278 results on '"al-Awqati Q"'
Search Results
2. Mutations in DSTYK and Dominant Urinary Tract Malformations
- Author
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Sanna-Cherchi, S., Sampogna, R. V., Papeta, N., Burgess, K. E., Nees, S. N., Perry, B. J., Choi, M., Bodria, M., Liu, Y., Weng, P. L., Lozanovski, V. J., Verbitsky, M., Lugani, F., Sterken, R., Paragas, N., Caridi, G., Carrea, A., Dagnino, M., Materna-Kiryluk, A., Santamaria, G., Murtas, C., Ristoska-Bojkovska, N., Izzi, C., Kacak, N., Bianco, B., Giberti, S., Gigante, M., Piaggio, G., Gesualdo, L., Kosuljandic Vukic, D., Vukojevic, K., Saraga-Babic, M., Saraga, M., Gucev, Z., Allegri, L., Latos-Bielenska, A., Casu, D., State, M., Scolari, F., Ravazzolo, R., Kiryluk, K., Al-Awqati, Q., DʼAgati, V. D., Drummond, I. A., Tasic, V., Lifton, R. P., Ghiggeri, G. M., and Gharavi, A. G.
- Published
- 2013
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3. Hepato-renal confusion
- Author
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Al-Awqati, Q
- Published
- 2007
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4. Abstract of the 68th Meeting (Spring Meeting) 6–9 March 1990, Heidelberg
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Sakmann, B., Schrader, J., Brenner, B., Murer, H., Boeckh, J., Handwerker, H. O., HonerjÄger, P., Dugas, M., Wang, G., DeLuca, A., Brinkmeier, H., Fakler, B., Pröbstle, T., Rüdel, R., Pohl, J. -A., Meves, H., Kroll, B., Bremer, S., Tümmler, B., Frömter, E., Schwegler, J. S., Steigner, W., Silbernagl, S., Pusch, Michael, Niemann, P., Schmidtmayer, J., Ulbricht, W., Hansen, G., Lönnendonker, U., Neumcke, B., Eickhorn, R., Hornung, D., Antoni, H., Penner, R., Neher, E., Takeshima, H., Nishimura, S., Numa, S., Melzer, W., Feldmeyer, D., Pohl, B., Zöllner, P., Müller, T. H., Swandulla, D., Misgeld, U, Ganitkevich, V. Ya., Isenberg, G., Cavalié, A., Allen, T. J. A., Trautwein, W., Pelzer, Siegried, Shuba, Yaroslav M., Asai, Tatsuya, Trautwein, Wolfgang, Brown, Arthur M., Birnbauner, Lutz, McDonald, Terence F., Pelzer, Dieter, Eckert, R., Hescheler, J., Rosenthal, W., Offermann, S., Krautwurst, D., Schultz, G., Kettenmahn, Helmut, Trotter, J., Verkhratsky, Alexe J N., Savtchenko, Alexej N., Verkhratsky, Alexej N., Schiefer, A., Klöckner, U., Partridge, L. D., SchÄfer, S., Jonas, P., Koh, D. S., Kampe, K., Hermsteiner, M., Vogel, W., Bauer, C. K., Schwarz, J. R., Fink, R. H. A., Wettwer, E., Weik, R., Schlatter, E., Bleich, M., Granitzer, M., Leal, T., Nagel, W., Crabbé, J., Lang, F., Kahn, E., Friedrich, F., Paulmichl, M., Hammerer, M., Maly, K., Grunicke, H., Böhm, T., Nilius, B., Gögelein, H., Dahlem, D., Weiss, H., Waldegger, S., Woell, E., Paulmichl, R., Ruppersberg, J. P., Schröter, K. H., Stocker, M., Pongs, O., Wittka, R., Boheim, G., Lichtinghagen, R, Augustine, C. K., Stühmer, W., Hoppe, Dorothe, Hoppe, D., Zittlau, K. E., Walther, C., Hatt, H., Franke, C., Quasthoff, S., Wischmeyer, E., Jockusch, H., Friedrich, M., Benndorf, K., Bollmann, G., Hirche, Hj., Hollunder-Reese, F., Mohrmann, M., Greger, R., Weber-Schürholz, S., Schürholz, T., Akabas, M., Landry, D., Al-Awqati, Q., Guse, A. H., Gercken, G., Meyerhof, W., Westphale, H. -J., Kerstins, U., Oberleithner, H., Tilmann, M., Kunzelmann, K., Klitsch, T., Siemen, D., Draguhn, A., Verdoorn, T. A., Pritchett, D. B., Seeburg, P. H., Malherbe, P., Möhler, H., Sakmann, B., Hatt H., Dudel, J., Stern, P., Zufall, F., Rosenheimer, J., Smith, D. O., Dörner, R., Ballanyi, K., Schlue, W. -R., Kalthof, B., Pott, L., Busch, C., Konno, T., Stenql, M., Reinhardt, Ch., Kaiser, H., Baumann, R., Wilimzig, M., Eichenlaub, R., Neumann, E., Lessmann, V., Gottmann, K., Dietzel, I. D., Keller, B. U., Yaari, Y., Konnerth, A., Backus, K. H., Giller, T., Knoflach, F., Pflimlin, P., Trübe, G., von Blankenfeld, G., Ymer, S., Sontheimer, H., Ewert, M., Seeburg, P. H., Kettenmann, H., Schneggenburger, R., Paschke, D., Hülser, D. F., Ubl, J., Kolb, H. A., Ströttchen, J., Boheim, S., Wehner, F., Guth, D., Kinne, R. K. H., Hülser, D. F., Polder, H. R., Bödeker, D., Hoppe, Susanne, Höller, H., Hampe, W., Ruf, H., Schulz, I., Dehlinger-Kremer, M., Ozawa, T., Vasilets, L., Schmalzing, G., MÄdefessel, K., Biel, H., Schwarz, W., Burckhardt, B. C., Stallmach, N., MairbÄurl, H., Hoffman, J. F., Schömig, E., Heuner, A., Göbel, B. O., Siffert, W., Butke, A., Hoffmann, G., zu Brickwedde, M. -K. Meyer, Vetter, H., Düsing, R., Rosskopf, D., Osswald, U., Steffgen, J., Koepsell, H., Martens, H., Rübbelke, M., GÄbel, G., Arens, J., Stabel, J., Fischer, Y., Thomas, J., Rose, H., Kammermeier, H., Munsch, Thomas, Deitmer, Joachim W., Engelmann, B., Duhm, J., Deitmer, Joachim W., Gunzel, D., Galler, S., Fischer, H., Clauss, W., Van Driessche, W., Köckerling, A, Schulzke, JD, Sorgenfrei, D, Fromm, M, Simon, B., Ganapathy, V., Leibach, F. H., Burckhardt, G., Krattenmacher, R., Voigt, Rosita, Dietrich, S., Leyssens, A., Zhang, S. L., Weltens, R., Steels, P., Hoffmann, B., Heinz, M., Habura, B., Dörge, A., Rechkemmer, G., von Engelhardt, W., StrauB, O., Wiederholt, M., Margineanu, D. -G., Van Driessche, W., Kreusel, K. M., Fromm, M., Lempart, U., Sorgenfrei, D., Hegel, U., Augustin, A. J., . Goldstein, R., Purucker, E., Lutz, J., Illek, B., Thiele, K -P., Schwealer, JS., Dittmer J., Bauer C., Eckardt, K. -U., Dittmer, J., Neumann, R., Bauer, C., Kurtz, A., Fromm, H., Schulzke, J. D., Clausen, P., Krohn, A., Lüderitz, S., Hierholzer, K., Kersting, U., Woinowski, L., Gro\mann, R., Bin, X. U., Ellendorff, F., Nitschke, R., Fröbe, U., Scholz, H., della Bruna, R., Ehmke, H., Persson, P. B., Seyfarth, M., Kirchheim, H. R., Dietrich, M. S., Parekh, N., Steinhausen, M., Bührle, C. P., Nobiling, R., Ullrich, K. J., Rumrich, G., Klöss, S., Papavassiliou, F., Hoyer, J., Schmitt, C., Jungwirth, A., Ritter, M., Westphale, H. J., Bevan, C., Theiss, C., Denek, Liliana, Schwegler, Johann S., SchÄfer, Roland, Augustin, Albert J., Heidland, August, Nafz, B., Just, A., Steidl, M., Pinggera, G., Gerstberger, R., Schütz, H., Simon, E., Lohrmann, E., Masereel, B., Delarge, J., Lang, H. J., Englert, H. C., Caliebe, D., Mályusz, M., Wrigge, P., Gronow, G., Klause N., Mályusz, M., Zinnert, H., Fagel, H., Jelkmann, W., Weiss, Ch., Augustin, A. J., Keil, R., Schmidt, W., Kröger, C., Brabant, E. G., Hilgendorf, A., Strauch, S., Lane, F., Prick, A., Golenhofen, N., Mildenberger, S., Schwegler, J. S., Flemming, B., Roloff, D., Wronski, T., Drews, G., Debuyser, A., Henquin, J. C., Jackson, M. B., DeRiemer, S. A., Schmid, A., Schnefel, S., Pröfrock, A., Hinsch, K. -D., Milz, J., Lamprecht, G., Seidler, U., Silen, W., Aziz, O., Reschke, W., Fischer, G., De Decker, N., Hayes, T., Coast, G., Van Kerkhove, E., von zur Mühlen, F., Eckstein, F., Hegel, U, Bentzel, CJ, Riecken, EO, Siemer, C., Rothenpieler, P., Smith, E., Lutnicki, K. R., Wróbel, J. T., Ledwożyw, A., PietraŚ, E., Sender, S., Jürgens, Klaus D., Kleinschmidt, T., Werkmeister, F., Kiwull-Schöne, H., Kiwull, P., Vahle, J., Ott, M., Zimmermann, R. E., Elsing, J. G., Million, D., Zillner, P., Thiel, M., Bardenheuer, H., Peter, K., Fandrey, J., Siegers, C. P., Rupp, H., Elimban, V., Dhalla, N. S., Morano, I., Agostini, B., Mühleisen, M., Mommaerts, W. F. H. M., Ono, K., Wussling, M., Schenk, W., Boldt, W., Lipp, P., Schüttler, K., Szymanski, G., Wendt-Gallitelli, M. F., Herzig, J. W., Depersin, H., Grupp, G., Grupp, I., Glitsch, H. G., Pusch, H., Zylka, Ch., Brāndle, M., Jacob, R., Stein, T., Isselhard, W., Sturz, J., Minor, T., Wingenfeld, P., Siegmund, B., Klietz, T., Schwartz, P., Piper, H. M., Linder, Christa, SchÄfer, Stefan, Heusch, Gerd, Becker, B. F., Reinholz, N., Raschke, P., Leipert, B., Gerlach, E., Dierberger, B., Gülch, R. W., Leverkus, M., Mitsuiye, T., Pohl, U., Wang, S. Y., Meyer, R., Haas, H. G., Christmann, H. Ph, Dörner, Th, Hock, D., Hertel, R., Gagelmann, M., Forssmann, W. G., Leijendekker, W. J., Kissling, G., Michel, H., Goetz, A., Freya, M., Fleckenstein-Grün, G., Schipke, Jochen D., Harasawa, Yasuhiko, Sugiura, Seiryo, Alexander, Joe, Burkhoff, Daniel, Kling, L., Müller-Beckmann, B., Schroth, M., Sponer, G., Böhm, E., Strein, K., Dorszewski, A., Arnold, G., Pike, G. K., Bryant, D. J., Roberts, M. L., Fink, R. H., Ross, Ch., Skyschally, A., Schulz, R., Linder, C., Heusch, G., Schipke, J. D., Burkhoff, D., Alexander, J., Gollnick, F., Peter, Kh., Franken-Weyers, R., Borst, M. M., Deussen, A., Pöpping, S., Hose, H., Strotmann, K. H., Lukascek, B., Karnath, T., Güttier, K., Klaus, W., Haverkampf, K., Guhlmann, M., Schmidt-Ott, S., Heuschen, U., Mall, G., Pfitzer, G., Rösch, J., Arner, A., Rüegg, J. C., Kröger, K., Schipke, J. D., ThÄmer, V., Ehring, Thomas, ThÄmer, Volker, Guth, B. D., Schnabel, Ph A., Schmiedl, A., Gebhard, M. M., Richter, J., Bretschneider, H. J., Guth, B. D., Oudiz, R. J., Schnabel, Ph., Richter, J ., Watanabe, H., Spahr, R., Piper, H. M., Obst, O., Mertens, H., Mülsch, A., Busse, R., Lamontagne, D., Herlan, K., Huang, A., Bassenae, E., Mackert, J. R. L., Schilling, L., Parsons, A. A., Wahl, M., Hock, D., Christmann, M. Ph., Thimm, F., Frey, M., Fleckenstein, a. A., Theilen, H., Göbel, U., Kuschinsky, W., Elbert, Th., Tafil-Klawe, M., Rau, H., Lutzenberger, W., Fleckenstein, A., Forst, H., Haller, M., Santjohanser, C., Lauterjung, L., Smieško, Y., Lang, D. J., Johnson, P. C., Schröck, H., Rau H., Elbert T., Geiger B, Lutzenberger W., Koch, G., Koralewski, H. E., Perschel, F. H., Wagner, K., Krüger, U., Albrecht, M., Hohlbach, G., Maassen, N., Foerster, M., Mühling, J., Bari, F., Pleschka, K., Schmidt, H. D., Gro\, H., Loock, W., Stick, C., Diefenbacher, U., Gronewold, D., Tobinsky, M., Walther-Behrends, A., Witzleb, E., Brummermann, M., Reinertsen, R. E., Rogausch, H., Rohn, W. M., Acker, H., Delpiano, M., Dufau, E., Hentschel, J., Heller, H., Schuster, K. -D., Siekmeier, R., Kronenberger, H., Lintl, H., Schiller-Scotland, Ch. F., Gebhart, J., Heyder, J., Meier-Sydow, J., Stahlhofen, W., Mottaghy, K., Geisen, C., Richter, W., Beckman, J., Marek, W., Ulmer, W. T., Thiele, A. E., Raschke, F., Peter, J. H., Hildebrandt, G., Kullmer, T., Kozianka-Burghof, G., Thiele, A. E., Schlaefke, M. E., Gnuschke, H., Schaefer, T., Schaefer, D., Schaefer, C., Bradley, Ronald J., Sterz, Raimund, Peper, Klaus, Benterbusch, R., Kraft, Th., Yu, L. C., Kuhn, H. J., Blankenbach, K., Asmussen, G., Kunze, I., Pieper, K. -S., Steinmetz, J., Schmidt, H., Krippeit-Drews, P., Hübschen, U., Nacimiento, A. C., Günzel, D., Rathmayer, W., Gaunitz, U., Költgen, D., Zachar, E., Soltau, B., De Martino, L., Hasselbach, W., Kössler, F., Lange, P., Küchler, G., Zeugner, C., Van Eyk, J., Hodges, R. S., Lorkovic, H., Clemens, N., Scheid, P., Noack, Th., Deitmer, P., Golenhofen, K., Lammel, E., Welling, Andrea, Felbel, Jochen, Hofmann, Franz, Katoch, S., Watanabe, T., Mandrek, K., Milenov, K., Hammer, K., Rössler, W., Sann, H., Pierau, Fr -K., Nguyen-Duong, H., Schneider, P., Stahl, F., Lepple-Wienhues, A., Korbmacher, C., Haller, H., Gebauer, M., Willner, U., Bialojan, C., Lengsfeld, M., Kyrtatas, V., Dartsch, Peter C., Boels, P. J., Fischer, W., Lenz, T., Thei\, U., Kreye, V. A. W., Ohkubo, T., Kupp, H., Vonderlage, M., Schreiner, V., Dorlöchter, M., Brinkers, M., Irintchev, A., Wernig, A., Langenfeld, B., Finger, W., Wolburg, H., Beer, A., Schwejda, Ch., Scheller, D., Heister, U., Tegtmeier, F., Knöpfel, Thomas, Spuler, Andreas, Grafe, Peter, GÄhwiler, Beat, Bijak, M., Misgeld, U., Müller, W., Rausche, G., Leweke, F M., Bingmann, D., Moraidis, I., Speckmann, E. -J., Madeja, M., Mu\hoff, U., Lehmenkühler, A, Kuhlmann, D., Hans, M., Lux, H. D., StrÄub, H., Waiden, J., Baker, R. E., Grantyn, R., Perouansky, M., Kraszewski, K, Lehmenkühler, Chr, Dodt, H. U., ZieglgÄnsberger, W., Pawelzik, H., ZieglgÄngsberger, W., Mann, K., Wiethölter, H., Albrecht, D., Dreier, J., Ficker, E., Beck, H., Corrette, B J., Dreyer, F., Repp, H., Dreessen, J., Augustine, G. J., Lehmenkühler, A., Büsselberg, D., Heimrich, B., Haas, H. L., Birnstiel, S., Haas, H. L., Schönrock, B., Altrup, U., Reith, H., Speckmann, E. -J., Alzheimer, C., Bruagencate, G. ten, Fruhstorfer, B., Mignot, E., Nishino, S., Dement, W. C., Guilleminault, C., Simon-Oppermann, Christa, Günther, Olaf, Stehle, J., Reuss, S., Seidel, A., Riemann, R., Vollrath, L., Reimer, Susanne, HölIt, Volker, Sonnhof, U., Krupp, J., Claus, H, Hinckel, P., Dick, H. B. H., Hiemke, C., Jussofie, A., Dorn, T., Uhlig, S., Witte, O. W., Bother B., Eiselt M., Witte H., Zwiener ö, Rother M, Eiseit H., Taghavy, A., KrÄtzer, A., Clusmann, H., Heinemann, U., Block, F., Sonatg, K. -H., Falkeristein, M., Hohnsbein, J., Hoormann, J., Frieling, A., Tarkka, I. M., Kullmann, W., Bromm, B., Hirsch, M. Chr, Wissing, H., Braun, H. A., Igelmund, P., Klu\mann, F. W., Ehrenstein, W. H., Yakimoff, N., Mateeff, S., Zeise, M. L., Arriagada, J., Teschemacher, A., ZieglgÄnsberger, W., Pöppelmann, T., Köhling, R., Boerrigter, P., Reith, H., Anders, K., Ohndorf, W., Dermietzel, R., Richter, D. W., Tölle, T. R., Castro-Lopes, J. M., Neuropharmakologie, Klinische, Sandkühler, J., Leah, J. D., Herdegen, T., Zimmermann, M., Vaitl, D., Gnippe, H., Herbert, M. K., Mengel, M. K. C., Kniffki, K. -D., Linke, R., Vahle-Hinz, C., Schenda, J., Matsumura, K., Herdegen, T., fu, Q. -G., Forster, C., Hutchison, W. D., Morton, C. R., Aschoff, J., Wilhelm, Z., Schwarzacher, S. W., Wasserschaff, M, Hörner, M., Kümmel, H., Windhorst, U., Feldman, J. L., Schmid, K., Foutz, A. S., Denavit-Saubié, M., Pak, M. A., Wehling, P., Evans, C., Bandara, G., Awiszus, F., Feistner, H., Heinze, H. -J., Illert, M., Wasserschaff, M., Kleinebeckel, D., Böhmer, G., Schauer, W., Abel, H. -H., Klü\endorf, D., Koepchen, H. P., Jarolimek, W, König, St, Czachurski, J., Seller, H., Meckler, R. L., McLachlan, E. M., Boczek-Funcke, A., HÄbler, H. -J., JÄnig, W., Michaelis, M., Dembowsky, K., Königr, S., Rau, Harald, HÄbler, H. -J., Unger, M., Merker, G., Roth, J., Zeisberger, E., Gao, H., Hunold, M., Kirchner, F., Takano, K., Schulze, K., Pokorski, M., Sakakibara, Y., Masuda, A., Morikawa, T., Ahn, B., Takaishi, S., Paulev, P. -E., Honda, Y., Flügge, G., Fuchs, E., König, S., Eysel, U. Th., Schmidt-Kastner, R., Skrandies, W., Geib, T., Baumann, C., Schmidt, K. -F., Knapp, A. G., Dowling, J. E., Kuba, M., Toyonaga, N., Kubová, Z., Ehrenstein, W. H., Jacobi, P., Schmidt, K. -F., Nöll, G. N., Baumann, Ch., Tabata, M., Martin, Ch., Meissl, H., Knottenberg, Th., Scheibner, H., Zenner, Hans P., Zimmennann, Ulrike, Gitter, Alfred H., Ding, D., Smolders, J. W. T., Klinke, R., Boekhoff, I., Raming, K., Krieger, J., Tareilus, E., Strotinann, J., Breer, H., Schild, D., DeSimone, J. A., Hellwig, S., Gitter, A. H., Plinkert, P. K., Zenner, H. P., Koltzenbwg, M., Pinter, E., SchÄfer, K., Braun, H. A., Necker, R., Hanesch, U., Heppelmann, B., Schmidt, R. F., Mense, S., Hoheisel, U., Steen, K. H., Anton, F., Reek, P. W., Handwerker, H. O., Lewin, G. R., McMahon, S. B., Heyer, G., Hornstein, O. P., Klement, W., Arndt, J. O., Maeerl, W., GrÄmer, G., Schepelmann, K., Me\linger, K., Schaible, H. -G., Treede, R. D., Meyer, R. A., Campbell, J. N., Claus, D., Neundörfer, B., Ernst, R., Tick-Waider, A. M., Bretschneider, F., Peters, R. C., Tennis, P. F. M., Teunis, P. F. M., Hoheisel, D., Scherotzke, R., Bub, A., Manzl, G., Forssmann, W. G., Jessen, C., Nuesslein, B., Schmidt, I., Wetzig, J., Reiser, M., Bregenzer, N., von Baumgarten, R. J., Mohr, E., Krzywanek, H., Warncke, G., Schuchmann, K. -L., Linow, H., Klu\mann, F. H., Redlin, U., Heldmaier, G., Bamler, A, Koller, A., Felber, S., Haid, C., Wicke, K., Raas, E., Xuemin, Wang, Kerning, Chen, Ying, Shi, Hanping, Shi, Warncke, Günther, Voisord, R., Dortsch, P. C., Betz, E., Karbach, U., Walenta, S., Gross, M. W., Mueller-Klieser, W., Vaupel, P., Okunieff, P., Mayer, W. -K., Stohrer, M., Krüger, W., Müller-Klieser, W., Strupp, M., Weial, P., Bostock, H., Piwernetz, K., Renner, R., Grafe, P., Lankers, J., Zangemeister, W., Kunze, K., Tries, S., Heinle, H., Beckerath, N. V., Maier-Rudolph, W., Mehrke, G., Günther, K., Goedel-Meinen, L., Daut, J., Piper, H. M., Kopp, A., Noll, T., Goellner, A., Gerlach, S., Teutsch, H. F., Schienger, K., Schwab, R., Höckel, M., Fotev, Z., Nienhaus, M., Kaczmarczyk, Gabriele, Richter, Dinah, Korte, Gabriele, Förther, J., Reinhardt, H. W., Schreiber, R., Rupp, J., Murphy, G., Fingerle, J., Kloiber, O., Miyazawa, T., Höhn-Berlage, M., Hossmann, K. -A., Schad, H., Heimisch, W., Blasini, R., Haas, F., Mendier, M., Spuler, A., Lehmann-Hom, F., Wolfram, U., Fenske, M., Sachser, N., Weis, Ch., Marktl, W., Kopta, B., Klammer, N., Rudas, B., Pohl, H., Nienartowicz, A., Moll, W., Klempt, M., Blum, S., Bühler, H., Lichtenstein, I., Novak, A., Siebe, H., Hierholzer, K., and Peper, K.
- Published
- 1990
- Full Text
- View/download PDF
5. Proteoglycan desulfation determines the efficiency of chondrocyte autophagy and the extent of FGF signaling during endochondral ossification. Gene Dev. 22(19):2645-50, 2008
- Author
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SETTEMBRE, CARMINE, Arteaga Solis E, McKee MD, dePablo R, Al Awqati Q, Karsenty G., BALLABIO, ANDREA, Settembre, Carmine, Arteaga Solis, E, Mckee, Md, Depablo, R, Al Awqati, Q, Ballabio, Andrea, and Karsenty, G.
- Published
- 2008
6. Mutations in DSTYK and dominant urinary tract malformations
- Author
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Sanna Cherchi, S, Sampogna, Rv, Papeta, N, Burgess, Ke, Nees, Sn, Perry, Bj, Choi, M, Bodria, M, Liu, Y, Weng, Pl, Lozanovski, Vj, Verbitsky, M, Lugani, F, Sterken, R, Paragas, N, Caridi, G, Carrea, A, Dagnino, M, Materna Kiryluk, A, Santamaria, G, Murtas, C, Ristoska Bojkovska, N, Izzi, C, Kacak, N, Bianco, B, Giberti, S, Gigante, M, Piaggio, G, Gesualdo, L, Kosuljandic Vukic, D, Vukojevic, K, Saraga Babic, M, Saraga, M, Gucev, Z, Allegri, L, Latos Bielenska, A, Casu, D, State, M, Scolari, F, Ravazzolo, Roberto, Kiryluk, K, Al Awqati, Q, D'Agati, Vd, Drummond, Ia, Tasic, V, Lifton, Rp, Ghiggeri, Gm, and Gharavi, Ag
- Subjects
Male ,Kidney Disease ,Genetic Linkage ,030232 urology & nephrology ,Genome-wide association study ,Bioinformatics ,medicine.disease_cause ,Fibroblast growth factor ,Kidney ,Medical and Health Sciences ,Mice ,0302 clinical medicine ,2.1 Biological and endogenous factors ,Exome ,RNA, Small Interfering ,Aetiology ,Urinary Tract ,Child ,Pediatric ,0303 health sciences ,Mutation ,General Medicine ,3. Good health ,Pedigree ,medicine.anatomical_structure ,Receptor-Interacting Protein Serine-Threonine Kinases ,Gene Knockdown Techniques ,Female ,Biotechnology ,Adult ,Urologic Diseases ,Heterozygote ,Urinary system ,1.1 Normal biological development and functioning ,Molecular Sequence Data ,Renal and urogenital ,Small Interfering ,03 medical and health sciences ,Young Adult ,Clinical Research ,Underpinning research ,General & Internal Medicine ,medicine ,Genetics ,Animals ,Humans ,030304 developmental biology ,Base Sequence ,business.industry ,Human Genome ,Infant ,Heterozygote advantage ,Urogenital Abnormalities ,Etiology ,RNA ,Congenital Structural Anomalies ,business ,Genome-Wide Association Study - Abstract
BackgroundCongenital abnormalities of the kidney and the urinary tract are the most common cause of pediatric kidney failure. These disorders are highly heterogeneous, and the etiologic factors are poorly understood.MethodsWe performed genomewide linkage analysis and whole-exome sequencing in a family with an autosomal dominant form of congenital abnormalities of the kidney or urinary tract (seven affected family members). We also performed a sequence analysis in 311 unrelated patients, as well as histologic and functional studies.ResultsLinkage analysis identified five regions of the genome that were shared among all affected family members. Exome sequencing identified a single, rare, deleterious variant within these linkage intervals, a heterozygous splice-site mutation in the dual serine-threonine and tyrosine protein kinase gene (DSTYK). This variant, which resulted in aberrant splicing of messenger RNA, was present in all affected family members. Additional, independent DSTYK mutations, including nonsense and splice-site mutations, were detected in 7 of 311 unrelated patients. DSTYK is highly expressed in the maturing epithelia of all major organs, localizing to cell membranes. Knockdown in zebrafish resulted in developmental defects in multiple organs, which suggested loss of fibroblast growth factor (FGF) signaling. Consistent with this finding is the observation that DSTYK colocalizes with FGF receptors in the ureteric bud and metanephric mesenchyme. DSTYK knockdown in human embryonic kidney cells inhibited FGF-stimulated phosphorylation of extracellular-signal-regulated kinase (ERK), the principal signal downstream of receptor tyrosine kinases.ConclusionsWe detected independent DSTYK mutations in 2.3% of patients with congenital abnormalities of the kidney or urinary tract, a finding that suggests that DSTYK is a major determinant of human urinary tract development, downstream of FGF signaling. (Funded by the National Institutes of Health and others.).
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- 2013
7. Indanyloxyacetic acid-sensitive chloride channels from outer membranes of skeletal muscle
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Weber-Schürholz, S, Wischmeyer, E, Laurien, M, Jockusch, Harald, Schürholz, T, Landry, DW, and al-Awqati, Q
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Muscles ,Cell Membrane ,Membrane Proteins ,Cell Fractionation ,Chromatography, Affinity ,Ion Channels ,Glycolates ,Membrane Potentials ,Mice ,Sarcolemma ,Chlorides ,Chloride Channels ,Centrifugation, Density Gradient ,Animals ,Rabbits ,Protein Binding - Abstract
In mature mammalian muscle, the chloride conductance of the membrane is an important factor in the regulation of excitability. Up to now, no ligand was available for the biochemical characterization of muscle chloride channels. In order to localize and characterize these channels, we have used indanyloxyacetic acid (IAA)-94, a ligand previously used for epithelial Cl- channels (Landry, D. W., Reitman, M., Cragoe, E. J., Jr., and Al-Awqati, Q. (1987) J. Gen. Physiol. 90, 779-798; Landry, D. W., Akabas, M. H., Redhead, C., Edelman, A., Cragoe, E. J., Jr., and Al-Awqati, Q. (1989) Science 244, 1469-1472). IAA induced myotonic responses when microinjected into mature mouse muscle fibers, indicating a blockade of Cl- channels from the cytoplasmic side. Membrane vesicles were prepared from rabbit skeletal muscle and separated by sucrose gradient centrifugation. Fractions obtained (in the order of increasing density) were sarcolemma (SL), T-tubules (TT), sarcoplasmatic reticulum (SR), and triads and mitochondria (TR/M). The fraction enriched for SL was characterized by high specific binding capacity for [H-3]saxitoxin (Na+ channel), whereas TT-rich fractions bound [H-3]PN 200-110 (dihydropyridine receptor) with high specific activity. Upon patch-clamping of lipid supplemented vesicles, IAA-sensitive Cl- channels were found in the SL fraction but not in the SR. Highest specific activities in electrical diffusion potential sensitive Cl-36 transport and [H-3]IAA-94 binding were found in the SL. SL vesicles were solubilized with 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate and subjected to IAA-Sepharose affinity chromatography. Specifically bound protein was eluted with 100 muM IAA-94 and either analyzed by SDS-gel electrophoresis or reconstituted into phospholipid vesicles. The eluate contained four polypeptides (specifically bound, m(app) 110-120 and 60 kDa; unspecifically bound m(app) 67 and 50 kDa) and was highly enriched for IAA-sensitive chloride channels as shown by patch-clamping after reconstitution. The IAA-sensitive 100/280-picosiemens chloride channels of the sarcolemma are likely to be responsible for its major chloride conductance and thereby for the stabilization of resting potential.
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- 1993
8. Response
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Al-Awqati, Q., primary
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- 2007
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9. Showing Some Skin
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Al-Awqati, Q., primary
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- 2007
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10. A fork in the road of cell differentiation in the kidney tubule
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Al-Awqati, Q., primary
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- 2004
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11. Terminal Differentiation of Epithelia
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Al-Awqati, Q., primary, Vijayakumar, S., additional, and Takito, J., additional
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- 2003
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12. Size does matter: Will knockout of p21WAF1/CIP1 save the kidney by limiting compensatory renal growth?
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Al-Awqati, Q., primary and Preisig, P. A., additional
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- 1999
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13. Expression of green fluorescent protein in the ureteric bud of transgenic mice: A new tool for the analysis of ureteric bud morphogenesis
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Srinivas, S., primary, Goldberg, M.R., additional, Watanabe, T., additional, D'Agati, V., additional, Al-Awqati, Q., additional, and Costantini, F., additional
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- 1999
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14. An endothelial growth factor involved in rat renal development.
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Oliver, J A, primary and Al-Awqati, Q, additional
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- 1998
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15. Endothelial cell targeting during renal development: use of monoclonal antibodies
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Oliver, J. A., primary, Goldberg, M. R., additional, and Al-Awqati, Q., additional
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- 1997
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16. Spatial and temporal expression of cell surface molecules during nephrogenesis
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Goldberg, M. R., primary, Barasch, J., additional, Shifteh, A., additional, D'Agati, V., additional, Oliver, J. A., additional, Hu, C., additional, and al-Awqati, Q., additional
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- 1997
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17. Hensin, a new collecting duct protein involved in the in vitro plasticity of intercalated cell polarity.
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Takito, J, primary, Hikita, C, additional, and Al-Awqati, Q, additional
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- 1996
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18. Plasticity in epithelial polarity of renal intercalated cells: targeting of the H(+)-ATPase and band 3
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Al-Awqati, Q., primary
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- 1996
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19. Regulation of ion channels by ABC transporters that secrete ATP
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al-Awqati, Q., primary
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- 1995
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20. Cystic fibrosis epithelial cells have a receptor for pathogenic bacteria on their apical surface.
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Imundo, L, primary, Barasch, J, additional, Prince, A, additional, and Al-Awqati, Q, additional
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- 1995
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21. Secretogogue-induced gating of chloride channels in the secretory vesicles of parafollicular cells.
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Tamir, H, primary, Piscopo, I, additional, Liu, K P, additional, Hsiung, S C, additional, Adlersberg, M, additional, Nicolaides, M, additional, al-Awqati, Q, additional, Nunez, E A, additional, and Gershon, M D, additional
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- 1994
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22. Molecular cloning and characterization of p64, a chloride channel protein from kidney microsomes
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Landry, D., primary, Sullivan, S., additional, Nicolaides, M., additional, Redhead, C., additional, Edelman, A., additional, Field, M., additional, al-Awqati, Q., additional, and Edwards, J., additional
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- 1993
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23. The apical Cl/HCO3 exchanger of beta intercalated cells
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van Adelsberg, J.S., primary, Edwards, J.C., additional, and al-Awqati, Q., additional
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- 1993
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24. Apoptosis in metanephric development.
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Koseki, C, primary, Herzlinger, D, additional, and al-Awqati, Q, additional
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- 1992
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25. Identification and modulation of a voltage-dependent anion channel in the plasma membrane of guard cells by high-affinity ligands.
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Marten, I., primary, Zeilinger, C., additional, Redhead, C., additional, Landry, D.W., additional, al-Awqati, Q., additional, and Hedrich, R., additional
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- 1992
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26. Conditional immortalization of bicarbonate-secreting intercalated cells from rabbit
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Edwards, J. C., primary, van Adelsberg, J., additional, Rater, M., additional, Herzlinger, D., additional, Lebowitz, J., additional, and al-Awqati, Q., additional
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- 1992
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27. A ubiquitous 64-kDa protein is a component of a chloride channel of plasma and intracellular membranes.
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Redhead, C R, primary, Edelman, A E, additional, Brown, D, additional, Landry, D W, additional, and al-Awqati, Q, additional
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- 1992
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28. A replica filter assay for expression of ion transport proteins
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Obici, S., primary, al-Awqati, Q., additional, Avvedimento, E. V., additional, and Gottesman, M. E., additional
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- 1991
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29. Integration of embryonic nephrogenic cells carrying a reporter gene into functioning nephrons
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Koseki, C., primary, Herzlinger, D., additional, and al-Awqati, Q., additional
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- 1991
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30. Cellular and molecular mechanisms of renal development and tubulogenesis.
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Al-Awqati, Qais and al-Awqati, Q
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- 1992
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31. Regulation of Transepithelial H+ Transport by Exocytosis and Endocytosis.
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Schwartz, G J and Al-Awqati, Q
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- 1986
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32. Metabolic pathways coupled to H+ transport in turtle urinary bladder.
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Kelly, S, Dixon, T E, and Al-Awqati, Q
- Abstract
Active H+ transport in the turtle urinary bladder is mediated by an ATPase. Although the source of ATP is usually mitochondrial oxidative phosphorylation, it is possible because of intracellular compartmentalization or cellular heterogeneity that one metabolic pathway exclusively provides ATP to the pump. To examine this we performed several types of experiments. In one, the coupling between the rate of transport and the rate of oxidation of 14C-labeled substrates was studied. We found that there was coupling between H+ transport and glucose, butyrate oleate, and beta-OH-butyrate oxidation. In another set of experiments we depleted turtle bladders of their endogenous substrates and tested the effect of a number of substrates on the rate of transport. We found that glucose, pyruvate, lactate, actetate, butyrate and beta-OH butyrate all stimulated H+ transport. In a third set of experiments we found no coupling between H+ transport and lactate production. Finally, we found that reduction of H+ transport by mucosal acidification resulted in an increase in epithelial cell ATP concentrations and a decrease in ADP levels. These results suggest that the H+ pump receives its ATP from carbohydrate and fatty acid oxidation. The changes in ATP and ADP levels provide an initial explanation for the coupling of H+ transport to the rate of cellular oxidative metabolism. [ABSTRACT FROM AUTHOR]
- Published
- 1980
33. Proton-Translocating Atpases.
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Al-Awqati, Q
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- 1986
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34. Identification of electrophysiologically distinct subpopulations of rat taste cells.
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Akabas, Myles, Dodd, Jane, Al-Awqati, Qais, Akabas, M, Dodd, J, and al-Awqati, Q
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BIOLOGICAL transport ,ANIMAL experimentation ,CALCIUM ,CELL culture ,CELLULAR signal transduction ,COMPARATIVE studies ,RESEARCH methodology ,MEDICAL cooperation ,MEMBRANE proteins ,POTASSIUM ,RATS ,RESEARCH ,RESEARCH funding ,TASTE ,EVALUATION research ,TASTE buds ,PHYSIOLOGY - Abstract
The gustatory sensory system provides animals with a rapid chemical analysis of a potential food substance providing information necessary to facilitate ingestion or rejection of the food. The process of gustatory transduction is initiated in the taste cells in the lingual epithelium. However, due to the small size, scarcity of the cells and their location, embedded in a keratinized squamous epithelium, it has been difficult to study the primary events in the transduction process. Recently, we have developed a preparation of dissociated rat taste cells that permits studies of the taste transduction process in single isolated cells. We have now investigated the electrophysiological properties of the rat taste cells using the patch-clamp technique. We have identified two populations of cells within the taste bud: one expressing a voltage-dependent potassium current and the second containing both voltage-dependent sodium and potassium currents. The potassium current in both cell groups is blocked by external TEA, Ba2+, and quinine. Two types of K+ channels have been identified: a 90-pS delayed rectifier K+ channel and a "maxi" calcium-activated K+ channel. The sodium current is blocked by TTX, but not by amiloride. [ABSTRACT FROM AUTHOR]
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- 1990
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35. Only multimeric hensin located in the extracellular matrix can induce apical endocytosis and reverse the polarity of intercalated cells.
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Hikita, C, Takito, J, Vijayakumar, S, and Al-Awqati, Q
- Abstract
When an intercalated epithelial cell line was seeded at low density and allowed to reach confluence, it located the anion exchanger band 3 in the apical membrane and an H+-ATPase in the basolateral membrane. The same clonal cells seeded at high density targeted these proteins to the reverse location. Furthermore, high density cells had vigorous apical endocytosis, and low density cells had none. The extracellular matrix of high density cells was capable of inducing apical endocytosis and relocation of band 3 to the basolateral membrane in low density cells. A 230-kDa extracellular matrix (ECM) protein termed hensin, when purified to near-homogeneity, was able to reverse the phenotype of the low density cells. Antibodies to hensin prevented this effect, indicating that hensin is necessary for conversion of polarity. We show here that hensin was synthesized by both low density and high density cells. Whereas both phenotypes secreted soluble hensin into their media, only high density cells localized it in their ECM. Analysis of soluble hensin by sucrose density gradients showed that low density cells secreted monomeric hensin, and high density cells secreted higher order multimers. When 35S-labeled monomeric hensin was added to high density cells, they induced its aggregation suggesting that the multimerization was catalyzed by surface events in the high density cells. Soluble monomeric or multimeric hensin did not induce apical endocytosis in low density cells, whereas the more polymerized hensin isolated from insoluble ECM readily induced it. These multimers could be disaggregated by sulfhydryl reagents and by dimethylmaleic anhydride, and treatment of high density ECM by these reagents prevented the induction of endocytosis. These results demonstrate that hensin, like several ECM proteins, needs to be precipitated in the ECM to be functional.
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- 1999
36. Isolation and culture of HCO3- -secreting intercalated cells
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Van Adelsberg, J., Edwards, J. C., Herzlinger, D., Cannon, C., Rater, M., and al-Awqati, Q.
- Abstract
Intercalated cells of the distal nephron secrete either H+ or HCO3-. We have succeeded in isolating HCO3- -secreting intercalated cells from the rabbit kidney. When seeded onto collagen-coated permeable supports, these cells form monolayers with a resistance of 595 +/- 75 omega.cm2. The monolayers maintain the characteristics of an epithelium, with apical microvillae and tight junctions. They display the same polarity as do HCO3- -secreting intercalated cells in vivo, namely apical peanut lectin binding and apical Cl- -HCO3- exchange. The monolayers are capable of transepithelial HCO3- transport via this exchanger. The rate of Cl- -dependent transepithelial HCO3- transport is 4 +/- 0.4 nmol.min-1.cm-2. Transepithelial HCO3- transport is completely abolished by 50 microM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid applied to the apical side of the monolayer. These cultured HCO3- -secreting intercalated cells should prove useful for defining the cellular regulation of HCO3- secretion.
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- 1989
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37. Metanephric mesenchyme contains multipotent stem cells whose fate is restricted after induction.
- Author
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Herzlinger, D, Koseki, C, Mikawa, T, and al-Awqati, Q
- Abstract
At least fourteen epithelial cell types of the mammalian nephron develop from the metanephric mesenchyme. To distinguish whether this single embryological primordium contains a heterogenous population of committed renal cell lines or a multipotent stem cell, the lac-Z gene was introduced into individual renal progenitors by retroviral mediated gene transfer. The differentiated fate of lac-Z-tagged daughters derived from single metanephric mesenchymal cells was characterized after cytodifferentiation. We found that the metanephric mesenchyme contains multipotent stem cells that can generate at least three distinct cell types; glomerular, proximal and distal epithelia. After induction the fate of this multipotent cell becomes restricted to populate a single nephron segment.
- Published
- 1992
38. Thyrotropin induces the acidification of the secretory granules of parafollicular cells by increasing the chloride conductance of the granular membrane.
- Author
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Barasch, J, Gershon, M D, Nunez, E A, Tamir, H, and al-Awqati, Q
- Abstract
Secretory granules of sheep thyroid parafollicular cells contain serotonin, a serotonin-binding protein, and calcitonin. Parafollicular cells, isolated by affinity chromatography, were found to secrete serotonin when activated by thyrotropin (TSH) or elevated [Ca2+]e. TSH also induced a rise in [Ca2+]i. We studied the effect of these secretogogues on the pH difference (delta pH) across the membranes of the secretory granules of isolated parafollicular cells. The trapping of the weak bases, acridine orange or 3-(2,4 dinitro anilino)-3'-amino-N-methyl dipropylamine (DAMP), within the granules was used to evaluate delta pH. In contrast to lysosomes, which served as an internal control, the secretory granules of resting parafollicular cells displayed a limited and variable ability to trap either acridine orange or 3-(2,4 dinitro anilino)-3'-amino-N-methyl dipropylamine; however, when parafollicular cells were stimulated with TSH or elevated [Ca2+]e, the granules acidified. Weak base trapping was also used to evaluate the ATP-driven H+ translocation into isolated parafollicular granules. The isolated parafollicular granules did not acidify in response to addition of ATP unless their transmembrane potential was collapsed by the K+ ionophore, valinomycin. Secretory granules isolated from TSH-treated parafollicular cells had a high chloride conductance than did granules isolated similarly from untreated cells. Furthermore, ATP-driven H+ translocation into parafollicular granules isolated from TSH-stimulated parafollicular cells occurred even in the absence of valinomycin. These results demonstrate that secretogogues can regulate the internal pH of the serotonin-storing secretory granules of parafollicular cells by opening a chloride channel associated with the granule membrane. This is the first demonstration that the pH of secretory vesicles may be modified by altering the conductance of a counterion for the H+ translocating ATPase.
- Published
- 1988
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39. New amiloride analogue as hapten to raise anti-amiloride antibodies
- Author
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Kleyman, T. R., Rajagopalan, R., Cragoe, E. J., Erlanger, B. F., and Al-Awqati, Q.
- Abstract
A new amiloride analogue, "amiloride-caproic acid," was synthesized, coupled to albumin, and used as a hapten to raise anti-amiloride antibodies in rabbits. The antibodies were affinity purified with an amiloride affinity column and characterized. Binding studies using [3H]benzamil showed a dissociation constant of 0.8 nM. Amiloride and amiloride-caproate inhibited [3H]benzamil binding; epsilon-guanidinocaproic acid showed no inhibition. Anti-amiloride antibodies reversed the inhibition by amiloride of sodium transport across toad urinary bladder. Anti-amiloride antibodies and an amiloride affinity column should provide useful tools for the characterization of the epithelial sodium channel.
- Published
- 1986
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40. Fura-2 fluorescence is localized to mitochondria in endothelial cells
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Steinberg, S. F., Bilezikian, J. P., and Al-Awqati, Q.
- Abstract
The new, highly fluorescent, calcium-sensitive dye, fura-2, can be loaded nondisruptively into intact cells by means of its permeant ester and used to measure the free calcium ion concentration in individual cells. For fura-2 to signal cytosolic calcium, it must be distributed homogeneously and exclusively throughout the cytoplasmic space. However, microscopic examination of bovine aortic endothelial cells loaded with fura-2 by exposure to its permeant ester reveals fluorescence associated with discrete intracellular structures rather than the homogeneous distribution expected for a cytosolic stain. Simultaneous labeling of bovine aortic endothelial cells with fura-2 and rhodamine 123 (a mitochondrial fluorescent vital stain) identifies these structures as mitochondria. Subcellular dye localizations are not observed when the cells are loaded with other putative cytosolic stains that gain access to the cytosol by means of a membrane permeant ester. Both carboxyfluorescein and indo-1 (another member of the family of second generation calcium indicators) stain the cytoplasm diffusely. It is suggested that fura-2 fluorescence accumulates in certain cells in association with mitochondria. It is important to assess the intracellular distribution of fura-2 when this indicator is used to measure the free cytosolic calcium ion concentration.
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- 1987
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41. Urinary acidification in turtle bladder is due to a reversible proton-translocating ATPase.
- Author
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Dixon, T E and Al-Awqati, Q
- Abstract
Adverse proton electrochemical gradients (delta muH) applied across the turtle urinary bladder decrease active H+ transport in this epithelium. A delta muH of 180 mV abolishes both transport and its tightly coupled metabolic reaction. Larger gradients should, in theory, reverse the direction of H+ transport and the metabolic reaction leading to synthesis of ATP if the pump is an ATPase, or cause an increase in the oxidized state of a redox pair if it is a redox pump. To distinguish between these two possibilities, we measured ATP levels in epithelial cells that were poisoned to inhibit cellular mechanisms of ATP synthesis. At delta muH of 120 mV or less no ATP synthesis was found. At delta muH of greater than 120 mV there was a linear increase in ATP synthesis. Dinitrophenol, a H+ carrier, prevented synthesis at delta muH of 310 mV. Dicyclohexylcarbodiimide, an inhibitor of H+ transport that works at the cell surface, prevented ATP synthesis at delta muH of 310 mV. These results demonstrate that a reversible proton-translocating ATPase in the mucosal border of the bladder is the H+ pump responsible for urinary acidification.
- Published
- 1979
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42. Kanadaptin is a protein that interacts with the kidney but not the erythroid form of band 3.
- Author
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Chen, J, Vijayakumar, S, Li, X, and Al-Awqati, Q
- Abstract
Although epithelial membrane proteins are separately targeted to apical or basolateral domains, some are apically located in one cell type but are basolateral in others. More dramatically, the anion exchanger of a clonal cell line of intercalated cells derived from the kidney can be retargeted from the apical to basolateral domain. This Cl:HCO3 exchanger, kAE1, is an alternately spliced form of the erythroid anion exchanger (AE1, band 3), but unlike band 3 it does not bind ankyrin. Here we identify a new protein (kanadaptin) that binds to the cytoplasmic domain of kAE1 in vitro and in vivo but not to the erythroid AE1 or to ankyrin. No significant homologous proteins have been reported so far. Kanadaptin is widely expressed in epithelial (kidney, lung, and liver) and non-epithelial cells (brain and skeletal and cardiac muscle). In kidney, we found by immunocytochemistry that kanadaptin was only expressed in the collecting tubule. In the intercalated cells of this segment, it colocalized with kAE1 in cytoplasmic vesicles but not when the exchanger was in the basolateral membrane. These results raised the possibility that this protein is involved in the targeting of kAE1 vesicles to their final destination.
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- 1998
43. The proton translocating ATPase responsible for urinary acidification.
- Author
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Gluck, S, Kelly, S, and Al-Awqati, Q
- Abstract
H+ secretion by the turtle urinary bladder is produced by a proton pump located in the luminal membrane. We show that a microsomal fraction of these cells contains an electrogenic proton translocating ATPase that is inhibited by dicyclohexylcarbodiimide but not oligomycin or vanadate. On a sucrose density gradient, this ATPase co-migrated with luminal membranes labeled with concanavalin A, but was separate from a lysosomal marker. This enzyme is therefore the H+ ATPase that causes urinary acidification.
- Published
- 1982
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44. Regulation of the sodium permeability of the luminal border of toad bladder by intracellular sodium and calcium: role of sodium-calcium exchange in the basolateral membrane.
- Author
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Chase, H S and Al-Awqati, Q
- Abstract
Sodium movement across the luminal membrane of the toad bladder is the rate-limiting step for active transepithelial transport. Recent studies suggest that changes in intracellular sodium regulate the Na permeability of the luminal border, either directly or indirectly via increases in cell calcium induced by the high intracellular sodium. To test these proposals, we measured Na movement across the luminal membrane (th Na influx) and found that it is reduced when intracellular Na is increased by ouabain or by removal of external potassium. Removal of serosal sodium also reduced the influx, suggesting that the Na gradient across the serosal border rather than the cell Na concentration is the critical factor. Because in tissues such as muscle and nerve a steep transmembrane sodium gradient is necessary to maintain low cytosolic calcium, it is possible that a reduction in the sodium gradient in the toad bladder reduces luminal permeability by increasing the cell calcium activity. We found that the inhibition of the influx by ouabain or low serosal Na was prevented, in part, by removal of serosal calcium. To test for the existence of a sodium-calcium exchanger, we studied calcium transport in isolated basolateral membrane vesicles and found that calcium uptake was proportional to the outward directed sodium gradient. Uptake was not the result of a sodium diffusion potential. Calcium efflux from preloaded vesicles was accelerated by an inward directed sodium gradient. Preliminary kinetic analysis showed that the sodium gradient changes the Vmax but not the Km of calcium transport. These results suggest that the effect of intracellular sodium on the luminal sodium permeability is due to changes in intracellular calcium.
- Published
- 1981
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45. Calcium reduces the sodium permeability of luminal membrane vesicles from toad bladder. Studies using a fast-reaction apparatus.
- Author
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Chase, H S and Al-Awqati, Q
- Abstract
Regulation of the sodium permeability of the luminal membrane is the major mechanism by which the net rate of sodium transport across tight epithelia is varied. Previous evidence has suggested that the permeability of the luminal membrane might be regulated by changes in intracellular sodium or calcium activities. To test this directly, we isolated a fraction of the plasma membrane from the toad urinary bladder, which contains a fast, amiloride-sensitive sodium flux with characteristics similar to those of the native luminal membrane. Using a flow-quench apparatus to measure the initial rate of sodium efflux from these vesicles in the millisecond time range, we have demonstrated that the isotope exchange permeability of these vesicles is very sensitive to calcium. Calcium reduces the sodium permeability, and the half-maximal inhibitory concentration is 0.5 microM, well within the range of calcium activity found in cells. Also, the permeability of the luminal membrane vesicles is little affected by the ambient sodium concentration. These results, when taken together with studies on whole tissue, suggest that cell calcium may be an important regulator of transepithelial sodium transport by its effect on luminal sodium permeability. The effect of cell sodium on permeability may be mediated by calcium rather than by sodium itself.
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- 1983
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46. Golgi membranes contain an electrogenic H+ pump in parallel to a chloride conductance.
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Glickman, J, Croen, K, Kelly, S, and Al-Awqati, Q
- Abstract
Rat liver Golgi vesicles were isolated by differential and density gradient centrifugation. A fraction enriched in galactosyl transferase and depleted in plasma membrane, mitochondrial, endoplasmic reticulum, and lysosomal markers was found to contain an ATP-dependent H+ pump. This proton pump was not inhibited by oligomycin but was sensitive to N-ethyl maleimide, which distinguishes it from the F0-F1 ATPase of mitochondria. GTP did not induce transport, unlike the lysosomal H+ pump. The pump was not dependent on the presence of potassium nor was it inhibited by vanadate, two of the characteristics of the gastric H+ ATPase. Addition of ATP generated a membrane potential that drove chloride uptake into the vesicles, suggesting that Golgi membranes contain a chloride conductance in parallel to an electrogenic proton pump. These results demonstrate that Golgi vesicles can form a pH difference and a membrane potential through the action of an electrogenic proton translocating ATPase.
- Published
- 1983
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47. Regulation of cell pH by Ca+2-mediated exocytotic insertion of H+-ATPases.
- Author
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van Adelsberg, J and Al-Awqati, Q
- Abstract
Exposure to CO2 acidifies the cytosol of mitochondria-rich cells in turtle bladder epithelium. The result of the decrease in pH in these, the acid-secreting cells of the epithelium, is a transient increase in cell calcium, which causes exocytosis of vesicles containing proton-translocating ATPase. Because mitochondria-rich cells have rapid luminal membrane turnover, we were able to identify single mitochondria-rich cells by their endocytosis of rhodamine-tagged albumin. Using fluorescence emission of 5,6-carboxyfluorescein at two excitation wavelengths, we measured cell pH in these identified mitochondria-rich cells and found that although the cell pH fell, it recovered within 5 min despite continuous exposure to CO2. This pH recovery also occurred at the same rate in Na+-free media. However, pH recovery did not occur when luminal pH was 5.5, a condition under which the H+-pump does not function, suggesting that recovery of cell pH is due to the luminally located H+ ATPase. Chelation of extracellular calcium by EGTA prevented the CO2-induced rise in cell calcium measured with the intracellular fluorescent dyes Quin 2 or Fura 2 and also prevented recovery of cell pH. When the change in cell calcium was buffered by loading the cells with high concentrations of Quin 2, the CO2-induced decrease in pH did not return back to basal levels. We had found previously that buffering intracellular calcium transients prevented CO2-stimulated exocytosis. Further, we show here that the increased H+ current in voltage-clamped turtle bladders, which is directly proportional to the number of H+-pump-containing vesicles that fuse with the luminal membrane, was significantly reduced in calcium-depleted bladders. These results suggest that pH regulation in these acid-secreting cells occurs by calcium-dependent exocytosis of vesicles containing proton pumps, whose subsequent turnover restores the cell pH to its initial levels.
- Published
- 1986
- Full Text
- View/download PDF
48. Photoaffinity labeling of the epithelial sodium channel.
- Author
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Kleyman, T R, Yulo, T, Ashbaugh, C, Landry, D, Cragoe, E, Karlin, A, and Al-Awqati, Q
- Abstract
Sodium enters tight epithelia across the apical plasma membrane through a sodium channel, a process inhibited by submicromolar concentrations of amiloride and benzamil. Using membrane vesicles from bovine kidney cortex, we found that sodium transport through the sodium channel was inhibited by benzamil with an IC50 of 4 nM. Amiloride (IC50 = 400 nM) was a weaker inhibitor of sodium transport. [3H]Benzamil bound to the vesicles at a single class of high affinity binding sites with a Kd of 5 nM, the similarity of which to the IC50 suggests that these binding sites are associated with the sodium channel. Amiloride displaced bound [3H]benzamil with a Ki of 2,500 nM. Bromobenzamil is a photoactive amiloride analog with potency similar to benzamil in inhibiting sodium transport (IC50 = 5 nM) and binding to the sodium channel (Kd = 6 nM). [3H]Bromobenzamil was specifically photoincorporated into three molecular weight classes of polypeptides with apparent Mr values of 176,000, 77,000, and 47,000. The photoincorporation of [3H]bromobenzamil into these three classes of polypeptides was blocked by addition of excess benzamil and by amiloride in a dose-dependent manner. These data suggest that these polypeptides are components of the epithelial sodium channel.
- Published
- 1986
- Full Text
- View/download PDF
49. Epithelial chloride channel. Development of inhibitory ligands.
- Author
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Landry, D W, Reitman, M, Cragoe, E J, and Al-Awqati, Q
- Abstract
Chloride channels are present in the majority of epithelial cells, where they mediate absorption or secretion of NaCl. Although the absorptive and secretory channels are well characterized in terms of their electrophysiological behavior, there is a lack of pharmacological ligands that can aid us in further functional and eventually molecular characterization. To obtain such ligands, we prepared membrane vesicles from bovine kidney cortex and apical membrane vesicles from trachea and found that they contain a chloride transport process that is electrically conductive. This conductance was reduced by preincubating the vesicles in media containing ATP or ATP-gamma-S, but not beta-methylene ATP, which suggests that the membranes contain a kinase that can close the channels. We then screened compounds derived from three classes: indanyloxyacetic acid (IAA), anthranilic acid (AA), and ethacrynic acid. We identified potent inhibitors from the IAA and the AA series. We tritiated IAA-94 and measured binding of this ligand to the kidney cortex membrane vesicles and found a high-affinity binding site whose dissociation constant (0.6 microM) was similar to the inhibition constant (1 microM). There was a good correlation between the inhibitory potency of several IAA derivatives and their efficacy in displacing [3H]IAA-94 from its binding site. Further, other chloride channel inhibitors, including AA derivatives, ethacrynic acid, bumetanide, and DIDS, also displaced the ligand from its binding site. A similar conductance was found in apical membrane vesicles from bovine trachea that was also inhibited by IAA-94 and AA-130B, but the inhibitory effects of these compounds were weaker than their effects on the renal cortex channel. The two drugs were also less potent in displacing [3H]IAA-94 from the tracheal binding site.
- Published
- 1987
- Full Text
- View/download PDF
50. Active H+ transport in the turtle urinary bladder. Coupling of transport to glucose oxidation.
- Author
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Beauwens, R and Al-Awqati, Q
- Abstract
The turtle urinary bladder acidifies the contents of its lumen by actively transporting protons. H+ secretion by the isolated bladder was measured simultaneously with the rate of 14CO2 evolution from [14C]glucose. The application of an adverse pH gradient resulted in a decline in the rate of H+ secretion (JH) and in the rate of glucose oxidation (JCO2). The changes in JH and JCO2 were linear functions of the pH difference across the membrane. Hence, JH and JCO2 were linearly related to each other. The slope, deltaJH/deltaJCO2 was found to be similar in half-bladders from the same animal but was seen to vary widely in a population of turtles. To investigate the effect of pH gradients on deltaJH/deltaJCO2, two experiments were performed in each of 14 hemibladders. In one, JH and JCO2 were altered by changing the luminal pH. In the other, they were altered by changing the ambient pCO2 while the luminal pH was kept constant. The average slope, deltaJH/deltaJCO2, in the presence of pH gradients was 14.45 eq-mol-1. In the absence of gradients in the same hemibladders it was 14.72, delta = 0.27 +/- 1.46. The results show that H+ transport is organized in such a way that leaks to protons in parallel to the pump are negligible. Analysis of the transport system by use of the Essig-Caplan linear irreversible thermodynamic formalism shows that the system is tightly coupled. The degree of coupling, q, given by that analysis was measured and found to be at or very near the maximum theoretical value.
- Published
- 1976
- Full Text
- View/download PDF
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