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المؤلفون: Esen Kiyan, Hacer Durmus, Zuleyha Bingol, Aylin Pihtili, Yesim Parman
المصدر: Muscle & Nerve. 63:683-689
مصطلحات موضوعية: Male, 0301 basic medicine, Vital capacity, Physiology, Diaphragm, Vital Capacity, Diaphragmatic breathing, Polysomnography, 030105 genetics & heredity, Ambulatory Care Facilities, Hypoxemia, Hypercapnia, 03 medical and health sciences, Cellular and Molecular Neuroscience, FEV1/FVC ratio, 0302 clinical medicine, Physiology (medical), Humans, Medicine, Outpatient clinic, Aged, Retrospective Studies, medicine.diagnostic_test, business.industry, Amyotrophic Lateral Sclerosis, Middle Aged, medicine.disease, Respiratory Function Tests, Obstructive sleep apnea, Pulse oximetry, Anesthesia, Female, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery
الوصف: INTRODUCTION In this study, we aimed to evaluate diaphragmatic dysfunction (DD) by using a practical approach in patients with amyotrophic lateral sclerosis (ALS) at the first visit to a chest diseases outpatient clinic. METHODS Patients with ALS seen in our outpatient clinic for the past 5 y and followed up for at least 1 y, were retrospectively evaluated. Having at least one of the following three criteria was accepted as DD: (a) paradoxical abdominal movement (PAM), (b) sitting-supine forced vital capacity (FVC) difference ≥ 20%, (c) sitting-supine arterial oxygen saturation measured by pulse oximetry (SpO2 ) difference ≥ 4%. Respiratory symptoms, arterial blood gas analysis, sleep studies, noninvasive mechanical ventilation use, and mortality were recorded. RESULTS Five-hundred patients with ALS were included (female/male: 220/280, age: 58.9 ± 11.3 y). Of the patients, 22.8% had daytime hypercapnia. DD was observed in 55% of the patients (PAM in 112, sitting-supine FVC difference ≥ 20% in 50, and sitting-supine SpO2 difference ≥ 4% in 113 patients). Of the patients with DD, 31.6% (n = 87) had no respiratory symptoms, 46.4% had FVC > 70% and 33.5% had FVC
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7cda2c360f31c96a868ac69dfa556585Test
https://doi.org/10.1002/mus.27200Test -
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المؤلفون: David Adams, Michael Polydefkis, Alejandra González-Duarte, Jonas Wixner, Arnt V Kristen, Hartmut H Schmidt, John L Berk, Inés Asunción Losada López, Angela Dispenzieri, Dianna Quan, Isabel M Conceição, Michel S Slama, Julian D Gillmore, Theodoros Kyriakides, Senda Ajroud-Driss, Márcia Waddington-Cruz, Michelle M Mezei, Violaine Planté-Bordeneuve, Shahram Attarian, Elizabeth Mauricio, Thomas H Brannagan, Mitsuharu Ueda, Emre Aldinc, Jing Jing Wang, Matthew T White, John Vest, Erhan Berber, Marianne T Sweetser, Teresa Coelho, Giuseppe Vita, Vincenzo Rizzo, Massimo Russo, Anna Mazzeo, Luca Gentile, Caitlin Brueckner, Victoria Lazzari, Janice Wiesman, Douglas DeLong, Jennifer Victory, James Dalton, John May, Catherine Gilmore, Saran Diallo, Emilien Delmont, Jean Pouget, Annie Verschueren, Aude-Marie Grapperon, Emmanuelle Campana-Salort, Ana Lopes, Filipa Lamas, Carlos Neves, Jose Castro, Pedro Pereira, Isabel Castro, Ana Franco, Miguel Oliveira Santos, Conceição de Azevedo Coutinho, Catarina Falcao de Campos, Antonio Hipólito Reis, Nuno Correia, Javier M Perez, Ana Martins da Silva, Cristina Alves, Marcio Cardoso, Katia Valdrez, Julia R Monte, Bernardete Pessoa, Nadia Guimaraes, Monica Freitas, Joana Ramalho, Natalia Ferreira, Daisuke Kuzume, Celine Tard, Nawal Waucquier, Isabelle Rougeaux, Sylvie Brice, Emmanuelle Kasprzyk, Elise Elrezzi, Sayah Meguig, Eric Hachulla, Clement Gauvain, Maria-Claire Migaud-Chervy, Dominique Deplanque, Elsa Jozefowicz, Loic Lebellec, Line Balaya-Gouraya, Nathalie Jehan Lacour, Halima Bournane, Nathalie Martin, Mongia Elabed, Niamey Sacko, Yasmine Boubrit, Amina Gaouar, Fetra Rakotondratafika, Marie Théaudin-Saliou, Cécile Cauquil-Michon, Celine Labeyrie, Adeline Not, Abdallah Al-Salameh, Anne-Lise Lecoq, Maeva Stephant, Andoni Echaniz-Laguna, Laurent Becquemont, Guillemette Beaudonnet, Vincent Algalarrondo, Ludivine Eliahou, Antoine Rousseau, Aissatou Signate, Emeline Berthelot, Jocelyn Inamo, Laetitia Vervoitte, Cecile Focseneanu, Thierry Gendre, Raphaele Arrouasse, Samar S. Ayache, Laura Ernande, Philippe Le Corvoisier, Hayet Salhi, Ariane Choumert, Vincent Ehinger, Julie Ruiz, Cyril Charlin, Thomas Megelin, Thomas H Brannagan III, Raisy Fayerman, Arreum Kim, Allan Paras, Leidy J Gonzalez, Steven Tsang, Fernanda Wajnsztajn, Jeffrey Shije, Christina Ulane, Inna Kleyman, Louis Weimer, Comana Cioroiu, Sakis Lambrianides, Rana Abu-Manneh, Eleni Zamba-Papanicolaou, Petros Agathangelou, Eleni Leonidou, Satoshi Tada, Akemi Fujita, Masahiro Nagai, Rina Ando, Yuko Hosokawa, Yuki Yamanishi, J. Scott Overcash, Elena Giardino, Leslie Boyer, Lien Dang, An Le, Tyler Nguyen, Lien Giang, Peter Sellers, Leyla Tran, Nghi Truong, Maita Vinas, Nicole Hrkman, Sarah Miller, David Nguyen, Ashley Smith, Helen Pu, Steve Li, Thao Vuong, Holly Dioso, Sinikka Green, Kia Lee, Hanh Chu, Michael Waters, Derya J Coskun, Karla A Zepeda, William O'Riordan, Laura Obici, Andrea Cortese, Alessandro Lozza, Giampaolo Merlini, Vittorio Rosti, Mario Sabatelli, Giulia Bisogni, Daniela Bernardo, Marco Luigetti, Andrea Di Paolantonio, Valeria Guglielmino, Angela Romano, Hans Nienhuis, Janita Bulthuis-Kuiper, Olga Gerk, Hannah Ulbricht, Lenka Taylor, Eva Meyle, Natalia Kleinschmidt, David Meyrath, Simone Noe-Schwenn, Ulrike Meng, Ralf Bauer, Fabian aus dem Siepen, Selina Hein, Tetsuya Takahashi, Tomohiko Oshita, Yoko Koujin, Shuichiro Neshige, Tomohisa Nezu, Akiko Segawa, Hiroki Ueno, Hiroyuki Morino, Josep M Campistol, Lida Maria Rodas Marin, Josep Miquel Blasco Pelicano, Lucía Galán Dávila, Marta Palacios, Vanesa Pytel Cordoba, Antonio Guerrero Sola, Alejandro Horga, Julián García Feijoo, Leopoldo Perez de Isla, Wilson Marques Júnior, Mariana Moscardini, Debora Cristina Litcanov, Ana Flavia Viera Lima, Leonardo Rodrigues, Barbara Marques Coutinho, Carolina Lavigne Moreira, Vanessa Daccach Marques, Francisco Munoz Beamud, Álvaro Gragera Martínez, Cristina Borrachero, Eugenia Cisneros Barroso, Adrián Rodríguez Rodríguez, Monica Sanz, Elena Rigo Oliver, Juan González Moreno, Jose M Gamez Martinez, Cristina Descals, Mercedes Uson, Francisco Jose Vega, Antoni Figuerola, Carles Montala, Moises Dias da Silva, Renata Gervais de Santa Rosa, Luiz Felipe Pinto, Marcus Vinicius Pinto, Amanda Cardoso Berensztejn, Fabio Barroso, Andrea Lautre, Lucas G Orellana, Maria Alejandra González-Duarte Briseño, Karla Cárdenas-Soto, Brenda Poled Jiménez López, Sandra Lorena Pérez-Castañeda, Carlos Gerardo Cantú Brito, David Rivera de la Parra, Jose Pablo Hernandez Reyes, Maria del Mar Saniger Alba, Elia Criollo Mora, Yesim Parman, Kus Jülide Rezzan, Erdi Sahin, Nail G Serbest, Hacer Durmus, Arman Cakar, Nuriye Ilknur Tugal Tutkun, Sacit Karamursel, Ali Elitok, Nermin G Sirin Inan, Emre Altinkurt, Jing Ye, Adriane C Allen, Vinay Chaudhry, Raquel Jarrett, Neil Bressler, Kathleen L Burks, Qingfeng Liu, Mohammad Khoshnoodi, Daniel P Judge, Geno Vista, Syed Mahmood Shah, Hirotoshi Hamaguchi, Junko Oda, Emi Fukase, Ikuko Taniguchi, Tetsuya Oda, Hironobu Endo, Masahiro Shimomura, Kimitaka Katanazaka, Shusuke Koto, Takahiro Nakano, Christof Scheid, Andreas Zueiter, Lars Pester, Doreen Walter, Betül Özdemir, Lukas F Frenzel, Udo Holtick, Jeeyoung Oh, Hee Jin Kim, Hyun Jin Shin, Kyomin Choi, Taro Yamashita, Teruaki Masuda, Yohei Misumi, Akihiko Ueda, Keiichi Nakahara, Akiko Yorita, Seiko Tsuruhisa, Takayuki Taniwaki, Masaya Harada, Taiga Moritaka, Naonori Sakurada, Elizabeth A Mauricio, Amber Baskin, Elliot Dimberg, Amie Fonder, Miriam Hobbs, Stephen J Russell, Peter Dyck, Wilson Gonsalves, Nelson Leung, Thomas E Witzig, Steven R Zeldenrust, Lisa Hwa, Prashant Kapoor, Shaji K Kumar, Yi Lin, John A Lust, Vincent S Rajkumar, David Dingli, Morie A Gertz, Ronald Go, Suzanne R Hayman, Samir Dalia, Esmeralda Carrillo, Peter Gorevic, Garnette Mason, Chi-Chao Chao, Ming-Jen Lee, Jen-Jen Su, Sung-Tsang Hsieh, Li-Kai Tsai, Shin-Joe Yeh, Chih-Chao Yang, Senda Ajroud-Driss Ajroud-Driss, Patricia Casey, Benjamin C Joslin, Miriam Freimer, Alison Sankey, Amanda Kenepp, Sarah Heintzman, Samantha LoRusso, Youichi Hokezu, Byoung-Joon Kim, JuHyeon Kim, Ga Yeon Lee, Eun Bin Cho, Eun-Seok Jeon, Ju-Hong Min, Jin Myoung Seok, Hye Lim Lee, Jae Hong Park, Yoshiki Sekijima, Chinatsu Miyazawa, Nagaaki Kato, Dai Kishida, Akiyo Hineno, Minori Kodaira, Tsuneaki Yoshinaga, Teruyoshi Miyahara, Akira Imai, Kazuhiko Matsumoto, Kon-Ping Lin, Yi-Chung Lee, Malin Falk, Bjorn Pilebro, Ole Suhr, Per Lindqvist, Karin Soderberg, Fatima Pedrosa-Domellöf, Intissar Anan, Erik Nordh, Ivaylo Tournev, Sashka Zhelyazkova-Glaveeva, Zheyna Cherneva, Staiko Sarafov, Teodora Chamova, Sylvia Cherninkova-Gopina, Frauke Friebel, Andree Zibert, Natasa Mihailovic, Friederike Schubert, Elena Vorona, Larissa Lahme, Anna Huesing-Kabar, Matthias Schilling, Iyad Kabar, Ana Martinez-Naharro, Liza Chacko, Oliver Cohen, Steven Law, Tamer Rezk, Helen J Lachmann, Brianna Blume, Stacy Dixon, Soon Chai Low, Soo Looi Chan, He Eng Li Lim, Khean Jin Goh, Deborah Kraus, Kristin Jack, N. Kevin Wade, Glenn Lopate, Brittany Zwijack, Julaine Florence, R. Brian Sommerville, Graeme Stewart, Julie Ryder, Linda Mekhael, Mark Taylor, Daniel Suan, Karen Wells, Paula Stone, Amenze Itoya, Mercy Owusu-Sekyere, Desmond Thai, Ilonah Chahine, Salve Pedrosa, Thi Hoa (Therese) Do
المساهمون: Repositório da Universidade de Lisboa
المصدر: The Lancet Neurology. 20:49-59
مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, 030204 cardiovascular system & hematology, Placebo, Severity of Illness Index, Polyneuropathies, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Internal medicine, Outcome Assessment, Health Care, Severity of illness, medicine, Humans, Prealbumin, RNA, Small Interfering, Infusions, Intravenous, Adverse effect, Aged, Amyloid Neuropathies, Familial, business.industry, Middle Aged, medicine.disease, Interim analysis, amyloidosis, transthyretin, polyneuropathy, patisiran, OLE study, Clinical trial, Female, Neurology (clinical), business, Polyneuropathy, 030217 neurology & neurosurgery, Progressive disease
الوصف: © 2020 Elsevier Ltd. All rights reserved.
Background: Hereditary transthyretin-mediated amyloidosis is a rare, inherited, progressive disease caused by mutations in the transthyretin (TTR) gene. We assessed the safety and efficacy of long-term treatment with patisiran, an RNA interference therapeutic that inhibits TTR production, in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Methods: This multicentre, open-label extension (OLE) trial enrolled patients at 43 hospitals or clinical centres in 19 countries as of Sept 24, 2018. Patients were eligible if they had completed the phase 3 APOLLO or phase 2 OLE parent studies and tolerated the study drug. Eligible patients from APOLLO (patisiran and placebo groups) and the phase 2 OLE (patisiran group) studies enrolled in this global OLE trial and received patisiran 0·3 mg/kg by intravenous infusion every 3 weeks with plans to continue to do so for up to 5 years. Efficacy assessments included measures of polyneuropathy (modified Neuropathy Impairment Score +7 [mNIS+7]), quality of life, autonomic symptoms, nutritional status, disability, ambulation status, motor function, and cardiac stress, with analysis by study groups (APOLLO-placebo, APOLLO-patisiran, phase 2 OLE patisiran) based on allocation in the parent trial. The global OLE is ongoing with no new enrolment, and current findings are based on the interim analysis of the patients who had completed 12-month efficacy assessments as of the data cutoff. Safety analyses included all patients who received one or more dose of patisiran up to the data cutoff. This study is registered with ClinicalTrials.gov, NCT02510261. Findings: Between July 13, 2015, and Aug 21, 2017, of 212 eligible patients, 211 were enrolled: 137 patients from the APOLLO-patisiran group, 49 from the APOLLO-placebo group, and 25 from the phase 2 OLE patisiran group. At the data cutoff on Sept 24, 2018, 126 (92%) of 137 patients from the APOLLO-patisiran group, 38 (78%) of 49 from the APOLLO-placebo group, and 25 (100%) of 25 from the phase 2 OLE patisiran group had completed 12-month assessments. At 12 months, improvements in mNIS+7 with patisiran were sustained from parent study baseline with treatment in the global OLE (APOLLO-patisiran mean change -4·0, 95 % CI -7·7 to -0·3; phase 2 OLE patisiran -4·7, -11·9 to 2·4). Mean mNIS+7 score improved from global OLE enrolment in the APOLLO-placebo group (mean change from global OLE enrolment -1·4, 95% CI -6·2 to 3·5). Overall, 204 (97%) of 211 patients reported adverse events, 82 (39%) reported serious adverse events, and there were 23 (11%) deaths. Serious adverse events were more frequent in the APOLLO-placebo group (28 [57%] of 49) than in the APOLLO-patisiran (48 [35%] of 137) or phase 2 OLE patisiran (six [24%] of 25) groups. The most common treatment-related adverse event was mild or moderate infusion-related reactions. The frequency of deaths in the global OLE was higher in the APOLLO-placebo group (13 [27%] of 49), who had a higher disease burden than the APOLLO-patisiran (ten [7%] of 137) and phase 2 OLE patisiran (0 of 25) groups. Interpretation: In this interim 12-month analysis of the ongoing global OLE study, patisiran appeared to maintain efficacy with an acceptable safety profile in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Continued long-term follow-up will be important for the overall assessment of safety and efficacy with patisiran.وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ce6a19ce91101df4f11e95eb6d009161Test
https://doi.org/10.1016/s1474-4422Test(20)30368-9 -
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المؤلفون: Hülya Kayserili, Haluk Topaloglu, Ayaz Aghayev, Zehra Oya Uyguner, Sahin Avci, Hacer Durmus, Zuhal Yapici, Pinar Tekturk, Seher Başaran, Yesim Parman, Umut Altunoglu, Piraye Oflazer-Serdaroglu, B Sevinc Rustemoglu, Gulendam Bagirova, Feza Deymeer, Güven Toksoy, Birsen Karaman
المصدر: Neuromuscular Disorders. 29:601-613
مصطلحات موضوعية: Adult, Male, 0301 basic medicine, Turkey, Duchenne muscular dystrophy, Genetic counseling, In silico, Genetic Counseling, Chromosomal translocation, Biology, Carrier testing, medicine.disease_cause, Cohort Studies, Dystrophin, Young Adult, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Multiplex ligation-dependent probe amplification, Child, Genetics (clinical), Genetics, Mutation, High-Throughput Nucleotide Sequencing, Infant, Karyotype, Sequence Analysis, DNA, medicine.disease, Muscular Dystrophy, Duchenne, Phenotype, 030104 developmental biology, Neurology, Child, Preschool, Pediatrics, Perinatology and Child Health, Female, Neurology (clinical), 030217 neurology & neurosurgery
الوصف: We genetically evaluated 260 dystrophinopathy patients from Turkey. Karyotyping as an initial test in female patients, followed stepwise by multiplex ligation-dependent probe amplification and by targeted next-generation sequencing of DMD revealed definitive genetic diagnoses in 214 patients (82%), with gross deletions/duplications in 153 (59%), pathogenic sequence variants in 60 (23%), and X-autosome translocation in one. Seven of the gross and 27 of the sequence variants found novel. In silico prediction, co-segregation and transcript assays supported the pathogenic nature of the novel silent (p.Lys534=) and the splice site (c.4345-12C>G) alterations. From a total of 189 singleton cases, 154 (82%) had pathogenic alterations. From 138 of those who had maternal carrier testing, 68 out of 103 (66%) showed gross and 11 out of 35 (31%) showed small pathogenic variants. This suggests that the de novo occurrences in DMD appear approximately 2.1 times more frequently in meiotic unequal crossing-over than in uncorrected replication errors. Our study also disclosed three mothers as obligate gonadal mosaic carriers. Family-based investigation of dystrophinopathy patients is crucial for the ascertainment of novel or rare variants and also for counseling and follow-up care of the families.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::190147c364cb01ee776840e7569ad457Test
https://doi.org/10.1016/j.nmd.2019.03.012Test -
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المصدر: Neurophysiologie Clinique. 48:261-267
مصطلحات موضوعية: Adult, Male, 0301 basic medicine, Weakness, Needle electrode, Facial Muscles, Newly diagnosed, Generalized weakness, Concentric, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), Myasthenia Gravis, otorhinolaryngologic diseases, medicine, Humans, Repetitive nerve stimulation, Muscle, Skeletal, Electrodes, Aged, Jitter, Neurologic Examination, Electromyography, business.industry, General Medicine, Middle Aged, medicine.disease, Electric Stimulation, Myasthenia gravis, 030104 developmental biology, Neurology, Needles, Anesthesia, Female, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery
الوصف: Summary Introduction The aim of this study was to define the diagnostic accuracy of concentric needle (CN)-jitter in newly diagnosed myasthenia gravis (MG) patients and to compare CN-jitter with repetitive nerve stimulation. Methods In 30 MG patients, repetitive nerve stimulation in 4 muscles (orbicularis oculi, nasalis, trapezius and abductor digiti minimi) and CN-jitter of extensor digitorum (ED) and frontalis muscles were evaluated. Results Twenty-eight of 30 patients (93%) had high jitter in at least one muscle. Repetitive nerve stimulation was abnormal in 23 of the patients (77%). Eighty-six percent of the patients in whom repetitive nerve stimulation test was negative could be diagnosed with CN-jitter. The most frequent muscle showing abnormal decrement was orbicularis oculi. The results of CN-jitter were similar between patients with different serological groups. Of 13 patients with generalized weakness, all had high jitter in both muscles studied whereas of 17 patients only with ocular weakness, 15 had high jitter in at least one muscle studied. Conclusion Abnormal RNS was present in 77% of newly diagnosed MG patients, being less than CN-jitter (93%) but more than antibody positivity (73.3%).
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fb77037b631f07801a79c8c2a72ebe06Test
https://doi.org/10.1016/j.neucli.2018.01.003Test -
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المصدر: Acta neurologica Belgica. 121(6)
مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Neurology, Mutation, Missense, Action Potentials, Bioinformatics, medicine.disease_cause, Neuromuscular junction, Protein Structure, Secondary, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Fluoxetine, medicine, Missense mutation, Humans, Receptors, Cholinergic, 030212 general & internal medicine, Amino Acid Sequence, Muscle, Skeletal, Exome sequencing, Sanger sequencing, Myasthenic Syndromes, Congenital, Mutation, Dose-Response Relationship, Drug, business.industry, General Medicine, Compound muscle action potential, Pedigree, Protein Structure, Tertiary, Nicotinic acetylcholine receptor, medicine.anatomical_structure, Treatment Outcome, symbols, Neurology (clinical), business, 030217 neurology & neurosurgery
الوصف: Congenital myasthenic syndromes are rare hereditary disorders caused by mutations associated with proteins of the neuromuscular junction. Abnormal ‘‘gain of function’’ mutations result in prolonged nicotinic acetylcholine receptor channel open state causing a rare subtype of CMS, slow-channel CMS (SCCMS). Mutations in the delta subunit encoding the gene, CHRND, resulting in SCCMS are extremely rare. An important clue to the diagnosis of SCCMS is repetitive CMAP’s. Fluoxetine, usually at high doses, is used to treat SCCMS. The mutation, recently described in one patient, was identified by whole exome sequencing and validated, and its segregation with the disease was ascertained by Sanger sequencing. Here, we describe clinical and genetic findings of an early onset SCCMS patient carrying a very rare missense mutation c.880C > T in CHRND causing a highly conserved leucine to phenylalanine substitution in the M2 domain of CHRND. The patient had no repetitive CMAP. He had a dramatic response to fluoxetine at low–moderate doses (40 mg/day), increasing over months: Being wheelchair bound, he could walk independently after treatment. Rare cases may offer insight into the pathological gating mechanism leading to CMS. SCCMS should be suspected even without a repetitive CMAP. Fluoxetine at relatively low doses can be a very effective treatment.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a83fd445ee709d38451a4488d96f3715Test
https://pubmed.ncbi.nlm.nih.gov/33030681Test -
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المؤلفون: Yesim Parman, Vuslat Yilmaz, Güher Saruhan-Direskeneli, Hacer Durmus, Piraye Oflazer, Fikret Aysal, Erdem Tüzün, Ozlem Gungor-Tuncer, Feza Deymeer
المصدر: Journal of neuroimmunology. 349
مصطلحات موضوعية: 0301 basic medicine, Adult, Male, Adolescent, medicine.medical_treatment, Immunology, CD38, CD19, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Myasthenia Gravis, medicine, Immunology and Allergy, Humans, B-cell activating factor, Child, B cell, Aged, B-Lymphocytes, biology, business.industry, Immunosuppression, Middle Aged, medicine.disease, Myasthenia gravis, Pathophysiology, 030104 developmental biology, medicine.anatomical_structure, Treatment Outcome, Neurology, biology.protein, Female, Neurology (clinical), Antibody, business, 030217 neurology & neurosurgery, Biomarkers, Immunosuppressive Agents
الوصف: B cells play a major role in the pathophysiology of myasthenia gravis (MG) with their ability to produce disease specific, pathogenic antibodies. However, their status during disease development and follow-up stages of the disease in the peripheral blood may need further studies to determine useful markers. In this study, we aimed to detect B cell associated factors concerning immunosuppressive treatment in generalized non-thymomatous MG patients. Although CD19(+) B cell distribution did not vary among disease subgroups, expressions of both CD38 and BAFFR were altered on B cells in MG patients under immunosuppressive therapy. Serum levels of BAFF were elevated in untreated MG patients as compared to treated MG patients and healthy controls. B cell activation factors may show profound alterations due to immunosuppression.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f5ce74a658149bb47de6d62c23141cf3Test
https://pubmed.ncbi.nlm.nih.gov/32977248Test -
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المؤلفون: Melih Tutuncu, Oner Dogan, Fikret Aysal, Merve Cebi, Arman Çakar, Yesim Parman, Berker Özkan, Mehmet Hocaoglu, Metin Mercan, Vildan Yayla, Onur Akan, Güher Saruhan-Direskeneli, Gizem Engin Gül, Sibel P. Yentür, Hacer Durmus
المساهمون: İÜC, Cerrahpaşa Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü
المصدر: Frontiers in Immunology
Frontiers in Immunology, Vol 11 (2020)مصطلحات موضوعية: 0301 basic medicine, CD4-Positive T-Lymphocytes, Male, Chemokine, medicine.medical_treatment, Programmed Cell Death 1 Receptor, Chemokine receptor, 0302 clinical medicine, PD-1, IL-21, Immunology and Allergy, Receptors, Cholinergic, Original Research, biology, Chemistry, Interleukin-17, Middle Aged, IL-17, Cytokine, medicine.anatomical_structure, Female, Interleukin 17, Antibody, Immunosuppressive Agents, Signal Transduction, lcsh:Immunologic diseases. Allergy, Adult, Adolescent, T Follicular Helper Cells, T cell, Immunology, Inducible T-Cell Co-Stimulator Protein, 03 medical and health sciences, Young Adult, Myasthenia Gravis, medicine, Humans, Interleukin 4, Aged, Autoantibodies, Immunosuppression Therapy, myasthenia gravis, Interleukins, IL-4, CXCR5, Thymectomy, 030104 developmental biology, ICOS, biology.protein, T follicular helper cells, Interleukin-4, lcsh:RC581-607, 030215 immunology
الوصف: WOS:000538882900001 PubMed ID: 32508812 Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies predominantly against the acetylcholine receptor (AChR). Specific T cell subsets are required for long-term antibody responses, and cytokines secreted mainly from CD4(+) T cells regulate B cell antibody production. The aim of this study was to assess the differences in the cytokine expressions of CD4(+) T cells in MG patients with AChR antibodies (AChR-MG) and the effect of immunosuppressive (IS) therapy on cytokine activity and to test these findings also in MG patients without detectable antibodies (SN-MG). Clinically diagnosed AChR-MG and SN-MG patients were included. The AChR-MG patients were grouped as IS-positive and -negative and compared with age- and sex-matched healthy controls. Peripheral blood mononuclear cells were used for ex vivo intracellular cytokine production, and subsets of CD4(+) T cells and circulating follicular helper T (cTfh) cells were detected phenotypically by the expression of the chemokine and the costimulatory receptors. Thymocytes obtained from patients who had thymectomy were also analyzed. IL-21, IL-4, IL-10, and IL-17A productions in CD4(+) T cells were increased in AChR-MG compared to those in healthy controls. IS treatment enhanced IL-10 and reduced IFN-gamma production in AChR-MG patients compared to those in IS-negative patients. Increased IL-21 and IL-4 productions were also demonstrated in SN-MG patients. Among CD4(+) T cells, Th17 cells were increased in both disease subgroups. Treatment induced higher proportions of Th2 cells in AChR-MG patients. Both CXCR5(+) and CXCR5(-) CD4(+) T cells expressed higher programmed cell death protein 1 (PD-1) and inducible costimulatory (ICOS) in AChR-MG and SN-MG groups, mostly irrespective of the treatment. Based on chemokine receptors on CXCR5(+)PD-1(+) in CD4(+) T (cTfh) cells, in AChR-MG patients without treatment, the proportions of Tfh17 cells were higher than those in the treated group, whereas the Tfh1 cells were decreased compared with those in the controls. The relevance of CXCR5 and PD-1 in the pathogenesis of AChR-MG was also suggested by the increased presence of these molecules on mature CD4 single-positive thymocytes from the thymic samples. The study provides further evidence for the importance of IL-21, IL-17A, IL-4, and IL-10 in AChR-MG. Disease-related CD4(+)T cells are identified mainly as PD-1(+) or ICOS+ with or without CXCR5, resembling cTfh cells in the circulation or probably in the thymus. AChR-MG and SN-MG seem to have some similar characteristics. IS treatment has distinctive effects on cytokine expression. TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [116S317]; Istanbul University Research FundIstanbul University This study was supported by TUBITAK (116S317) and Istanbul University Research Fund.
وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::273c967f5cde2dabc6846cda979ed160Test
https://hdl.handle.net/20.500.12511/5437Test -
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المؤلفون: Bülent Kara, Piraye Serdaroglu-Oflazer, Xin Ming Shen, Yesim Parman-Gulsen, Joan M. Brengman, Coşkun Özdemir, Andrew G. Engel, Feza Deymeer, Hacer Durmus
المصدر: Neuromuscular Disorders. 28:315-322
مصطلحات موضوعية: Male, 0301 basic medicine, medicine.medical_specialty, Pathology, Adolescent, Neuromuscular Junction, Muscle Proteins, Disease, Gastroenterology, Article, Neuromuscular junction, Young Adult, 03 medical and health sciences, 0302 clinical medicine, health services administration, Internal medicine, COLQ, medicine, Humans, CHRNE, Receptors, Cholinergic, health care economics and organizations, Genetics (clinical), Retrospective Studies, Acetylcholine receptor, Myasthenic Syndromes, Congenital, biology, business.industry, Muscle weakness, Prognosis, Choline acetyltransferase, Phenotype, 030104 developmental biology, medicine.anatomical_structure, Neurology, Pyridostigmine, Mutation, Pediatrics, Perinatology and Child Health, Acetylcholinesterase, biology.protein, Female, Collagen, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, Follow-Up Studies, medicine.drug
الوصف: Congenital myasthenic syndromes (CMS) are a group of hereditary disorders affecting the neuromuscular junction. Here, we present clinical, electrophysiological and genetic findings of 69 patients from 51 unrelated kinships from Turkey. Genetic tests of 60 patients were performed at Mayo Clinic. Median follow-up time was 9.8 years (range 1-22 years). The most common CMS was primary acetylcholine receptor (AChR) deficiency (31/51) and the most common mutations in AChR were c.1219 + 2T G (12/51) and c.1327delG (6/51) in CHRNE. Four of our 5 kinships with AChE deficiency carried p.W148X that truncates the collagen domain of COLQ, and was previously reported only in patients from Turkey. These were followed by GFPT1 deficiency (4/51), DOK7 deficiency (3/51), slow channel CMS (3/51), fast channel CMS (3/51), choline acetyltransferase deficiency (1/51) and a CMS associated with desmin deficiency (1/51). Distribution of muscle weakness was sometimes useful in giving a clue to the CMS subtype. Presence of repetitive compound muscle action potentials pointed to AChE deficiency or slow channel CMS. Our experience confirms that one needs to be cautious using pyridostigmine, since it can worsen some types of CMS. Ephedrine/salbutamol were very effective in AChE and DOK7 deficiencies and were useful as adjuncts in other types of CMS. Long follow-up gave us a chance to assess progression of the disease, and to witness 12 mainly uneventful pregnancies in 8 patients. In this study, we describe some new phenotypes and detail the clinical features of the well-known CMS.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0c8a17c575429d766f1cd587ba6a605aTest
https://doi.org/10.1016/j.nmd.2017.11.013Test -
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المؤلفون: Yesim Parman, Vuslat Yilmaz, Feza Deymeer, Guher Saruhan Direskeneli, Hacer Durmus, Piraye Oflazer, Senay Yildiz Celik
المصدر: Acta neurologica Belgica. 120(1)
مصطلحات موضوعية: Male, medicine.medical_specialty, Neurology, Azathioprine, Late onset, Disease, Outcome (game theory), Severity of Illness Index, Serology, 03 medical and health sciences, 0302 clinical medicine, Prednisone, Internal medicine, Myasthenia Gravis, Outcome Assessment, Health Care, medicine, Humans, Connectin, Receptors, Cholinergic, 030212 general & internal medicine, Age of Onset, Aged, Autoantibodies, business.industry, Remission Induction, Receptor Protein-Tyrosine Kinases, General Medicine, Middle Aged, medicine.disease, Myasthenia gravis, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug, Follow-Up Studies
الوصف: Late-onset myasthenia gravis (LOMG) is a unique MG subgroup. More information is needed on its subgroups such as non-thymomatous generalized LOMG. We evaluated the effect of demographic, clinical, and serological factors as well as different immunosuppressive modalities on outcome in generalized non-thymomatous LOMG with onset ≥ 50 years. Myasthenia Gravis Foundation of America (MGFA) Clinical Classification, MGFA postintervention score (MGFA PIS) and MG Composite scores were obtained to define the severity of disease and clinical outcome. In 95 patients with generalized non-thymomatous LOMG, 60 (63%) were men, 45 (47%) had mild disease, 80 (84%) were anti-AChR, and 56 (61%) were anti-titin positive. In those who received immunosuppressives and provided the clinical scores (84 patients), 50 (60%) had favorable outcome (MGFA PIS categories of complete stable remission, pharmacological remission and minimal manifestations) at the end of 3 years. Use of prednisone + azathioprine had significantly positive effect on outcome. The presence of anti-titin antibodies had no significant effect on severity and outcome. Five anti-MuSK-positive patients had favorable outcome. In conclusion, the presence of neither anti-titin nor anti-MuSK antibodies points to unfavorable outcome. Prednisone and azathioprine combination has beneficial effects in non-thymomatous generalized LOMG.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1267f516054ed11f00fe58ec6c3a3f44Test
https://pubmed.ncbi.nlm.nih.gov/31811563Test -
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المؤلفون: Yesim Parman, Arman Çakar, Gulshan Yunisova, Ayse Candayan, A. Nazli Basak, Esra Battaloglu, Hacer Durmus
المصدر: Neurogenetics. 21(1)
مصطلحات موضوعية: 0301 basic medicine, Adult, Male, congenital, hereditary, and neonatal diseases and abnormalities, Ataxia, Adolescent, Turkey, Mutation, Missense, Biology, Compound heterozygosity, 03 medical and health sciences, Cellular and Molecular Neuroscience, Young Adult, 0302 clinical medicine, Charcot-Marie-Tooth Disease, Iron-Binding Proteins, Genetics, medicine, Missense mutation, Humans, Family, Gene, Genetics (clinical), Homozygote, Human genetics, nervous system diseases, Pedigree, 030104 developmental biology, Phenotype, Mutation (genetic algorithm), Frataxin, biology.protein, Female, medicine.symptom, Trinucleotide repeat expansion, 030217 neurology & neurosurgery
الوصف: Charcot-Marie-Tooth (CMT) disease is the most common inherited neuropathy with a prevalence of 1 in 2500 individuals worldwide. Here, we report three Turkish siblings from consanguineous parents presenting with a CMT-like phenotype who carry a homozygous c.493C>T, p.Arg165Cys mutation in the FXN gene that is the only known causative gene for Friedreich's ataxia (FRDA). The identified missense mutation has been reported previously in two FRDA cases in compound heterozygosity with the common GAA repeat expansion in the first intron of the FXN gene. Analysis of skin biopsy samples from our family indicated that the mutation does not affect the expression levels of the frataxin, pointing to functional impairment of the corresponding protein. The CMT phenotype in the siblings was associated with visual impairment, optic nerve atrophy, and dysarthria. To the best of our knowledge, this family represents the first FXN missense mutation in homozygosity and challenges the notion that missense mutations have not been reported yet due to their embryonic lethality. Furthermore, this finding poses an interesting genetic overlap between autosomal recessive CMT and FRDA that we believe may have important implications on understanding the pathogenesis of these neurological disorders.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::030ae525e1f6e06ec13f92250de1d7e1Test
https://pubmed.ncbi.nlm.nih.gov/31673878Test
