otruba, P., Zapletalová, O., Hradilek, P., Ddolezil, D. Dolezil, Woznicova, I., Höfer, R., Ambler J. Fiedler, Z. Ambler J. Fiedler, Sucha, J., Matousek, V., Rektor, I., Dufek, M., Mikulik, R., Mastik, J., Tyrlikova, I., General, Teaching Hospital, Prague, E. Havrdová, Horakova, D., Kalistová, H., Týblová, M., Ehler, E., Novotná, A., Geier, P., Soelberg Sorensen, P., Ravnborg, M., Petersen, B., Blinkenberg, M., Färkkilä, M., Harno, H., Kallela, M., Häppölä, O., Elovaara, I., Kuusisto, H., Ukkonen, M., Peltola, J., Palmio, J., Pelletier, J., Feuillet, L., Suchet, L., Dalecky, A., Tammam, D., Edan, G., Le Page, E., Mérienne, M., Yaouanq, J., Clanet, M., Mekies, C., Azais Vuillemin, C., Senard, A., Lau, G., Steinmetz, G., Warter V. Wolff, J. Warter V. Wolff, Fleury, M., Tranchant, C., Stark, E., Buckpesch Heberer, U., Henn, K. H., Skoberne, T., Schimrigk, S., Hellwig, K., Brune, N., Weiller, C., Gbadamosi, J., Röther, J., Heesen, C., Buhmann, C., Karageorgiou, C., Korakaki, D., Giannoulis, D. r., Tsiara, S., Thomaides, T., Thomopoulos, I., Papageorgiou, H., Armakola, F., Komoly, S., Rózsa, C., Matolcsi, J., Szabó, G. y., Molnár, B., Lovas, G., Dioszeghy, P., Szulics, P., Magyar, Z., Incze, J., Farkas, J., Clemens, B., Kánya, J., Valicskó, Z. s., Bense, E., Nagy, Z. s., Geréby, G., Perényi, J., Simon, Z. s., Szapper, M., Gedeon, L., Csanyi, A., Rum, G., Lipóth, S., Szegedi, A., Jávor, L., Nagy, I., Adám, I., Szirmai, I., Simó, M., Ertsey, C., I, Amrein, Kamondi, A., Harcos, P., Dobos, E., Szabó, B., Balas, V., Guseo, A., Fodor, E., Jófejü, E., Eizler, K., Csiba, L., Csépány, T., Pallagi, E., Bereczki, D., Jakab, G., Juhász, M., Bszabó, B. Szabó I. Mayer, Katona, G., Hutchinson, M., O’Dwyer, J., O’Rourke, K., Sanders, E. A. C. M., Rijk van Andel, J. F., Bomhof, M. A. M., van Erven, P., Hintzen I. Hoppenbrouwers, R. Q. Hintzen I. Hoppenbrouwers, Neuteboom, R. F., Zemel, D., van Doorn, P. A., Jacobs, B. C., Munster, E. T. h. L. Van, ter Bruggen, J. P., Bernsen, R., Jongen, P. J. H., de Smet, E. A. A., Tacken, H. F. H., Polman, C., Zwemmer, J., Nielsen, J., Kalkers, N., Kragt, J., Jasperse, B., Willoughby, E., Anderson, N. E., Barber, A., Anderson, T., Parkin, P. J., Fink, J., Avery, S., Mason, D., Kwiecinski, H., Zakrzewska Pniewska, B., Kaminska, A., Podlecka, A., Nojszewska, M., Czlonkowska, A., Zaborski, J., Wicha, W., Kruszewska Ozimowska, J., Darda Ledzion, L., Selmaj, K., Mochecka Thoelke, A., Pentela Nowicka, J., Walczak, A., Stasiolek, M., Stelmasiak, Z., Bartosik Psujek, H., Mitosek Szewczyk, K., Belniak, E., Chyrchel, U., Maciejowski, M., Strzyzewska Lubos, L., Lubos, L., Matusik, E., Maciejek, Z., Niezgodzinska Maciejek, A., Sobczynska, D., Slotala, T., Wawrzyniak, S., Kochanowicz K. Kuczynski, J. Kochanowicz K. Kuczynski, Zimnoch, R., Pryszmont, M., Drozdowski, W., Baniukiewicz, E., Kulakowska, A., Borowik, H., Lewonowska, M., Szczudlik, A., Róg, T., Gryz Kurek, E., Pankiewicz, J., Furgal, J., Kimkowicz, A., Fryze, W., Wierbicki, T., Michalak, L., Kowalewska, J., Swiatkiewicz, J., Hillert, J., Åkesson, E, Fredrikson, S., Diener, P, Olsson, T., Wallström, E., Fpiehl, F. Piehl L. Hopia, Brundin, L., Marta, M., Andersson, M., Lycke, J., Runmarker, B., Malmeström, C., Vaghfeldt, P., Skoog, B., Schluep, M., Bogousslavskyr, J., Du Pasquier, R., Achtnichts, L., Kuhle, J., Buitrago Telez, C., Schläger, R., Naegelin, Y., Eraksoy, M., Bebek, N., Akman Demir, G., Topcuoglu, B., Kurtuncu, M., Istanbul, University, Istanbul:, A. Siva, Saip, S., Altintas, A., Kiyat, A., Sharief, M., Kasti, M., Lim, E. T., Rashid, W., Silber, E., Saldanha, G., Hawkins, C., Mamutse, G., Woolmore, J., Hawkes, C., Findley, L., Dasilva, R., Gunasekara, H., Palace, J., Cader, Z., Littleton, E., Burke, G., Sharrack O. Suliman, B. Sharrack O. Suliman, Klaffke, S., Swash, M., Dhillon, H., Bates, D., Westwood, M., Nichol, P., Barnes, D., Wren, D., Stoy, N., Robertson, N., Pickersgill, T., Pearson, O., Lawthom, C., Young, C., Mills, R., Lecky, B., Ford, C., Katzman, J., Rosenberg, G., Cooper, J., Wrubel, B., Richardson, B., Lynch, S., Ridings, L., Mcvey, A., Nowack, W., Rae Grant, A., Mackin, G. A., Castaldo, J. E., Spikol, L. J., Carter, J., Wingerchuk, D., Caselli, R., Dodick, D., Scarberry, S., Bailly, R., Garnaas, K., Haake, B., Rossman, H., Belkin, M., Boudouris, W. D., Pierce, R. P., Mass, M., Yadav, V., Bourdette, D., Whitham, R. H., Heitzman, D., Martin, A., Greenfield, C. F., Agius, M., Richman, D. P., Vijayan, N., Wheelock, V. L., Reder, A., Arnason, B., Noronha, A., Balabanov, R., Ray, A., Sheremata, W., Delgado, S., Shebert, B., Maldonado, J., Bowen, J., Garden, G. A., Distad, B. J., Carrithers, M., Rizzo, M., Vollmer, T., Reiningerova, J., Guarnaccia, J., Lo, A., Richardson, G. B., Fazekas, F., Enzinger, C., Seifert, T., Storch, M., Strasser Fuchs, S., Berger, T., Dilitz, E., Egg, R., Deisenhammer, F., Decoo, : D, Lampaert, J., Bartholome, E., Bier, J., Stenager, : E., Rasmussen, M., Binzer, M., Shorsh, K., Christensen, M., Soelberg Sørensen, P., Hansen, H. J., Bech, E., Petersen, T., Kirkegaard, M., Eralinna, : J., Ruutiainen, J., Soilu Hänninen, M., Säkö, E., Laaksonen, M., Reunanen, M., Remes, A., Keskinarkaus, I., Moreau, : T., Noblet, M., Rouaud, O., Couvreur, G., Lepage, E., Drapier, S., De Burghgraeve, V., Merienne, M., Cahagne, V., Gout, O., Deschamps, R., Le Canuet, P., Moulignier, A., Vermersch, P., De Seze, J., Stojkovic, T., Griffié, G., Engles, Ferriby, D., Debouverie, M., Pittion Vouyouvitch, S., Lacour, J. C., Lubetzki, C., Youssov, K., Mrejen, S., Charles, P., Yaici, S., Clavelou, P., Aufauvre, D., Renouil Guy, N., Cesaro, P., Degos, F., Benisty, S., Rumbach, L., Decavel, P., Blanc, S., Aubertin, P., Riche, G., Brochet, B., Ouallet, J. C., Anne, O., Menck, : S., Grupe, A., Gutmann, E., Lensch, E., Fucik, E., Heitmann, S., Hartung, H. P., Schröter, M., Kurz, F. M. W., Heidenreich, F., Trebst, C., Pul, R., Hohlfeld, R., Krumbholz, M., Pellkofer, H., Haas, J., Segert, A., Meyer, R., Anagnostou, P., Kabus, C., Poehlau, D., Schneider, K., Hoffmann, V., Zettl, U., Steinhagen, V., Adler, S., Steinbrecher E. Rothenfusser Körber, A. Steinbrecher E. Rothenfusser Körber, Zellner, R., Baum, K., Günther, A., Bläsing, H., Stoll, G., Gold, R., Bayas, A., Kleinschnitz, C., Limmroth, V., Katsarava, Z., Kastrup, O., Haller, P., Stoeve, S., Höbel, D., Oschmann, P., Voigt, K., Burger, C. V., Abramsky, : O., Karusiss, D., Achiron, A., Kishner, I., Stern, Y., Sarove Pinhas, I., Dolev, M., Magalashvili, D., Pozzili, : C., Lenzi, D., Scontrini, A., Millefiorini, E., Buttinelli, C., Gallo, P., Ranzato, F., Tiberio, M., Perini, P., Laroni, Alice, Marrosu, M., Cocco P. Marchi, E. Cocco P. Marchi, Spinicci, G., Massole, S., Mascia, M., Floris, G., Trojano, M., Bellacosa, A., Paolicelli, D., Bosco Zimatore, G., Simone, I. L., Giorelli, M., Di Monte, E., Mancardi, GIOVANNI LUIGI, Pizzorno, M., Murialdo, A., Narciso, E., Capello, A., Comi, G., Martinelli, V., Rodegher, M., Esposito, F., Colombo, B., Rossi, P., Polman, : C. H., Jasperse, M. M. S., Zwemmer, J. N. P., Kragt, J. J., De Smet, E., Tacken, H., Frequin, S. T. F. M., Siegers, H. P., Mauser, H. W., Fernandez Fernandez, : O., León, A., Romero, F., Alonso, A., Tamayo, J., Montalban, X., Nos, C., Pelayo, R., Tellez, N., Rio, J., Tintore, M., Arbizu, T., Romero, L., Moral, E., Martinez, S., Kappos, : L., Wilmes, S., Karabudak, : R., Kurne, A., Erdem, S., Siva, A., Atamer, A., Bilgili, F., Topcular, B., Giovannoni, : G., Lava, : N., Murnane, M., Dentinger, M., Zimmerman, E., Reiss, M., Gupta, V., Scott, T., Brillman, J., Kunschner, L., Wright, D., Perel, A., Babu, A., Rivera, V., Killian, J., Hutton, G., Lai, E., Picone, M., Cadivid, D., Kamin, S., Shanawani, M., Gauthier, S., Morgan, A., Buckle, G., Margolin, D., Kwen, P. L., Garg, N., Munschauer, F., Khatri, B., Rassouli, M., Saxena, V., Ahmed, A., Turner, A., Fox, E., Couch, C., Tyler, R., Horvit, A., Fodor, P., Humphries, S., Wynn, D., Nagar, C., O’Brien, D., Allen, N., Turel, A., Friedenberg, S., Carlson, J., Hosey, J., Crayton, H., Richert, J., Tornatore, C., Sirdofsky, M., Greenstein, J., Shpigel, Y., Mandel, S., Adbelhak, T., Schmerler, M., Zadikoff, C., Rorick, M., Reed, R., Elias, S., Feit, H., Angus, E., Sripathi, N., Herbert, J., Kiprovski, K., Qu, X., Del Bene, M., Mattson, D., Hingtgen, C., Fleck, J., Horak, H., Javerbaum, J., Elmore, R., Garcia, E., Tasch, E., Gruener, G., Celesia, G., Chawla, J., Miller, A., Drexler, E., Keilson, M., Wolintz, R., Drasby, E., Muscat, P., Belden, J., Sullivan, R., Cohen, J., Stone, L., Marrie, R. A., Fox, R., Hughes, B., Babikian, P., Jacoby, M., Doro, J., Puricelli, M., Boudoris, W., Pierce, R., Eggenberger, E., Birbeck, G., Martin, J., Kaufman, D., Stuart, W., English, J. B., Stuart, D. S., Gilbert, R. W., Kaufman, M., Putman, S., Diedrich, A., Follmer, R., Pelletier, D., Waubant, E., Cree, B., Genain, C., Goodin, D., Patwa, H., Rizo, M., Kitaj, M., Blevins, J., Smith, T., Mcgee, F., Honeycutt, W., Brown, M., Isa, A., Nieves Quinones, D., Krupp, L., Smiroldo, J., Zarif, M., Perkins, C., Sumner, A., Fisher, A., Gutierrez, A., Jacoby, R., Svoboda, S., Dorn, D., Groeschel, A., Steingo, B., Kishner, R., Cohen, B., Melen, O., Simuni, T., Zee, P., Cohan, S., Yerby, M., Hendin, B., Levine, T., Tamm, H., Travis, L. H., Freedman, S. M., Tim, R., Ferrell, W., Stefoski, D., Stevens, S., Katsamakis, G., Topel, J., Ko, M., Gelber, D., Fortin, C., Green, B., Logan, W., Carpenter, D., Temple, L., Sadiq, S., Sylvester, A., Sim, G., Mihai, C., Vertino, M., Jubelt, B., Mejico, L., Riskind, P., Cabo, A., Paskavitz, J., Moonis, M., Bashir J. Brockington, K. Bashir J. Brockington, Nicholas, A., Slaughter, R., Archer S. Harik, R. Archer S. Harik, Haddad, N., Pippenger, M. A., Van den Noort, S., Thai, G., Olek, M., Demetriou, M., Shin, R., Calabresi, P., Rus, H., Bever, C., Johnson, K., Sherbert, R., Herndon, R., Uschmann, H., Chandler, A., Markowitz, C., Jacobs, D., Balcer, L., Mitchell, G., Chakravorty, S., Heyman, R., Stauber, Z., Goodman, A., Segal, B., Schwid, S., Samkoff, L., Levin, M., Jacewicz, M., Menkes, D., Pulsinelli, W., Frohman, E., Racke, M., Hawker, K., Ulrich, R., Panitch, H., Hamill, R., Tandon, R., Dulaney, E., Simnad, V., Miller, J., Wooten, G. F., Harrison, M., Doherty, M., Wundes, A., Distad, J., Kachuck, N., Berkovich, R., Burnett, M., Sahai, S., Bandari, D., Weiner, L., Storey, J. R., Beesley, B., Hart, D., Moses, H., Sriram, S., Fang, J., O’Duffy, A., Kita, M., Taylor, L., Elliott, M., Roberts, J., Jeffery, D., Maxwell, S., Lefkowitz, D., Kumar, S., Sinclair, M., Radue, E. W., de Vera, A., Bacelar, O., and Kuster, P.
- Subjects
Adult ,Male ,medicine.medical_specialty ,Multiple Sclerosis ,Visual analogue scale ,Health Status ,Population ,Pain ,Comorbidity ,Placebo ,Antibodies ,law.invention ,Natalizumab ,Randomized controlled trial ,Quality of life ,Double-Blind Method ,law ,Internal medicine ,Surveys and Questionnaires ,Monoclonal ,medicine ,Prevalence ,Humans ,Longitudinal Studies ,education ,Humanized ,education.field_of_study ,Expanded Disability Status Scale ,Neuroscience (all) ,business.industry ,Antibodies, Monoclonal ,Antibodies, Monoclonal, Humanized ,Female ,Patient Satisfaction ,Treatment Outcome ,United States ,Quality of Life ,Multiple sclerosis ,medicine.disease ,Neurology ,Physical therapy ,Neurology (clinical) ,business ,medicine.drug - Abstract
Objective To report the relationship between disease activity and health-related quality of life (HRQoL) in relapsing multiple sclerosis, and the impact of natalizumab. Methods HRQoL data were available from 2,113 multiple sclerosis patients in natalizumab clinical studies. In the Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis (AFFIRM) study, patients received natalizumab 300mg (n = 627) or placebo (n = 315); in the Safety and Efficacy of Natalizumab in Combination with Interferon Beta-1a in Patients with Relapsing Remitting Multiple Sclerosis (SENTINEL) study, patients received interferon beta-1a (IFN-β-1a) plus natalizumab 300mg (n = 589), or IFN-β-1a plus placebo (n = 582). The Short Form-36 (SF-36) and a subject global assessment visual analog scale were administered at baseline and weeks 24, 52, and 104. Prespecified analyses included changes from baseline to week 104 in SF-36 and visual analog scale scores. Odds ratios for clinically meaningful improvement or worsening on the SF-36 Physical Component Summary (PCS) and Mental Component Summary were calculated. Results Mean baseline SF-36 scores were significantly less than the general US population and correlated with Expanded Disability Status Scale scores, sustained disability progression, relapse number, and increased volume of brain magnetic resonance imaging lesions. Natalizumab significantly improved SF-36 PCS and Mental Component Summary scores at week 104 in AFFIRM. PCS changes were significantly improved by week 24 and at all subsequent time points. Natalizumab-treated patients in both studies were more likely to experience clinically important improvement and less likely to experience clinically important deterioration on the SF-36 PCS. The visual analog scale also showed significantly improved HRQoL with natalizumab. Interpretation HRQoL was impaired in relapsing multiple sclerosis patients, correlated with severity of disease as measured by neurological ratings or magnetic resonance imaging, and improved significantly with natalizumab. Ann Neurol 2007
- Published
- 2007
16. Peritoneal Transport of Macromolecules in Patients on CAPD
- Author
-
Krediet, R. T., primary, Struijk, D. G., additional, Koomen, G. C. M., additional, Zemel, D., additional, Boeschoten, E. W., additional, Hoek, F. J., additional, and Arisz, L., additional
- Full Text
- View/download PDF
17. Impact of different dialysis solutions on solute and water transport
- Author
-
Krediet, R. T., Douma, C. E., Ho-Dac-Pannekeet, M. M., Imholz, A. L., Zemel, D., Zweers, M. M., Smit, W., Struijk, D. G., and Other departments
- Published
- 1997
18. Intraperitoneal interleukin-8 and neutrophil influx in the initial phase of a CAPD peritonitis
- Author
-
Michiel Betjes, Ce, Visser, Zemel D, Cw, Tuk, Dg, Struijk, Rt, Krediet, Arisz L, and Rh, Beelen
- Subjects
Adult ,Male ,Neutrophils ,Interleukin-8 ,Middle Aged ,Peritonitis ,Chemotaxis, Leukocyte ,Leukocyte Count ,Peritoneal Dialysis, Continuous Ambulatory ,Cell Movement ,Dialysis Solutions ,Humans ,Female ,Leukocyte Elastase ,Peritoneal Cavity ,Granulocytes - Abstract
To investigate whether or not a change in dialysate interleukin-8 (IL-8) concentration precedes the onset of clinically overt peritonitis and is significant in the recruitment of granulocytes during continuous ambulatory peritoneal dialysis (CAPD)-related peritonitis.CAPD patients stored their overnight effluent at 4 degrees C, which was routinely thrown away after 2 days. If peritonitis developed, patients delivered their effluent of the preceding two nights and the peritonitis effluent for analysis. A control study was performed 1 to 3 months after recovery. Dialysate samples were analyzed for number of cells, differential cell count, IL-8 and elastase concentrations, and their neutrophil chemoattractive capacity. In addition, serum samples during peritonitis were analyzed for IL-8 concentrations.Ten peritonitis episodes in 7 patients were analyzed. Numbers of neutrophils and levels of dialysate IL-8 and elastase started to increase 4 to 12 hours before the first peritonitis effluent. The dialysate/serum IL-8 ratio was 423.5 during peritonitis and 7.0 in the postperitonitis controls. There was a significant correlation between the number of neutrophils and IL-8 concentration in the dialysate. The in vitro neutrophil chemotaxis was increased toward the peritonitis effluents, as compared to control effluents. Incubation of the peritonitis effluents with anti-IL-8 monoclonal antibody blocked the increase in neutrophil chemotaxis above control levels by an average of 26.7%.IL-8 is produced in the peritoneal cavity during CAPD treatment and may mediate part of the neutrophil recruitment and degranulation in the initial phase of a CAPD peritonitis.
- Published
- 1996
19. Intraperitoneal interleukin-8 and neutrophil influx in the initial phase of a CAPD peritonitis
- Author
-
Betjes, M. G., Visser, C. E., Zemel, D., Tuk, C. W., Struijk, D. G., Krediet, R. T., Arisz, L., Beelen, R. H., and Other departments
- Abstract
OBJECTIVE: To investigate whether or not a change in dialysate interleukin-8 (IL-8) concentration precedes the onset of clinically overt peritonitis and is significant in the recruitment of granulocytes during continuous ambulatory peritoneal dialysis (CAPD)-related peritonitis. DESIGN: CAPD patients stored their overnight effluent at 4 degrees C, which was routinely thrown away after 2 days. If peritonitis developed, patients delivered their effluent of the preceding two nights and the peritonitis effluent for analysis. A control study was performed 1 to 3 months after recovery. Dialysate samples were analyzed for number of cells, differential cell count, IL-8 and elastase concentrations, and their neutrophil chemoattractive capacity. In addition, serum samples during peritonitis were analyzed for IL-8 concentrations. RESULTS: Ten peritonitis episodes in 7 patients were analyzed. Numbers of neutrophils and levels of dialysate IL-8 and elastase started to increase 4 to 12 hours before the first peritonitis effluent. The dialysate/serum IL-8 ratio was 423.5 during peritonitis and 7.0 in the postperitonitis controls. There was a significant correlation between the number of neutrophils and IL-8 concentration in the dialysate. The in vitro neutrophil chemotaxis was increased toward the peritonitis effluents, as compared to control effluents. Incubation of the peritonitis effluents with anti-IL-8 monoclonal antibody blocked the increase in neutrophil chemotaxis above control levels by an average of 26.7%. CONCLUSION: IL-8 is produced in the peritoneal cavity during CAPD treatment and may mediate part of the neutrophil recruitment and degranulation in the initial phase of a CAPD peritonitis
- Published
- 1996
20. Impaired initial cell reaction in CAPD-related peritonitis
- Author
-
Jg, Koopmans, Ew, Boeschoten, Mm, Pannekeet, Michiel Betjes, Zemel D, Ej, Kuijper, and Rt, Krediet
- Subjects
Adult ,Male ,Adolescent ,Interleukin-6 ,Neutrophils ,Tumor Necrosis Factor-alpha ,Interleukin-8 ,Bacterial Infections ,Macrophage Activation ,Middle Aged ,Peritonitis ,Staphylococcal Infections ,Leukocyte Count ,Peritoneal Dialysis, Continuous Ambulatory ,Prostaglandins ,Humans ,Kidney Failure, Chronic ,Female ,Aged ,Retrospective Studies - Abstract
Our objective was to determine the incidence of peritonitis episodes with an impaired initial cell reaction (IICR:neutrophil number100 x 10(6)/L) over a period of ten years, and to find possible explanations for this unusual presentation of peritonitis. A retrospective review of the files of continuous ambulatory peritoneal dialysis (CAPD) patients included in the CAPD program 1984 and 1993 was done. Analysis of cytokine and prostanoid patterns during four peritonitis episodes with an IICR was compared to 12 episodes with a normal initial cell reaction (NICR). Dialysate cell numbers and immunoeffector characteristics of peritoneal cells were compared in 7 IICR patients in a stable situation and a control group of 70 stable CAPD patients. The setting was a CAPD unit in the Academic Medical Center in Amsterdam. Thirty-five CAPD patients who had one or more peritonitis episodes with an IICR and a control group of 249 CAPD patients were included in the study. The incidence of peritonitis with an IICR was 6%. These episodes occurred more than once in 51% of the patients who presented with IICR. In 72% the cell reaction was only delayed: a cell number exceeding 100 x 10(6)/L was reached later. Staphylococcus aureus was significantly more frequently the causative microorganism compared to all peritonitis episodes (PE) that occurred during the study period. Patients with IICR had lower dialysate cell counts in a stable situation, compared to a control group (p0.01). This was caused by a lower number of macrophages and CD4 positive lymphocytes. The phagocytosis capacity of the macrophages appeared to be normal. In a comparison of four PE with an IICR and 12 episodes with an NICR, the tumor necrosis factor-alpha (TNF-alpha) response was similar and occurred on day 1, also pointing to normally functioning macrophages. However, the maximal appearance rates of interleukin-6 (IL-6) and IL-8 occurred later in the episodes with IICR compared to NICR (day 2 vs day 1, p0.05). No differences were found in vasodilating prostaglandins, mesothelial cell markers (cancer antigen 125, phospholipids, hyaluronan), and mesothelial cell numbers in the stable situation nor during peritonitis. Peritonitis can present as abdominal pain in the absence of a cloudy dialysate. In some of the patients this presentation occurred more than once. This impaired, most often delayed, cell reaction was associated with a delayed secondary cytokine response. As IL-6 and IL-8 can be synthesized by mesothelial cells, this suggests an impaired functioning mesothelium. This could not be confirmed, however, by a lower number of mesothelial cells in effluent or lower dialysate levels of mesothelial cell markers.
- Published
- 1996
21. Markers of peritoneal membrane status
- Author
-
Krediet, R. T., Pannekeet, M. M., Zemel, D., Koomen, G. C., Struijk, D. G., Hoek, F. J., and Other departments
- Published
- 1996
22. Effects of intraperitoneal cyclooxygenase inhibition on inflammatory mediators in dialysate and peritoneal membrane characteristics during peritonitis in continuous ambulatory peritoneal dialysis
- Author
-
Zemel, D., Struijk, D. G., Dinkla, C., Stolk, L. M., ten Berge, I. J., Krediet, R. T., and Other departments
- Abstract
Peritonitis complicating continuous ambulatory peritoneal dialysis (CAPD) can be used as an in vivo model to study the contribution of mediators in dialysate to the regulation of peritoneal permeability. Previously we reported that changes in the peritoneal appearance rates of the cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF alpha) were related to alterations in the effective peritoneal surface area. Changes in the intrinsic peritoneal permeability were mainly related to those in the peritoneal appearance rate of the prostanoid prostaglandin E2 (PGE2) and partly also to that of IL-6. In this intervention study the role of these mediators was further analyzed. Eleven peritonitis episodes were followed on 8 consecutive days from the start of the infection and once after recovery. Indomethacin was given intraperitoneally during the first 3 days. beta 2-Microglobulin clearance was used as indicator of the effective peritoneal surface area. The intrinsic peritoneal permeability was characterized functionally by the restriction coefficient. The 15 peritonitis episodes studied previously served as the control group. This study supports the formerly obtained relationships in two ways. First, significant reductions were observed for peritoneal PGE2, 6-keto-PGF1 alpha, and TxB2 during cyclooxygenase inhibition to 6%, 0.6%, and 9% of the values on day 1, whereas simultaneously the intrinsic permeability was less increased. This indomethacin effect on intrinsic permeability was not entirely significant, probably because of the additional role of IL-6, which was not influenced by indomethacin. Also, the appearance rate of TNF alpha in the effluent was not affected by cyclooxygenase inhibition. Accordingly, the changes in the effective surface area were similar to those in the control group. Second, in 8 of the 11 cases, new rises both in peritoneal PGE2 and in intrinsic permeability occurred after discontinuation of indomethacin. Rebounds were not seen for TNF alpha or IL-6, and, consistently, not for the effective surface area. In conclusion, local cyclooxygenase inhibition results in a less-increased intrinsic permeability during peritonitis but has no effect on the effective surface area. These data support our previous finding that IL-6 and TNF alpha contribute to alterations in surface area, whereas PGE2 is more involved in intrinsic peritoneal permeability changes
- Published
- 1995
23. Dialysate markers of peritoneal tissue during peritonitis and in stable CAPD
- Author
-
Pannekeet, M. M., Zemel, D., Koomen, G. C., Struijk, D. G., Krediet, R. T., and Other departments
- Subjects
female genital diseases and pregnancy complications - Abstract
OBJECTIVE: To investigate whether dialysate concentrations of substances that are locally produced within the peritoneal cavity can be used to study the effects of inflammation on peritoneal tissue. DESIGN: We followed the appearance rates (AR) of concentrations of cancer antigen (CA) 125, phospholipids (PHL), hyaluronan (HA), and the procollagen peptides PICP (procollagen 1 C-terminal) and PIIINP (procollagen 3 N-terminal) in dialysate during peritonitis (8 consecutive days) and after recovery. Data were compared with the stable situation. SETTING: CAPD (continuous ambulatory peritoneal dialysis) unit in the Academic Medical Center in Amsterdam. PATIENTS: Twelve CAPD patients with a total of 16 episodes of peritonitis and 10 clinically stable CAPD patients were studied. RESULTS: All substances showed temporal increments in dialysate during peritonitis compared to control. No difference was found between the control day of peritonitis and the stable patients. Maximum AR were reached in the acute phase of peritonitis for CA125, PHL, and HA and on day 4 for both PICP and PIIINP. A second increment in CA125 occurred on days 4 to 6. These findings indicate acute damage to the mesothelium (CA125) and other cells (PHL) by the infection. HA may reflect stromal changes. Subsequently, peritoneal healing (PICP,PIIINP) and remesothelialization (second peak CA125) are likely to occur. CONCLUSIONS: Dialysate concentrations of these substances can be used as markers for the effects of peritonitis on the peritoneum of CAPD patients in vivo. The similarity between the marker concentrations in the effluent after recovery from peritonitis and those in stable CAPD patients implies that complete peritoneal healing is likely to occur after uncomplicated peritonitis
- Published
- 1995
24. Analysis of inflammatory mediators and peritoneal permeability to macromolecules shortly before the onset of overt peritonitis in patients treated with CAPD
- Author
-
Zemel, D., Betjes, M. G., Dinkla, C., Struijk, D. G., Krediet, R. T., and Other departments
- Abstract
OBJECTIVE: To investigate whether changes in peritoneal membrane characteristics and inflammatory mediators in dialysate precede the onset of overt infection during continuous ambulatory peritoneal dialysis (CAPD)-related peritonitis. DESIGN: CAPD patients with a high peritonitis incidence stored every night bag at 4 degrees C. Routinely, each bag was thrown away after two days. Only if patients developed peritonitis, all bags were delivered for study. Thus, two night bags immediately prior to the first peritonitis bag were available for analysis. A control study was done 14 days after recovery. Dialysate samples were measured for TNF alpha, IL-6, PGE2, 6-keto-PGF1 alpha, TxB2, and serum proteins. The clearance of beta 2-microglobulin was used as an indicator of the effective peritoneal surface area. The intrinsic peritoneal permeability was characterized by the restriction coefficient. RESULTS: Eight episodes occurred in 5 patients. The night dwells available prior to the first peritonitis effluent were drained maximally nine dwells and minimally one dwell before the first peritonitis bag. Dialysate leukocyte counts exceeded 100 x 10(6)/L only on the day of manifest infection. However, bacterial cultures were already positive at least one day before overt infection in four episodes and in three of these cases two days before. No changes were observed prior to peritonitis for the clearance of beta 2-microglobulin or the restriction coefficient. In contrast to these permeability characteristics, the cytokines, TNF alpha and, though less significant, also IL-6, were increased in dialysate one day prior to overt infection, when compared to the values obtained at the control investigation. This was especially evident in effluents drained no longer than two dwells before the first peritonitis bag. Prostaglandin concentrations in dialysate were not different before the onset of manifest peritonitis from the values measured after recovery. CONCLUSION: In this study, the increased effective peritoneal surface area and intrinsic peritoneal permeability during acute infection appeared to be preceded by elevations in the cytokines TNF alpha and, to a lesser extent, IL-6. These increments occurred only very shortly before the onset of clinical symptoms
- Published
- 1995
25. Interleukin-8 during peritonitis in patients treated with CAPD; an in-vivo model of acute inflammation
- Author
-
Zemel, D., Krediet, R. T., Koomen, G. C., Kortekaas, W. M., Geertzen, H. G., ten Berge, R. J., and Other departments
- Abstract
CAPD-related peritonitis was used as an in-vivo model to study Il-8 during peritoneal inflammation. Eleven episodes were studied in nine patients, who were followed on 8 consecutive days from the start of peritonitis and once after recovery (control). Il-8 was measured in dialysate (night dwells) and serum. The Il-8 time course was compared to Il-6 and TNF alpha. In addition, an in-vivo relationship between dialysate Il-8 and intraperitoneal accumulation of neutrophils was studied. A highly increased peritoneal appearance rate of Il-8 was found in the acute phase that decreased to control values during recovery. A remarkable parallelism was observed for dialysate Il-8 and Il-6 with respect to the time course and the peritoneal appearance rate. In contrast, the appearance rate of TNF alpha was much less and had a different time course. In three of four cases where the dialysate Il-8 peak occurred on day 2, the dialysate Il-6 peak still coincided with Il-8, in contrast to TNF alpha (always day 1). Dialysate Il-8 generally exceeded serum concentrations during the entire follow-up, indicating intraperitoneal Il-8 synthesis. A positive correlation was present between the dialysate Il-8 peak and the maximal number of neutrophils in dialysate. This relationship was absent for Il-6 and TNF alpha. In five of six episodes where neutrophils were quantified on both day 1 and 2, the Il-8 peak occurred simultaneously with the neutrophil peak. These findings suggest that Il-8 is involved in the recruitment of neutrophils towards the dialysate during peritonitis
- Published
- 1994
26. Cancer antigen 125 is locally produced in the peritoneal cavity during continuous ambulatory peritoneal dialysis
- Author
-
Koomen, G. C., Betjes, M. G., Zemel, D., Krediet, R. T., Hoek, F. J., and Other departments
- Abstract
The local production of cancer antigen (CA) 125 in the peritoneal cavity of 14 continuous ambulatory peritoneal dialysis patients was studied. In addition, the relationship between the concentration of mesothelial cells and CA 125 in the peritoneal dialysate effluent was examined. The median results and ranges were as follows: plasma CA 125 14 U/mL (range 10-23), dialysate CA 125 18 U/mL (range 5.2-76), dialysate/plasma ratio 1.9 (range 0.61-5.4), and number of mesothelial cells 400/mL (range 10-5000). Peritoneal concentrations of mesothelial cells and CA 125 were positively correlated (r = 0.50, p < 0.01). Using a monoclonal antibody, CA 125-positive cells were found in the cytospin preparations of the cells of dialysis effluents. All these CA 125 positive cells were also positive for cytokeratin used as a mesothelial cell marker. In vitro experiments using mesothelial cells in monolayers showed a linear increase in CA 125 concentration both in time and in relation to the number of mesothelial cells. From these experiments a production rate of 24 U/hour/10(6) cells could be calculated. It is therefore concluded that CA 125 is locally produced in the peritoneal cavity during CAPD and that the mesothelial cells are the major source of this CA 125
- Published
- 1994
27. Analysis of the peritoneal cellular immune system during CAPD shortly before a clinical peritonitis
- Author
-
Betjes, M. G., Tuk, C. W., Visser, C. E., Zemel, D., Krediet, R. T., Arisz, L., Beelen, R. H., and Other departments
- Abstract
We analysed the peritoneal cellular immune system 24-48 h before the onset of a clinical peritonitis. Peritoneal cells were obtained from the overnight dialysis effluents 1 or 2 days (day-1 and day-2) preceding the day of peritonitis, the last overnight effluent before the peritonitis effluent (day P), and the first peritonitis effluent. Nine peritonitis episodes of six patients were studied. The number of Fc receptor positive cells, the chemotactic activity, and immunophenotype of the peritoneal cell population at day-2 and day-1 were similar to the postperitonitis control effluent. However, immunophagocytosis and phagocytosis capacity of the peritoneal macrophages was decreased in five of six episodes at day-2 and -1 compared to control peritoneal macrophages. The overnight effluents of day P revealed a moderate influx of neutrophilic granulocytes and an increase of bacterial killing capacity and chemotactic activity. Activation of the peritoneal T cells at day P was shown by the increase in MHC class II positive T cells and an increase in the CD4/CD8 ratio. Bacterial cell cultures of the effluents were positive in three episodes 24-48 h before peritonitis, and of all overnight effluents at day P. These results indicate that malfunctioning of phagocytosis by peritoneal macrophages may contribute to the development of a CAPD peritonitis
- Published
- 1994
28. Impact of surface area and permeability on solute clearances
- Author
-
Krediet, R. T., Zemel, D., Imholz, A. L., Struijk, D. G., and Other departments
- Published
- 1994
29. Indices of peritoneal permeability and surface area
- Author
-
Krediet, R. T., Zemel, D., Imholz, A. L., Koomen, G. C., Struijk, D. G., Arisz, L., and Other departments
- Published
- 1993
30. Relationship of TNF-alpha, interleukin-6, and prostaglandins to peritoneal permeability for macromolecules during longitudinal follow-up of peritonitis in continuous ambulatory peritoneal dialysis
- Author
-
Zemel, D., Koomen, G. C., Hart, A. A., ten Berge, I. J., Struijk, D. G., Krediet, R. T., and Other departments
- Subjects
lipids (amino acids, peptides, and proteins) - Abstract
Infectious reactions are known to comprise changes in vasopermeability and inflammatory mediators. We used peritonitis that complicated continuous ambulatory peritoneal dialysis (CAPD) as an in vivo inflammation model to study the time courses of peritoneal permeability characteristics and mediators in dialysate. Sixteen episodes of peritonitis were prospectively followed on eight consecutive days from the onset of the infection and once after recovery (control). Dialysate night dwells were examined for marker proteins of peritoneal permeability, cytokines (tumor necrosis factor-alpha [TNF-alpha], interleukin-6 [IL-6] and prostaglandins (PGE2, 6-keto-PGF1 alpha, and thromboxane B2 [TxB2]). The clearance of beta 2-microglobulin was used as indicator of the effective peritoneal surface area. The intrinsic permeability was characterized functionally by the peritoneal restriction coefficient. All protein clearances were increased during the acute phase of peritonitis and subsequently decreased to control. Likewise, the intrinsic peritoneal permeability was elevated, as demonstrated by a decrease of the peritoneal restriction coefficient. Peritoneal appearance rates of TNF-alpha, IL-6, and prostaglandins were also increased during the acute phase. Peak values were reached on day 1. The largest increase was observed for IL-6 (median 854-fold), followed by TNF-alpha (35-fold). The vasodilating PGE2 and 6-keto-PGF1 alpha were increased 12-fold and the vasoconstricting TxB2 was increased threefold. Evidence was obtained for local intraperitoneal synthesis of IL-6 and prostaglandins. TNF-alpha production appeared to be present only during the early acute inflammatory response. Analysis of variance for repeated measurements revealed that changes in the clearance of beta 2-microglobulin were related to those in IL-6 and marginally also to TNF-alpha in dialysate. Changes in the peritoneal restriction coefficient were also related to IL-6, but were more closely related to alterations in dialysate PGE2. These findings suggest that TNF-alpha, IL-6, and PGE2 are involved in the changes in permeability characteristics during CAPD-related peritonitis
- Published
- 1993
31. Interleukin-6 in CAPD patients without peritonitis: relationship to the intrinsic permeability of the peritoneal membrane
- Author
-
Zemel D, Rj, Ten Berge, Dg, Struijk, Elisabeth Bloemena, Gc, Koomen, and Rt, Krediet
- Subjects
Time Factors ,Peritoneal Dialysis, Continuous Ambulatory ,Interleukin-6 ,Humans ,Kidney Failure, Chronic ,Peritoneum ,Peritonitis ,Permeability - Abstract
We investigated whether day to day changes in the transport characteristics of the peritoneal membrane to macromolecules in patients treated with CAPD, were related to the levels of interleukin-6 (IL-6) in the effluent of an overnight dwell. Four stable CAPD patients without peritonitis collected all "nightbags" on consecutive days during 2 months for the determination of peritoneal IgG clearance. Serum samples were obtained weekly. IL-6 was determined in the effluent on all occasions where the IgG clearance was less than mean - SD or greater than mean + SD. On these days clearances of beta 2-microglobulin, albumin and alpha 2-macroglobulin were determined as well, to calculate the peritoneal restriction coefficient, i.e. the slope of the power relationship between protein clearances and their free diffusion coefficient in water. This coefficient was used as a parameter of the intrinsic permeability of the membrane. IL-6 was measured by a sensitive and specific bioassay, using the B13.29, subclone 9.9 hybridoma cell assay. Dialysate IL-6 was measured on 43 occasions when IgG clearance was high and on 37 occasions when IgG clearance was low. In all 4 patients indirect evidence was found for local production of IL-6 within the peritoneal cavity: mean dialysate/serum ratios were 15 to 452 times higher than could be expected when IL-6 would enter the dialysate by diffusion only. The patient with the highest dialysate/serum ratio showed higher clearances of albumin, IgG and alpha 2-macroglobulin than the other 3 patients (p less than 0.001) and a lower restriction coefficient (p less than 0.001), indicating a high intrinsic permeability.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1992
32. Interleukin-6 in CAPD patients without peritonitis:Relationship to the intrinsic permeability of the peritoneal membrane
- Author
-
Zemel, D., Ten Berge, R. J.M., Struijk, D. G., Bloemena, E., Koomen, G. C.M., and Krediet, R. T.
- Abstract
We investigated whether day to day changes in the transport characteristics of the peritoneal membrane to macromolecules in patients treated with CAPD, were related to the levels of interleukin-6 (IL-6) in the effluent of an overnight dwell. Four stable CAPD patients without peritonitis collected all 'nightbags' on consecutive days during 2 months for the determination of peritoneal IgG clearance. Serum samples were obtained weekly. IL-6 was determined in the effluent on all occasions where the IgG clearance was < x̄ - SD or > x̄ + SD. On these days clearances of β2-microglobulin, albumin and α2-macroglobulin were determined as well, to calculate the peritoneal restriction coefficient, i.e. the slope of the power relationship between protein clearances and their free diffusion coefficient in water. This coefficient was used as a parameter of the intrinsic permeability of the membrane. IL-6 was measured by a sensitive and specific bioassay, using the B13.29, subclone 9.9 hybridoma cell assay. Dialysate IL-6 was measured on 43 occasions when IgG clearance was high and on 37 occasions when IgG clearance was low. In all 4 patients indirect evidence was found for local production of IL-6 within the peritoneal cavity: mean dialysate/serum ratios were 15 to 452 times higher than could be expected when IL-6 would enter the dialysate by diffusion only. The patient with the highest dialysate/serum ratio showed higher clearances of albumin, IgG and α2-macroglobulin than the other 3 patients (p 2-macroglobulin (p = 0.002), than on days when IL-6 was within the normal distribution. The outliers also showed lower restriction coefficients (p = 0.002), whereas no difference was found for β2-microglobulin clearance, used as an indicator of effective peritoneal surface area. It is concluded that IL-6 can be produced locally within the peritoneal cavity in stable CAPD patients without infection. Very high dialysate IL-6 concentrations were associated with increased intrinsic permeability of the peritoneum, but not with the effective surface area.
- Published
- 1992
33. Peritoneal transport of macromolecules in patients on CAPD
- Author
-
Krediet, R. T., Struijk, D. G., Koomen, G. C., Zemel, D., Boeschoten, E. W., Hoek, F. J., Arisz, L., and Other departments
- Published
- 1991
34. Serum lnterleukin-6 in Continuous Ambulatory Peritoneal Dialysis in Patients
- Author
-
Zemel, D., primary, ten Berge, R.J.M., additional, Koomen, G.C.M., additional, Struijk, D.G., additional, and Krediet, R.T., additional
- Published
- 1993
- Full Text
- View/download PDF
35. Prostaglandin inhibition by intraperitoneal indomethacin has no effect on peritoneal permeability during stable CAPD.
- Author
-
Douma, C E, de Waart, D R, Zemel, D, Struijk, D G, and Krediet, R T
- Abstract
Prostaglandins can affect the vascular response and are locally produced in the peritoneal cavity. Prostaglandin inhibition in continuous ambulatory peritoneal dialysis (CAPD) patients during peritonitis using indomethacin intraperitoneally was found to decrease the intrinsic permeability to macromolecules.
- Published
- 2001
- Full Text
- View/download PDF
36. Impaired initial cell reaction in CAPD-related peritonitis
- Author
-
Koopmans, J. G., Boeschoten, E. W., Pannekeet, M. M., Betjes, M. G. H., Zemel, D., Ed Kuijper, Krediet, R. T., and Other departments
- Abstract
Our objective was to determine the incidence of peritonitis episodes with an impaired initial cell reaction (IICR:neutrophil number < 100 x 10(6)/L) over a period of ten years, and to find possible explanations for this unusual presentation of peritonitis. A retrospective review of the files of continuous ambulatory peritoneal dialysis (CAPD) patients included in the CAPD program 1984 and 1993 was done. Analysis of cytokine and prostanoid patterns during four peritonitis episodes with an IICR was compared to 12 episodes with a normal initial cell reaction (NICR). Dialysate cell numbers and immunoeffector characteristics of peritoneal cells were compared in 7 IICR patients in a stable situation and a control group of 70 stable CAPD patients. The setting was a CAPD unit in the Academic Medical Center in Amsterdam. Thirty-five CAPD patients who had one or more peritonitis episodes with an IICR and a control group of 249 CAPD patients were included in the study. The incidence of peritonitis with an IICR was 6%. These episodes occurred more than once in 51% of the patients who presented with IICR. In 72% the cell reaction was only delayed: a cell number exceeding 100 x 10(6)/L was reached later. Staphylococcus aureus was significantly more frequently the causative microorganism compared to all peritonitis episodes (PE) that occurred during the study period. Patients with IICR had lower dialysate cell counts in a stable situation, compared to a control group (p < 0.01). This was caused by a lower number of macrophages and CD4 positive lymphocytes. The phagocytosis capacity of the macrophages appeared to be normal. In a comparison of four PE with an IICR and 12 episodes with an NICR, the tumor necrosis factor-alpha (TNF-alpha) response was similar and occurred on day 1, also pointing to normally functioning macrophages. However, the maximal appearance rates of interleukin-6 (IL-6) and IL-8 occurred later in the episodes with IICR compared to NICR (day 2 vs day 1, p < 0.05). No differences were found in vasodilating prostaglandins, mesothelial cell markers (cancer antigen 125, phospholipids, hyaluronan), and mesothelial cell numbers in the stable situation nor during peritonitis. Peritonitis can present as abdominal pain in the absence of a cloudy dialysate. In some of the patients this presentation occurred more than once. This impaired, most often delayed, cell reaction was associated with a delayed secondary cytokine response. As IL-6 and IL-8 can be synthesized by mesothelial cells, this suggests an impaired functioning mesothelium. This could not be confirmed, however, by a lower number of mesothelial cells in effluent or lower dialysate levels of mesothelial cell markers
37. Is empathy related to work participation, work role functioning and productivity in multiple sclerosis patients?
- Author
-
Gorp, D.A.M. van, Hiele, van der K., Heerings, M., Jongen, P.J., van Lieshout, I., Reneman, M.F., van der Klink, J.J.L., Arnoldus, E., Beenakker, E.A.C., Bos, H.M., van Eijk, J.J.J., Fermont, J., Frequin, S., van Geel, B.M., Hengstman, G.J.D., Hoitsma, E., Hupperts, R.M.M., Moll, J.W.B., Mostert, J.P., Pop, P., Verhagen, W., Verheul, F., Zemel, D., Middelkoop, H.A.M., Visser, L. H., Extremities Pain and Disability (EXPAND), A just and caring society, University of Humanistic Studies, and Care Ethics
- Abstract
Background: Empathy refers to the ability to understand other persons intentions, predict their behaviour and experience an emotion triggered by their emotion. It allows us to interact with the social world and has been associated with improved labor climate and teamwork. Empathy has a down side as well, considering its associations with Neuroticism and fatigue in professionals caring for suffering people. A few studies have reported reduced degrees of empathy, empathic concern and fantasy in multiple sclerosis (MS) patients. The current study examines relations between empathy and work participation, work role functioning , productivity and other clinical and personal variables in employed relapsing-remitting MS patients. Methods: In the context of the MS@Work study, 19 unemployed and 148 employed patients with relapsing-remitting MS completed the Baron-Cohen"s Empathy Quotient and questionnaires on demographics, work role functioning and productivity, physical and cognitive functioning, fatigue, depression, anxiety, personality and coping. Mann-Whitney U-tests were used to examine group differences in empathy. Correlation analyses and stepwise linear regression analysis were used to examine relations between empathy and work role functioning, productivity, demographic, clinical and personal variables in employed MS patients. The significance level was set at 0.05. We used p< =0.001 for the correlations. Results: Empathy was, although not statistically significant, lower in unemployed as compared with employed MS patients (U=1059.50, p=.081, r=.14). Empathy was higher in females (U=1409.50, p=.002, ) and in patients with a higher educational level (H(7)=17,99, p=.012). We found significant relations between empathy and the personality traits Agreeableness (rs=.560, p < .001), Conscientiousness (rs=.287, p< .001) and Extraversion (rs=.263, p=.001). Empathy did not correlate with work role functioning and productivity. In a stepwise linear regression, controlling for gender and education, the personality trait Agreeableness (β=.50, t(147) = 7.21, p< .001) was positively associated with empathy (R²=.41, p< .001). Conclusions: Empathy did not differ significantly between employed and unemployed MS patients. Empathy was not associated with work role functioning and productivity in employed MS patients, but was associated with the personality trait Agreeableness. Longitudinal studies are needed to examine further relations between empathy and employment.
38. Spike ripples in striatum correlate with seizure risk in two mouse models.
- Author
-
Shi W, Zemel D, Sridhar S, Mount RA, Richardson RM, Eden UT, Han X, Kramer MA, and Chu CJ
- Abstract
Epilepsy biomarkers from electroencephalogram recordings are routinely used to assess seizure risk and localization. Two widely adopted biomarkers include: (i) interictal spikes, and (ii) high frequency ripple oscillations. The combination of these two biomarkers, ripples co-occurring with spikes (spike ripples), has been proposed as an improved biomarker for the epileptogenic zone and epileptogenicity in humans and rodent models. Whether spike ripples translate to predict seizure risk in rodent seizure models is unknown. Further, recent evidence suggests ictal networks can include deep gray nuclei in humans. Whether pathologic spike ripples and seizures are also observed in the basal ganglia in rodent models has not been explored. We addressed these questions using local field potential recordings from mice with and without striatal seizures after carbachol or 6-hydroxydopamine infusions into the striatum. We found increased spike ripples in the interictal and ictal periods in mice with seizures compared to pre-infusion and post-infusion seizure-free recordings. These data provide evidence of electrographic seizures involving the striatum in mice and support the candidacy of spike ripples as a translational biomarker for seizure risk in mouse models., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)
- Published
- 2022
- Full Text
- View/download PDF
39. Dopamine depletion selectively disrupts interactions between striatal neuron subtypes and LFP oscillations.
- Author
-
Zemel D, Gritton H, Cheung C, Shankar S, Kramer M, and Han X
- Subjects
- Animals, Corpus Striatum metabolism, Female, Locomotion physiology, Male, Mice, Neurons pathology, Parkinsonian Disorders metabolism, Corpus Striatum physiopathology, Dopamine metabolism, Neurons metabolism, Parkinsonian Disorders physiopathology
- Abstract
Dopamine degeneration in Parkinson's disease (PD) dysregulates the striatal neural network and causes motor deficits. However, it is unclear how altered striatal circuits relate to dopamine-acetylcholine chemical imbalance and abnormal local field potential (LFP) oscillations observed in PD. We perform a multimodal analysis of the dorsal striatum using cell-type-specific calcium imaging and LFP recording. We reveal that dopamine depletion selectively enhances LFP beta oscillations during impaired locomotion, supporting beta oscillations as a biomarker for PD. We further demonstrate that dynamic cholinergic interneuron activity during locomotion remains unaltered, even though cholinergic tone is implicated in PD. Instead, dysfunctional striatal output arises from elevated coordination within striatal output neurons, which is accompanied by reduced locomotor encoding of parvalbumin interneurons and transient pathological LFP high-gamma oscillations. These results identify a pathological striatal circuit state following dopamine depletion where distinct striatal neuron subtypes are selectively coordinated with LFP oscillations during locomotion., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
40. Region-specific effects of ultrasound on individual neurons in the awake mammalian brain.
- Author
-
Tseng HA, Sherman J, Bortz E, Mohammed A, Gritton HJ, Bensussen S, Tang RP, Zemel D, Szabo T, and Han X
- Abstract
Ultrasound modulates brain activity. However, it remains unclear how ultrasound affects individual neurons in the brain, where neural circuit architecture is intact and different brain regions exhibit distinct tissue properties. Using a high-resolution calcium imaging technique, we characterized the effect of ultrasound stimulation on thousands of individual neurons in the hippocampus and the motor cortex of awake mice. We found that brief 100-ms-long ultrasound pulses increase intracellular calcium in a large fraction of individual neurons in both brain regions. Ultrasound-evoked calcium response in hippocampal neurons exhibits a rapid onset with a latency shorter than 50 ms. The evoked response in the hippocampus is shorter in duration and smaller in magnitude than that in the motor cortex. These results demonstrate that noninvasive ultrasound stimulation transiently increases intracellular calcium in individual neurons in awake mice, and the evoked response profiles are brain region specific., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)
- Published
- 2021
- Full Text
- View/download PDF
41. A Dutch validation study of the Multiple Sclerosis Work Difficulties Questionnaire in relapsing remitting multiple sclerosis.
- Author
-
van Egmond E, van Gorp D, Honan C, Heerings M, Jongen P, van der Klink J, Reneman M, Beenakker E, Frequin S, de Gans K, Hengstman G, Hoitsma E, Mostert J, Verhagen W, Zemel D, Middelkoop H, Visser L, and van der Hiele K
- Subjects
- Employment, Humans, Quality of Life, Reproducibility of Results, Surveys and Questionnaires, Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting
- Abstract
Purpose: The current study aimed to evaluate the psychometric properties of the Dutch version of the Multiple Sclerosis Work Difficulties Questionnaire-23 (MSWDQ-23)., Methods: Two hundred and thirty-nine employed persons with multiple sclerosis (MS) and 59 healthy controls completed the MSWDQ-23. To verify the factor structure, a confirmatory factor analysis was conducted. To assess construct validity, the MSWDQ-23 scores were correlated to measures of physical disability, fatigue, cognitive and neuropsychiatric problems, depression, health-related quality of life, and work-related variables. MSWDQ-23 scores were compared within different age groups, gender, education levels, and job types. Predictive validity was assessed using a logistic regression analysis to predict a deterioration in employment status after one year based on MSWDQ-23 scores., Results: The internal consistency of the MSWDQ-23 was acceptable ( α = 0.913, 95% CI = 0.897-0.928) and the results indicated a fair fit. The MSWDQ-23 showed acceptable construct validity, confirming 94% of the hypotheses. The total scale and the psychological/cognitive subscale were able to predict a deterioration in employment status after one year ( χ
2 (1)=18.164, p < 0.001)., Conclusions: The Dutch version of the MSWDQ-23 is a valid and internally consistent instrument to measure self-reported work difficulties in persons with MS.Implications for rehabilitationThe Dutch version of the 23-item Multiple Sclerosis Work Difficulties Questionnaire (MSWDQ-23) is a reliable and valid tool to measure self-reported work difficulties in people with multiple sclerosis (MS).More psychological and cognitive work difficulties are predictive of a deteriorated employment status after one year.The MSWDQ-23 is a helpful tool for researchers and (occupational) health professionals to identify current work difficulties in persons with MS and identify persons at risk for a deterioration in employment one year later.- Published
- 2021
- Full Text
- View/download PDF
42. High-contrast multifocus microscopy with a single camera and z-splitter prism.
- Author
-
Xiao S, Gritton H, Tseng HA, Zemel D, Han X, and Mertz J
- Abstract
Optical microscopy has been an indispensable tool for studying complex biological systems, but is often hampered by problems of speed and complexity when performing 3D volumetric imaging. Here, we present a multifocus imaging strategy based on the use of a simple z-splitter prism that can be assembled from off-the-shelf components. Our technique enables a widefield image stack to be distributed onto a single camera and recorded simultaneously. We exploit the volumetric nature of our image acquisition by further introducing a novel extended-volume 3D deconvolution strategy to suppress far-out-of-focus fluorescence background to significantly improve the contrast of our recorded images, conferring to our system a capacity for quasi-optical sectioning. By swapping in different z-splitter configurations, we can prioritize high speed or large 3D field-of-view imaging depending on the application of interest. Moreover, our system can be readily applied to a variety of imaging modalities in addition to fluorescence, such as phase-contrast and darkfield imaging. Because of its simplicity, versatility, and performance, we believe our system will be a useful tool for general biological or biomedical imaging applications., Competing Interests: Disclosures. The authors declare no conflicts of interest.
- Published
- 2020
- Full Text
- View/download PDF
43. A Viral Toolbox of Genetically Encoded Fluorescent Synaptic Tags.
- Author
-
Bensussen S, Shankar S, Ching KH, Zemel D, Ta TL, Mount RA, Shroff SN, Gritton HJ, Fabris P, Vanbenschoten H, Beck C, Man HY, and Han X
- Abstract
Fibronectin intrabodies generated with mRNA display (FingRs) are a recently developed tool for labeling excitatory or inhibitory synapses, with the benefit of not altering endogenous synaptic protein expression levels or synaptic transmission. Here, we generated a viral vector FingR toolbox that allows for multi-color, neuron-type-specific labeling of excitatory or inhibitory synapses in multiple brain regions. We screened various fluorophores, FingR fusion configurations, and transcriptional control regulations in adeno-associated virus (AAV) and retrovirus vector designs. We report the development of a red FingR variant and demonstrated dual labeling of excitatory and inhibitory synapses in the same cells. Furthermore, we developed cre-inducible FingR AAV variants and demonstrated their utility, finding that the density of inhibitory synapses in aspiny striatal cholinergic interneurons remained unchanged in response to dopamine depletion. Finally, we generated FingR retroviral vectors, which enabled us to track the development of excitatory and inhibitory synapses in hippocampal adult-born granule cells., Competing Interests: Declaration of Interests The authors declare no competing financial interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
44. Cognitive functioning as a predictor of employment status in relapsing-remitting multiple sclerosis: a 2-year longitudinal study.
- Author
-
van Gorp DAM, van der Hiele K, Heerings MAP, Jongen PJ, van der Klink JJL, Reneman MF, Arnoldus EPJ, Beenakker EAC, van Eijk JJJ, Frequin STFM, de Gans K, Hoitsma E, Mostert JP, Verhagen WIM, Zemel D, Visser LH, and Middelkoop HAM
- Subjects
- Adult, Female, Humans, Longitudinal Studies, Male, Middle Aged, Young Adult, Attention physiology, Cognitive Dysfunction physiopathology, Employment, Executive Function physiology, Fatigue physiopathology, Multiple Sclerosis, Relapsing-Remitting physiopathology, Severity of Illness Index
- Abstract
Background: Cognitive functioning has been linked to employment outcomes in multiple sclerosis (MS) in cross-sectional studies. Longitudinal studies are however lacking and previous studies did not extensively examine executive functioning., Objectives: We examined whether baseline cognitive functioning predicts a change in employment status after 2 years, while taking into account mood, fatigue and disability level., Methods: A total of 124 patients with relapsing-remitting MS (pwMS) and 60 healthy controls were included. They underwent neurological and neuropsychological examinations and completed online questionnaires. PwMS were divided into a stable and deteriorated employment status group (SES and DES), based on employment status 2 years after baseline. We first examined baseline differences between the SES and DES groups in cognitive functioning, mood, fatigue and disability level. A logistic regression analysis was performed, with change in employment status (SES/DES) as dependent variable., Results: The DES group included 22% pwMS. Group differences were found in complex attention, executive functioning, self-reported cognitive functioning, fatigue and physical disability. More physical disability (OR = 1.90, p = 0.01) and lower executive functioning (OR = 0.30, p = 0.03) were retained as independent predictors of DES (R
2 = 0.22, p ≤ 0.001)., Conclusions: Baseline physical disability and executive functioning, but none of the other variables, moderately predicted a deterioration in employment status 2 years later., Trial Registration: This observational study is registered under NL43098.008.12: 'Voorspellers van arbeidsparticipatie bij mensen met relapsing-remitting Multiple Sclerose'. This study is registered at the Dutch CCMO register (https://www.toetsingonline.nl).- Published
- 2019
- Full Text
- View/download PDF
45. Unique contributions of parvalbumin and cholinergic interneurons in organizing striatal networks during movement.
- Author
-
Gritton HJ, Howe WM, Romano MF, DiFeliceantonio AG, Kramer MA, Saligrama V, Bucklin ME, Zemel D, and Han X
- Subjects
- Animals, Calcium Signaling, Female, Interneurons metabolism, Male, Mice, Transgenic, Neural Pathways metabolism, Neural Pathways physiology, Optical Imaging, Cholinergic Neurons physiology, Corpus Striatum physiology, Interneurons physiology, Locomotion, Parvalbumins metabolism
- Abstract
Striatal parvalbumin (PV) and cholinergic interneurons (CHIs) are poised to play major roles in behavior by coordinating the networks of medium spiny cells that relay motor output. However, the small numbers and scattered distribution of these cells have hindered direct assessment of their contribution to activity in networks of medium spiny neurons (MSNs) during behavior. Here, we build on recent improvements in single-cell calcium imaging combined with optogenetics to test the capacity of PVs and CHIs to affect MSN activity and behavior in mice engaged in voluntary locomotion. We find that PVs and CHIs have unique effects on MSN activity and dissociable roles in supporting movement. PV cells facilitate movement by refining the activation of MSN networks responsible for movement execution. CHIs, in contrast, synchronize activity within MSN networks to signal the end of a movement bout. These results provide new insights into the striatal network activity that supports movement.
- Published
- 2019
- Full Text
- View/download PDF
46. CD148 tyrosine phosphatase promotes cadherin cell adhesion.
- Author
-
Takahashi K, Matafonov A, Sumarriva K, Ito H, Lauhan C, Zemel D, Tsuboi N, Chen J, Reynolds A, and Takahashi T
- Subjects
- Cell Line, Drosophila Proteins metabolism, Humans, Phosphorylation, Receptor-Like Protein Tyrosine Phosphatases, Class 3 genetics, Receptor-Like Protein Tyrosine Phosphatases, Class 3 metabolism, Tyrosine metabolism, beta Catenin metabolism, cdc42 GTP-Binding Protein metabolism, rac GTP-Binding Proteins metabolism, rhoA GTP-Binding Protein metabolism, Cadherins metabolism, Cell Adhesion physiology
- Abstract
CD148 is a transmembrane tyrosine phosphatase that is expressed at cell junctions. Recent studies have shown that CD148 associates with the cadherin/catenin complex and p120 catenin (p120) may serve as a substrate. However, the role of CD148 in cadherin cell-cell adhesion remains unknown. Therefore, here we addressed this issue using a series of stable cells and cell-based assays. Wild-type (WT) and catalytically inactive (CS) CD148 were introduced to A431D (lacking classical cadherins), A431D/E-cadherin WT (expressing wild-type E-cadherin), and A431D/E-cadherin 764AAA (expressing p120-uncoupled E-cadherin mutant) cells. The effects of CD148 in cadherin adhesion were assessed by Ca2+ switch and cell aggregation assays. Phosphorylation of E-cadherin/catenin complex and Rho family GTPase activities were also examined. Although CD148 introduction did not alter the expression levels and complex formation of E-cadherin, p120, and β-catenin, CD148 WT, but not CS, promoted cadherin contacts and strengthened cell-cell adhesion in A431D/E-cadherin WT cells. This effect was accompanied by an increase in Rac1, but not RhoA and Cdc42, activity and largely diminished by Rac1 inhibition. Further, we demonstrate that CD148 reduces the tyrosine phosphorylation of p120 and β-catenin; causes the dephosphorylation of Y529 suppressive tyrosine residue in Src, a well-known CD148 site, increasing Src activity and enhancing the phosphorylation of Y228 (a Src kinase site) in p120, in E-cadherin contacts. Consistent with these findings, CD148 dephosphorylated both p120 and β-catenin in vitro. The shRNA-mediated CD148 knockdown in A431 cells showed opposite effects. CD148 showed no effects in A431D and A431D/E-cadherin 764AAA cells. In aggregate, these findings provide the first evidence that CD148 promotes E-cadherin adhesion by regulating Rac1 activity concomitant with modulation of p120, β-catenin, and Src tyrosine phosphorylation. This effect requires E-cadherin and p120 association.
- Published
- 2014
- Full Text
- View/download PDF
47. Clinical aspects of comorbid schizophrenia and idiopathic Parkinson's disease.
- Author
-
de Jong MH, Zemel D, and Van Gool AR
- Subjects
- Antiparkinson Agents therapeutic use, Antipsychotic Agents therapeutic use, Brain diagnostic imaging, Carbidopa therapeutic use, Catechols therapeutic use, Clozapine therapeutic use, Diagnosis, Differential, Fluphenazine therapeutic use, Follow-Up Studies, Humans, Levodopa therapeutic use, Male, Middle Aged, Nitriles therapeutic use, Parkinson Disease drug therapy, Schizophrenia drug therapy, Tomography, Emission-Computed, Single-Photon methods, Treatment Outcome, Parkinson Disease complications, Parkinson Disease diagnosis, Schizophrenia complications
- Abstract
The comorbidity of schizophrenia and idiopathic Parkinson's disease (IPD) is illustrated by a case description of a schizophrenic patient who develops motor symptoms finally diagnosed and treated as comorbid IPD. Several aspects of the clinical challenges of this comorbidity are discussed and an overview of earlier reported cases is presented. IPD must be distinguished from neuroleptic-induced parkinsonism by clinical course and characteristics. A SPECT scan is helpful for diagnosis. We recommend antiparkinsonian treatment to be prescribed only with the protection of antipsychotic agents, of which clozapine and quetiapine are the best choices.
- Published
- 2014
- Full Text
- View/download PDF
48. High-dose norepinephrine treatment: determinants of mortality and futility in critically ill patients.
- Author
-
Döpp-Zemel D and Groeneveld AB
- Subjects
- Aged, Aged, 80 and over, Dose-Response Relationship, Drug, Female, Hospital Mortality, Humans, Male, Middle Aged, Retrospective Studies, Time Factors, Critical Illness mortality, Intensive Care Units statistics & numerical data, Medical Futility, Norepinephrine administration & dosage, Shock drug therapy, Shock mortality, Vasoconstrictor Agents administration & dosage
- Abstract
Background: Critically ill patients with circulatory shock sometimes need rescue treatment with high doses of norepinephrine, a treatment that may be associated with a poor outcome because of excessive vasoconstriction., Objective: To evaluate the outcome of treatment and its determinants in patients with circulatory shock who received high doses of norepinephrine in the intensive care unit and to identify indicators of futility for the treatment., Methods: A retrospective study was done on 113 consecutive patients with circulatory shock who received 0.9 μg/kg per minute or greater of norepinephrine during at least 1 hour at any time in the intensive care unit. Data were extracted from the electronic patient data management system according to a predefined checklist., Results: A total of 39 patients survived for 28 days after admission to the intensive care unit. The variables independently associated with 28-day mortality in multivariable models included low urine flow, high lactate levels, high organ failure score, high prothrombin time, and need for epinephrine cotreatment. The reason, dose, and duration of norepinephrine administration did not have prognostic significance. Scores greater than 40 on the Acute Physiology and Chronic Health Evaluation II, bicarbonate levels less than 9.0 mEq/L, or receipt of an epinephrine dose of 0.25 μg/kg per minute or greater were associated with 100% mortality., Conclusions: Although the cause of shock and treatment with norepinephrine were not predictive of death when high doses of the drug were deemed necessary, rescue treatment with high-dose norepinephrine is futile in patients with severe disease and metabolic acidemia.
- Published
- 2013
- Full Text
- View/download PDF
49. Assessment of renal function in mice with unilateral ureteral obstruction using 99mTc-MAG3 dynamic scintigraphy.
- Author
-
Tantawy MN, Jiang R, Wang F, Takahashi K, Peterson TE, Zemel D, Hao CM, Fujita H, Harris RC, Quarles CC, and Takahashi T
- Subjects
- Animals, Male, Mice, Mice, Inbred C57BL, Radioisotope Renography methods, Radionuclide Imaging methods, Tomography, Emission-Computed, Single-Photon methods, Ureteral Obstruction physiopathology, Kidney diagnostic imaging, Kidney physiology, Radiopharmaceuticals, Technetium Tc 99m Mertiatide, Ureteral Obstruction diagnostic imaging
- Abstract
Background: Renal scintigraphy using 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) is widely used for the assessment of renal function in humans. However, the application of this method to animal models of renal disease is currently limited, especially in rodents. Here, we have applied 99mTc-MAG3 renal scintigraphy to a mouse model of unilateral ureteral obstruction (UUO) and evaluated its utility in studying obstructive renal disease., Methods: UUO mice were generated by complete ligation of the left ureter. Sham-operated mice were used as a control. Renal function was investigated on days 0, 1, 3, and 6 post-surgery using dynamic planar imaging of 99mTc-MAG3 activity following retro-orbital injection. Time-activity curves (TACs) were produced for individual kidneys and renal function was assessed by 1) the slope of initial 99mTc-MAG3 uptake (SIU), which is related to renal perfusion; 2) peak activity; and 3) the time-to-peak (TTP). The parameters of tubular excretion were not evaluated in this study as 99mTc-MAG3 is not excreted from UUO kidneys., Results: Compared to sham-operated mice, SIU was remarkably (>60%) reduced in UUO kidneys at day 1 post surgery and the TACs plateaued, indicating that 99mTc-MAG3 is not excreted in these kidneys. The plateau activity in UUO kidneys was relatively low (~40% of sham kidney's peak activity) as early as day1 post surgery, demonstrating that uptake of 99mTc-MAG3 is rapidly reduced in UUO kidneys. The time to plateau in UUO kidneys exceeded 200 sec, suggesting that 99mTc-MAG3 is slowly up-taken in these kidneys. These changes advanced as the disease progressed. SIU, peak activity and TTPs were minimally changed in contra-lateral kidneys during the study period., Conclusions: Our data demonstrate that renal uptake of 99mTc-MAG3 is remarkably and rapidly reduced in UUO kidneys, while the changes are minimal in contra-lateral kidneys. The parametric analysis of TACs suggested that renal perfusion as well as tubular uptake is reduced in UUO kidneys. This imaging technique should allow non-invasive assessments of UUO renal injury and enable a more rapid interrogation of novel therapeutic agents and protocols.
- Published
- 2012
- Full Text
- View/download PDF
50. [Improvement of vision in nursing home patients through eyeglasses].
- Author
-
Koole FD, Polak BC, van der Heijde GL, Zemel DA, Breedijk TR, and Tijmes NT
- Subjects
- Age Factors, Aged, Aged, 80 and over, Female, Humans, Hyperopia rehabilitation, Male, Myopia rehabilitation, Netherlands epidemiology, Refractive Errors diagnosis, Refractive Errors epidemiology, Refractometry, Vision Screening, Accidental Falls prevention & control, Eyeglasses, Homes for the Aged, Inpatients statistics & numerical data, Nursing Homes, Refractive Errors rehabilitation
- Abstract
Adequate refraction correction may contribute to the quality of life of elderly persons who will be less dependent on care in daily life and will be less prone to fall. In nearly 20% of 102 nursing home residents binocular visual acuity improved with at least one line on the Snellen Chart by adjustment of refractive correction.
- Published
- 2001
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.