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1. Selective lentiviral gene delivery to CD133-expressing human glioblastoma stem cells.

Author

N Sumru Bayin, Aram S Modrek, August Dietrich, Jonathan Lebowitz, Tobias Abel, Hae-Ri Song, Markus Schober, David Zagzag, Christian J Buchholz, Moses V Chao, and Dimitris G Placantonakis

Subjects
Medicine, Science
Abstract

Glioblastoma multiforme (GBM) is a deadly primary brain malignancy. Glioblastoma stem cells (GSC), which have the ability to self-renew and differentiate into tumor lineages, are believed to cause tumor recurrence due to their resistance to current therapies. A subset of GSCs is marked by cell surface expression of CD133, a glycosylated pentaspan transmembrane protein. The study of CD133-expressing GSCs has been limited by the relative paucity of genetic tools that specifically target them. Here, we present CD133-LV, a lentiviral vector presenting a single chain antibody against CD133 on its envelope, as a vehicle for the selective transduction of CD133-expressing GSCs. We show that CD133-LV selectively transduces CD133+ human GSCs in dose-dependent manner and that transduced cells maintain their stem-like properties. The transduction efficiency of CD133-LV is reduced by an antibody that recognizes the same epitope on CD133 as the viral envelope and by shRNA-mediated knockdown of CD133. Conversely, the rate of transduction by CD133-LV is augmented by overexpression of CD133 in primary human GBM cultures. CD133-LV selectively transduces CD133-expressing cells in intracranial human GBM xenografts in NOD.SCID mice, but spares normal mouse brain tissue, neurons derived from human embryonic stem cells and primary human astrocytes. Our findings indicate that CD133-LV represents a novel tool for the selective genetic manipulation of CD133-expressing GSCs, and can be used to answer important questions about how these cells contribute to tumor biology and therapy resistance.

Published
2014
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2. Zoom Objective Structured Clinical Exams: Virtually the Same as the Real Thing?

Author

Purnahamsi V. Desai, Heather B. Howell, Meaghan McGrath, Rachel Ramsey, Jonathan Lebowitz, Brit Trogen, Christine Cha, Kristyn A. Pierce, and Sondra Zabar

Subjects
Pediatrics, Perinatology and Child Health
Abstract

Objective structured clinical exams (OSCE) are used to train and assess resident foundational family-centered communication skills incorporating key stakeholders. In 2020 encounters were conducted virtually. We sought to compare standardized patient (SP) and family faculty (FF) assessment across OSCE and virtual OSCE (VOSCE) formats.The intern classes of 2019 and 2020 completed a live OSCE and VOSCE respectively where they disclosed an error to an SP. The 10 minute encounter was observed by an FF and facilitator followed by a 20 minute debrief. The SP and FF completed a behavioral checklist to evaluate skill mastery.Eighteen (90%) of the 20 interns completed the encounter each year. Total mastery scores were significantly higher for SP assessment than for FF assessment in both OSCE [68% vs 46% (z = -3.005, P.05)] and VOSCE formats [68% vs 53% (z = -2.105, P.05)]. Total mastery scores of SPs across OSCE and VOSCE formats did not significantly differ, nor did FF scores based on evaluation format.Our current experience suggests VOSCEs are a viable alternative to in person sessions given the comparable assessment across the two modalities. The ease of participating in virtual sessions may provide a way to more easily partner with key stakeholders.

Published
2022

3. Health status after invasive or conservative care in coronary and advanced kidney disease

Author

Spertus J. A., Jones P. G., Maron D. J., Mark D. B., O'Brien S. M., Fleg J. L., Reynolds H. R., Stone G. W., Sidhu M. S., Chaitman B. R., Chertow G. M., Hochman J. S., Bangalore S, ISCHEMIA-CKD Research Group: Abdallah M Abdallah, Abel E Moreyra, Abhay A Laddu, Abhishek Dubey, Abhishek Goyal, Abigail Knighton, Adedayo Adeboye, Agne Juceviciene, Agne Urboniene, Agnieszka Szramowska, Ahmed Abdel-Latif, Ahmed Ayoub, Ahmed Elghamaz, Ahmed Kamal, Ahmed Talaat, Ajay Sharma, Ajit Singh Narula, Akshay Bagai, Akvile Smigelskaite, Alain Raymond, Alain Rheault, Alaine Melanie Loehr, Albert Varga, Aldo P Maggioni, Alec Moorman, Alejandro Chevaile Ramos, Alejandro Gisbert, Aleksandra Fratczak, Aleksandras Laucevicius, Alexander M Chernyavskiy, Alexander Sergeevich Borisov, Alexandra Craft, Alexandra Hunter, Alexandre Ciappina Hueb, Alexandre Schaan de Quadros, Alice Manica Muller, Aline Peixoto Deiro, Allegra Stone, Almudena Castro, Amar Uxa, Amaryllis Van Craenenbroeck, Ambuj Roy, Amit Kakkar, Amy Flowers, Amy Iskandrian, Ana D Djordjevic-Dikic, Ana Gomes Almeida, Ana Rita Francisco, Ana S Mladenovic, Ana Santana, Anandaroop Lahiri, Anastasia M Kuzmina-Krutetskaya, Anastasia Vamvakidou, Andras Vertes, Andre Gabriel, Andrea Bartykowszki, Andrea Lorimer, Andrea Pascual, Andreia Coelho, Andreia Rocha, Andrés García-Rincón, Andrew Starovoytov, Andrzej Łabyk, Anelise Kawakami, Angela Hoye, Angelo Nobre, Anjali Acharya, Anjali Anand, Anjana Rishmawi, Ann Banfield, Ann Luyten, Anna Cichocka-Radwan, Anna Fojt, Anna Plachcinska, Anna Teresinska, Anne Marie Webb, Anne Heath, Anoop Mathew, Antonia Vega, Antonio Carvalho, Antonio Colombo, Antonio Fiarresga, Anu Tharini, Anupama Rao, Aquiles Valdespino-Estrada, Ariel Diaz, Arif Asif, Arnold H Seto, Arturo S Campos-Santaolalla, Asim N Cheema, Asker Ahmed, Atul Mathur, Audrey W Leong, Axel Åkerblom, Axelle Fuentes, Aynun Naher, Badhma Valaiyapathi, Balaji Srinivasan, Baljeet Kaur, Balram Bhargava, Bandula Guruge, Barbara Wicklund, Bartosz Czarniak, Bebek Singh, Begoña Igual, Bela Merkely, Benoy N Shah, Bernard de Bruyne, Beth Abramson, Beth Stefanchik, Bethany Harvey, Bharati Shivalkar, Bilal Malik, Binoy Mannekkattukudy Kurian, Bougrida Hammouche, Branko D Beleslin, Bruce Ferguson, Bruce McManus, Bruna Maria Ascoli, Bryn Smith, Byron J Allen, C Michael Gibson, C Noel Bairey Merz, Calin Pop, Carl-Éric Gagné, Carly Ohmart, Carol M Kartje, Caroline Alsweiler, Caroline Rodgers, Caroline Spindler, Carolyn J Gruber, Catherine Albert, Catherine Bone, Catherine Lemay, Cezary Kepka, Chandini Suvarna, Chantale Mercure, Charlene Wiyarand, Chetan Patel, Chiara Attanasio, Chi-Ming Chow, Ching Min Er, Ching-Ching Ong, Cholenahally Nanjappa Manjunath, Chris Buller, Christel Vassaliere, Christiaan Vrints, Christian Witzke, Christie Ballantyne, Christina Björklund, Christine Roraff, Christophe Laure, Christophe Thuaire, Christopher Chan, Christopher Fordyce, Christopher Kinsey, Chunli Xia, Cidney Schultz, Claes Held, Claudia Cortés, Claudia Escobar, Cláudia Freixo, Clemens T Kadalie, Corine Thobois, Courtney Page, Cristina Bare, Dalisa Espinosa, Dan Gao, Dana Rizk, Daniela Puzhevsky, Data Analyst, David M Charytan, David O Williams, David Booth, David Charytan, David Cohen, David DeMets, David Foo, David Goldfarb, David Schlichting, David Sisson, David Taggart, David Waters, David Wheeler, David Williams, Davis Vo, Dawid Teodorczyk, Dawn D Shelstad, Dean Kereiakes, Deborah Yip, Deepa Ramaswamy, Deirdre Mattina, Deirdre Murphy, Dengke Jiang, Derek Cyr, Diana Cukali, Diane Camara, Dimitrios Stournaras, Dipti Patel, Dongze Li, Donna Exley, Doreen Reimann, Doron Schwartz, Duarte Cacela, Dwayne S G Conway, Eapen Punnoose, Edgar L Tay, Edgar Karanjah, Eduardo Gomes Lima, Eduardo Hernandez-Rangel, Edward D Nicol, Edyta Kaczmarska, Elena Refoyo Salicio, Eli Feen, Elihú Durán-Cortés, Elisabeth M Janzen, Elise van Dongen, Elissa Restelli Piloto, Elizabeta Srbinovska Kostovska, Elizabeth Capasso-Gulve, Elizaveta V Zbyshevskaya, Ellie Fridell, Ellis W Lader, Elvira Gosmanova, Emilie Tachot, Emma Howard, Emmanuel Sorbets, Encarnación Alonso-Álvarez, Eric Daugas, Erick Alexánderson Rosas, Estelle Montpetit, Eugene Passamani, Evgeny Shutov, Ewa Szczerba, Ewelina Wojtala, Expedito Eustáquio Ribeiro Silva, Fabio Fimiani, Fadi Hage, Fahim Haider Jafary, Fang Feng, Fatima Ranjbaran, Fausto J Pinto, Fernando Caeiro, Fernando Nolasco, Filipa Silva, Filippo Ottani, Firas Al Solaiman, Flávia Egydio, Florina Chereches, Francesca De Micco, Francesca Bianchini, Francesca Pietrucci, Francesco Orso, Francesco Pisano, Francisca Patuleia Figueiras, François Madore, Frank Harrell, Frank Rockhold, Frans Van de Werf, Franziska Guenther, Fred Mohr, G Karthikeyan, Gabriel Galeote, Gabriel Grossmann, Gabriel Steg, Gabriela Guzman, Gabriele Gabrielli, Gang Chen, Gautam Sharma, Gaylin Petty, Gelmina Mikolaitiene, Gennie Yee, Gerard Patrick Devlin, Gerard Esposito, Gergely Ágoston, Gervasio Lamas, Gia Cobb, Gian Piero Perna, Gianpiero Leone, Girish Mishra, Gonzalo Barge-Caballero, Grace M Young, Graciela Scaro, Graham Wong, Gregg Pressman, Gregor Simonis, Gudrun Steinmaurer, Guilherme Portugal, Guilhermina Cantinho Lopes, Guillermo Garcia-Garcia, Guoqin Wang, Gurpreet S Wander, Gurpreet Gulati, Haibo Zhang, Halina Marciniak, Hao Dai, Haojian Dong, Harold Franch, Harvey White, Hatem Elabd, Hayley Pomeroy, Heather Golden, Heidi Wilson, Helene Abergel, Hemalata Siddaram, Hemant Shakhar Mahapatra, Henry C Stokes, Hermine Osseni, Herwig Schuchlenz, Hicham Skali, Holly Mattix-Kramer, Hong Cheng, Hossam Mahrous, Hristo Pejkov, Hugo Marques, Hui Zhong, Hussien El Fishawy, Ian Webb, Iftikhar Kullo, Igor O Grazhdankin, Ikraam Hassan, Ileana L Pina, Ilona Tamasauskiene, Inês Zimbarra Cabrita, Ines Rodrigues, Inga Soveri, Irena Peovska Mitevska, Irene Marthe Lang, Irina Subbotina, Irma Kalibataite-Rutkauskiene, Isabelle Roy, Ishita Tejani, Ivan A Naryshkin, Ivana Jankovic, Iwona Niedzwiecka, Jacek Kusmierek, Jackie Chow, Jaekyeong Heo, Jakub Maksym, James E Davies, James J Jang, James Hirsch, James Tatoulis, Jan Henzel, Janaina Oliveira, Janani Rangaswami, Jane Eckstein, Janitha Raj, Jaqueline Pozzibon, Jaroslaw Drozdz, Jason Loh Kwok Kong, Jason T Call, Jason Linefsky, Javier J Garcia, Jay Meisner, Jayne Scales, Jean Michel Juliard, Jean Diodati, Jean-Michel Juliard, Jeanne Russo, Jeannette J M Schoep, Jeff Leimberger, Jeffrey C Milliken, Jeffrey Anderson, Jeffrey Kanters, Jeffrey Lorin, Jeffrey Moses, Jelena J Stepanovic, Jelena Celutkiene, Jelena Stojkovic, Jenne M Jose, Jennifer L Stanford, Jennifer Hogan, Jennifer Horst, Jennifer Isaacs, Jennifer Thomson, Jennifer Tomfohr, Jennifer White, Jerry Yee, Jessica Berg, Jesus Peteiro, Jesús Peteiro, Jia Li, Jiamin Liu, Jianxin Zhang, Jill Marcus, Jim Blankenship, Jing Dong, Jiyan Chen, Jo Evans, Joaquín V Peñafiel, Joe Sabik, Johann Christopher, John B Kostis, John Joseph Graham, John Doan, John Jose, John Kotter, John Lehman, John Middleton, John Pownall, Jonathan M Gleadle, Jonathan S Chavez-Iñiguez, Jonathan Byrne, Jonathan Himmelfarb, Jonathan Lebowitz, Jonean Thorsen, Jorge Carrillo Calvillo, Jorge Escobedo, José A Ortega-Ramírez, José J Cuenca-Castillo, Jose L Diez, José Luis Narro Villanueva, José Luiz da Costa Vieira, José M Flores-Palacios, Jose Fragata, Jose Lopes, Jose Lopez-Sendon, José Lopez-Sendon, Jose Rueda, Joseph B Selvanayagam, Joseph Sacco, Joshua P Loh, Joy Burkhardt, Juan Manuel López Quijano, Juan Gaztanaga, Judit Sebo, Judith Wright, Juergen Stumpf, Julia de Aveiro Morata, Julio César Figal, Julio Hernandez Jaras, Junqing Yang, Jyotsna Garg, K Manjula Rani, K Preethi, Kaatje Goetschalckx, Karen Calfas, Karen Petrosyan, Karen Servilla, Karen Swan, Karin Ploetze, Karolina Kryczka, Karolina Wojtczak-Soska, Karolina Wojtera, Karthik Ramasamy, Katarzyna Łuczak, Katarzyna Malinowska, Katharina Knaut, Katherine Martin, Kathleen Claes, Kathryn Mason, Ken Mahaffey, Kenneth Gin, Kerry Lee, Kerstin Bonin, Kerstin Mikes, Kevin R Bainey, Kevin T Harley, Kevin Marzo, Kevin McMahon, Khaled Abdul-Nour, Khaled Alfakih, Khaled Dajani, Khrystyna Kushniriuk, Kian-Keong Poh, Kim Holland, Kimberly E Halverson, Kinnari Murphy, Kiran Reddy, Kirsten J Quiles, Kirsty Abercrombie, Klaus Matschke, Konrad Szymczyk, Koo Hui Chan, Kreton Mavromatis, Krishnakumar Hongalgi, Kristian Thygesen, Kristin M Salmi, Kristin Newby, Kristine Arges, Kristine Teoh, Krzysztof Drzymalski, Lalathaksha Kumbar, Laszlone Matics, LaTonya J Hickson, Laura Keinaite, Laura Sarti, Laura True, Lawrence M Phillips, Lawrence Friedman, Leandro C Maranan, Leda Lotaif, Lekshmi Dharmarajan, Leo A Bockeria, Leonardo Pizzol Caetano, Leonardo Bridi, Leonid L Bershtein, Li Hai Yan, Li Li, Lidia Sousa, Lihong Xu, Lihua Zhang, Lili Zhang, Lilian Mazza Barbosa, Liljana Tozija, Linda Arcand, Lino Patricio, Liping Zhang, Lisa Hatch, Lixin Jiang, Liz Low, Loay Salman, Lorena Lopez, Lori Pritchard, Luis Bernanrdes, Luis Guzman, Lynette L Teo, M Sowjanya Reddy, Maarten Simoons, Maayan Konigstein, Mafalda Selas, Magdalena Madero, Magdalena Miller, Magdalena Misztal-Teodorczyk, Magdy Abdelhamid, Magid Fahim, Mahevamma Mylarappa, Majo X Joseph, Malgorzata Frach, Manjula Rani, Marcello Galvani, Marcin Demkow, Marcin Szkopiak, Marco De Fabritis, Marco Magnoni, Marco Marini, Marco Sicuro, Marek Roik, Maria A Alfonso, Maria Antonieta Pereira de Moraes, María Dolores Martínez-Ruíz, Maria Eugenia Canziani, Maria Eugenia Martin, Maria Inês Caetano, Maria P Corral, Maria Pérez García, Maria Andreasson, Maria Posada, Marianna D A Dracoulakis, Mariano Rubio, Marija T Petrovic, Marina Vieira, Mario J Garcia, Mario D'arezzo, Maris Orgera, Marius Miglinas, Mark Garand, Mark Peterson, Mark Xavier, Marlowe Mosley, Marta Capinha, Marta Swiderek, Martha Meyer, Martina Ceseri, Martinia Tricoli, Mary Wiilliams, Mary Ann Champagne, Mary Streif, Massoud Leesar, Matei Claudia, Mateusz Solecki, Matías Nicolás Mungo, Matthew Shinseki, Matthew Weir, Maura Carina Nédio, Max-Paul Winter, Mayil S Krishnam, Meenakshi Mishra, Mei Hwang, Melemadathil Srilatha, Melissa LeFevre, Mengistu Simegn, Michael A Gibson, Michael B Rubens, Michael D Shapiro, Michael Chobanian, Michael Davidson, Michael Farkouh, Michael Mack, Michal Wlodarczyk, Michel G Khouri, Michelle Crowder, Michelle Ratliff, Miguel Borges Santos, Miguel Nobre Menezes, Miguel Perez Fontan, Miguel Barrero, Mihaly Tapolyai, Mikhail T Torosoff, Milan R Dobric, Milind Avdhoot Gadkari, Min Tun Kyaw, Miri Revivo, Mitchel B Lustre, Mohamed Adel, Mohamed Hassan, Mohammad El-Hajjar, Mohammed Hussain, Mohammed Saleem, Moisés Blanco-Calvo, Moisés Jiménez-Santos, Monika Laukyte, Muhamed Saric, Myrthes Emy Takiuti, Nadia Asif, Nagaraja Moorthy, Naima L Ogletree, Nana O Katamadze, Nandita Nataraj, Naomi Uchida, Nasrul Ismail, Natalia S Oliveira, Natalia de Carvalho Maffei, Nathalie Brosens, Naved Aslam, Naveed Akhtar, Neamat Mowafy, Neeraj Pandit, Neeraj Parakh, Neesh Pannu, Neill Duncan, Nevena Garcevic, Ngaire Meadows, Nicholas Danchin, Nicole Deming, Nikola N Boskovic, Nikolaos Karogiannis, Ning Zhang, Nirmal Kumar, Niruta Sharma, Nitika Chadha, Nitish Naik, Noelle M Durfee, Nora M Cosgrove, Norbert Urbanski, Norma Hogg, Olga Walesiak, Olga Zdończyk, Olga Zhdanova, Olivia Anaya, Olugbenga Bello, Omar Almousalli, Omar Thompson, Orit Kliuk, Oscar Méndiz, Óscar Prada-Delgado, Oz Shapira, Pablo Raffaele, Page Salanger, Pal Maurovich-Horvat, Pallav Garg, Paloma Moraga, Pam Singh, Pamela Ouyang, Pamela Woodard, Paola Emanuela Poggio Smanio, Paola Smanio, Paolo Calabro, Patricia K Nguyen, Patricia Alarie, Patricia Carrilho, Patricia Endsley, Patricia Pellikka, Patrycja Lebioda, Paul Der Mesropian, Paul Hauptman, Paula García-González, Paula Wilson, Paulo Cury Rezende, Paulo Novis Rocha, Pedro Canas Silva, Pedro Farto E Abreu, Pedro Píccaro de Oliveira, Pedro Carvalho, Pedro Modas, Pedro Rio, Peiyu He, Peter A McCullough, Peter H Stone, Peter Douglass, Peter Sizeland, Peter Voros, Philippe Gabriel Steg, Philippe Genereux, Philippe Généreux, Philippe Menasche, Philippe Rheault, Piero Tassinario, Pierre Gervais, Pilar Calvillo, Ping Chai, Piotr Jakubowski, Piotr Pruszczyk, Poay-Huan Loh, Pouneh Samadi, Prakash Deedwania, Pranav M Patel, Praneeth Polamuri, Pratiksha Sharma, Preeti Kamath, Prince Thomas, Priyadarshani Arambam, Puneet Sodhi, Pushpa Naik, Qi Zhong, Qian Zhao, Qianqian Yuan, Qiulan Xie, Rachel Murphy, Radmila Lyubarova, Radmilar Lyubarova, Raewyn Fisher, Rafael Diaz, Rafael Maldonado, Rafael Selgas, Raffaele Bugiardini, Rafia Chaudhry, Raisa Kavalakkat, Rajalekshmi Vs, Rajesh Gopalan Nair, Rajiv Narang, Rakesh Yadav, Ramiro Carvalho, Ramon de Jesús-Pérez, Ran Leng, Ranjan Kachru, Raquel Sanchez, Raven R Dwyer, Raven Lee, Ray Wyman, Raymond C Wong, Reinette Hampson, Renato Abdala Karam Kalil, Renato D Lopes, Renato George Eick, Renato Lopes, Reshma Ravindran, Reto Andreas Gamma, Ricardo Costa, Richa Bhatt, Richard H J Trimlett, Risha Patel, Rita Coram, Robert K Riezebos, Robert M Donnino, Robert Guyton, Robert Harrington, Robert Malecki, Roberto René Favaloro, Robyn Elliott, Rodolfo G S D Lima, Rohit Tandon, Rolf Doerr, Roma Tewari, Ron Wald, Rongrong Hu, Rory Collins, Roxana Mehran, Roxy Senior, Rubén Baleón-Espinosa, Ruben Ramos, Rui Ferreira, Ruth Kirby, Ruth Pérez-Fernández, S Ramakrishnan, S K Dwivedi, Sadath Lubna, Sadiq Ahmed, Sajeev Chakanalil Govindan, Salamah Alfalahi, Salvador Cruz-Flores, Salvatore P Costa, Sampoornima Setty, Samuel Nwosu, Sandeep Mahajan, Sandeep Seth, Sandeep Singh, Sander R Niehe, Sandy Carr, Sanja Simic Ogrizovic, Sanja Ogrizovic, Sanjeev Gulati, Sanjeev Sharma, Sara Fernandez, Sarah Williams, Sarju Ralhan, Sasko Kedev, Satinder Singh, Satish Sankaranarayanan, Satvic Cholenahally Manjunath, Sau Lee, Schawana Thaxton, Sean M O'Brien, Sebastian Sobczak, Seema Nour, Sergey A Sayganov, Sérgio Bravo Baptista, Sergio Draibe, Seth Sokol, Sharad Chandra, Shari Mackedanz, Shaun Goodman, Shayan Shirazian, Sheetal Rupesh Karwa, Sheri Ussery, Sheromani Bajaj, Shirin Heydari, Shiv Kumar Choudhary, Shivali Patel, Shruti Pandey, Shuyang Zhang, Siddharth Gadage, Sik-Yin V Tan, Sílvia Zottis Poletti, Silvia Valbuena, Simone Savaris, Solomon Yakubov, Songlin Zhu, Sonika Gupta, Sorin Brener, Sothinathan Gurunathan, Soundarya Nayak, Sowjanya Reddy, Stanley E Cobos, Stefan Weikl, Stephanie M Lane, Stephanie Ferket, Stephanie Mavromichalis, Stephen Fremes, Steven A Fein, Steven P Sedlis, Steven Giovannone, Steven Weitz, Subhash Banerjee, Sudhanva S Hegde, Suellen Hosino, Sulagna Mookherjee, Suman Singh, Sumith Abeygunasekara, Sundeep Mishra, Sunil Kumar Verma, Suresh Kumar, Suryaprakash Narayanappa, Susan K Milbrandt, Susana Silva, Susanna Stevens, Suvarna Kolhe, Suzana Tavares, Suzanne Welsh, T A Kishore, Tamara Colaiácovo Soares, Tapan Umesh Pillay, Tarek Rashid, Tarun K Mittal, Tauane Bello Duarte, Téodora Dutoiu, Teresa Delgadillo, Terrance Chua, Terrance Welch, Theodoros Kofidis, Thierry Lefevre, Tiago Silva, Timea Boros, Titus Lau, Tiziana Formisano, Tomasz Ciurus, Tomasz Tarchalski, Tracy Tan, Umesh Lingaraj, V K Bahl, V S Narain, Valentina Pellu, Valentine Lobo, Valerie Robesyn, Vandana Yadav, Veerabhadra Gupta, Verghese Mathew, Vicente Miro, Victoria Gumerova, Victoria Hernandez, Vijay Kher, Vijay Kumar, Vikas Makkar, Vikranth Reddy, Viktoria Bulkley, Vinoi George David, Virendra Misra, Virginia Fernández-Figares, Vladimir Ryasniansky, Vojislav L Giga, Wael A Almahmeed, Wan Xian Chan, Wanda C Marfori, Wanda Parker, Wayne Pennachi, Wei Ling Lau, Weibing Xing, Weijing Bian, Wendy L Stewart, Wendy Drewes, Whady Hueb, William Weintraub, Winnie C Sia, Xacobe Flores-Ríos, Xiang Ma, Xiangqiong Gu, Xiaomei Li, Xiaoyi Xu, Xin Fu, Xuemei Li, Xutong Wang, Yanek Pépin-Dubois, Yaron Arbel, Yechen Han, Yiming Lit, Ying Tung Sia, Ying Wang, Yining Yang, Yitong Ma, Yolayfi Peralta, Yves Smets, Yvonne Taul, Zalina Kudzoeva, Zeljko Z Markovic, Zhangsuo Liu, Zhenyu Liu, Zhiming Ye, Zixiang Yu, Zoltan Davidovits, Zvezdana Petronijevic, Spertus J.A., Jones P.G., Maron D.J., Mark D.B., O'Brien S.M., Fleg J.L., Reynolds H.R., Stone G.W., Sidhu M.S., Chaitman B.R., Chertow G.M., Hochman J.S., Bangalore S, and ISCHEMIA-CKD Research Group: Abdallah M Abdallah, Abel E Moreyra, Abhay A Laddu, Abhishek Dubey, Abhishek Goyal, Abigail Knighton, Adedayo Adeboye, Agne Juceviciene, Agne Urboniene, Agnieszka Szramowska, Ahmed Abdel-Latif, Ahmed Ayoub, Ahmed Elghamaz, Ahmed Kamal, Ahmed Talaat, Ajay Sharma, Ajit Singh Narula, Akshay Bagai, Akvile Smigelskaite, Alain Raymond, Alain Rheault, Alaine Melanie Loehr, Albert Varga, Aldo P Maggioni, Alec Moorman, Alejandro Chevaile Ramos, Alejandro Gisbert, Aleksandra Fratczak, Aleksandras Laucevicius, Alexander M Chernyavskiy, Alexander Sergeevich Borisov, Alexandra Craft, Alexandra Hunter, Alexandre Ciappina Hueb, Alexandre Schaan de Quadros, Alice Manica Muller, Aline Peixoto Deiro, Allegra Stone, Almudena Castro, Amar Uxa, Amaryllis Van Craenenbroeck, Ambuj Roy, Amit Kakkar, Amy Flowers, Amy Iskandrian, Ana D Djordjevic-Dikic, Ana Gomes Almeida, Ana Rita Francisco, Ana S Mladenovic, Ana Santana, Anandaroop Lahiri, Anastasia M Kuzmina-Krutetskaya, Anastasia Vamvakidou, Andras Vertes, Andre Gabriel, Andrea Bartykowszki, Andrea Lorimer, Andrea Pascual, Andreia Coelho, Andreia Rocha, Andrés García-Rincón, Andrew Starovoytov, Andrzej Łabyk, Anelise Kawakami, Angela Hoye, Angelo Nobre, Anjali Acharya, Anjali Anand, Anjana Rishmawi, Ann Banfield, Ann Luyten, Anna Cichocka-Radwan, Anna Fojt, Anna Plachcinska, Anna Teresinska, Anne Marie Webb, Anne Heath, Anoop Mathew, Antonia Vega, Antonio Carvalho, Antonio Colombo, Antonio Fiarresga, Anu Tharini, Anupama Rao, Aquiles Valdespino-Estrada, Ariel Diaz, Arif Asif, Arnold H Seto, Arturo S Campos-Santaolalla, Asim N Cheema, Asker Ahmed, Atul Mathur, Audrey W Leong, Axel Åkerblom, Axelle Fuentes, Aynun Naher, Badhma Valaiyapathi, Balaji Srinivasan, Baljeet Kaur, Balram Bhargava, Bandula Guruge, Barbara Wicklund, Bartosz Czarniak, Bebek Singh, Begoña Igual, Bela Merkely, Benoy N Shah, Bernard de Bruyne, Beth Abramson, Beth Stefanchik, Bethany Harvey, Bharati Shivalkar, Bilal Malik, Binoy Mannekkattukudy Kurian, Bougrida Hammouche, Branko D Beleslin, Bruce Ferguson, Bruce McManus, Bruna Maria Ascoli, Bryn Smith, Byron J Allen, C Michael Gibson, C Noel Bairey Merz, Calin Pop, Carl-Éric Gagné, Carly Ohmart, Carol M Kartje, Caroline Alsweiler, Caroline Rodgers, Caroline Spindler, Carolyn J Gruber, Catherine Albert, Catherine Bone, Catherine Lemay, Cezary Kepka, Chandini Suvarna, Chantale Mercure, Charlene Wiyarand, Chetan Patel, Chiara Attanasio, Chi-Ming Chow, Ching Min Er, Ching-Ching Ong, Cholenahally Nanjappa Manjunath, Chris Buller, Christel Vassaliere, Christiaan Vrints, Christian Witzke, Christie Ballantyne, Christina Björklund, Christine Roraff, Christophe Laure, Christophe Thuaire, Christopher Chan, Christopher Fordyce, Christopher Kinsey, Chunli Xia, Cidney Schultz, Claes Held, Claudia Cortés, Claudia Escobar, Cláudia Freixo, Clemens T Kadalie, Corine Thobois, Courtney Page, Cristina Bare, Dalisa Espinosa, Dan Gao, Dana Rizk, Daniela Puzhevsky, Data Analyst, David M Charytan, David O Williams, David Booth, David Charytan, David Cohen, David DeMets, David Foo, David Goldfarb, David Schlichting, David Sisson, David Taggart, David Waters, David Wheeler, David Williams, Davis Vo, Dawid Teodorczyk, Dawn D Shelstad, Dean Kereiakes, Deborah Yip, Deepa Ramaswamy, Deirdre Mattina, Deirdre Murphy, Dengke Jiang, Derek Cyr, Diana Cukali, Diane Camara, Dimitrios Stournaras, Dipti Patel, Dongze Li, Donna Exley, Doreen Reimann, Doron Schwartz, Duarte Cacela, Dwayne S G Conway, Eapen Punnoose, Edgar L Tay, Edgar Karanjah, Eduardo Gomes Lima, Eduardo Hernandez-Rangel, Edward D Nicol, Edyta Kaczmarska, Elena Refoyo Salicio, Eli Feen, Elihú Durán-Cortés, Elisabeth M Janzen, Elise van Dongen, Elissa Restelli Piloto, Elizabeta Srbinovska Kostovska, Elizabeth Capasso-Gulve, Elizaveta V Zbyshevskaya, Ellie Fridell, Ellis W Lader, Elvira Gosmanova, Emilie Tachot, Emma Howard, Emmanuel Sorbets, Encarnación Alonso-Álvarez, Eric Daugas, Erick Alexánderson Rosas, Estelle Montpetit, Eugene Passamani, Evgeny Shutov, Ewa Szczerba, Ewelina Wojtala, Expedito Eustáquio Ribeiro Silva, Fabio Fimiani, Fadi Hage, Fahim Haider Jafary, Fang Feng, Fatima Ranjbaran, Fausto J Pinto, Fernando Caeiro, Fernando Nolasco, Filipa Silva, Filippo Ottani, Firas Al Solaiman, Flávia Egydio, Florina Chereches, Francesca De Micco, Francesca Bianchini, Francesca Pietrucci, Francesco Orso, Francesco Pisano, Francisca Patuleia Figueiras, François Madore, Frank Harrell, Frank Rockhold, Frans Van de Werf, Franziska Guenther, Fred Mohr, G Karthikeyan, Gabriel Galeote, Gabriel Grossmann, Gabriel Steg, Gabriela Guzman, Gabriele Gabrielli, Gang Chen, Gautam Sharma, Gaylin Petty, Gelmina Mikolaitiene, Gennie Yee, Gerard Patrick Devlin, Gerard Esposito, Gergely Ágoston, Gervasio Lamas, Gia Cobb, Gian Piero Perna, Gianpiero Leone, Girish Mishra, Gonzalo Barge-Caballero, Grace M Young, Graciela Scaro, Graham Wong, Gregg Pressman, Gregor Simonis, Gudrun Steinmaurer, Guilherme Portugal, Guilhermina Cantinho Lopes, Guillermo Garcia-Garcia, Guoqin Wang, Gurpreet S Wander, Gurpreet Gulati, Haibo Zhang, Halina Marciniak, Hao Dai, Haojian Dong, Harold Franch, Harvey White, Hatem Elabd, Hayley Pomeroy, Heather Golden, Heidi Wilson, Helene Abergel, Hemalata Siddaram, Hemant Shakhar Mahapatra, Henry C Stokes, Hermine Osseni, Herwig Schuchlenz, Hicham Skali, Holly Mattix-Kramer, Hong Cheng, Hossam Mahrous, Hristo Pejkov, Hugo Marques, Hui Zhong, Hussien El Fishawy, Ian Webb, Iftikhar Kullo, Igor O Grazhdankin, Ikraam Hassan, Ileana L Pina, Ilona Tamasauskiene, Inês Zimbarra Cabrita, Ines Rodrigues, Inga Soveri, Irena Peovska Mitevska, Irene Marthe Lang, Irina Subbotina, Irma Kalibataite-Rutkauskiene, Isabelle Roy, Ishita Tejani, Ivan A Naryshkin, Ivana Jankovic, Iwona Niedzwiecka, Jacek Kusmierek, Jackie Chow, Jaekyeong Heo, Jakub Maksym, James E Davies, James J Jang, James Hirsch, James Tatoulis, Jan Henzel, Janaina Oliveira, Janani Rangaswami, Jane Eckstein, Janitha Raj, Jaqueline Pozzibon, Jaroslaw Drozdz, Jason Loh Kwok Kong, Jason T Call, Jason Linefsky, Javier J Garcia, Jay Meisner, Jayne Scales, Jean Michel Juliard, Jean Diodati, Jean-Michel Juliard, Jeanne Russo, Jeannette J M Schoep, Jeff Leimberger, Jeffrey C Milliken, Jeffrey Anderson, Jeffrey Kanters, Jeffrey Lorin, Jeffrey Moses, Jelena J Stepanovic, Jelena Celutkiene, Jelena Stojkovic, Jenne M Jose, Jennifer L Stanford, Jennifer Hogan, Jennifer Horst, Jennifer Isaacs, Jennifer Thomson, Jennifer Tomfohr, Jennifer White, Jerry Yee, Jessica Berg, Jesus Peteiro, Jesús Peteiro, Jia Li, Jiamin Liu, Jianxin Zhang, Jill Marcus, Jim Blankenship, Jing Dong, Jiyan Chen, Jo Evans, Joaquín V Peñafiel, Joe Sabik, Johann Christopher, John B Kostis, John Joseph Graham, John Doan, John Jose, John Kotter, John Lehman, John Middleton, John Pownall, Jonathan M Gleadle, Jonathan S Chavez-Iñiguez, Jonathan Byrne, Jonathan Himmelfarb, Jonathan Lebowitz, Jonean Thorsen, Jorge Carrillo Calvillo, Jorge Escobedo, José A Ortega-Ramírez, José J Cuenca-Castillo, Jose L Diez, José Luis Narro Villanueva, José Luiz da Costa Vieira, José M Flores-Palacios, Jose Fragata, Jose Lopes, Jose Lopez-Sendon, José Lopez-Sendon, Jose Rueda, Joseph B Selvanayagam, Joseph Sacco, Joshua P Loh, Joy Burkhardt, Juan Manuel López Quijano, Juan Gaztanaga, Judit Sebo, Judith Wright, Juergen Stumpf, Julia de Aveiro Morata, Julio César Figal, Julio Hernandez Jaras, Junqing Yang, Jyotsna Garg, K Manjula Rani, K Preethi, Kaatje Goetschalckx, Karen Calfas, Karen Petrosyan, Karen Servilla, Karen Swan, Karin Ploetze, Karolina Kryczka, Karolina Wojtczak-Soska, Karolina Wojtera, Karthik Ramasamy, Katarzyna Łuczak, Katarzyna Malinowska, Katharina Knaut, Katherine Martin, Kathleen Claes, Kathryn Mason, Ken Mahaffey, Kenneth Gin, Kerry Lee, Kerstin Bonin, Kerstin Mikes, Kevin R Bainey, Kevin T Harley, Kevin Marzo, Kevin McMahon, Khaled Abdul-Nour, Khaled Alfakih, Khaled Dajani, Khrystyna Kushniriuk, Kian-Keong Poh, Kim Holland, Kimberly E Halverson, Kinnari Murphy, Kiran Reddy, Kirsten J Quiles, Kirsty Abercrombie, Klaus Matschke, Konrad Szymczyk, Koo Hui Chan, Kreton Mavromatis, Krishnakumar Hongalgi, Kristian Thygesen, Kristin M Salmi, Kristin Newby, Kristine Arges, Kristine Teoh, Krzysztof Drzymalski, Lalathaksha Kumbar, Laszlone Matics, LaTonya J Hickson, Laura Keinaite, Laura Sarti, Laura True, Lawrence M Phillips, Lawrence Friedman, Leandro C Maranan, Leda Lotaif, Lekshmi Dharmarajan, Leo A Bockeria, Leonardo Pizzol Caetano, Leonardo Bridi, Leonid L Bershtein, Li Hai Yan, Li Li, Lidia Sousa, Lihong Xu, Lihua Zhang, Lili Zhang, Lilian Mazza Barbosa, Liljana Tozija, Linda Arcand, Lino Patricio, Liping Zhang, Lisa Hatch, Lixin Jiang, Liz Low, Loay Salman, Lorena Lopez, Lori Pritchard, Luis Bernanrdes, Luis Guzman, Lynette L Teo, M Sowjanya Reddy, Maarten Simoons, Maayan Konigstein, Mafalda Selas, Magdalena Madero, Magdalena Miller, Magdalena Misztal-Teodorczyk, Magdy Abdelhamid, Magid Fahim, Mahevamma Mylarappa, Majo X Joseph, Malgorzata Frach, Manjula Rani, Marcello Galvani, Marcin Demkow, Marcin Szkopiak, Marco De Fabritis, Marco Magnoni, Marco Marini, Marco Sicuro, Marek Roik, Maria A Alfonso, Maria Antonieta Pereira de Moraes, María Dolores Martínez-Ruíz, Maria Eugenia Canziani, Maria Eugenia Martin, Maria Inês Caetano, Maria P Corral, Maria Pérez García, Maria Andreasson, Maria Posada, Marianna D A Dracoulakis, Mariano Rubio, Marija T Petrovic, Marina Vieira, Mario J Garcia, Mario D'arezzo, Maris Orgera, Marius Miglinas, Mark Garand, Mark Peterson, Mark Xavier, Marlowe Mosley, Marta Capinha, Marta Swiderek, Martha Meyer, Martina Ceseri, Martinia Tricoli, Mary Wiilliams, Mary Ann Champagne, Mary Streif, Massoud Leesar, Matei Claudia, Mateusz Solecki, Matías Nicolás Mungo, Matthew Shinseki, Matthew Weir, Maura Carina Nédio, Max-Paul Winter, Mayil S Krishnam, Meenakshi Mishra, Mei Hwang, Melemadathil Srilatha, Melissa LeFevre, Mengistu Simegn, Michael A Gibson, Michael B Rubens, Michael D Shapiro, Michael Chobanian, Michael Davidson, Michael Farkouh, Michael Mack, Michal Wlodarczyk, Michel G Khouri, Michelle Crowder, Michelle Ratliff, Miguel Borges Santos, Miguel Nobre Menezes, Miguel Perez Fontan, Miguel Barrero, Mihaly Tapolyai, Mikhail T Torosoff, Milan R Dobric, Milind Avdhoot Gadkari, Min Tun Kyaw, Miri Revivo, Mitchel B Lustre, Mohamed Adel, Mohamed Hassan, Mohammad El-Hajjar, Mohammed Hussain, Mohammed Saleem, Moisés Blanco-Calvo, Moisés Jiménez-Santos, Monika Laukyte, Muhamed Saric, Myrthes Emy Takiuti, Nadia Asif, Nagaraja Moorthy, Naima L Ogletree, Nana O Katamadze, Nandita Nataraj, Naomi Uchida, Nasrul Ismail, Natalia S Oliveira, Natalia de Carvalho Maffei, Nathalie Brosens, Naved Aslam, Naveed Akhtar, Neamat Mowafy, Neeraj Pandit, Neeraj Parakh, Neesh Pannu, Neill Duncan, Nevena Garcevic, Ngaire Meadows, Nicholas Danchin, Nicole Deming, Nikola N Boskovic, Nikolaos Karogiannis, Ning Zhang, Nirmal Kumar, Niruta Sharma, Nitika Chadha, Nitish Naik, Noelle M Durfee, Nora M Cosgrove, Norbert Urbanski, Norma Hogg, Olga Walesiak, Olga Zdończyk, Olga Zhdanova, Olivia Anaya, Olugbenga Bello, Omar Almousalli, Omar Thompson, Orit Kliuk, Oscar Méndiz, Óscar Prada-Delgado, Oz Shapira, Pablo Raffaele, Page Salanger, Pal Maurovich-Horvat, Pallav Garg, Paloma Moraga, Pam Singh, Pamela Ouyang, Pamela Woodard, Paola Emanuela Poggio Smanio, Paola Smanio, Paolo Calabro, Patricia K Nguyen, Patricia Alarie, Patricia Carrilho, Patricia Endsley, Patricia Pellikka, Patrycja Lebioda, Paul Der Mesropian, Paul Hauptman, Paula García-González, Paula Wilson, Paulo Cury Rezende, Paulo Novis Rocha, Pedro Canas Silva, Pedro Farto E Abreu, Pedro Píccaro de Oliveira, Pedro Carvalho, Pedro Modas, Pedro Rio, Peiyu He, Peter A McCullough, Peter H Stone, Peter Douglass, Peter Sizeland, Peter Voros, Philippe Gabriel Steg, Philippe Genereux, Philippe Généreux, Philippe Menasche, Philippe Rheault, Piero Tassinario, Pierre Gervais, Pilar Calvillo, Ping Chai, Piotr Jakubowski, Piotr Pruszczyk, Poay-Huan Loh, Pouneh Samadi, Prakash Deedwania, Pranav M Patel, Praneeth Polamuri, Pratiksha Sharma, Preeti Kamath, Prince Thomas, Priyadarshani Arambam, Puneet Sodhi, Pushpa Naik, Qi Zhong, Qian Zhao, Qianqian Yuan, Qiulan Xie, Rachel Murphy, Radmila Lyubarova, Radmilar Lyubarova, Raewyn Fisher, Rafael Diaz, Rafael Maldonado, Rafael Selgas, Raffaele Bugiardini, Rafia Chaudhry, Raisa Kavalakkat, Rajalekshmi Vs, Rajesh Gopalan Nair, Rajiv Narang, Rakesh Yadav, Ramiro Carvalho, Ramon de Jesús-Pérez, Ran Leng, Ranjan Kachru, Raquel Sanchez, Raven R Dwyer, Raven Lee, Ray Wyman, Raymond C Wong, Reinette Hampson, Renato Abdala Karam Kalil, Renato D Lopes, Renato George Eick, Renato Lopes, Reshma Ravindran, Reto Andreas Gamma, Ricardo Costa, Richa Bhatt, Richard H J Trimlett, Risha Patel, Rita Coram, Robert K Riezebos, Robert M Donnino, Robert Guyton, Robert Harrington, Robert Malecki, Roberto René Favaloro, Robyn Elliott, Rodolfo G S D Lima, Rohit Tandon, Rolf Doerr, Roma Tewari, Ron Wald, Rongrong Hu, Rory Collins, Roxana Mehran, Roxy Senior, Rubén Baleón-Espinosa, Ruben Ramos, Rui Ferreira, Ruth Kirby, Ruth Pérez-Fernández, S Ramakrishnan, S K Dwivedi, Sadath Lubna, Sadiq Ahmed, Sajeev Chakanalil Govindan, Salamah Alfalahi, Salvador Cruz-Flores, Salvatore P Costa, Sampoornima Setty, Samuel Nwosu, Sandeep Mahajan, Sandeep Seth, Sandeep Singh, Sander R Niehe, Sandy Carr, Sanja Simic Ogrizovic, Sanja Ogrizovic, Sanjeev Gulati, Sanjeev Sharma, Sara Fernandez, Sarah Williams, Sarju Ralhan, Sasko Kedev, Satinder Singh, Satish Sankaranarayanan, Satvic Cholenahally Manjunath, Sau Lee, Schawana Thaxton, Sean M O'Brien, Sebastian Sobczak, Seema Nour, Sergey A Sayganov, Sérgio Bravo Baptista, Sergio Draibe, Seth Sokol, Sharad Chandra, Shari Mackedanz, Shaun Goodman, Shayan Shirazian, Sheetal Rupesh Karwa, Sheri Ussery, Sheromani Bajaj, Shirin Heydari, Shiv Kumar Choudhary, Shivali Patel, Shruti Pandey, Shuyang Zhang, Siddharth Gadage, Sik-Yin V Tan, Sílvia Zottis Poletti, Silvia Valbuena, Simone Savaris, Solomon Yakubov, Songlin Zhu, Sonika Gupta, Sorin Brener, Sothinathan Gurunathan, Soundarya Nayak, Sowjanya Reddy, Stanley E Cobos, Stefan Weikl, Stephanie M Lane, Stephanie Ferket, Stephanie Mavromichalis, Stephen Fremes, Steven A Fein, Steven P Sedlis, Steven Giovannone, Steven Weitz, Subhash Banerjee, Sudhanva S Hegde, Suellen Hosino, Sulagna Mookherjee, Suman Singh, Sumith Abeygunasekara, Sundeep Mishra, Sunil Kumar Verma, Suresh Kumar, Suryaprakash Narayanappa, Susan K Milbrandt, Susana Silva, Susanna Stevens, Suvarna Kolhe, Suzana Tavares, Suzanne Welsh, T A Kishore, Tamara Colaiácovo Soares, Tapan Umesh Pillay, Tarek Rashid, Tarun K Mittal, Tauane Bello Duarte, Téodora Dutoiu, Teresa Delgadillo, Terrance Chua, Terrance Welch, Theodoros Kofidis, Thierry Lefevre, Tiago Silva, Timea Boros, Titus Lau, Tiziana Formisano, Tomasz Ciurus, Tomasz Tarchalski, Tracy Tan, Umesh Lingaraj, V K Bahl, V S Narain, Valentina Pellu, Valentine Lobo, Valerie Robesyn, Vandana Yadav, Veerabhadra Gupta, Verghese Mathew, Vicente Miro, Victoria Gumerova, Victoria Hernandez, Vijay Kher, Vijay Kumar, Vikas Makkar, Vikranth Reddy, Viktoria Bulkley, Vinoi George David, Virendra Misra, Virginia Fernández-Figares, Vladimir Ryasniansky, Vojislav L Giga, Wael A Almahmeed, Wan Xian Chan, Wanda C Marfori, Wanda Parker, Wayne Pennachi, Wei Ling Lau, Weibing Xing, Weijing Bian, Wendy L Stewart, Wendy Drewes, Whady Hueb, William Weintraub, Winnie C Sia, Xacobe Flores-Ríos, Xiang Ma, Xiangqiong Gu, Xiaomei Li, Xiaoyi Xu, Xin Fu, Xuemei Li, Xutong Wang, Yanek Pépin-Dubois, Yaron Arbel, Yechen Han, Yiming Lit, Ying Tung Sia, Ying Wang, Yining Yang, Yitong Ma, Yolayfi Peralta, Yves Smets, Yvonne Taul, Zalina Kudzoeva, Zeljko Z Markovic, Zhangsuo Liu, Zhenyu Liu, Zhiming Ye, Zixiang Yu, Zoltan Davidovits, Zvezdana Petronijevic

Subjects
Male, Intention to Treat Analysi, medicine.medical_treatment, Health Status, Myocardial Ischemia, 030204 cardiovascular system & hematology, Coronary Angiography, law.invention, Health Statu, 0302 clinical medicine, Randomized controlled trial, law, Surveys and Questionnaires, Odds Ratio, Surveys and Questionnaire, 030212 general & internal medicine, Myocardial infarction, Coronary Artery Bypass, medicine.diagnostic_test, General Medicine, Middle Aged, Intention to Treat Analysis, Cardiology, Female, Human, medicine.medical_specialty, Revascularization, Follow-Up Studie, 03 medical and health sciences, Percutaneous Coronary Intervention, Internal medicine, medicine, Humans, cardiovascular diseases, Healthy Lifestyle, Renal Insufficiency, Chronic, Proportional Hazards Models, Aged, Intention-to-treat analysis, business.industry, Coronary Artery Bypa, Percutaneous coronary intervention, Odds ratio, medicine.disease, Angiography, Exercise Test, Proportional Hazards Model, business, Kidney disease, Follow-Up Studies
Abstract

BACKGROUND In the ISCHEMIA-CKD trial, the primary analysis showed no significant difference in the risk of death or myocardial infarction with initial angiography and revascularization plus guideline-based medical therapy (invasive strategy) as compared with guideline-based medical therapy alone (conservative strategy) in participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease (an estimated glomerular filtration rate of

Published
2020

4. Current State of the Workforce in Nephrology

Author

Eleanor Lederer and Jonathan Lebowitz

Subjects
Nephrology, medicine.medical_specialty, 030232 urology & nephrology, Ethnic group, Workload, 030204 cardiovascular system & hematology, Job Satisfaction, Nephrologists, 03 medical and health sciences, 0302 clinical medicine, Nursing, Internal medicine, Health care, Ethnicity, medicine, Humans, Health Workforce, Sex Distribution, Career Choice, business.industry, Scope of Practice, Work-Life Balance, Work–life balance, medicine.disease, United States, Workforce, Organizational structure, business, Kidney disease, Diversity (business)
Abstract

The number of individuals with CKD and end-stage kidney disease continues to rise as the interest in nephrology as a career choice is declining among internal medicine residents. Simultaneously, the emergence of integrated healthcare delivery models encompassing multiple levels of nonphysician healthcare workers plus advanced technological capabilities offer innovative mechanisms for the delivery of optimal care for patients at risk for and suffering from CKD. Critical to the success of these models is the identification of aspects of nephrology care specific to and appropriate for each type of kidney care professional and the development of organizational structures that both define and facilitate the flow of patient care. However, several factors in addition to the declining interest in nephrology pose significant obstacles to the development of the optimal nephrology work force including gender imbalance in leadership and nonleadership positions, gender disparity in compensation, inadequate diversity in ethnicity of nephrologists, and perceptions of inadequate compensation and a poor work life balance. Recent studies suggest that some, but not all, of these challenges are being addressed, though full resolution will require creative and concerted efforts.

Published
2020
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5. Role of Coronary Angiography in the Assessment of Cardiovascular Risk in Kidney Transplant Candidates

Author

Sonalis Fernandez, Elizabeth A. Melita, Adena J. Osband, Zahidul Mondal, Abel E. Moreyra, Meelie Debroy, David A. Laskow, James Coromilas, Richard A. Mann, David M. Mann, Jonathan Lebowitz, and Tudor Vagaonescu

Subjects
Male, medicine.medical_specialty, Waiting Lists, medicine.medical_treatment, 030232 urology & nephrology, Coronary Artery Disease, 030204 cardiovascular system & hematology, Revascularization, Coronary Angiography, Body Mass Index, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, Myocardial infarction, Renal Insufficiency, Dialysis, Kidney transplantation, Cause of death, Aged, Retrospective Studies, medicine.diagnostic_test, business.industry, Mortality rate, Middle Aged, medicine.disease, Kidney Transplantation, Survival Analysis, Angiography, Cardiology, Exercise Test, Female, Cardiology and Cardiovascular Medicine, business
Abstract

Cardiovascular disease is the leading cause of death among those with renal insufficiency, those requiring dialysis, and in recipients of kidney transplants reflecting the greatly increased cardiovascular burden that these patients carry. The best method by which to assess cardiovascular risk in such patients is not well established. In the present study, 1,225 patients seeking a kidney transplant, over a 30-month period, underwent cardiovascular evaluation. Two hundred twenty-five patients, who met selected criteria, underwent coronary angiography that revealed significant coronary artery disease (CAD) in 47%. Those found to have significant disease underwent revascularization. Among the patients found to have significant CAD, 74% had undergone a nuclear stress test before angiography and 65% of these stress tests were negative for ischemia. The positive predictive value of a nuclear stress test in this patient population was 0.43 and the negative predictive value was 0.47. During a 30-month period, 28 patients who underwent coronary angiography received an allograft. None of these patients died, experienced a myocardial infarction, or lost their allograft. The annual mortality rate of those who remained on the waiting list was well below the national average. In conclusion, our results indicate that, in renal failure patients, noninvasive testing fails to detect the majority of significant CAD, that selected criteria may identify patients with a high likelihood of CAD, and that revascularization reduces mortality both for those on the waiting list and for those who receive an allograft.

Published
2016

6. IκB Kinase-β (IKKβ) Modulation of Epithelial Sodium Channel Activity

Author

Sergio A. Onate, Bing An, Robert S. Edinger, Thomas R. Kleyman, Clint J. Perry, John P. Johnson, and Jonathan Lebowitz

Subjects
inorganic chemicals, Epithelial sodium channel, urogenital system, Kinase, Immunoprecipitation, I-Kappa-B Kinase, Cell Biology, Transfection, IκB kinase, respiratory system, Biology, Biochemistry, Molecular biology, Luciferase, Patch clamp, Molecular Biology, hormones, hormone substitutes, and hormone antagonists
Abstract

Using the yeast two-hybrid system, we identified a number of proteins that interacted with the carboxyl termini of murine epithelial sodium channel (ENaC) subunits. Initial screens indicated an interaction between the carboxyl terminus of beta-ENaC and IkappaB kinase-beta (IKKbeta), the kinase that phosphorylates Ikappabeta and results in nuclear targeting of NF-kappaB. A true two-hybrid reaction employing full-length IKKbeta and the carboxyl termini of all three subunits confirmed a strong interaction with beta-ENaC, a weak interaction with gamma-ENaC, and no interaction with alpha-ENaC. Co-immunoprecipitation studies for IKKbeta were performed in a murine cortical collecting duct cell line that endogenously expresses ENaC. Immunoprecipitation with beta-ENaC, but not gamma-ENaC, resulted in co-immunoprecipitation of IKKbeta. To examine the direct effects of IKKbeta on ENaC activity, co-expression studies were performed using the two-electrode voltage clamp technique in Xenopus oocytes. Oocytes were injected with cRNAs for alphabetagamma-ENaC with or without cRNA for IKKbeta. Co-injection of IKKbeta significantly increased the amiloride-sensitive current above controls. Using cell surface ENaC labeling, we determined that an increase of ENaC in the plasma membrane accounted for the increase in current. The injection of kinase-dead IKKbeta (K44A) in ENaC-expressing oocytes resulted in a significant decrease in current. Treatment of mpkCCD(c14) cells with aldosterone increased whole cell amounts of IKKbeta. Because this result suggested that aldosterone might activate NF-kappaB, mpkCCD(c14) cells were transiently transfected with a luciferase reporter gene responsive to NF-kappaB activation. Both aldosterone and tumor necrosis factor-alpha (TNFalpha) stimulation caused a similar and significant increase in luciferase activity as compared with controls. We conclude that IKKbeta interacts with ENaC by up-regulating ENaC at the plasma membrane and that the presence of IKKbeta is at very least permissive to ENaC function. These studies also suggest a previously unexpected interaction between the NF-kappaB transcription pathway and steroid regulatory pathways in epithelial cells.

Published
2004
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7. Selective lentiviral gene delivery to CD133-expressing human glioblastoma stem cells

Author

Hae-Ri Song, Tobias Abel, August Dietrich, Aram S. Modrek, Markus Schober, Moses V. Chao, Dimitris G. Placantonakis, Christian J. Buchholz, David Zagzag, Jonathan Lebowitz, and N. Sumru Bayin

Subjects
Carcinogenesis, Cell, lcsh:Medicine, Mice, SCID, Epitope, Transduction (genetics), fluids and secretions, Mice, Inbred NOD, Transduction, Genetic, Animal Cells, Cancer Stem Cells, Tumor Cells, Cultured, Medicine and Health Sciences, AC133 Antigen, lcsh:Science, Neurological Tumors, Cultured Tumor Cells, Gene knockdown, Multidisciplinary, Brain Neoplasms, Stem Cells, Gene Transfer Techniques, Gene Therapy, 3. Good health, medicine.anatomical_structure, Neurology, Oncology, embryonic structures, cardiovascular system, Neoplastic Stem Cells, Biological Cultures, Stem cell, Cellular Types, Research Article, Glioblastoma Cells, Genetic Vectors, Biology, Gene delivery, Research and Analysis Methods, Viral vector, Antigens, CD, medicine, Animals, Humans, ddc:610, Molecular Biology Techniques, neoplasms, Molecular Biology, Glycoproteins, Tumor Stem Cells, lcsh:R, Lentivirus, Biology and Life Sciences, Cancers and Neoplasms, Cell Biology, Cell Cultures, Embryonic stem cell, Virology, carbohydrates (lipids), Cancer research, lcsh:Q, Glioblastoma, Peptides, Glioblastoma Multiforme
Abstract

Glioblastoma multiforme (GBM) is a deadly primary brain malignancy. Glioblastoma stem cells (GSC), which have the ability to self-renew and differentiate into tumor lineages, are believed to cause tumor recurrence due to their resistance to current therapies. A subset of GSCs is marked by cell surface expression of CD133, a glycosylated pentaspan transmembrane protein. The study of CD133-expressing GSCs has been limited by the relative paucity of genetic tools that specifically target them. Here, we present CD133-LV, a lentiviral vector presenting a single chain antibody against CD133 on its envelope, as a vehicle for the selective transduction of CD133-expressing GSCs. We show that CD133-LV selectively transduces CD133+ human GSCs in dose-dependent manner and that transduced cells maintain their stem-like properties. The transduction efficiency of CD133-LV is reduced by an antibody that recognizes the same epitope on CD133 as the viral envelope and by shRNA-mediated knockdown of CD133. Conversely, the rate of transduction by CD133-LV is augmented by overexpression of CD133 in primary human GBM cultures. CD133-LV selectively transduces CD133-expressing cells in intracranial human GBM xenografts in NOD.SCID mice, but spares normal mouse brain tissue, neurons derived from human embryonic stem cells and primary human astrocytes. Our findings indicate that CD133-LV represents a novel tool for the selective genetic manipulation of CD133-expressing GSCs, and can be used to answer important questions about how these cells contribute to tumor biology and therapy resistance.

Published
2014

8. Contrast-enhanced hepatic mri

Author

Douglas R De Corato, Neil M. Rofsky, Jeffery C. Weinreb, Glenn A. Krinsky, Jonathan Lebowitz, and James P. Earls

Subjects
Contrast enhancement, business.industry, Gadolinium, media_common.quotation_subject, Significant difference, chemistry.chemical_element, Lesion, chemistry, Gadolinium DTPA, T1 weighted, medicine, Contrast (vision), Radiology, Nuclear Medicine and imaging, medicine.symptom, Nuclear medicine, business, Gradient echo, media_common
Abstract

The objective of this article was to compare half-dose (0.05 mm/kg) gadolinium-enhanced dynamic hepatic MR imaging to standard doses (0.10 mm/kg). Eighteen patients for follow-up hepatic MR received 0.05 mm/kg of gadolinium DTPA dynamically with gradient-echo imaging. Imaging parameters were identical to a 0.10-mm/kg study; patients were imaged during multiple phases of contrast enhancement. Two readers assessed for enhancement patterns and characterization. Quantitative signal-to-noise ratios (S/N) were obtained for abdominal viscera and contrast-to-noise ratios (C/N) were obtained on up to three lesions. No significant difference for the arterial dominant phase (P > 0.05) was found. Significant differences were found in all categories during the portal venous phase (except pancreas) and equilibrium phase (except liver). Lesion C/N ratios were not significant at any point (P > 0.05). Sixty-two out of 64 lesions (97%) were identically characterized. Therefore, half-dose dynamic gadolinium-enhanced MR may have diagnostic value.

Published
1999
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9. Morbid obesity is not an independent predictor of graft failure or patient mortality after kidney transplantation

Author

Adena J. Osband, David A. Laskow, Daniel Pieloch, Viktor Y. Dombrovskiy, and Jonathan Lebowitz

Subjects
Adult, Graft Rejection, Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Medicine (miscellaneous), Kaplan-Meier Estimate, Logistic regression, Body Mass Index, Young Adult, medicine, Humans, Contraindication, Dialysis, Survival analysis, Kidney transplantation, Aged, Proportional Hazards Models, Retrospective Studies, Aged, 80 and over, Nutrition and Dietetics, business.industry, Contraindications, Graft Survival, Middle Aged, medicine.disease, Obesity, Kidney Transplantation, Surgery, Obesity, Morbid, Transplantation, Survival Rate, Treatment Outcome, Nephrology, Multivariate Analysis, Kidney Failure, Chronic, Female, business, Body mass index
Abstract

Obesity is often an absolute contraindication to kidney transplant, but an internal analysis of our center's recipients suggests that not all obese populations exhibit poor outcomes. We used national data to compare outcomes in select groups of morbidly obese and normal-weight recipients after kidney transplant.This study was a retrospective analysis of the Organ Procurement and Transplant Network/United Network for Organ Sharing database.The study sample consisted of 30,132 morbidly obese (body mass index [BMI] 35-40 kg/m(2)) and normal-weight (BMI 18.5-24.9 kg/m(2)) patients who underwent primary kidney-only transplantation between 2001 and 2006.Crude 3-year graft and patient survival rates of morbidly obese and normal-weight subgroups were evaluated. Logistic regression modeling compared 3-year graft failure and patient mortality in morbidly obese and normal-weight subgroups with opposite characteristics. Kaplan-Meier survival curves were created for 3-year graft and patient survival. Cox proportional hazard regression modeling was used to determine hazards for patient and graft mortality.No differences in crude graft and patient survival rates were seen between normal weight and morbidly obese recipients who were African American, diabetic, and 50 to 80 years of age. Morbidly obese recipients who were nondialysis dependent, nondiabetic, had good functional status, and received living-donor transplants had significantly lower 3-year graft failure and patient mortality risk compared with normal-weight recipients who were dialysis dependent, diabetic, had poor functional status, and received a deceased-donor transplant, respectively (P.01). Morbidly obese recipients have significantly lower graft and patient survival curves compared with normal-weight recipients; however, multivariate regression analysis reveals that morbid obesity is not an independent predictor of graft failure or patient mortality.Morbid obesity is not independently associated with graft failure or patient mortality; therefore, it should not be used as a contraindication to kidney transplantation.

Published
2013

10. Sarcoidosis within a renal allograft: a case report and review of the literature

Author

Adena J. Osband, Billie Fyfe, David A. Laskow, Jonathan Lebowitz, J. Jones, D. M. Mann, and Richard A. Mann

Subjects
Male, medicine.medical_specialty, Time Factors, Sarcoidosis, Biopsy, Treatment outcome, MEDLINE, Recurrence, medicine, Humans, Renal Insufficiency, Transplantation, medicine.diagnostic_test, business.industry, Incidence (epidemiology), Middle Aged, medicine.disease, Kidney Transplantation, Surgery, surgical procedures, operative, Treatment Outcome, Renal allograft, Etiology, Kidney Diseases, Lymph Nodes, business, Immunosuppressive Agents
Abstract

Sarcoidosis is an unusual disorder of unknown etiology. Clinically apparent renal involvement is rare in sarcoidosis. The incidence of recurrence in transplant recipients is unknown with few cases having been reported previously. Herein we report a case of sarcoidosis involving a renal allograft that occurred 3 years after transplantation and provide a literature review.

Published
2012

11. Functional regulation of the epithelial Na+ channel by IkappaB kinase-beta occurs via phosphorylation of the ubiquitin ligase Nedd4-2

Author

John P. Johnson, Kenneth R. Hallows, Robert S. Edinger, Huamin Wang, Hui Li, Rodrigo Alzamora, and Jonathan Lebowitz

Subjects
Epithelial sodium channel, inorganic chemicals, Nedd4 Ubiquitin Protein Ligases, Ubiquitin-Protein Ligases, Xenopus, NEDD4, IκB kinase, macromolecular substances, Protein Serine-Threonine Kinases, Xenopus Proteins, Biochemistry, Cell Line, Immediate-Early Proteins, Mice, Xenopus laevis, Animals, Humans, Kidney Tubules, Collecting, Phosphorylation, Protein kinase A, Epithelial Sodium Channels, Molecular Biology, biology, Endosomal Sorting Complexes Required for Transport, urogenital system, Cell Membrane, Cell Polarity, Cell Biology, respiratory system, biology.organism_classification, Molecular biology, Ubiquitin ligase, Cell biology, I-kappa B Kinase, Membrane Transport, Structure, Function, and Biogenesis, Gene Expression Regulation, Mutation, biology.protein, SGK1, RNA Interference, hormones, hormone substitutes, and hormone antagonists
Abstract

We have previously shown that IkappaB kinase-beta (IKKbeta) interacts with the epithelial Na+ channel (ENaC) beta-subunit and enhances ENaC activity by increasing its surface expression in Xenopus oocytes. Here, we show that the IKKbeta-ENaC interaction is physiologically relevant in mouse polarized kidney cortical collecting duct (mpkCCDc14) cells, as RNA interference-mediated knockdown of endogenous IKKbeta in these cells by approximately 50% resulted in a similar reduction in transepithelial ENaC-dependent equivalent short circuit current. Although IKKbeta binds to ENaC, there was no detectable phosphorylation of ENaC subunits by IKKbeta in vitro. Because IKKbeta stimulation of ENaC activity occurs through enhanced channel surface expression and the ubiquitin-protein ligase Nedd4-2 has emerged as a central locus for ENaC regulation at the plasma membrane, we tested the role of Nedd4-2 in this regulation. IKKbeta-dependent phosphorylation of Xenopus Nedd4-2 expressed in HEK-293 cells occurred both in vitro and in vivo, suggesting a potential mechanism for regulation of Nedd4-2 and thus ENaC activity. 32P labeling studies utilizing wild-type or mutant forms of Xenopus Nedd4-2 demonstrated that Ser-444, a key SGK1 and protein kinase A-phosphorylated residue, is also an important IKKbeta phosphorylation target. ENaC stimulation by IKKbeta was preserved in oocytes expressing wild-type Nedd4-2 but blocked in oocytes expressing either a dominant-negative (C938S) or phospho-deficient (S444A) Nedd4-2 mutant, suggesting that Nedd4-2 function and phosphorylation by IKKbeta are required for IKKbeta regulation of ENaC. In summary, these results suggest a novel mode of ENaC regulation that occurs through IKKbeta-dependent Nedd4-2 phosphorylation at a recognized SGK1 and protein kinase A target site.

Published
2008

12. The epithelial sodium channel (ENaC) traffics to apical membrane in lipid rafts in mouse cortical collecting duct cells

Author

Jonathan Lebowitz, Robert S. Edinger, Huamin Wang, John P. Johnson, Michael B. Butterworth, Warren G. Hill, Raymond A. Frizzell, and Kathryn W. Peters

Subjects
Epithelial sodium channel, medicine.medical_specialty, Green Fluorescent Proteins, Biology, Biochemistry, Caveolins, Models, Biological, chemistry.chemical_compound, Mice, Membrane Microdomains, Internal medicine, Caveolae, SNAP23, Caveolin, medicine, Animals, Protein Isoforms, Cycloheximide, Kidney Tubules, Collecting, Epithelial Sodium Channels, Molecular Biology, Lipid raft, Cells, Cultured, Genes, Dominant, Cyclodextrins, Forskolin, urogenital system, Cell Membrane, Colforsin, Cell Biology, respiratory system, Apical membrane, Cell biology, Protein Transport, Endocrinology, chemistry, Caveolin 1, lipids (amino acids, peptides, and proteins), hormones, hormone substitutes, and hormone antagonists
Abstract

We previously showed that ENaC is present in lipid rafts in A6 cells, a Xenopus kidney cell line. We now demonstrate that ENaC can be detected in lipid rafts in mouse cortical collecting duct ((MPK)CCD(14)) cells by detergent insolubility, buoyancy on density gradients using two distinct approaches, and colocalization with caveolin 1. Less than 30% of ENaC subunits were found in raft fractions. The channel subunits also colocalized on sucrose gradients with known vesicle targeting and fusion proteins syntaxin 1A, Vamp 2, and SNAP23. Hormonal stimulation of ENaC activity by either forskolin or aldosterone, short or long term, did not alter the lipid raft distribution of ENaC. Methyl-beta-cyclodextrin added apically to (MPK)CCD(14) cells resulted in a slow decline in amiloride-sensitive sodium transport with short circuit current reductions of 38.1 +/- 9.6% after 60 min. The slow decline in ENaC activity in response to apical cyclodextrin was identical to the rate of decline seen when protein synthesis was inhibited by cycloheximide. Apical biotinylation of (MPK)CCD(14) cells confirmed the loss of ENaC at the cell surface following cyclodextrin treatment. Acute stimulation of the recycling pool of ENaC was unaffected by apical cyclodextrin application. Expression of dominant negative caveolin isoforms (CAV1-eGFP and CAV3-DGV) which disrupt caveolae, reduced basal ENaC currents by 72.3 and 78.2%, respectively; but, as with cyclodextrin, the acute response to forskolin was unaffected. We conclude that ENaC is present in and regulated by lipid rafts. The data are consistent with a model in which rafts mediate the constitutive apical delivery of ENaC.

Published
2007

13. Ikappab kinase-beta (ikkbeta) modulation of epithelial sodium channel activity

Author

Jonathan, Lebowitz, Robert S, Edinger, Bing, An, Clint J, Perry, Sergio, Onate, Thomas R, Kleyman, and John P, Johnson

Subjects
Patch-Clamp Techniques, Xenopus, Membrane Proteins, Epithelial Cells, Protein Serine-Threonine Kinases, Transfection, Sodium Channels, I-kappa B Kinase, Mice, Two-Hybrid System Techniques, Oocytes, Animals, Epithelial Sodium Channels, Aldosterone, Cell Line, Transformed, Protein Binding
Abstract

Using the yeast two-hybrid system, we identified a number of proteins that interacted with the carboxyl termini of murine epithelial sodium channel (ENaC) subunits. Initial screens indicated an interaction between the carboxyl terminus of beta-ENaC and IkappaB kinase-beta (IKKbeta), the kinase that phosphorylates Ikappabeta and results in nuclear targeting of NF-kappaB. A true two-hybrid reaction employing full-length IKKbeta and the carboxyl termini of all three subunits confirmed a strong interaction with beta-ENaC, a weak interaction with gamma-ENaC, and no interaction with alpha-ENaC. Co-immunoprecipitation studies for IKKbeta were performed in a murine cortical collecting duct cell line that endogenously expresses ENaC. Immunoprecipitation with beta-ENaC, but not gamma-ENaC, resulted in co-immunoprecipitation of IKKbeta. To examine the direct effects of IKKbeta on ENaC activity, co-expression studies were performed using the two-electrode voltage clamp technique in Xenopus oocytes. Oocytes were injected with cRNAs for alphabetagamma-ENaC with or without cRNA for IKKbeta. Co-injection of IKKbeta significantly increased the amiloride-sensitive current above controls. Using cell surface ENaC labeling, we determined that an increase of ENaC in the plasma membrane accounted for the increase in current. The injection of kinase-dead IKKbeta (K44A) in ENaC-expressing oocytes resulted in a significant decrease in current. Treatment of mpkCCD(c14) cells with aldosterone increased whole cell amounts of IKKbeta. Because this result suggested that aldosterone might activate NF-kappaB, mpkCCD(c14) cells were transiently transfected with a luciferase reporter gene responsive to NF-kappaB activation. Both aldosterone and tumor necrosis factor-alpha (TNFalpha) stimulation caused a similar and significant increase in luciferase activity as compared with controls. We conclude that IKKbeta interacts with ENaC by up-regulating ENaC at the plasma membrane and that the presence of IKKbeta is at very least permissive to ENaC function. These studies also suggest a previously unexpected interaction between the NF-kappaB transcription pathway and steroid regulatory pathways in epithelial cells.

Published
2004

14. Effect of altered Na+ entry on expression of apical and basolateral transport proteins in A6 epithelia

Author

Mark L. Zeidel, John P. Johnson, Robert S. Edinger, Jonathan Lebowitz, and Bing An

Subjects
Epithelial sodium channel, Physiology, Biology, Sodium Channels, Cell Line, Amiloride, In vivo, medicine, Animals, Na+/K+-ATPase, Aldosterone, Ion Transport, Cell Membrane, Sodium, Cell Polarity, Epithelial Cells, Apical membrane, Epithelium, Transport protein, Cell biology, medicine.anatomical_structure, Biochemistry, Gene Expression Regulation, Cell culture, Sodium-Potassium-Exchanging ATPase, medicine.drug
Abstract

In several in vivo settings, prolonged alterations in the rate of apical Na+entry into epithelial cells alter the ability of these cells to reabsorb Na+. We previously modeled this load dependence of transport in A6 cells by either decreasing Na+entry via apical Na+removal or amiloride or enhancing Na+entry by chronic short-circuiting (Rokaw MD, Sarac E, Lechman E, West M, Angeski J, Johnson JP, and Zeidel ML. Am J Physiol Cell Physiol 270: C600-C607, 1996). Inhibition of Na+entry by either method was associated with striking downregulation of transport rate as measured by short-circuit current ( Isc), which recovered to basal levels of transport over a period of hours. Conversely, upregulation of Na+entry by short-circuiting resulted in a sustained increase in transport rate that also returned to basal levels over a period of hours. The current studies were undertaken to determine whether these conditions were associated with alterations in either the whole cell content or apical membrane distribution of sodium channel (ENaC) subunits or on basolateral expression of either of the subunits of the Na+-K+-ATPase. We compared these effects to those achieved by chronic upregulation of Na+transport by aldosterone. Whole cell levels of ENaC subunits were measured by immunoblot following 18-h inhibition of Na+entry achieved by either tetramethylammonium replacement of Na+or apical amiloride or after an 18-h increase in Na+entry achieved by chronic short-circuiting. None of these maneuvers significantly altered the whole cell content of any of the ENaC subunits compared with control cells. We then examined the effects of these maneuvers on apical membrane ENaC expression using domain-specific biotinylation and immunoblot. Inhibition of Na+entry by either method was associated with a profound decrease in apical membrane β-ENaC without significant changes in apical membrane α-or γ-ENaC amounts. Restoration of apical Na+and/or removal of amiloride resulted in return of Iscto control levels over 2 h and coincided with return of apical β-ENaC to control levels without change in apical α- or γ-ENaC. Stimulation of Na+transport by short-circuiting, in contrast, did not significantly alter apical membrane composition of any of the ENaC subunits. Basolateral expression of Na+-K+-ATPase was also measured by biotinylation and immunoblot and was unchanged under all conditions. Aldosterone increased basolateral expression of the α-subunit of Na+-K+-ATPase. These results suggest that chronic downregulation of transport is mediated, in part, by a selective decrease in apical membrane ENaC expression, consistent with our previous observations of noncoordinate regulation of ENaC expression under varying transport conditions in A6 cells. The chronic increase in the rate of Na+entry is not associated with any of the changes in transporter density at either apical or basolateral membrane seen with aldosterone, suggesting that these two mechanisms of augmenting transport are completely distinct.

Published
2003

15. Gadolinium-enhanced 3D MRA of the aortic arch vessels in the detection of atherosclerotic cerebrovascular occlusive disease

Author

Glenn A. Krinsky, Jay Earls, Evan Kaminer, Jonathan Lebowitz, Neil M. Rofsky, Gary Giangola, Andrew W. Litt, Peter Kim Nelson, L T Masters, Jeffrey H. Weinreb, Menahem Maya, and M. M. Ambrosino

Subjects
Aortic arch, Adult, Gadolinium DTPA, Male, medicine.medical_specialty, Vertebral artery, Contrast Media, Aorta, Thoracic, Sensitivity and Specificity, Statistics, Nonparametric, Jugular vein, medicine.artery, Medicine, Humans, Radiology, Nuclear Medicine and imaging, Aged, Aged, 80 and over, Analysis of Variance, medicine.diagnostic_test, business.industry, Vascular disease, Angiography, Digital Subtraction, Digital subtraction angiography, Middle Aged, medicine.disease, Intracranial Arteriosclerosis, Contrast medium, Cerebral blood flow, Great vessels, cardiovascular system, Female, Radiology, business, Magnetic Resonance Angiography
Abstract

Purpose: Our goal was to evaluate non-breath-hold Gd-enhanced 3D MR angiography (MRA) for the detection of atherosclerotic occlusive disease of the aortic arch vessels and to compare image quality with two breath-hold techniques. Method: One hundred sixty consecutive patients with known or clinically suspected atherosclerotic cerebrovascular occlusive disease underwent Gd-enhanced 3D MRA of the aortic arch and great vessels. One hundred twenty-six examinations were performed with the body coil after infusion of 40 ml of Gd-DTPA; 89 of these were performed without breath-holding and 37 were acquired during suspended respiration. Thirty-four examinations were performed in a body phased-array coil with breath-holding, a timing examination, and 20 ml of contrast agent by manual In = 17) or power In = 17) injection. Images were evaluated for the presence of blurring and ghosting artifacts and venous enhancement. Of the 27 patients who underwent non-breath-hold MRI and digital subtraction angiography (DSA), two readers blinded to the DSA results retrospectively evaluated the MRA examinations for the presence of occlusive disease of the innominate, carotid, subclavian, and vertebral arteries. DSA correlation was not evaluated for the 71 breath-hold studies. Results: Sensitivity and specificity for arch vessel occlusive disease with non-breath-hold MRA were 38 and 94% for Reader A and 38 and 95% for Reader B. Breath-holding significantly reduced blurring and ghosting artifacts (p < 0.001) when compared with non-breath-hold imaging, and use of 20 ml of contrast medium, with a timing examination, resulted in significantly less venous enhancement than seen with 40 ml (p < 0.001). Conclusion: Non-breath-hold Gd-enhanced 3D MRA is insensitive for detecting arch vessel occlusive disease. Breath-hold imaging, in conjunction with a timing examination and a lower dose of contrast agent, improves image quality, but further studies are needed to assess diagnostic accuracy.

Published
1998

16. Gadolinium-enhanced body MR venography with subtraction technique

Author

Glenn A. Krinsky, Neil M. Rofsky, Jonathan Lebowitz, and Jeffrey C. Weinreb

Subjects
Adult, Gadolinium DTPA, Male, Adolescent, Gadolinium, chemistry.chemical_element, Contrast Media, Image processing, Paramagnetic Contrast Agent, Veins, Nuclear magnetic resonance, Image Processing, Computer-Assisted, Organometallic Compounds, Medicine, Humans, Radiology, Nuclear Medicine and imaging, Mr venography, Child, Aged, Aged, 80 and over, business.industry, Subtraction, Extremities, General Medicine, Middle Aged, Pentetic Acid, Thrombophlebitis, chemistry, Subtraction Technique, Female, Nuclear medicine, business, Magnetic Resonance Angiography
Published
1997

17. Ureteral lymphoma: MRI demonstration

Author

Jeffrey C. Weinreb, Jonathan Lebowitz, Neil M. Rofsky, and P. Friedmann

Subjects
Gadolinium DTPA, Male, medicine.medical_specialty, Hypertension, Renal, Urology, medicine.medical_treatment, Contrast Media, Gadolinium, urologic and male genital diseases, Ureter, Meglumine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Organometallic Compounds, Humans, Radiology, Nuclear Medicine and imaging, Hydronephrosis, Chemotherapy, Radiological and Ultrasound Technology, urogenital system, business.industry, Ureteral Neoplasms, Gastroenterology, Soft tissue, General Medicine, Hepatology, Middle Aged, Pentetic Acid, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, Magnetic Resonance Imaging, female genital diseases and pregnancy complications, Lymphoma, Drug Combinations, medicine.anatomical_structure, Radiology, Urinary tract obstruction, business, Infiltration (medical)
Abstract

A case of ureteral lymphoma with no other areas of involvement was incidentally discovered on MRI examination. Bilateral ureteral soft tissue infiltration, asymmetrical hydronephrosis, and abnormal enhancement of lymphomatous tissue were noted. A follow-up MRI after chemotherapy demonstrated significant decrease in the size of the periureteral disease and improvement in the extent of hydronephrosis.

Published
1995

18. Induction of amiloride-sensitive sodium transport in the rat colon by mineralocorticoids

Author

Peter C. Will, Jonathan Lebowitz, and Ulrich Hopfer

Subjects
Male, medicine.medical_specialty, Colon, Physiology, Chemistry, Sodium, Action Potentials, chemistry.chemical_element, Spironolactone, Membrane Potentials, Rats, Amiloride, Endocrinology, Furosemide, Internal medicine, medicine, Animals, Drug Therapy, Combination, Desoxycorticosterone, Aldosterone, medicine.drug
Abstract

Page F261: Peter C. Will, Jonathan L. Lebowitz, and Ulrich Hopfer. “Induction of amiloride-sensitive sodium transport in the rat colon by mineralocorticoids.” Page F267: the second equation in the appendix should read (See PDF)

Published
1980
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19. Effect of altered Na+ entry on expression of apical and basolateral transport proteins in A6 epithelia.

Author

Jonathan, Lebowitz, Bing, An, S, Edinger Robert, L, Zeidel Mark, and P, Johnson John

Abstract

In several in vivo settings, prolonged alterations in the rate of apical Na+ entry into epithelial cells alter the ability of these cells to reabsorb Na+. We previously modeled this load dependence of transport in A6 cells by either decreasing Na+ entry via apical Na+ removal or amiloride or enhancing Na+ entry by chronic short-circuiting (Rokaw MD, Sarac E, Lechman E, West M, Angeski J, Johnson JP, and Zeidel ML. Am J Physiol Cell Physiol 270: C600-C607, 1996). Inhibition of Na+ entry by either method was associated with striking downregulation of transport rate as measured by short-circuit current (Isc), which recovered to basal levels of transport over a period of hours. Conversely, upregulation of Na+ entry by short-circuiting resulted in a sustained increase in transport rate that also returned to basal levels over a period of hours. The current studies were undertaken to determine whether these conditions were associated with alterations in either the whole cell content or apical membrane distribution of sodium channel (ENaC) subunits or on basolateral expression of either of the subunits of the Na+-K+-ATPase. We compared these effects to those achieved by chronic upregulation of Na+ transport by aldosterone. Whole cell levels of ENaC subunits were measured by immunoblot following 18-h inhibition of Na+ entry achieved by either tetramethylammonium replacement of Na+ or apical amiloride or after an 18-h increase in Na+ entry achieved by chronic short-circuiting. None of these maneuvers significantly altered the whole cell content of any of the ENaC subunits compared with control cells. We then examined the effects of these maneuvers on apical membrane ENaC expression using domain-specific biotinylation and immunoblot. Inhibition of Na+ entry by either method was associated with a profound decrease in apical membrane beta-ENaC without significant changes in apical membrane alpha-or gamma-ENaC amounts. Restoration of apical Na+ and/or removal of amiloride resulted in return of Isc to control levels over 2 h and coincided with return of apical beta-ENaC to control levels without change in apical alpha- or gamma-ENaC. Stimulation of Na+ transport by short-circuiting, in contrast, did not significantly alter apical membrane composition of any of the ENaC subunits. Basolateral expression of Na+-K+-ATPase was also measured by biotinylation and immunoblot and was unchanged under all conditions. Aldosterone increased basolateral expression of the alpha-subunit of Na+-K+-ATPase. These results suggest that chronic downregulation of transport is mediated, in part, by a selective decrease in apical membrane ENaC expression, consistent with our previous observations of noncoordinate regulation of ENaC expression under varying transport conditions in A6 cells. The chronic increase in the rate of Na+ entry is not associated with any of the changes in transporter density at either apical or basolateral membrane seen with aldosterone, suggesting that these two mechanisms of augmenting transport are completely distinct.

Published
2003

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