scholarly journals MYOTONIC DYSTROPHIES: GENETICALLY-BASED DISEASES DUE TO TOXIC RNA

2014 ◽  
pp. 5-8
Author(s):  
Carlo Pellicciari
Keyword(s):  
Skeletal Muscles ◽  
Nuclear Protein ◽  
Cell Function ◽  
Muscle Relaxation ◽  
Neuromuscular Diseases ◽  
Basic Research ◽  
Voluntary Contraction ◽  
Duchenne Dystrophy ◽  
Pathogenetic Factor ◽  
Toxic Rna

Myotonic dystrophies (DMs, the second most diffuse forms of muscular dystrophy, after Duchenne dystrophy) are genetically-based degenerative neuromuscular diseases exhibiting widely variable clinical features and characterized by myotonia (i.e., a prolonged contraction of skeletal muscles after short stimulation) and a delayed muscle relaxation after voluntary contraction. There are two form of DMs: the more severe DM1 (or Steinert’s disease), and the milder form DM2. The intranuclear accumulation of expanded RNAs is considered as the pathogenetic factor of DMs: the presence of these RNAs exerts a toxic action on cell function which essentially depends on the ectopic sequestration of nuclear protein factors involved in the processing of transcripts. The aim of this mini-symposium is to describe the genetic and cellular bases of DMs, showing how the results of basic research may provide important clues for both diagnosis and therapy.

scholarly journals Spinal and bulbar muscular atrophy with pseudomyotonia phenomena: a clinical case report

2020 ◽  
Vol 9 (4) ◽  
pp. 51-56
Author(s):  
S. S. Nikitin ◽  
V. N. Grigoryeva ◽  
K. A. Mashkovich ◽  
O. L. Mironovich ◽  
N. V. Ryadninskaya ◽  
...  
Keyword(s):  
Skeletal Muscles ◽  
Clinical Case ◽  
Muscular Atrophy ◽  
Muscle Relaxation ◽  
Serum Testosterone ◽  
Voluntary Contraction ◽  
Muscle Stiffness ◽  
Gene Coding ◽  
Trinucleotide Expansion ◽  
Clinical Description

A clinical description of a 28-year-old man with spinal and bulbar muscular atrophy diagnosed on the basis of the CAG-trinucleotide expansion in the gene coding androgen receptor is presented. He exhibited skeletal muscles and tongue fasciculations, gynecomastia, increased serum testosterone and creatine kinase levels. The peculiarities of the case were the gynecomastia under the age of 7, development of fasciculations at the age of 11 and appearance of hard muscle stiffness with delayed muscle relaxation after voluntary contraction at the age of 15, which resembled typical myotonia. Electromyography showed few signs of mild without myotonic discharge, contrasting with giant motor unit potentials and reduced recruitment. The cause of myotonia-like symptom without myotonic discharge as a feature of skeletal muscles disorder is discussed with the modern view of spinal and bulbar muscular atrophy as a multisystem genetic pathology.

Plantarflexor stretch training increases reciprocal inhibition measured during voluntary dorsiflexion

2012 ◽  
Vol 107 (1) ◽  
pp. 250-256 ◽  
Author(s):  
A. J. Blazevich ◽  
A. D. Kay ◽  
C. Waugh ◽  
F. Fath ◽  
S. Miller ◽  
...  
Keyword(s):  
Skeletal Muscles ◽  
Evoked Potential ◽  
Maximum Voluntary Contraction ◽  
Reciprocal Inhibition ◽  
Voluntary Contraction ◽  
Joint Angles ◽  
Muscle Stretching ◽  
Tibial Nerve Stimulation ◽  
Research Goal ◽  
Passive Muscle

Agonist-mediated reciprocal inhibition (RI) in distal skeletal muscles is an important neurophysiological phenomenon leading to improved movement coordination and efficiency. It has been shown to be reduced in aged and clinical populations, so the development of interventions augmenting RI is an important research goal. We examined the efficacy of using chronic passive muscle stretching to augment RI. The influence of 3 wk of plantarflexor stretching (4 × 30 s, two times/day) on RI of soleus and gastrocnemius initiated by tonic, voluntary dorsiflexion contractions [20% of maximum voluntary contraction (MVC)] was examined in 11 healthy men who performed stretch training and in nine nontraining controls. Hoffmann's reflexes (H-reflexes) were elicited by tibial nerve stimulation during both weak isometric (2% MVC) plantarflexions and dorsiflexion contractions at 20% MVC. Changes were examined at three joint angles, normalized to each subject's range of motion (ROM; plantarflexed = 10 ± 0°, neutral = −3.3 ± 2.9°, dorsiflexed = −16.5 ± 5.6°). No changes were detected in controls. A 20% increase in ROM in the stretch subjects was associated with a significant decrease in maximum H-reflex (Hmax): maximum evoked potential (Mmax), measured during 2% plantarflexion at the plantarflexed and neutral angles in soleus and at the plantarflexed angle in gastrocnemius ( P < 0.05–0.01). By contrast, decreases in Hmax:Mmax during 20% dorsiflexion contract were also seen at each angle in soleus and at the dorsiflexed angle in gastrocnemius. However, a greater decrease in Hmax:Mmax measured during voluntary dorsiflexion rather than during plantarflexion, which indicates a specific change in RI, was detected only at the dorsiflexed angle (−30.7 ± 9.4% and −35.8 ± 6.8% for soleus and gastrocnemius, respectively). These results demonstrate the efficacy of soleus-gastrocnemius stretch training in increasing agonist-mediated RI from tibialis anterior onto soleus-gastrocnemius in young, healthy individuals at dorsiflexed, but not plantarflexed, joint angles.

scholarly journals Nuclear protein spreading: implication for pathophysiology of neuromuscular diseases

2014 ◽  
Vol 23 (15) ◽  
pp. 4125-4133 ◽  
Author(s):  
Maxime Ferreboeuf ◽  
Virginie Mariot ◽  
Denis Furling ◽  
Gillian Butler-Browne ◽  
Vincent Mouly ◽  
...  
Keyword(s):  
Nuclear Protein ◽  
Neuromuscular Diseases

scholarly journals Calcium Channels: Noteworthy Regulators and Therapeutic Targets in Dermatological Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Min Wang ◽  
Yaoxiang Sun ◽  
Linli Li ◽  
Peipei Wu ◽  
Ocansey DKW ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Transient Receptor Potential ◽  
Cell Function ◽  
Calcium Influx ◽  
Receptor Potential ◽  
Basic Research ◽  
Bioactive Molecules ◽  
Skin Wound Healing ◽  
Voltage Gated ◽  
Calcium Sensing

Dysfunctional skin barrier and impaired skin homeostasis may lead to or aggravate a series of dermatologic diseases. A large variety of biological events and bioactive molecules are involved in the process of skin wound healing and functional recovery. Calcium ions (Ca2+) released from intracellular stores as well as influx through plasma membrane are essential to skin function. Growing evidence suggests that calcium influx is mainly regulated by calcium-sensing receptors and channels, including voltage-gated, transient potential receptor, store-operated, and receptor-operated calcium channels, which not only maintain cellular Ca2+ homeostasis, but also participate in cell proliferation and skin cell homeostasis through Ca2+-sensitive proteins such as calmodulin (CaM). Furthermore, distinct types of Ca2+ channels not merely work separately, they may work concertedly to regulate cell function. In this review, we discussed different calcium-sensing receptors and channels, including voltage-gated, transient receptor potential, store-operated, and receptor-operated calcium channels, particularly focusing on their regulatory functions and inherent interactions as well as calcium channels-related reagents and drugs, which is expected to bridge basic research and clinical applications in dermatologic diseases.

scholarly journals Rules of tissue packing involving different cell types: human muscle organization

2016 ◽  
Author(s):  
Daniel Sanchez-Gutierrez ◽  
Aurora Saez ◽  
Carmen Paradas ◽  
Luis M. Escudero
Keyword(s):  
Motor Neurons ◽  
Skeletal Muscles ◽  
Spatial Organization ◽  
Biceps Brachii ◽  
Relative Size ◽  
Neuromuscular Diseases ◽  
Cell Types ◽  
Quadriceps Muscle ◽  
Relative Distribution ◽  
Mathematical Concepts

Natural packed tissues are assembled as tessellations of polygonal cells that do not leave empty spaces between them. They include the epithelial sheets and the skeletal muscles. Epithelia are formed by equivalent cells that change shape and organization through development. The skeletal muscles appear as a mosaic composed by two different types of cells: the slow and fast fibres that are determined by the identities of the motor neurons that innervate them. Their relative distribution is important for the muscle function and can be altered in some neuromuscular diseases. Little is known about how the spatial organization of fast and slow fibres is established and maintained. In this work we use computerized image analysis and mathematical concepts to capture the organizational pattern in two different healthy muscles: biceps brachii and quadriceps. Here we show that each type of muscle portrays a characteristic topological pattern that allows distinguishing between them. The biceps brachii muscle presents a particular arrange based on the different size of slow and fast fibres, contrary to the quadriceps muscle where an unbiased distribution exists. Our results indicate that the relative size of each cellular type imposes an intrinsic organization into the tissue. These findings establish a new framework for the analysis of packed tissues where two or more cell types exist.

scholarly journals Non-quantal acetylcholine release at the neuromuscular junction

2009 ◽  
pp. 763-784
Author(s):  
F Vyskočil ◽  
AI Malomouzh ◽  
EE Nikolsky
Keyword(s):  
Skeletal Muscles ◽  
Acetylcholine Release ◽  
Chloride Transport ◽  
Motor Nerve ◽  
Basic Research ◽  
Motor Nerve Terminal ◽  
Receptor Desensitization ◽  
Quantal Acetylcholine Release ◽  
Endplate Potentials ◽  
Developing Muscle

There are two principal mechanisms of acetylcholine (ACh) release from the resting motor nerve terminal: quantal and nonquantal (NQR); the former being only a small fraction of the total, at least at rest. In the present article we summarize basic research about the NQR that is undoubtedly an important trophic factor during endplate development and in adult neuromuscular contacts. NQR helps to eliminate the polyneural innervation of developing muscle fibers, ensures higher excitability of the adult subsynaptic membrane by surplus polarization and protects the RMP from depolarization by regulating the NO cascade and chloride transport. It shortens the endplate potentials by promoting postsynaptic receptor desensitization when AChE is inhibited during anti-AChE poisoning. In adult synapses, it can also activate the electrogenic Na+/K+-pump, change the degree of synchronization of quanta released by the nerve stimulation and affects the contractility of skeletal muscles.

scholarly journals Functional state of motor units of skeletal muscles in chronic diseases of motoneurons and their axones

1995 ◽  
Vol XXVII (1-2) ◽  
pp. 5-10
Author(s):  
L. F. Kasatkina
Keyword(s):  
Motor Neuron ◽  
Chronic Diseases ◽  
Functional State ◽  
Skeletal Muscles ◽  
Neuromuscular Diseases ◽  
Motor Units ◽  
Peripheral Motor ◽  
Partial Compensation

Electromyographic examination of the potentials of motor units in 498 patients with different forms of peripheral motor neuron pathology allowed to distinguish electromyographic criteria of estimation of the denervationreinnervation processes. Determination of phases of full, partial compensation and of decompensation phase may be used for examination of pathogenesis of neuromuscular diseases, their diagnosis and assessment of their progress.

Decreased water T2in fatty infiltrated skeletal muscles of patients with neuromuscular diseases

2019 ◽  
pp. e4111 ◽  
Author(s):  
Sarah Schlaeger ◽  
Dominik Weidlich ◽  
Elisabeth Klupp ◽  
Federica Montagnese ◽  
Marcus Deschauer ◽  
...  
Keyword(s):  
Skeletal Muscles ◽  
Neuromuscular Diseases

scholarly journals Recessive myotonia congenita caused by a homozygous splice site variant in CLCN1 gene: a case report

2020 ◽  
Vol 21 (S1) ◽  
Author(s):  
Peter Sparber ◽  
Margarita Sharova ◽  
Alexandra Filatova ◽  
Olga Shchagina ◽  
Evgeniya Ivanova ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Splice Site ◽  
Muscle Relaxation ◽  
Neuromuscular Disorders ◽  
Voluntary Contraction ◽  
Muscle Stiffness ◽  
Loss Of Function ◽  
Myotonia Congenita ◽  
Clcn1 Gene ◽  
Splice Site Variant

Abstract Background Myotonia congenita is a rare neuromuscular disease, which is characterized by a delay in muscle relaxation after evoked or voluntary contraction. Myotonia congenita can be inherited in a dominant (Thomsen disease) and recessive form (Becker disease) and both are caused by pathogenic variants in the CLCN1 gene. Noncanonical splice site variants are often classified as variants of uncertain significance, due to insufficient accuracy of splice-predicting tools. Functional analysis using minigene plasmids is widely used in such cases. Moreover, functional analysis is very useful in investigation of the disease pathogenesis, which is necessary for development of future therapeutic approaches. To our knowledge only one noncanonical splice site variant in the CLCN1 gene was functionally characterized to date. We further contribute to this field by evaluation the molecular mechanism of splicing alteration caused by the c.1582 + 5G > A in a homozygous state. Case presentation We report a clinical case of an affected 6-y.o boy with athletic appearance due to muscle hypertrophy, calf muscle stiffness, cramping and various myotonic signs in a consanguineous family with no history of neuromuscular disorders. The neurological examination showed percussion-activated myotonia in the hands and legs. Plasma creatine kinase enzyme and transaminases levels were normal. Electromyography at the time of examination shows myotonic runs in the upper and lower extremities. Conclusions Functional analysis of the variant in a minigene system showed alteration of splicing leading to loss of function, thereby confirming that the variant is pathogenic.

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