23 results on '"Stephen Reddel"'
Search Results
2. 3209 Ptosis: when is it not myasthenia?
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Irene Tan, Stephen Reddel, Molly Reynolds, Aicee D Calma, Veronica Cheung, and Elizabeth Veitch
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Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Published
- 2024
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3. Comparison of IVIg and TPE efficacy in the treatment of neurological disorders: a systematic literature review
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Ashwin A. Pinto, Jerome De Seze, Anu Jacob, Stephen Reddel, Anna Yudina, and Kevin Tan
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Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Background: Intravenous immunoglobulin (IVIg) and therapeutic plasma exchange (TPE) are among the main immunotherapies for neurological disorders. Their benefit is greatest in immune-mediated conditions, but their distinct efficacy cannot be simply explained. Objectives: This review aimed to systematically identify studies comparing the efficacy of TPE and IVIg treatments for selected autoimmune neurological disorders and identify optimal therapies for each condition. Data Sources and Methods: PubMed, MEDLINE and Embase databases were searched for original publications from 1990 to 2021. Additional publications were identified via expert recommendations. Conference abstracts older than 2017, review articles and articles without information on TPE and IVIg comparison in title and abstract were excluded. Risks of bias were descriptively addressed, without a meta-analysis. Results: Forty-four studies were included on Guillain–Barré syndrome (20 studies – 12 adult, 5 paediatric, 3 all ages), myasthenia gravis (11 studies –8 adult, 3 paediatric), chronic immune–mediated polyradiculoneuropathy (3 studies –1 adult, 2 paediatric), encephalitis (1 study in adults), neuromyelitis optica spectrum disorders (5 studies –2 adult, 3 all ages) and other conditions (4 studies – all ages). TPE and IVIg were mostly similarly efficacious, measured by clinical outcomes and disease severity scores. Some studies recommended IVIg as easy to administer. TPE procedures, however, have been simplified and the safety has been improved. TPE is currently recommended for management of neuromyelitis optica spectrum disorder relapses and some myasthenia gravis subtypes, in which rapid removal of autoantibodies is crucial. Conclusion: Despite some limitations (e.g. the low evidence levels), this review provides an extensive 30-year-long overview of treatments for various conditions. Both IVIg and TPE are usually comparably efficacious options for autoimmune neurological disorders, with few exceptions. Treatment choices should be patient-tailored and based on available clinical resources. Better designed studies are needed to provide higher-level quality of evidence regarding clinical efficacy of TPE and IVIg treatments.
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- 2023
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4. Refractory Mycobacterium genavense infection secondary to thymoma-associated endogenous IL-12 inhibitor
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MaiAnh Nguyen, Jessie Chen, Stephen Reddel, Elaine Cheong, D Sean Riminton, and Hannah Hu
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Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Case A 39-year-old man with thymoma-associated acetylcholine receptor antibody myasthenia gravis (MG) presented with fevers, night sweats, abdominal pain and weight loss. Marked splenomegaly and intra-abdominal lymphadenopathy were found. Biopsies confirmed disseminated Mycobacterium genavense infection. Despite antimicrobials and reduced immunosuppressive medications, he worsened. We suspected a thymoma-associated cytokine inhibitory antibody. The addition of subcutaneous interferon-gamma (IFN-γ) induced clinical and radiological improvement. His antimicrobials were able to be ceased. MG remained stable. Subsequent testing demonstrated an endogenous interleukin-12 (IL-12) inhibitor, likely inhibiting the IL-12/IFN-γ axis crucial for defence against mycobacterial infections.Discussion This case illustrates the autoimmune manifestations that can occur with thymoma. It illustrates the benefit of exogenous IFN-γ in overcoming the immune deficit. In this case, its use did not exacerbate existing autoimmune disease or trigger others. We raise awareness of the need to consider cytokine pathway defects as a contributing factor to refractory atypical infections in patients with thymoma-associated MG.
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- 2022
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5. Risks and risk management in modern multiple sclerosis immunotherapeutic treatment
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Luisa Klotz, Joachim Havla, Nicholas Schwab, Reinhard Hohlfeld, Michael Barnett, Stephen Reddel, and Heinz Wiendl
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Neurology. Diseases of the nervous system ,RC346-429 - Abstract
In recent years, there has been a paradigm shift in the treatment of multiple sclerosis (MS) owing to the approval of a number of new drugs with very distinct mechanisms of action. All approved disease-modifying drugs primarily work directly on the immune system. However, the identification of an ‘optimal choice’ for individual patients with regard to treatment efficacy, treatment adherence and side-effect profile has become increasingly complex including conceptual as well as practical considerations. Similarly, there are peculiarities and specific requirements with regard to treatment monitoring, especially in relation to immunosuppression, the development of secondary immune-related complications, as well as the existence of drug-specific on- and off-target effects. Both classical immunosuppression and selective immune interventions generate a spectrum of potential therapy-related complications. This article provides a comprehensive overview of available immunotherapeutics for MS and their risks, detailing individual mechanisms of action and side-effect profiles. Furthermore, practical recommendations for patients treated with modern MS immunotherapeutics are provided.
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- 2019
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6. Simulations of active zone structure and function at mammalian NMJs predict that loss of calcium channels alone is not sufficient to replicate LEMS effects
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Scott P. Ginebaugh, Yomna Badawi, Rozita Laghaei, Glenn Mersky, Caleb J. Wallace, Tyler B. Tarr, Cassandra Kaufhold, Stephen Reddel, and Stephen D. Meriney
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Physiology ,General Neuroscience - Abstract
We used a computational model of the active zone (AZ) in the mammalian neuromuscular junction to investigate Lambert-Eaton myasthenic syndrome (LEMS) pathophysiology. This model suggests that disruptions in presynaptic active zone organization and protein content (particularly synaptotagmin), beyond the simple removal of presynaptic calcium channels, play an important role in LEMS pathophysiology.
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- 2023
7. MGBase: The launch of an international electronic database for patients with Myasthenia Gravis (P7-8.014)
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Stephen Reddel, Carolina Barnett Tapia, Helmut Butzkueven, Katherine Buzzard, Gary Cutter, Henry Kaminski, Anneke Van Der Walt, and wen wen zhang
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- 2023
8. Long read sequencing overcomes challenges in the diagnosis of <scp> SORD </scp> neuropathy
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Bianca R. Grosz, Igor Stevanovski, Sara Negri, Melina Ellis, Stephanie Barnes, Stephen Reddel, Steve Vucic, Garth A. Nicholson, Andrea Cortese, Kishore R. Kumar, Ira W. Deveson, and Marina L. Kennerson
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General Neuroscience ,Neurology (clinical) - Published
- 2022
9. Application of diagnostic criteria for optic neuritis – Authors' reply
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Axel Petzold, Yaou Liu, Clare Fraser, Mathias Abegg, Raed Alroughani, Daniah Alshowaeir, Regina Alvarenga, Cécile Andris, Nasrin Asgari, Yael Barnett, Roberto Battistella, Raed Behbehani, Thomas Berger, Mukharram M. Bikbov, Damien Biotti, Valerie Biousse, Antonella Boschi, Milan Brazdil, Andrei Brezhnev, Peter Calabresi, Monique Cordonnier, Fiona Costello, Franz Marie Cruz, Leonardo Provetti Cunha, Smail Daoudi, Romain Deschamps, Jerome DeSeze, Ricarda Diem, Masoud Etemadifar, Jose Flores-Rivera, Pedro Fonseca, Jette Frederiksen, Elliot Frohman, Teresa Frohman, Caroline FromentTilikete, Kazuo Fujihara, Alberto Gálvez, Riadh Gouider, Fernando Gracia, Nikolaos Grigoriadis, José Manuel Guajardo, Mario Habek, Marko Hawlina, Elena Hernández-Martínez de Lapiscina, Juzar Hooker, Jyh Yung Hor, William Howlett, Yumin Huang-Link, Zhannat Idrissova, Zsolt Illes, Jasna Jancic, Panitha Jindahra, Dimitrios Karussis, Emilia Kerty, Ho Jin Kim, Wolf Lagrèze, Letizia Leocani, Netta Levin, Petra Liskova, Youssoufa Maiga, Romain Marignier, Chris McGuigan, Dália Meira, Harold Merle, Mário L.R. Monteiro, Anand Moodley, Frederico Moura, Silvia Muñoz, Sharik Mustafa, Ichiro Nakashima, Susana Noval, Carlos Oehninger, Olufunmilola Ogun, Afekhide Omoti, Lekha Pandit, Friedemann Paul, Gema Rebolleda, Stephen Reddel, Konrad Rejdak, Robert Rejdak, Alfonso Rodriguez-Morales, Marie-Bénédicte Rougier, Maria Jose Sa, Bernardo Sanchez-Dalmau, Deanna Saylor, Ismail Shatriah, Aksel Siva, Hadas Stiebel-Kalish, Gabriella Szatmary, Linh Ta, Sylvia Tenembaum, Huy Tran, Yevgen Trufanov, Vincent VanPesch, An-Guor Wang, Mike P. Wattjes, Ernie Willoughby, Magd Zakaria, Jasmin Zvornicanin, Laura Balcer, Gordon T. Plant, Neurology, Ophthalmology, APH - Mental Health, APH - Methodology, and Amsterdam Neuroscience - Neuroinfection & -inflammation
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Neurology (clinical) - Published
- 2023
10. MRI and laboratory monitoring of disease-modifying therapy efficacy and risks
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Michael Barnett, Yael Barnett, and Stephen Reddel
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Coronavirus ,COVID-19 Vaccines ,Multiple Sclerosis ,Neurology ,Artificial Intelligence ,COVID-19 ,Humans ,Neurology (clinical) ,Magnetic Resonance Imaging ,Biomarkers - Abstract
PURPOSE OF REVIEW: Increasingly, therapeutic strategy in multiple sclerosis (MS) is informed by imaging and laboratory biomarkers, in addition to traditional clinical factors. Here, we review aspects of monitoring the efficacy and risks of disease-modifying therapy (DMT) with both conventional and emerging MRI and laboratory measures. RECENT FINDINGS: The adoption of consensus-driven, stable MRI acquisition protocols and artificial intelligence-based, quantitative image analysis is heralding an era of precision monitoring of DMT efficacy. New MRI measures of compartmentalized inflammation, neuro-degeneration and repair complement traditional metrics but require validation before use in individual patients. Laboratory markers of brain cellular injury, such as neurofilament light, are robust outcomes in DMT efficacy trials; their use in clinical practice is being refined. DMT-specific laboratory monitoring for safety is critical and may include lymphocytes, immunoglobulins, autoimmunity surveillance, John Cunningham virus serology and COVID-19 vaccination seroresponse. SUMMARY: A biomarker-enhanced monitoring strategy has immediate clinical application, with growing evidence of long-term reductions in disability accrual when both clinically symptomatic and asymptomatic inflammatory activity is fully suppressed; and amelioration of the risks associated with therapy. Emerging MRI and blood-based measures will also become important tools for monitoring agents that target the innate immune system and promote neuro-repair.
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- 2022
11. Refractory
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Jessie, Chen, MaiAnh, Nguyen, Elaine, Cheong, D, Sean Riminton, and Stephen, Reddel
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A 39-year-old man with thymoma-associated acetylcholine receptor antibody myasthenia gravis (MG) presented with fevers, night sweats, abdominal pain and weight loss. Marked splenomegaly and intra-abdominal lymphadenopathy were found. Biopsies confirmed disseminatedThis case illustrates the autoimmune manifestations that can occur with thymoma. It illustrates the benefit of exogenous IFN-γ in overcoming the immune deficit. In this case, its use did not exacerbate existing autoimmune disease or trigger others. We raise awareness of the need to consider cytokine pathway defects as a contributing factor to refractory atypical infections in patients with thymoma-associated MG.
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- 2022
12. Diagnosis and classification of optic neuritis
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Axel Petzold, Clare L Fraser, Mathias Abegg, Raed Alroughani, Daniah Alshowaeir, Regina Alvarenga, Cécile Andris, Nasrin Asgari, Yael Barnett, Roberto Battistella, Raed Behbehani, Thomas Berger, Mukharram M Bikbov, Damien Biotti, Valerie Biousse, Antonella Boschi, Milan Brazdil, Andrei Brezhnev, Peter A Calabresi, Monique Cordonnier, Fiona Costello, Franz M Cruz, Leonardo Provetti Cunha, Smail Daoudi, Romain Deschamps, Jerome de Seze, Ricarda Diem, Masoud Etemadifar, Jose Flores-Rivera, Pedro Fonseca, Jette Frederiksen, Elliot Frohman, Teresa Frohman, Caroline Froment Tilikete, Kazuo Fujihara, Alberto Gálvez, Riadh Gouider, Fernando Gracia, Nikolaos Grigoriadis, José M Guajardo, Mario Habek, Marko Hawlina, Elena H Martínez-Lapiscina, Juzar Hooker, Jyh Yung Hor, William Howlett, Yumin Huang-Link, Zhannat Idrissova, Zsolt Illes, Jasna Jancic, Panitha Jindahra, Dimitrios Karussis, Emilia Kerty, Ho Jin Kim, Wolf Lagrèze, Letizia Leocani, Netta Levin, Petra Liskova, Yaou Liu, Youssoufa Maiga, Romain Marignier, Chris McGuigan, Dália Meira, Harold Merle, Mário L R Monteiro, Anand Moodley, Frederico Moura, Silvia Muñoz, Sharik Mustafa, Ichiro Nakashima, Susana Noval, Carlos Oehninger, Olufunmilola Ogun, Afekhide Omoti, Lekha Pandit, Friedemann Paul, Gema Rebolleda, Stephen Reddel, Konrad Rejdak, Robert Rejdak, Alfonso J Rodriguez-Morales, Marie-Bénédicte Rougier, Maria Jose Sa, Bernardo Sanchez-Dalmau, Deanna Saylor, Ismail Shatriah, Aksel Siva, Hadas Stiebel-Kalish, Gabriella Szatmary, Linh Ta, Silvia Tenembaum, Huy Tran, Yevgen Trufanov, Vincent van Pesch, An-Guor Wang, Mike P Wattjes, Ernest Willoughby, Magd Zakaria, Jasmin Zvornicanin, Laura Balcer, Gordon T Plant, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire
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Aquaporin 4 ,Optic Neuritis ,Multiple Sclerosis ,Neuromyelitis Optica ,Humans ,Neurology (clinical) ,610 Medicine & health ,Retrospective Studies ,Autoantibodies - Abstract
There is no consensus regarding the classification of optic neuritis, and precise diagnostic criteria are not available. This reality means that the diagnosis of disorders that have optic neuritis as the first manifestation can be challenging. Accurate diagnosis of optic neuritis at presentation can facilitate the timely treatment of individuals with multiple sclerosis, neuromyelitis optica spectrum disorder, or myelin oligodendrocyte glycoprotein antibody-associated disease. Epidemiological data show that, cumulatively, optic neuritis is most frequently caused by many conditions other than multiple sclerosis. Worldwide, the cause and management of optic neuritis varies with geographical location, treatment availability, and ethnic background. We have developed diagnostic criteria for optic neuritis and a classification of optic neuritis subgroups. Our diagnostic criteria are based on clinical features that permit a diagnosis of possible optic neuritis; further paraclinical tests, utilising brain, orbital, and retinal imaging, together with antibody and other protein biomarker data, can lead to a diagnosis of definite optic neuritis. Paraclinical tests can also be applied retrospectively on stored samples and historical brain or retinal scans, which will be useful for future validation studies. Our criteria have the potential to reduce the risk of misdiagnosis, provide information on optic neuritis disease course that can guide future treatment trial design, and enable physicians to judge the likelihood of a need for long-term pharmacological management, which might differ according to optic neuritis subgroups.
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- 2022
13. MR 'scalpel sign' of spinal arachnoid web
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Thomas Morrison, Raka Datta, Lynette Masters, Mike Boggild, Stephen Reddel, and Jeffrey Brennan
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Humans ,Neurology (clinical) ,General Medicine ,Magnetic Resonance Imaging ,Spinal Cord Diseases - Published
- 2021
14. RefractoryMycobacterium genavenseinfection secondary to thymoma-associated endogenous IL-12 inhibitor
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Jessie Chen, MaiAnh Nguyen, Hannah Hu, Elaine Cheong, D Sean Riminton, and Stephen Reddel
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Neurology ,Neurology (clinical) - Abstract
CaseA 39-year-old man with thymoma-associated acetylcholine receptor antibody myasthenia gravis (MG) presented with fevers, night sweats, abdominal pain and weight loss. Marked splenomegaly and intra-abdominal lymphadenopathy were found. Biopsies confirmed disseminatedMycobacterium genavenseinfection. Despite antimicrobials and reduced immunosuppressive medications, he worsened. We suspected a thymoma-associated cytokine inhibitory antibody. The addition of subcutaneous interferon-gamma (IFN-γ) induced clinical and radiological improvement. His antimicrobials were able to be ceased. MG remained stable. Subsequent testing demonstrated an endogenous interleukin-12 (IL-12) inhibitor, likely inhibiting the IL-12/IFN-γ axis crucial for defence against mycobacterial infections.DiscussionThis case illustrates the autoimmune manifestations that can occur with thymoma. It illustrates the benefit of exogenous IFN-γ in overcoming the immune deficit. In this case, its use did not exacerbate existing autoimmune disease or trigger others. We raise awareness of the need to consider cytokine pathway defects as a contributing factor to refractory atypical infections in patients with thymoma-associated MG.
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- 2022
15. 231st ENMC International Workshop
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Filip Eftimov, Carina Bunschoten, Yusuf Rajabally, Luis Querol, Max E. Adrichem, Jeffrey Allen, Jean-Cristophe Antoine, Ivana Basta, Peter Van den Bergh, Patricia Blomkwist-Markens, Alexandra Breukel, David Cornblath, Kathrin Doppler, Stephan Goedee, Robert Hadden, Thomas Harbo, Fu Liong Hiew, Bart C. Jacobs, Helmar Lehmann, Michael P. Lunn, Ingemar S.J. Merkies, Eduardo Nobile-Orazio, Stephen Reddel, Jean-Michel Vallat, and Antonino Uncini
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0301 basic medicine ,medicine.medical_specialty ,business.industry ,International standard ,MEDLINE ,Biobank ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Neurology ,Pediatrics, Perinatology and Child Health ,medicine ,Diagnostic data ,Medical physics ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Genetics (clinical) - Abstract
• International CIDP registries were compared to assess infrastructure and collected clinical data, diagnostic data and biomaterials to enhance future research and improve standards of care in CIDP.
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- 2018
16. Long-term effect of thymectomy plus prednisone versus prednisone alone in patients with non-thymomatous myasthenia gravis: 2-year extension of the MGTX randomised trial
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Gil I Wolfe, Henry J Kaminski, Inmaculada B Aban, Greg Minisman, Hui-Chien Kuo, Alexander Marx, Philipp Ströbel, Claudio Mazia, Joel Oger, J Gabriel Cea, Jeannine M Heckmann, Amelia Evoli, Wilfred Nix, Emma Ciafaloni, Giovanni Antonini, Rawiphan Witoonpanich, John O King, Said R Beydoun, Colin H Chalk, Alexandru C Barboi, Anthony A Amato, Aziz I Shaibani, Bashar Katirji, Bryan R F Lecky, Camilla Buckley, Angela Vincent, Elza Dias-Tosta, Hiroaki Yoshikawa, Márcia Waddington-Cruz, Michael T Pulley, Michael H Rivner, Anna Kostera-Pruszczyk, Robert M Pascuzzi, Carlayne E Jackson, Jan J G M Verschuuren, Janice M Massey, John T Kissel, Lineu C Werneck, Michael Benatar, Richard J Barohn, Rup Tandan, Tahseen Mozaffar, Nicholas J Silvestri, Robin Conwit, Joshua R Sonett, Alfred Jaretzki, John Newsom-Davis, Gary R Cutter, Gary Cutter, Inmaculada Aban, Michelle Feese, Gil Wolfe, Henry Kaminski, Joshua Sonett, Valeria Saluto, Moises Rosenberg, Valeria Alvarez, Lisa Rey, John King, Helmut Butzkueven, John Goldblatt, John Carey, John Pollard, Stephen Reddel, Nicholas Handel, Brian McCaughan, Linda Pallot, Ricardo Novis, Carlos Boasquevisque, Rubens Morato-Fernandez, Manoel Ximenes, Lineu Werneck, Rosana Scola, Paulo Soltoski, Colin Chalk, Fraser Moore, David Mulder, Lisa Wadup, Michele Mezei, Kenneth Evans, Theresa Jiwa, Anne Schaffar, Chris White, Cory Toth, Gary Gelfand, Susan Wood, Elizabeth Pringle, Jocelyn Zwicker, Donna Maziak, Farid Shamji, Sudhir Sundaresan, Andrew Seely, Gabriel Cea, Renato Verduga, Alberto Aguayo, Sebastian Jander, Philipp Zickler, Michael Klein, Cleo-Aron Weis, Arthur Melms, Felix Bischof, Hermann Aebert, Gerhard Ziemer, Björn Thümler, Thomas Wilhem-Schwenkmezger, Eckhard Mayer, Berthold Schalke, Peter Pöschel, Gisela Hieber, Karsten Wiebe, Alessandro Clemenzi, Vanessa Ceschin, Erino Rendina, Federico Venuta, Stefania Morino, Elisabetta Bucci, Luca Durelli, Alessia Tavella, Marinella Clerico, Giulia Contessa, Piero Borasio, Serenella Servidei, Pierluigi Granone, Renato Mantegazza, Emilia Berta, Lorenzo Novellino, Luisa Spinelli, Masakatsu Motomura, Hidenori Matsuo, Takeshi Nagayasu, Masaharu Takamori, Makoto Oda, Isao Matsumoto, Yutaka Furukawa, Daisuke Noto, Yuko Motozaki, Kazuo Iwasa, Daisuke Yanase, Guillermo Garcia Ramos, Bernardo Cacho, Lorenzo de la Garza, Anne Kostera-Pruszczyk, Marta Lipowska, Hubert Kwiecinski, Anna Potulska-Chromik, Tadeusz Orlowski, Ana Silva, Marta Feijo, António Freitas, Jeannine Heckmann, Andrew Frost, Edward Pan, Lawrence Tucker, Johan Rossouw, Fiona Drummond, Isabel Illa, Jorge Diaz, Carlos Leon, Jiann-Horng Yeh, Hou-Chang Chiu, Yei-San Hsieh, Supoch Tunlayadechanont, Sukasom Attanavanich, Jan Verschuuren, Chiara Straathof, Maarten Titulaer, Michel Versteegh, Arda Pels, Yvonne Krum, M. Isabel Leite, David Hilton-Jones, Chandi Ratnatunga, Maria Farrugia, Richard Petty, James Overell, Alan Kirk, Andrew Gibson, Chris McDermott, David Hopkinson, Bryan Lecky, David Watling, Dot Marshall, Sam Saminaden, Deborah Davies, Charlotte Dougan, Siva Sathasivam, Richard Page, Jon Sussman, John Ealing, Peter Krysiak, Anthony Amato, Mohammad Salajegheh, Michael Jaklitsch, Kristen Roe, Tetsuo Ashizawa, Robert Glenn Smith, Joseph Zwischenberg, Penny Stanton, Alexandru Barboi, Safwan Jaradeh, William Tisol, Mario Gasparri, George Haasler, Mary Yellick, Cedric Dennis, Richard Barohn, Mamatha Pasnoor, Mazen Dimachkie, April McVey, Gary Gronseth, Arthur Dick, Jeffrey Kramer, Melissa Currence, Laura Herbelin, Jerry Belsh, George Li, John Langenfeld, Mary Ann Mertz, Taylor Harrison, Seth Force, Sharon Usher, Said Beydoun, Frank Lin, Steve DeMeester, Salem Akhter, Ali Malekniazi, Gina Avenido, Brian Crum, Margherita Milone, Stephen Cassivi, Janet Fisher, Chad Heatwole, Thomas Watson, James Hilbert, Alexis Smirnow, B. Jane Distad, Michael Weiss, Douglas Wood, Joanna Haug, Raina Ernstoff, Jingyang Cao, Gary Chmielewski, Robert Welsh, Robin Duris, Laurie Gutmann, Gauri Pawar, Geoffrey Marc Graeber, Patricia Altemus, Christopher Nance, Ludwig Gutmann, Carlayne Jackson, Patrick Grogan, John Calhoon, Pamela Kittrell, Deborah Myers, Ghazala Hayat, Keith Naunheim, Susan Eller, Eve Holzemer, Amer Alshekhlee, Jason Robke, Brenda Karlinchak, Jonathan Katz, Robert Miller, Ralph Roan, Dallas Forshew, John Kissel, Bakri Elsheikh, Patrick Ross, Sharon Chelnick, Richard Lewis, Agnes Acsadi, Frank Baciewicz, Stacey Masse, Janice Massey, Vern Juel, Mark Onaitis, James Lowe, Bernadette Lipscomb, Gaby Thai, Jeffrey Milliken, Veronica Martin, Ronnie Karayan, Suraj Muley, Gareth Parry, Sara Shumway, Shin Oh, Gwen Claussen, Liang Lu, Robert Cerfolio, Angela Young, Marla Morgan, Robert Pascuzzi, John Kincaid, Kenneth Kesler, Sandy Guingrich, Angi Michaels, Lawrence Phillips, Ted Burns, David Jones, Cindy Fischer, Michael Pulley, Alan Berger, Harry D'Agostino, Lisa Smith, Michael Rivner, Jerry Pruitt, Kevin Landolfo, Demetric Hillman, Aziz Shaibani, Angelo Sermas, Ross Ruel, Farah Ismail, Mark Sivak, Martin Goldstein, Jorge Camunas, Joan Bratton, Hill Panitch, Bruce Leavitt, Marilee Jones, Srikanth Muppidi, Steven Vernino, Sharon Nations, Dan Meyer, and Nina Gorham
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0301 basic medicine ,Male ,medicine.medical_treatment ,Edrophonium ,law.invention ,0302 clinical medicine ,Randomized controlled trial ,law ,Prednisone ,Longitudinal Studies ,MGTX Study Group ,Thymectomy ,3. Good health ,Settore MED/26 - NEUROLOGIA ,Editorial Commentary ,Treatment Outcome ,6.1 Pharmaceuticals ,Female ,medicine.drug ,Adult ,medicine.medical_specialty ,Clinical Trials and Supportive Activities ,Clinical Sciences ,Autoimmune Disease ,Article ,03 medical and health sciences ,Young Adult ,Rare Diseases ,Clinical Research ,Internal medicine ,Myasthenia Gravis ,medicine ,Humans ,Adverse effect ,myasthenia gravis ,mgtx extension study ,Intention-to-treat analysis ,Neurology & Neurosurgery ,business.industry ,Neurosciences ,Evaluation of treatments and therapeutic interventions ,medicine.disease ,Myasthenia gravis ,Clinical trial ,030104 developmental biology ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
Summary Background The Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone (MGTX) showed that thymectomy combined with prednisone was superior to prednisone alone in improving clinical status as measured by the Quantitative Myasthenia Gravis (QMG) score in patients with generalised non-thymomatous myasthenia gravis at 3 years. We investigated the long-term effects of thymectomy up to 5 years on clinical status, medication requirements, and adverse events. Methods We did a rater-blinded 2-year extension study at 36 centres in 15 countries for all patients who completed the randomised controlled MGTX and were willing to participate. MGTX patients were aged 18 to 65 years at enrolment, had generalised non-thymomatous myasthenia gravis of less than 5 years' duration, had acetylcholine receptor antibody titres of 1·00 nmol/L or higher (or concentrations of 0·50–0·99 nmol/L if diagnosis was confirmed by positive edrophonium or abnormal repetitive nerve stimulation, or abnormal single fibre electromyography), had Myasthenia Gravis Foundation of America Clinical Classification Class II–IV disease, and were on optimal anticholinesterase therapy with or without oral corticosteroids. In MGTX, patients were randomly assigned (1:1) to either thymectomy plus prednisone or prednisone alone. All patients in both groups received oral prednisone at doses titrated up to 100 mg on alternate days until they achieved minimal manifestation status. The primary endpoints of the extension phase were the time-weighted means of the QMG score and alternate-day prednisone dose from month 0 to month 60. Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00294658. It is closed to new participants, with follow-up completed. Findings Of the 111 patients who completed the 3-year MGTX, 68 (61%) entered the extension study between Sept 1, 2009, and Aug 26, 2015 (33 in the prednisone alone group and 35 in the prednisone plus thymectomy group). 50 (74%) patients completed the 60-month assessment, 24 in the prednisone alone group and 26 in the prednisone plus thymectomy group. At 5 years, patients in the thymectomy plus prednisone group had significantly lower time-weighted mean QMG scores (5·47 [SD 3·87] vs 9·34 [5·08]; p=0·0007) and mean alternate-day prednisone doses (24 mg [SD 21] vs 48 mg [29]; p=0·0002) than did those in the prednisone alone group. 14 (42%) of 33 patients in the prednisone group, and 12 (34%) of 35 in the thymectomy plus prednisone group, had at least one adverse event by month 60. No treatment-related deaths were reported during the extension phase. Interpretation At 5 years, thymectomy plus prednisone continues to confer benefits in patients with generalised non-thymomatous myasthenia gravis compared with prednisone alone. Although caution is appropriate when generalising our findings because of the small sample size of our study, they nevertheless provide further support for the benefits of thymectomy in patients with generalised non-thymomatous myasthenia gravis. Funding National Institutes of Health, National Institute of Neurological Disorders and Stroke.
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- 2019
17. Alteration of visual cortical microstructure is associated with pathology along the optic radiation in patient with MS: an asymmetry analysis of posterior visual pathway
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Michael H. Barnett, Stephen Reddel, Justin Garber, Sidong Liu, and Chenyu Wang
- Published
- 2018
18. The Alemtuzumab MS Safety Systems (AMS3) study: clinical outcomes
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Stephen Reddel
- Published
- 2017
19. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial
- Author
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Coles, Alasdair J., Twyman, Cary L., Arnold, Douglas L., Cohen, Jeffrey A., Christian, Confavreux, Fox, Edward J., Hans Peter Hartung, Eva, Havrdova, Selmaj, Krzysztof W., Weiner, Howard L., Tamara, Miller, Elizabeth, Fisher, Rupert, Sandbrink, Lake, Stephen L., Margolin, David H., Pedro, Oyuela, Panzara, Michael A., Compston, D Alastair S., Gupta, the CARE MS II investigators: Ajay S., Edward, Fox, Glyman, Steven A., Thoits, Timothy K., Sullivan, Herman C., Cascione, Mark C., Rammohan, Kottil W., Gazda, Suzanne K., Wynn, Daniel R., Wray, Sibyl E., Stanton, Elias, Ford, Corey C., Andrew, Goodman, Hughes, Bruce L., Omar Azhar Khan, Vaishnav, Anand G., Stephen, Kirzinger, Lynch, Sharon G., Mattson, David H., Braley, Tiffany J., Mikol, Daniel D., Stephen, Krieger, Tamara Ann Miller, Riskind, Peter N., Roberto, Bomprezzi, Wingerchuk, Dean M., Brian, Steingo, Jeffrey Alan Cohen, Crayton, Heidi J., Cooper, Joanna A., Weiner, Leslie P., Harold Moses, J. r., Agius, Mark A., Ann Doan Do Bass, Lallana, Enrico C., Mitchell, Galen W., Krolczyk, Stanley J., Alireza, Minagar, Burk, Jubelt, Evans, Bradley K., Hunter, Samuel F., Rizvi, Syed A., Sheppard, Christopher A., David Honeycutt, W. M., Joseph, Herbert, Lathi, Ellen S., Gabriel, Pardo, Lily Jung Ilenson, Rothstein, Ted L., Thrower, Ben W., Mary Ann Picone, Mariko, Kita, Grazioli, Erica M., Silliman, Scott L., Thomas, Giancarlo, Gottesman, Malcolm H., Abou Zeid, Nuhad E., Rowe, Vernon D., Boutwell, Christine M., Schaeffer, John D., Riley, Claire S., Edwards, Keith R., Wendt, Jeanette K., G. Kim Bigley J. r., Shubin, Richard A., Silva Markovic Plese, Jones, Davis E., Gary, Clauser, Freedman, Mark S., Francois, Grand’Maison, Jacques, Francois H., Traboulsee, Anthony L., Brunet, Donald G., Marcelo, Kremenchutzky, Charles, Ayotte, Lava, Neil S., Waldman, Stephen R., Janus, Todd J., Stephen Gerard Vincent, Mark, Gudesblatt, Michael, Rossen, Stein, Lee S., Bennett Irving Machanic, Timothy, Vollmer, Gitt, Jeffrey S., Jeffrey, Dunn, Donald, Negroski, Fletcher, Mark H., Adil, Javed, Frohman, Elliot M., Richard, Macdonell, John Owen King, Paine, Mark A., Karyn, Boundy, Simon, Broadley, Steve, Vucic, Stephen, Reddel, Dreyer, Michael D., Raymond, Schwartz, Pamela Ann McCombe, Suzanne, Hodgkinson, Charles, Tilbery, Ferreira, Maria Lucia B., Dagoberto, Callegaro, Marcio Mena Barreto Martins, Jesus Arturo Violante Villanueva, Noemi Santos Caballero, Claudia Venzor Mendoza, Norma Haydee Deri, Alasdair, Coles, Neil James Scolding, Gavin, Giovannoni, Basil, Sharrack, Rog, David J., Giancarlo, Comi, Angelo, Ghezzi, Mancardi, Giovanni L., Durelli, Luca, Antonio, Bertolotto, Ruggero, Capra, Carlo, Pozzilli, Maria Giovanna Marrosu, Hupperts, Raymond M. M., Erik van Munster, Xavier, Montalbán, Rafael Arroyo González, Guillermo Izquierdo Ayuso, Óscar Fernández Fernández, Patrick, Vermersch, Jerome de Seze, Thibault, Moreau, Pierre, Clavelou, Catherine, Lubetzki, Michel, Clanet, Marc, Debouverie, Gilles, Edan, Judith, Haas, Martin, Stangel, Tjalf, Ziemssen, Bernhard, Hemmer, Karl, Baum, Klaus Zettl, U., Herrlinger, U., Wolfgang, Köhler, Gunter, Ochs, Patrick, Oschmann, Klaus Tiel Wilck, Hayrettin, Tumani, Urban, Peter P., Jan, Lycke, Anders, Svenningsson, Ivana, Kovarova, Marta, Vachova, Ivan, Rektor, Radomir, Talab, Krzysztof, Selmaj, Zbigniew, Stelmasiak, Wojciech, Kozubski, Dubois, Benedicte D. P., Dominique, Dive, Christian, Sindic, Karl, Vass, Per Soelberg Sørensen, Thor, Petersen, Mads, Ravnborg, Anat, Achiron, Adi Vaknin Dembinsky, Arnon, Karni, Gusev, Evgeny I., Stolyarov, Igor D., Zavalishin, Igor A., Skoromets, Alexander A., Boyko, Alexei N., Belova, Anna N., Malkova, Nadezhda A., Barantsevich, Evgeniy R., Yakupov, Eduard Z., Perfiliev, Semen V., Poverennova, Irina E., Voloshyna, Natalia P., Nehrych, Tetyana I., Kobys, Tetyana O., Mario, Habek, Vesna, Brinar, Zlatko, Trkanjec, Anton, Vladić, Spomenka Kidemet Piskać, Licia, Antonelli, Jelena, Drulović, Čongor, Nadj, Evica, Dinčić, Gordana, Tončev, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, Klinische Neurowetenschappen, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: MA Med Staf Spec Neurologie (9), RS: MHeNs School for Mental Health and Neuroscience, Radiology and nuclear medicine, and NCA - Multiple Sclerosis and Other Neuroinflammatory Diseases
- Subjects
Male ,Adult ,medicine.medical_specialty ,Adolescent ,CD52 ,multiple sclerosis ,Administration, Cutaneous ,Antibodies, Monoclonal, Humanized ,law.invention ,Young Adult ,Multiple Sclerosis, Relapsing-Remitting ,Adjuvants, Immunologic ,Randomized controlled trial ,Recurrence ,law ,Internal medicine ,Humans ,Medicine ,Glatiramer acetate ,Infusions, Intravenous ,Adverse effect ,Alemtuzumab ,disease ,business.industry ,Multiple sclerosis ,Interferon beta-1a ,Glatiramer Acetate ,General Medicine ,Middle Aged ,medicine.disease ,Treatment Outcome ,Immunology ,Female ,Ocrelizumab ,Peptides ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
The anti-CD52 monoclonal antibody alemtuzumab reduces disease activity in previously untreated patients with relapsing-remitting multiple sclerosis. We aimed to assess efficacy and safety of alemtuzumab compared with interferon beta 1a in patients who have relapsed despite first-line treatment.In our 2 year, rater-masked, randomised controlled phase 3 trial, we enrolled adults aged 18-55 years with relapsing-remitting multiple sclerosis and at least one relapse on interferon beta or glatiramer. Eligible participants were randomly allocated in a 1:2:2 ratio by an interactive voice response system, stratified by site, to receive subcutaneous interferon beta 1a 44 μg, intravenous alemtuzumab 12 mg per day, or intravenous alemtuzumab 24 mg per day. Interferon beta 1a was given three-times per week and alemtuzumab was given once per day for 5 days at baseline and for 3 days at 12 months. The 24 mg per day group was discontinued to aid recruitment, but data are included for safety assessments. Coprimary endpoints were relapse rate and time to 6 month sustained accumulation of disability, comparing alemtuzumab 12 mg and interferon beta 1a in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00548405.202 (87%) of 231 patients randomly allocated interferon beta 1a and 426 (98%) of 436 patients randomly allocated alemtuzumab 12 mg were included in the primary analyses. 104 (51%) patients in the interferon beta 1a group relapsed (201 events) compared with 147 (35%) patients in the alemtuzumab group (236 events; rate ratio 0·51 [95% CI 0·39-0·65]; p0·0001), corresponding to a 49·4% improvement with alemtuzumab. 94 (47%) patients in the interferon beta 1a group were relapse-free at 2 years compared with 278 (65%) patients in the alemtuzumab group (p0·0001). 40 (20%) patients in the interferon beta 1a group had sustained accumulation of disability compared with 54 (13%) in the alemtuzumab group (hazard ratio 0·58 [95% CI 0·38-0·87]; p=0·008), corresponding to a 42% improvement in the alemtuzumab group. For 435 patients allocated alemtuzumab 12 mg, 393 (90%) had infusion-associated reactions, 334 (77%) had infections (compared with 134 [66%] of 202 patients in the interferon beta 1a group) that were mostly mild-moderate with none fatal, 69 (16%) had thyroid disorders, and three (1%) had immune thrombocytopenia.For patients with first-line treatment-refractory relapsing-remitting multiple sclerosis, alemtuzumab could be used to reduce relapse rates and sustained accumulation of disability. Suitable risk management strategies allow for early identification of alemtuzumab's main adverse effect of secondary autoimmunity.Genzyme (Sanofi) and Bayer Schering Pharma.
- Published
- 2012
20. Extensive lip ulcers
- Author
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Stephen, Reddel
- Subjects
Erythema Multiforme ,Humans ,Female ,Lip Diseases ,Lip ,Ulcer - Published
- 2015
21. Treatment of myasthenia gravis
- Author
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Andrew Montanari and Stephen Reddel
- Subjects
medicine.medical_specialty ,business.industry ,medicine ,Pharmacology (medical) ,medicine.disease ,business ,Dermatology ,Myasthenia gravis - Abstract
The prevalence of myasthenia gravis (about 1 in 10 000 people) is such that every dentist will probably treat more...
- Published
- 2008
22. Heparin inhibits the binding of beta 2-glycoprotein I to phospholipids and promotes the plasmin-mediated inactivation of this blood protein. Elucidation of the consequences of the two biological events in patients with the anti-phospholipid syndrome
- Author
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Jan, Guerin, Yonghua, Sheng, Stephen, Reddel, G Michael, Iverson, Michael G, Chapman, and Steven A, Krilis
- Subjects
Binding Sites ,Time Factors ,Dose-Response Relationship, Drug ,Haptoglobins ,Cardiolipins ,Heparin ,Lysine ,Anticoagulants ,Antiphospholipid Syndrome ,Binding, Competitive ,Models, Biological ,Protein Structure, Tertiary ,beta 2-Glycoprotein I ,Mutation ,Mutagenesis, Site-Directed ,Humans ,Electrophoresis, Polyacrylamide Gel ,Fibrinolysin ,Peptides ,Phospholipids ,Glycoproteins ,Protein Binding - Abstract
The phospholipid-binding plasma protein beta2-glycoprotein I (beta2-GPI) is the primary antigen recognized by the circulating autoantibodies in patients with the "anti-phospholipid syndrome" (APS). Although heparin is routinely used in the treatment and prophylaxis of APS patients, the primary heparin-binding site within beta2-GPI has not been identified. More importantly, how heparin exerts its beneficial effects in vivo in APS patients has not been deduced at the molecular level. Using an expression/site-directed mutagenesis approach, we now show that the positively charged site that resides in the first domain of beta2-GPI is not the primary heparin-binding site. Rather it is the second positively charged site located within the fifth domain of the protein that also binds to phospholipids. Lys(284), Lys(286), and Lys(287) in this domain are essential for the interaction of beta2-GPI with heparin. These data indicate that beta2-GPI binds to heparin in a relatively specific manner even though the affinity for the interaction is rather low. Lys(317) resides in the center of the high affinity phospholipid-binding site. Surprisingly, heparin at concentrations that can be achieved in vivo during anticoagulation therapy greatly enhances the plasmin-mediated cleavage of the Lys(317)-Thr(318) site in beta2-GPI. Because the cleaved form cannot bind to phospholipids effectively, the combined actions of heparin and plasmin result in a diminished ability of beta2-GPI to recognize phospholipids. This, in turn, decreases the prothrombotic activity of the endogenous circulating anti-beta2-GPI antibodies in the patients. Thus, heparin exerts its beneficial effects in APS patients by at least two distinct mechanisms.
- Published
- 2001
23. Identification of basophilic cells that express mast cell granule proteases in the peripheral blood of asthma, allergy, and drug-reactive patients
- Author
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Li L, Li Y, Stephen Reddel, Cherrian M, Ds, Friend, Rl, Stevens, and Sa, Krilis
- Subjects
Adult ,Hypersensitivity, Immediate ,Male ,Carboxypeptidases A ,Staining and Labeling ,Serine Endopeptidases ,Convalescence ,Carboxypeptidases ,Middle Aged ,Asthma ,Basophils ,Drug Hypersensitivity ,Isoenzymes ,Leukocyte Count ,Chymases ,Enzyme Induction ,Acute Disease ,Humans ,Female ,Tryptases ,Mast Cells ,Biomarkers ,In Situ Hybridization - Abstract
Metachromatic cells in the peripheral blood of patients with asthma, allergy, or an allergic drug reaction were evaluated for their nuclear morphology, surface expression of the mast cell (MC) marker c-kit, surface expression of the basophil marker Bsp-1, and granule expression of MC proteases. Consistent with previous findings by others, Bsp-1+/metachromatic cells represented1% of the cells in the peripheral blood of normal individuals. These cells generally contained segmented nuclei. Very little, if any, tryptase (Try), chymase (Chy), or carboxypeptidase A (CPA) was found in their granules, and very little, if any, c-kit was observed on their surfaces. The number of metachromatic cells increased in the peripheral blood of the three groups of patients. Like the basophils in normal individuals, most of these metachromatic cells contained segmented nuclei and expressed Bsp-1. However, in contrast to the basophils in normal individuals, many of the metachromatic cells in the three patient groups expressed c-kit, Try, Chy, and/or CPA. That the metachromatic cells in the blood of our patients have some features of MCs and some features of basophils suggests that human basophils and MCs are derived from a common progenitor. As assessed by the chloroacetate esterase cytochemical assay, the immunoreactive Chy in the peripheral blood of these patients is enzymatically active. Because MC proteases regulate numerous immunologic and other biologic systems, the expression of Try, Chy, and/or CPA in a peripheral blood-localized cell in an individual having asthma, allergy, or an allergic drug reaction has important clinical implications.
- Published
- 1998
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