1,720,977 research outputs found
Disease specific enrichment of circulating let-7 family microRNA in MuSK+ myasthenia gravis.
Get PDFMyasthenia gravis (MG) patients with antibodies against the muscle specific tyrosine kinase (MuSK+) have predominantly involvement of cranio-bulbar muscles and do not display thymus pathology, as do acetylcholine receptor antibody seropositive (AChR+) MG patients. In search of novel biomarkers for MuSK+ MG, we evaluated circulating serum microRNAs. Four analyzed microRNAs were specifically elevated in MuSK+ MG patient serum samples: let-7a-5p, let-7f-5p, miR-151a-3p and miR-423-5p. The circulating microRNA profile in MuSK+ MG differs from the profile previously observed in the serum of AChR+ MG, thus indicating the etiological difference between these two entities. We propose that the identified microRNAs could serve as potential serum biomarkers for MuSK+ MG
Cognitive dysfunction in mice with passively induced MuSK antibody seropositive myasthenia gravis
No full textAbstract
Recent reports on cognitive dysfunction, in addition to skeletal muscle fatigue, in muscle-specific tyrosine kinase antibody seropositive (MuSK+) myasthenia gravis (MG) patients led us to study cognition in mice with MuSK+ passive transfer MG (PTMG). Twelve 7-week-old female wild-type C57BL/6J mice were passively immunized with IgG from MuSK+ MG patients and 12 control mice received intraperitoneal saline injections. Mice were evaluated with clinical, neurophysiological and behavioral tests (Barnes maze (BM) and novel object recognition (NOR)), and the muscles were immunostained to evaluate the neuromuscular junction in the end of the study. Two-thirds of the immunized mice developed clinically distinct MuSK+ PTMG. MuSK+ PTMG mice spent less time exploring the novel object in the NOR test (MuSK+ mice 36.4% ± 14.0 vs controls 52.4% ± 13.0, p = .02), unrelated to the muscle weakness and regardless of rodents' innate preference of novelty. In the BM test, control mice were more eager to use the direct strategy than the MuSK+ mice (MuSK+ 17.3% vs controls 29.5%, p = .02). Our findings shed new light on cognition dysfunction in human MuSK+ MG patients and indicate that recognition memory in the perirhinal cortex could be affected in MuSK+ MG
Disease specific signature of circulating miR-150-5p and miR-21-5p in myasthenia gravis patients
No full textPurpose: Reliable biological markers for patients with the autoimmune neuromuscular disorder myasthenia gravis (MG) are lacking. We determined whether levels of the circulating immuno-microRNAs miR-150-5p and miR-21-5p were elevated in sera from clinically heterogeneous MG patients, with and without immunosuppression, as compared to healthy controls and patients with other autoimmune disorders. Methods: Sera from 71 MG patients and 55 healthy controls (HC) were analyzed for the expression levels of miR-150-5p and miR-21-5p with qRT-PCR. Sera were also assayed from 23 patients with other autoimmune disorders (AID; psoriasis, Addison's and Crohn's diseases). Results: 34 MG patients had no immunosuppressive drug treatment (MG-0) and 37 patients were under stable immunosuppressive drug treatment since a 6 months (MG + IMM). Serum levels of miR-150-5p and miR-21-5p were higher in the MG-0 patients compared to HC (p < 0.0001). Further, miR-150-5p levels were 41% lower and miR-21-5p levels were 25% lower in the MG + IMM compared to MG-0 (p = 0.0051 and 0.0419). In the AID patients, mean miR-150-5p and miR-21-5p were comparable with healthy controls (p = 0.66). Conclusions: The immuno-microRNAs miR-150-5p and miR-21-5p show a disease specific signature, which suggests these microRNAs as possible biological autoimmune markers of MG. (C) 2015 The Authors. Published by Elsevier B.V
Muscle-specific regulation of the mTOR signaling pathway in MuSK antibody seropositive (MuSK plus ) experimental autoimmune Myasthenia gravis (EAMG)
No full textMyasthenia gravis (MG) patients with antibodies against muscle specific tyrosine kinase (MuSK+) typically present focal fatigue and atrophy of the facial and bulbar muscles, including the masseter muscle, whereas leg muscles often are clinically spared. This study addresses the regulation of the mTOR signaling pathway in the masseter muscle versus the leg muscle tibialis anterior (TA). We analyzed muscle morphology, protein levels of mTOR components as well as atrogenes and mitochondrial markers in these muscles of healthy control mice and mice with different clinical severity grades of MuSK+ experimental autoimmune MG (EAMG). Protein levels of mTOR components were reduced in the atrophic masseter muscle of MuSK+ EAMG mice, whereas enhanced accumulation of mTOR components was observed in the TA muscles. Two other muscles: omohyoid and soleus showed intermediate spectra. In conclusion, the anabolic mTOR signaling pathway is differentially regulated even in muscles with the same activity pattern in the same neuromuscular disease. This could in part explain the clinical phenotype in MuSK+ EAMG as well as in muscular dystrophies.</p
Regional Diffusion of Botulinum Toxin in Facial Muscles : A Randomised Double-blind Study and a Consideration for Clinical Studies with Split-face Design
No full textDespite the extensive use of botulinum toxin A (BoNTA) in medical and cosmetic treatments, the potential spreading of BoNTA to surrounding tissues remains unknown. A patient with hemifacial paralysis upon blepharospasm treatment with low dose of BoNTA, prompted us to investigate the spreading effect. A randomised, double-blind study was conducted in which 5 healthy women (33-52 years) were treated with different doses of onabotulinum toxin unilaterally in the corrugator muscle. Parameters of efficacy and diffusion (CMAP; EMG and jitter analysis) in both glabellar and frontalis muscles were assessed at baseline, 2 and 4 weeks following BoNTA injection. CMAP of the treated glabellar muscles was reduced to approximately 40% in all dose groups. Additionally, contralateral CMAP reduction was observed in 3 of 5 subjects. These data confirm regional diffusion of BoNTA in facial muscle application, which raises question on the reliability of split-face models in BoNTA studies
Correlation of Botulinum Toxin Dose with Neurophysiological Parameters of Efficacy and Safety in the Glabellar Muscles : A Double-blind, Placebo-controlled, Randomized Study
No full textDespite the extensive use of botulinum toxin type A (BoNT-A) in treatments for glabellar frown lines, the dose-response effect in the glabellar muscles remains unknown. The aim of this randomized, double-blind, placebo-controlled prospective study was to characterize the neurophysiological parameters that correlate with the effect of BoNT-A in the glabellar muscles and its diffusion to surrounding ocular muscles. Sixteen healthy women were recruited and randomized to 3 different dose-groups of onabotulinumtoxin A (Vistabel (R)) or placebo and followed 24 weeks by neurophysiological examinations. Efficacy of treatment on corrugator supercilii muscles was measured by compound motor action potential (CMAP) and electromyography (EMG). Photographs were used to score glabellar frown lines. Diffusion of the drug to surrounding muscles was assessed by CMAP of the nasalis muscle, EMG and concentric needle electrode jitter analysis (CNE) of the orbicularis oculi muscle. CMAP reduction correlated well with intramuscular BoNT-A dose. Muscle paralysis, measured by EMG, began from 2 weeks and was not entirely reversed at 24 weeks in individuals who received high dose of onabotulinumtoxin. Limited diffusion of orbicularis oculi was detected with CNE. In conclusion, we developed a novel neurophysiological strategy for effect evaluation of BoNT-A in glabellar muscles. CMAP and EMG correlated with given BoNT-A dose and are more defined effect measures than clinical glabellar photo scales.</p
Low vitamin D levels in healthy controls and patients with autoimmune neuromuscular disorders in Greece
No full textNormal autoimmune function is dependent on adequate levels of activated vitamin D, 25 hydroxy vitamin D [25(OH) D]. A recent study presented deficiency of 25(OH) D levels in Swedish MG patients. We aimed to study 25(OH) D levels in patients with MG and autoimmune polyneuropathies (PNP) at a southern latitude in Greece. Plasma levels of 25(OH) D were analyzed in Greek patients with MG (n = 19), immune-mediated PNP (N = 11) and in 30 Greek healthy age-and sex-matched controls. Ten MG patients received supplementation with vitamin D3. The MG Composite Score (MGC) and MG quality of life assessed disease severity in MG patients, whereas the INCAT Disability Scale assessed clinical features in the PNP patients. MG patients with and without vitamin D3 supplementation had higher 25(OH) D levels (mean 58.8 +/- 16.3 and 62.0 +/- 22.4 nmol/L, respectively) than PNP patients (mean 42.1 +/- 11.5 nmol/L, p = 0.01) and healthy controls (mean 45.7 +/- 13.8 nmol/L, p = 0.01). Plasma 25(OH) D levels was lower with age in all groups. There were no correlations between 25(OH) D and disease duration, MGC score, or INCAT score. Vitamin D deficiency was found in all Greek patient groups and healthy controls. Levels of 25(OH) D were higher in MG patients with as well as without vitamin D supplementation compared to healthy controls, whereas CIDP/GBS patients had levels similar to controls.</p
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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