المؤلفون: Walaa Karazi, Renata S. Scalco, Mads G. Stemmerik, Nicoline Løkken, Alejandro Lucia, Alfredo Santalla, Andrea Martinuzzi, Marinela Vavla, Gianluigi Reni, Antonio Toscano, Olimpia Musumeci, Carlyn V. Kouwenberg, Pascal Laforêt, Beatriz San Millán, Irene Vieitez, Gabriele Siciliano, Enrico Kühnle, Rebecca Trost, Sabrina Sacconi, Hacer Durmus, Biruta Kierdaszuk, Andrew Wakelin, Antoni L. Andreu, Tomàs Pinós, Ramon Marti, Ros Quinlivan, John Vissing, Nicol C. Voermans, EUROMAC Consortium

المصدر: Orphanet Journal of Rare Diseases, Vol 18, Iss 1, Pp 1-9 (2023)

مصطلحات موضوعية: McArdle disease, Glycogen storage disease V, Rare diseases, International registry, Health care, Medicine

الوصف: Abstract Background The European registry for individuals with GSD5 and other muscle glycogenosis (EUROMAC) was launched to register rare muscle glycogenosis in Europe, to facilitate recruitment for research trials and to learn about the phenotypes and disseminate knowledge about the diseases. A network of twenty collaborating partners from eight European countries and the US contributed data on rare muscle glycogenosis in the EUROMAC registry. Methods Following the initial report on demographics, neuromuscular features and comorbidity (2020), we here present the data on social participation, previous and current treatments (medication, supplements, diet and rehabilitation) and limitations. Furthermore, the following questionnaires were used: Fatigue severity scale (FSS), WHO Disability Assessment Scale (DAS 2.0), health related quality of life (SF36) and International Physical Activity Questionnaire (IPAQ). Results Of 282 participants with confirmed diagnoses of muscle glycogenosis, 269 had GSD5. Of them 196 (73%) completed all questionnaires; for the others, the data were incomplete. The majority, 180 (67%) were currently working. Previous medical treatments included pain medication (23%) and rehabilitation treatment (60%). The carbohydrate-rich diet was reported to be beneficial for 68%, the low sucrose diet for 76% and the ketogenic diet for 88%. Almost all participants (93%) reported difficulties climbing stairs. The median FSS score was 5.22, indicating severe fatigue. The data from the WHODAS and IPAQ was not of sufficient quality to be interpreted. Conclusions The EUROMAC registry have provided insight into the functional and social status of participants with GSD5: most participants are socially active despite limitations in physical and daily life activities. Regular physical activity and different dietary approaches may alleviate fatigue and pain.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1750-1172Test

الوصول الحر: https://doaj.org/article/36d94750141a4f249b7874ba6c6e46e8Test

المؤلفون: Sevim Erdem Ozdamar, Ayse Filiz Koc, Hacer Durmus Tekce, Dilcan Kotan, Ahmet Hakan Ekmekci, Ihsan Sukru Sengun, Ayse Nur Yuceyar, Kayihan Uluc

المصدر: Frontiers in Neurology, Vol 14 (2023)

مصطلحات موضوعية: late-onset Pompe disease, diagnostic delay, diagnostic algorithm, index of suspicion, treatment, outcome, Neurology. Diseases of the nervous system, RC346-429

الوصف: This consensus statement by a panel of neurology experts aimed to provide a practical and implementable guidance document to assist clinicians with the best clinical practice in terms of diagnosis, treatment, and monitoring of late-onset Pompe disease (LOPD). The participating experts consider the clinical suspicion of LOPD by the physician to be of utmost importance in the prevention of diagnostic and therapeutic delay in LOPD patients. A diagnostic algorithm is proposed to facilitate the diagnosis of LOPD in patients presenting with unexplained proximal/axial weakness (with or without respiratory symptoms) or restrictive respiratory insufficiency with hyperCKemia and/or exercise intolerance as the red flag symptoms/signs that raise the index of suspicion for LOPD diagnosis. The diagnosis is based on the subsequent use of dried blood spot (DBS) assay, and the DBS assay can be confirmed by acid alpha-glucosidase (GAA) tissue analysis in leukocytes, fibroblasts, or muscle fibers and/or genetic mutation analysis. Accordingly, experts consider increased awareness among physicians about potential presenting characteristics with a high index of suspicion for LOPD to be crucial to suspect and consider LOPD in the differential diagnosis, while strongly suggesting the use of a diagnostic algorithm combined with DBS assay and confirmatory tests in the timely diagnosis of LOPD and implementation of best practice patterns.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fneur.2023.1095134/fullTest; https://doaj.org/toc/1664-2295Test

الوصول الحر: https://doaj.org/article/7a4a0315371b4467a065b8add9f7fa11Test

المؤلفون: Merve Çebi, Hacer Durmus, Fikret Aysal, Berker Özkan, Gizem Engin Gül, Arman Çakar, Mehmet Hocaoglu, Metin Mercan, Sibel P. Yentür, Melih Tütüncü, Vildan Yayla, Onur Akan, Öner Dogan, Yeşim Parman, Güher Saruhan-Direskeneli

المصدر: Frontiers in Immunology, Vol 11 (2020)

مصطلحات موضوعية: T follicular helper cells, PD-1, ICOS, IL-21, IL-4, IL-17, Immunologic diseases. Allergy, RC581-607

الوصف: 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-γ 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.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/article/10.3389/fimmu.2020.00809/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/3433655cfa5e48098fc6b896eeae965eTest

المؤلفون: Katherine Johnson, Marta Bertoli, Lauren Phillips, Ana Töpf, Peter Van den Bergh, John Vissing, Nanna Witting, Shahriar Nafissi, Shirin Jamal-Omidi, Anna Łusakowska, Anna Kostera-Pruszczyk, Anna Potulska-Chromik, Nicolas Deconinck, Carina Wallgren-Pettersson, Sonja Strang-Karlsson, Jaume Colomer, Kristl G. Claeys, Willem De Ridder, Jonathan Baets, Maja von der Hagen, Roberto Fernández-Torrón, Miren Zulaica Ijurco, Juan Bautista Espinal Valencia, Andreas Hahn, Hacer Durmus, Tracey Willis, Liwen Xu, Elise Valkanas, Thomas E. Mullen, Monkol Lek, Daniel G. MacArthur, Volker Straub

المصدر: Skeletal Muscle, Vol 8, Iss 1, Pp 1-12 (2018)

مصطلحات موضوعية: Whole-exome sequencing, Dystroglycanopathies, Limb-girdle muscle weakness, Diseases of the musculoskeletal system, RC925-935

الوصف: Abstract Background Dystroglycanopathies are a clinically and genetically heterogeneous group of disorders that are typically characterised by limb-girdle muscle weakness. Mutations in 18 different genes have been associated with dystroglycanopathies, the encoded proteins of which typically modulate the binding of α-dystroglycan to extracellular matrix ligands by altering its glycosylation. This results in a disruption of the structural integrity of the myocyte, ultimately leading to muscle degeneration. Methods Deep phenotypic information was gathered using the PhenoTips online software for 1001 patients with unexplained limb-girdle muscle weakness from 43 different centres across 21 European and Middle Eastern countries. Whole-exome sequencing with at least 250 ng DNA was completed using an Illumina exome capture and a 38 Mb baited target. Genes known to be associated with dystroglycanopathies were analysed for disease-causing variants. Results Suspected pathogenic variants were detected in DPM3, ISPD, POMT1 and FKTN in one patient each, in POMK in two patients, in GMPPB in three patients, in FKRP in eight patients and in POMT2 in ten patients. This indicated a frequency of 2.7% for the disease group within the cohort of 1001 patients with unexplained limb-girdle muscle weakness. The phenotypes of the 27 patients were highly variable, yet with a fundamental presentation of proximal muscle weakness and elevated serum creatine kinase. Conclusions Overall, we have identified 27 patients with suspected pathogenic variants in dystroglycanopathy-associated genes. We present evidence for the genetic and phenotypic diversity of the dystroglycanopathies as a disease group, while also highlighting the advantage of incorporating next-generation sequencing into the diagnostic pathway of rare diseases.

وصف الملف: electronic resource

العلاقة: http://link.springer.com/article/10.1186/s13395-018-0170-1Test; https://doaj.org/toc/2044-5040Test

الوصول الحر: https://doaj.org/article/7b793b20033f4da8837130c6461f81e4Test

المؤلفون: Magdalena Mroczek, Hacer Durmus, Ana Töpf, Yesim Parman, Volker Straub

المصدر: Genes, Vol 11, Iss 7, p 716 (2020)

مصطلحات موضوعية: plectin, PLEC, myasthenia, limb-girdle muscular dystrophy, Genetics, QH426-470

الوصف: We identified the known c.1_9del mutation in the PLEC gene in four unrelated females from consanguineous families of Turkish origin. All individuals presented with slowly progressive limb-girdle weakness without any dermatological findings, and dystrophic changes observed in their muscle biopsies. Additionally, the neurological examination revealed ptosis, facial weakness, fatigability, and muscle cramps in all four cases. In two patients, repetitive nerve stimulation showed a borderline decrement and a high jitter was detected in all patients by single-fiber electromyography. Clinical improvement was observed after treatment with pyridostigmine and salbutamol was started. We further characterize the phenotype of patients with limb-girdle muscular dystrophy R17 clinically, by muscle magnetic resonance imaging (MRI) features and by describing a common 3.8 Mb haplotype in three individuals from the same geographical region. In addition, we review the neuromuscular symptoms associated with PLEC mutations and the role of plectin in the neuromuscular junction.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2073-4425/11/7/716Test; https://doaj.org/toc/2073-4425Test

الوصول الحر: https://doaj.org/article/a437fa1c358d4a679c0068bf1fd4ca90Test

المؤلفون: Vuslat Yilmaz, Piraye Oflazer, Fikret Aysal, Hacer Durmus, Kostas Poulas, Sibel P Yentur, Yesim Gulsen-Parman, Socrates Tzartos, Alexander Marx, Erdem Tuzun, Feza Deymeer, Güher Saruhan-Direskeneli

المصدر: PLoS ONE, Vol 10, Iss 4, p e0123546 (2015)

مصطلحات موضوعية: Medicine, Science

الوصف: Neuromuscular transmission failure in myasthenia gravis (MG) is most commonly elicited by autoantibodies (ab) to the acetylcholine receptor or the muscle-specific kinase, constituting AChR-MG and MuSK-MG. It is controversial whether these MG subtypes arise through different T helper (Th) 1, Th2 or Th17 polarized immune reactions and how these reactions are blunted by immunosuppression. To address these questions, plasma levels of cytokines related to various Th subtypes were determined in patients with AChR-MG, MuSK-MG and healthy controls (CON). Peripheral blood mononuclear cells (PBMC) were activated in vitro by anti-CD3, and cytokines were quantified in supernatants. In purified blood CD4+ T cells, RNA of various cytokines, Th subtype specific transcription factors and the co-stimulatory molecule, CD40L, were quantified by qRT-PCR. Plasma levels of Th1, Th2 and Th17 related cytokines were overall not significantly different between MG subtypes and CON. By contrast, in vitro stimulated PBMC from MuSK-MG but not AChR-MG patients showed significantly increased secretion of the Th1, Th17 and T follicular helper cell related cytokines, IFN-γ, IL-17A and IL-21. Stimulated expression of IL-4, IL-6, IL-10 and IL-13 was not significantly different. At the RNA level, expression of CD40L by CD4+ T cells was reduced in both AChR-MG and MuSK-MG patients while expression of Th subset related cytokines and transcription factors were normal. Immunosuppression treatment had two effects: First, it reduced levels of IL12p40 in the plasma of AChR-MG and MuSK-MG patients, leaving other cytokine levels unchanged; second, it reduced spontaneous secretion of IFN-γ and increased secretion of IL-6 and IL-10 by cultured PBMC from AChR-MG, but not MuSK-MG patients. We conclude that Th1 and Th17 immune reactions play a role in MuSK-MG. Immunosuppression attenuates the Th1 response in AChR-MG and MuSK-MG, but otherwise modulates immune responses in AChR-MG and MuSK-MG patients differentially.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/0de3ce75fb9243d1834b5949a1492d14Test

المؤلفون: Ozdamar, Sevim Erdem, Koc, Ayse Filiz, Tekce, Hacer Durmus, Kotan, Dilcan, Ekmekci, Ahmet Hakan, Sengun, Ihsan Sukru, Yuceyar, Ayse Nur, Uluc, Kayihan

المصدر: Frontiers in Neurology; 2023, p01-09, 9p

مصطلحات موضوعية: DELAYED diagnosis, TISSUE analysis, RESPIRATORY insufficiency, GLYCOGEN storage disease type II, GENETIC mutation, ADRENAL insufficiency, PHYSICIANS

مستخلص: This consensus statement by a panel of neurology experts aimed to provide a practical and implementable guidance document to assist clinicians with the best clinical practice in terms of diagnosis, treatment, and monitoring of late-onset Pompe disease (LOPD). The participating experts consider the clinical suspicion of LOPD by the physician to be of utmost importance in the prevention of diagnostic and therapeutic delay in LOPD patients. A diagnostic algorithm is proposed to facilitate the diagnosis of LOPD in patients presenting with unexplained proximal/axial weakness (with or without respiratory symptoms) or restrictive respiratory insufficiency with hyperCKemia and/or exercise intolerance as the red flag symptoms/signs that raise the index of suspicion for LOPD diagnosis. The diagnosis is based on the subsequent use of dried blood spot (DBS) assay, and the DBS assay can be confirmed by acid alpha-glucosidase (GAA) tissue analysis in leukocytes, fibroblasts, or muscle fibers and/or genetic mutation analysis. Accordingly, experts consider increased awareness among physicians about potential presenting characteristics with a high index of suspicion for LOPD to be crucial to suspect and consider LOPD in the di erential diagnosis, while strongly suggesting the use of a diagnostic algorithm combined with DBS assay and confirmatory tests in the timely diagnosis of LOPD and implementation of best practice patterns. [ABSTRACT FROM AUTHOR]

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المؤلفون: İlayda Altınönder, Mustafa Kaya, Sibel P. Yentür, Arman Çakar, Hacer Durmuş, Gülçin Yegen, Berker Özkan, Yeşim Parman, Amr H. Sawalha, Guher Saruhan-Direskeneli

المصدر: Journal of Neuroinflammation, Vol 21, Iss 1, Pp 1-10 (2024)

مصطلحات موضوعية: Thymoma, Thymus, Myasthenia gravis, Hypoxia-inducible factor-1, Neurology. Diseases of the nervous system, RC346-429

الوصف: Abstract Myasthenia gravis (MG) is an immune-mediated disease frequently associated with thymic changes. Increased T helper 17 (Th17) cell activity and dysfunctional regulatory T (Treg) cells have been demonstrated in subgroups of MG. On the other hand, hypoxia-inducible factor 1 (HIF-1) has been shown to regulate the Th17/Treg balance by inducing Th17 differentiation while attenuating Treg development. To identify the underlying mechanisms of different thymic pathologies in MG development, we evaluated thymic samples from thymoma-associated myasthenia gravis (TAMG), MG with hyperplasia (TFH-MG) and thymoma without MG (TOMA) patients. Differential gene expression analysis revealed that TAMG and TFH-MG cells are associated with different functional pathways. A higher RORC/FOXP3 ratio provided evidence for Th17/Treg imbalance in TAMG potentially related to increased HIF1A. The hypoxic microenvironment in thymoma may be a driver of TAMG by increasing HIF1A. These findings may lead to new therapeutic approaches targeting HIF1A in the development of TAMG.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1742-2094Test

الوصول الحر: https://doaj.org/article/22e3a343211b4a35a2bed8399f28723eTest

المؤلفون: Türkan Acar, Esra Acıman Demirel, Nazire Afşar, Aylin Akçalı, Gülşen Akman Demir, Aybala Neslihan Alagöz, Tuğçe Angın Mengi, Ethem Murat Arsava, Semih Ayta, Nerses Bebek, Başar Bilgiç, Cavit Boz, Arman Çakar, Neşe Çelebisoy, Mehmet Uğur Çevik, Firuze Delen, Hacer Durmuş Tekçe, Hakan Ekmekçi, Ayşe Deniz Elmalı, Oğuz Osman Erdinç, Füsun Ferda Erdoğan, Fettah Eren, Ufuk Ergün, Yeşim Gülşen Parman, Haluk Gümüş, Demet İlhan Algın, Rana Karabudak, Ömer Karadaş, Özlem Kayım Yıldız, Emine Rabia Koç, Demet Özbabalık Adapınar, Atilla Özcan Özdemir, Şerefnur Öztürk, Ayşe Sağduyu Kocaman, Şevki Şahin, Esen Saka Topçuoğlu, Özden Şener, F. İrsel Tezer, Rıfat Erdem Toğrol, Ayşe Bora Tokçaer, Mehmet Akif Topçuoğlu, Neşe Tuncer, Ali Ulvi Uca, Kayıhan Uluç, Erdem Yaka, Mehmet İlker Yön

المصدر: Türk Nöroloji Dergisi, Vol 26, Iss 2, Pp 58-108 (2020)

مصطلحات موضوعية: covid-19, nöroloji, covid-19 pandemisi, Medicine, Neurology. Diseases of the nervous system, RC346-429

وصف الملف: electronic resource

العلاقة: http://www.tjn.org.tr/jvi.aspx?pdir=tjn&plng=eng&un=TJN-73669Test; https://doaj.org/toc/1309-2545Test

الوصول الحر: https://doaj.org/article/9e059a592187495c841789571449a527Test

المؤلفون: Barbara Elsnicova, Daniela Hornikova, Veronika Tibenska, David Kolar, Tereza Tlapakova, Benjamin Schmid, Markus Mallek, Britta Eggers, Ursula Schlötzer-Schrehardt, Viktoriya Peeva, Carolin Berwanger, Bettina Eberhard, Hacer Durmuş, Dorothea Schultheis, Christian Holtzhausen, Karin Schork, Katrin Marcus, Jens Jordan, Thomas Lücke, Peter F. M. van der Ven, Rolf Schröder, Christoph S. Clemen, Jitka M. Zurmanova

المصدر: International Journal of Molecular Sciences, Vol 23, Iss 19, p 12020 (2022)

مصطلحات موضوعية: desmin, desminopathy, cardiomyopathy, mitochondriopathy, desmin knock-out metabolism, glucose, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Desmin mutations cause familial and sporadic cardiomyopathies. In addition to perturbing the contractile apparatus, both desmin deficiency and mutated desmin negatively impact mitochondria. Impaired myocardial metabolism secondary to mitochondrial defects could conceivably exacerbate cardiac contractile dysfunction. We performed metabolic myocardial phenotyping in left ventricular cardiac muscle tissue in desmin knock-out mice. Our analyses revealed decreased mitochondrial number, ultrastructural mitochondrial defects, and impaired mitochondria-related metabolic pathways including fatty acid transport, activation, and catabolism. Glucose transporter 1 and hexokinase-1 expression and hexokinase activity were increased. While mitochondrial creatine kinase expression was reduced, fetal creatine kinase expression was increased. Proteomic analysis revealed reduced expression of proteins involved in electron transport mainly of complexes I and II, oxidative phosphorylation, citrate cycle, beta-oxidation including auxiliary pathways, amino acid catabolism, and redox reactions and oxidative stress. Thus, desmin deficiency elicits a secondary cardiac mitochondriopathy with severely impaired oxidative phosphorylation and fatty and amino acid metabolism. Increased glucose utilization and fetal creatine kinase upregulation likely portray attempts to maintain myocardial energy supply. It may be prudent to avoid medications worsening mitochondrial function and other metabolic stressors. Therapeutic interventions for mitochondriopathies might also improve the metabolic condition in desmin deficient hearts.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/23/19/12020Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/9c11ad5ea2bd4158a3b2fce2b7923011Test