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Sample records for rod myopathy nrm

  1. Mutations in the nebulin gene in a child with nemaline (rod) myopathy.

    Science.gov (United States)

    Kapoor, Seema; Singh, Ankur; Lehtokari, Vilma-Lotta; Wallgren-Pettersson, Carina; Batra, Vineeta Vijay

    2013-08-01

    Nemaline myopathy, also called rod myopathy, is a relatively common congenital myopathy and probably second in incidence only to central core disease. The mainstay of diagnosis is histopathology, but detection of the causative mutation is mandatory for determining the mode of inheritance and for prenatal diagnosis. The authors report two siblings with nemaline myopathy caused by mutations in the nebulin gene.

  2. HIV, rods, and the muscles--a discussion about HIV-associated nemaline rod myopathy.

    Science.gov (United States)

    Madonia, Phillip; Wilson, Jon; Bican, Orhan; Willis, Megan; Bass, Pat

    2012-01-01

    This case reports a 21-year-old, homosexual African-American male who presented to our facility with a two-week history of progressive proximal muscle weakness. Quadriceps muscle biopsy showed a diagnosis of Nemaline Rod Myopathy, the presenting disease of his HIV infection. A review of the literature shows 13 prior case reports of similar disease process, often as the presenting symptom of the HIV disease. Anecdotal reports of effective treatment regimens include steroids and intravenous immune globulin; our patient had a profound response to high-dose steroids. This case report discusses this rare presentation of HIV in hopes to increase awareness amongst clinicians as the incidence and prevalence of HIV increases.

  3. Congenital myopathy with cap-like structures and nemaline rods: case report and literature review.

    Science.gov (United States)

    Piteau, Shalea J; Rossiter, John P; Smith, R Garth; MacKenzie, Jennifer J

    2014-08-01

    Cap myopathy is a rare congenital myopathy characterized by cap structures located at the periphery of the muscle fiber. Cap structures consist of disarranged thin filaments with enlarged Z discs. The clinical presentation and natural history of cap myopathy is variable and overlaps with other congenital myopathies. We describe a 10-year-old boy with cap myopathy and contrast him with 20 other individuals reported in the literature. Our patient presented at birth with hypotonia and weakness and subsequently developed respiratory failure in infancy. He is ambulatory but has increasing fatigue and requires a wheelchair by midafternoon. His muscle biopsy at 3 months revealed a nemaline myopathy and secondary fiber-type disproportion with type 1 hypotrophy and predominance. A repeat muscle biopsy at age 6 years revealed numerous peripherally located cap-like structures containing nemaline rods and exhibited a spectrum of Z-disk and myofibrillar abnormalities. Molecular genetic testing was performed for NEB, TPM2, TPM3, ACTA1, TNNT1, SEPN1, SMN1, DMPK, FSHMD1A, and mtDNA. A known pathogenic mutation, c.1152+1G>A, and a previously unreported variant, c.1782+4_1782+5delAG, were detected in NEB. Our patient has a more severe phenotype than most reported patients and is the first patient with cap myopathy to have a mutation in NEB. Our case supports the identification of cap myopathy as a congenital myopathy with significant overlapping features with nemaline myopathies and further elucidates the phenotype of this disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Immunofluorescence microscopy of a myopathy α-Actinin is a major constituent of nemaline rods

    NARCIS (Netherlands)

    Jockusch, B.M.; Veldman, H.; Griffiths, G.W.; Oost, B.A. van; Jennekens, F.G.I.

    A biopsy of skeletal muscle taken from a child with the clinical symptoms of congenital nemaline myopathy was studied. Light and electron microscopy revealed rod-like structures within the muscle fibres, and thus confirmed the clinical diagnosis. Indirect immunofluorescence, using specific

  5. [Nemaline rod myopathy revealed by acute respiratory failure after an outpatient cataract surgery].

    Science.gov (United States)

    Raveau, T; Lassalle, V; Dubourg, O; Legout, A; Tirot, P

    2012-01-01

    We report the case of a 63-year-old patient admitted to the ICU for an acute respiratory failure one week after an outpatient cataract surgery that revealed a nemaline rod myopathy. We present this rare myopathy whose particularities are its aetiology, which can be inherited, mostly with a congenital onset, or sporadic, and the variability of the age at presentation. We discuss the exceptional onset of severe unknown underlying diseases in the context of outpatient surgery. Copyright © 2012 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

  6. Nebulin (NEB) mutations in a childhood onset distal myopathy with rods and cores uncovered by next generation sequencing

    OpenAIRE

    Scoto, Mariacristina; Cullup, Thomas; Cirak, Sebahattin; Yau, Shu; Manzur, Adnan Y.; Feng, Lucy; Jacques, Thomas S; Anderson, Glenn; Abbs, Stephen; Sewry, Caroline; Jungbluth, Heinz; Muntoni, Francesco

    2013-01-01

    Recessive nebulin (NEB) mutations are a common cause of nemaline myopathy (NM), typically characterized by generalized weakness of early-onset and nemaline rods on muscle biopsy. Exceptional adult cases with additional cores and an isolated distal weakness have been reported. The large NEB gene with 183 exons has been an obstacle for the genetic work-up. Here we report a childhood-onset case with distal weakness and a core-rod myopathy, associated with recessive NEB mutations identified by ne...

  7. Cytoplasmic body pathology in severe ACTA1-related myopathy in the absence of typical nemaline rods.

    Science.gov (United States)

    Donkervoort, Sandra; Chan, Sophelia H S; Hayes, Leslie H; Bradley, Nathaniel; Nguyen, David; Leach, Meganne E; Mohassel, Payam; Hu, Ying; Thangarajh, Mathula; Bharucha-Goebel, Diana; Kan, Amanda; Ho, Ronnie S L; Reyes, Christine A; Nance, Jessica; Moore, Steven A; Foley, A Reghan; Bönnemann, Carsten G

    2017-06-01

    Mutations in ACTA1 cause a group of myopathies with expanding clinical and histopathological heterogeneity. We describe three patients with severe ACTA1-related myopathy who have muscle fiber cytoplasmic bodies but no classic nemaline rods. Patient 1 is a five-year-old boy who presented at birth with severe weakness and respiratory failure, requiring mechanical ventilation. Whole exome sequencing identified a heterozygous c.282C>A (p.Asn94Lys) ACTA1 mutation. Patients 2 and 3 were twin boys with hypotonia, severe weakness, and respiratory insufficiency at birth requiring mechanical ventilation. Both died at 6 months of age. The same heterozygous c.282C>A (p.Asn94Lys) ACTA1 mutation was identified by whole exome sequencing. We conclude that clinically severe ACTA1-related myopathy can present with muscle morphological findings suggestive of cytoplasmic body myopathy in the absence of definite nemaline rods. The Asn94Lys mutation in skeletal muscle sarcomeric α-actin may be linked to this histological appearance. These novel ACTA1 cases also illustrate the successful application of whole exome sequencing in directly arriving at a candidate genetic diagnosis in patients with unexpected phenotypic and histologic features for a known neuromuscular gene. Copyright © 2017. Published by Elsevier B.V.

  8. Myopathy

    Science.gov (United States)

    ... muscle work; include McArdle, Tarui, and DiMauro diseases dermatomyositis : an inflammatory myopathy of skin and muscle myositis ... muscle work; include McArdle, Tarui, and DiMauro diseases dermatomyositis : an inflammatory myopathy of skin and muscle myositis ...

  9. Myopathies

    Science.gov (United States)

    ... for contraction that makes resting muscle resistant to stretching. A toned muscle holds its shape and elasticity ... endocrine myopathies. The staff at your local MDA office is there to assist you in many ways. ...

  10. Coexistence of central nucleus, cores, and rods: Diagnostic relevance

    Science.gov (United States)

    Dhinakaran, Sathiyabama; Kumar, Rashmi Santhosh; Thakkar, Ravindra; Narayanappa, Gayathri

    2016-01-01

    Background: Congenital myopathies (CMs) though considered distinct disorders, simultaneous occurrence of central nucleus, nemaline rods, and cores in the same biopsy are scarcely reported. Objective: A retrospective reassessment of cases diagnosed as CMs to look for multiple pathologies missed, if any, during the initial diagnosis. Materials and Methods: Enzyme histochemical, and immunohistochemical-stained slides from 125 cases diagnosed as congenital myopathy were reassessed. Results: The study revealed 15 cases (12%) of congenital myopathy with more than one morphological feature. Central nucleus with cores (n = 11), central nucleus, nemaline rods and cores (n = 3), and nemaline rods with cores (n = 1). 4/11 cases were diagnosed as centronuclear myopathy (CNM) in the first instance; in addition, cores were revealed on reassessment. Discussion: The prevalence of CMs of all neuromuscular disorders is approximately 6 in 100,000 live births, with regional variations. Three main defined CMs include centro nuclear myopathy (CNM), nemaline rod myopathy (NRM), and central core disease (CCD). However, they are more diverse with overlapping clinical and histopathological features, thus broadening the spectra within each category of congenital myopathy. Conclusion: Identification of cases with overlap of pathological features has diagnostic relevance. PMID:27293330

  11. Coexistence of central nucleus, cores, and rods: Diagnostic relevance

    Directory of Open Access Journals (Sweden)

    Sathiyabama Dhinakaran

    2016-01-01

    Full Text Available Background: Congenital myopathies (CMs though considered distinct disorders, simultaneous occurrence of central nucleus, nemaline rods, and cores in the same biopsy are scarcely reported. Objective: A retrospective reassessment of cases diagnosed as CMs to look for multiple pathologies missed, if any, during the initial diagnosis. Materials and Methods: Enzyme histochemical, and immunohistochemical-stained slides from 125 cases diagnosed as congenital myopathy were reassessed. Results: The study revealed 15 cases (12% of congenital myopathy with more than one morphological feature. Central nucleus with cores (n = 11, central nucleus, nemaline rods and cores (n = 3, and nemaline rods with cores (n = 1. 4/11 cases were diagnosed as centronuclear myopathy (CNM in the first instance; in addition, cores were revealed on reassessment. Discussion: The prevalence of CMs of all neuromuscular disorders is approximately 6 in 100,000 live births, with regional variations. Three main defined CMs include centro nuclear myopathy (CNM, nemaline rod myopathy (NRM, and central core disease (CCD. However, they are more diverse with overlapping clinical and histopathological features, thus broadening the spectra within each category of congenital myopathy. Conclusion: Identification of cases with overlap of pathological features has diagnostic relevance.

  12. Actin myopathy with nemaline bodies, intranuclear rods, and a heterozygous mutation in ACTA1 (Asp154Asn).

    Science.gov (United States)

    Schröder, J M; Durling, H; Laing, N

    2004-09-01

    Mutations in the skeletal muscle alpha-actin gene ( ACTA1) are associated by and large with three muscle diseases (1) congenital actin myopathy, (2) nemaline myopathy, and (3) intranuclear rod myopathy. More than 70 mutations have now been identified. The majority of ACTA1 mutations are dominant, a small number are recessive and most isolated cases with no previous family history have de novo dominant mutations. The present case, a boy of healthy Turkish parents, had a severe form of the disease of the latter type due to a heterozygous, presumably de novo mutation of the ACTA1 gene in exon 4 (Asp154Asn), with lack of spontaneous movements at birth requiring immediate mechanical ventilation. He died at the age of 9 weeks due to respiratory failure, secondary pneumonia, and chylothorax. The biopsy specimen of the femoral muscle was characterized by pleomorphic alterations with numerous muscle fibers showing accumulation of actin filaments, but, in addition, both nemaline bodies and intranuclear rod bodies. This was also seen in several other muscles investigated at autopsy. No developmental abnormalities of the central nervous system, and no loss of spinal motor neurons were detected despite atrophy or hypotrophy of a considerable number of muscle fibers. The peripheral nervous system, which has not been studied before in patients with ACTA1 mutations, showed no loss of motor or sensory myelinated fibers and no loss of sensory neurons in spinal ganglia.

  13. Loss of Tropomodulin4 in the zebrafish mutant träge causes cytoplasmic rod formation and muscle weakness reminiscent of nemaline myopathy

    Directory of Open Access Journals (Sweden)

    Joachim Berger

    2014-12-01

    Full Text Available Nemaline myopathy is an inherited muscle disease that is mainly diagnosed by the presence of nemaline rods in muscle biopsies. Of the nine genes associated with the disease, five encode components of striated muscle sarcomeres. In a genetic zebrafish screen, the mutant träge (trg was isolated based on its reduction in muscle birefringence, indicating muscle damage. Myofibres in trg appeared disorganised and showed inhomogeneous cytoplasmic eosin staining alongside malformed nuclei. Linkage analysis of trg combined with sequencing identified a nonsense mutation in tropomodulin4 (tmod4, a regulator of thin filament length and stability. Accordingly, although actin monomers polymerize to form thin filaments in the skeletal muscle of tmod4trg mutants, thin filaments often appeared to be dispersed throughout myofibres. Organised myofibrils with the typical striation rarely assemble, leading to severe muscle weakness, impaired locomotion and early death. Myofibrils of tmod4trg mutants often featured thin filaments of various lengths, widened Z-disks, undefined H-zones and electron-dense aggregations of various shapes and sizes. Importantly, Gomori trichrome staining and the lattice pattern of the detected cytoplasmic rods, together with the reactivity of rods with phalloidin and an antibody against actinin, is reminiscent of nemaline rods found in nemaline myopathy, suggesting that misregulation of thin filament length causes cytoplasmic rod formation in tmod4trg mutants. Although Tropomodulin4 has not been associated with myopathy, the results presented here implicateTMOD4 as a novel candidate for unresolved nemaline myopathies and suggest that the tmod4trg mutant will be a valuable tool to study human muscle disorders.

  14. Loss of Tropomodulin4 in the zebrafish mutant träge causes cytoplasmic rod formation and muscle weakness reminiscent of nemaline myopathy.

    Science.gov (United States)

    Berger, Joachim; Tarakci, Hakan; Berger, Silke; Li, Mei; Hall, Thomas E; Arner, Anders; Currie, Peter D

    2014-12-01

    Nemaline myopathy is an inherited muscle disease that is mainly diagnosed by the presence of nemaline rods in muscle biopsies. Of the nine genes associated with the disease, five encode components of striated muscle sarcomeres. In a genetic zebrafish screen, the mutant träge (trg) was isolated based on its reduction in muscle birefringence, indicating muscle damage. Myofibres in trg appeared disorganised and showed inhomogeneous cytoplasmic eosin staining alongside malformed nuclei. Linkage analysis of trg combined with sequencing identified a nonsense mutation in tropomodulin4 (tmod4), a regulator of thin filament length and stability. Accordingly, although actin monomers polymerize to form thin filaments in the skeletal muscle of tmod4(trg) mutants, thin filaments often appeared to be dispersed throughout myofibres. Organised myofibrils with the typical striation rarely assemble, leading to severe muscle weakness, impaired locomotion and early death. Myofibrils of tmod4(trg) mutants often featured thin filaments of various lengths, widened Z-disks, undefined H-zones and electron-dense aggregations of various shapes and sizes. Importantly, Gomori trichrome staining and the lattice pattern of the detected cytoplasmic rods, together with the reactivity of rods with phalloidin and an antibody against actinin, is reminiscent of nemaline rods found in nemaline myopathy, suggesting that misregulation of thin filament length causes cytoplasmic rod formation in tmod4(trg) mutants. Although Tropomodulin4 has not been associated with myopathy, the results presented here implicateTMOD4 as a novel candidate for unresolved nemaline myopathies and suggest that the tmod4(trg) mutant will be a valuable tool to study human muscle disorders. © 2014. Published by The Company of Biologists Ltd.

  15. Desmin myopathy with severe cardiomyopathy in a Uruguayan family due to a codon deletion in a new location within the desmin 1A rod domain.

    Science.gov (United States)

    Vernengo, Luis; Chourbagi, Oussama; Panuncio, Ana; Lilienbaum, Alain; Batonnet-Pichon, Sabrina; Bruston, Francine; Rodrigues-Lima, Fernando; Mesa, Rosario; Pizzarossa, Carlos; Demay, Laurence; Richard, Pascale; Vicart, Patrick; Rodriguez, Maria-Mirta

    2010-03-01

    Desmin myopathy is a heterogeneous neuromuscular disorder characterized by skeletal myopathy and cardiomyopathy, inherited mostly in an autosomal dominant pattern. We report a five generation Uruguayan family with severe cardiomyopathy and skeletal myopathy. Its most striking features are: atrial dilation, arrhythmia, conduction block and sudden death due to conduction impairment. Affected skeletal muscle shows alteration of mitochondria with paracrystallin inclusions and granulofilamentous material scattered in the muscle fibres. This family carries an unusual deletion p.E114del within the 1A rod domain of desmin. Transfected cells expressing the mutated desmin show punctuated and speckled cytoplasmic aggregates. The mutation causes a local conformational change in heptads a/d residues and charge positions. These findings lead to the hypothesis that coiled-coil interactions may be impaired, resulting in severe alterations in the desmin network. This is the first time that a mutation affecting this domain in the desmin molecule is described in a desminopathy.

  16. Stable NRM and mineralogy in Allende - Chondrules

    Science.gov (United States)

    Wasilewski, P. J.; Saralker, C.

    The main objective of the present investigation is related to a description of the magnetic and mineralogic contrasts between chondrules which have a natural remanent magnetization (NRM) vector that is ultrastable during alternating field (AF) demagnetization, and those which have unstable NRM vectors when subjected to the same treatment. The results presented in the present investigation together with new magnetic results from Allende listed in a summary provided by Wasilewski (1981) are used as a basis to argue that the stable NRM in Allende was acquired during a sulfidation event. Attention is given to magnetic phases in Allende, experimental results obtained in magnetic studies conducted with 20 chondrules, and a magnetization model for Allende.

  17. Sagging Eye Syndrome or Nemaline Rod Myopathy? Divergence Insufficiency with Levator Dehiscence as an Overlapping Symptom between Two Diagnoses

    Science.gov (United States)

    Ghadiali, Larissa K.; Brannagan III, Thomas H.; Moonis, Gul; Faust, Phyllis L.; Odel, Jeffrey G.

    2017-01-01

    A 78-year-old woman complained of gradual, painless onset of horizontal binocular diplopia associated with progressive axial weakness. Physical examination revealed esotropia that was greater at distance than at near vision, bilateral levator dehiscence, and normal abducting saccadic speeds. Given the age of the patient and compatible clinical findings, the diagnosis of Sagging Eye Syndrome (SES) was made. However, further work-up with a muscle biopsy suggested Sporadic Late-Onset Nemaline Myopathy (SLONM) as the cause of her progressive muscle weakness. Although rare, external ophthalmoplegia has been described in the literature as a presenting symptom in SLONM. To elucidate the pathological mechanism for the patient's diplopia, an MRI of the orbits was performed, which revealed findings consistent with SES. This case aims to highlight the importance of integrating clinical findings during the diagnostic process and serves as a reminder that diplopia can be a common symptom for an uncommon diagnosis. PMID:28182120

  18. Sagging Eye Syndrome or Nemaline Rod Myopathy? Divergence Insufficiency with Levator Dehiscence as an Overlapping Symptom between Two Diagnoses

    Directory of Open Access Journals (Sweden)

    Stephanie S. L. Cheung

    2017-01-01

    Full Text Available A 78-year-old woman complained of gradual, painless onset of horizontal binocular diplopia associated with progressive axial weakness. Physical examination revealed esotropia that was greater at distance than at near vision, bilateral levator dehiscence, and normal abducting saccadic speeds. Given the age of the patient and compatible clinical findings, the diagnosis of Sagging Eye Syndrome (SES was made. However, further work-up with a muscle biopsy suggested Sporadic Late-Onset Nemaline Myopathy (SLONM as the cause of her progressive muscle weakness. Although rare, external ophthalmoplegia has been described in the literature as a presenting symptom in SLONM. To elucidate the pathological mechanism for the patient’s diplopia, an MRI of the orbits was performed, which revealed findings consistent with SES. This case aims to highlight the importance of integrating clinical findings during the diagnostic process and serves as a reminder that diplopia can be a common symptom for an uncommon diagnosis.

  19. Sagging Eye Syndrome or Nemaline Rod Myopathy? Divergence Insufficiency with Levator Dehiscence as an Overlapping Symptom between Two Diagnoses.

    Science.gov (United States)

    Cheung, Stephanie S L; Ghadiali, Larissa K; Brannagan Iii, Thomas H; Moonis, Gul; Faust, Phyllis L; Odel, Jeffrey G

    2017-01-01

    A 78-year-old woman complained of gradual, painless onset of horizontal binocular diplopia associated with progressive axial weakness. Physical examination revealed esotropia that was greater at distance than at near vision, bilateral levator dehiscence, and normal abducting saccadic speeds. Given the age of the patient and compatible clinical findings, the diagnosis of Sagging Eye Syndrome (SES) was made. However, further work-up with a muscle biopsy suggested Sporadic Late-Onset Nemaline Myopathy (SLONM) as the cause of her progressive muscle weakness. Although rare, external ophthalmoplegia has been described in the literature as a presenting symptom in SLONM. To elucidate the pathological mechanism for the patient's diplopia, an MRI of the orbits was performed, which revealed findings consistent with SES. This case aims to highlight the importance of integrating clinical findings during the diagnostic process and serves as a reminder that diplopia can be a common symptom for an uncommon diagnosis.

  20. Severe congenital actin related myopathy with myofibrillar myopathy features.

    Science.gov (United States)

    Selcen, Duygu

    2015-06-01

    Mutations in ACTA1 have been associated with different pathologic findings including nemaline myopathy, intranuclear rod myopathy, actin myopathy, cap myopathy, congenital fiber type disproportion, and core myopathy. Myofibrillar myopathies are morphologically distinct but genetically heterogeneous muscular dystrophies arising from mutations in Z-disk related proteins. We report a 26-month-old boy with significantly delayed motor development requiring mechanical ventilation and tube-feeding since birth. The muscle biopsy displayed typical features of myofibrillar myopathy with abnormal expression of multiple proteins. Whole exome sequencing revealed two-amino-acid duplication in ACTA1. In cell culture system, mutant actin was expressed at ~11% of wild-type, and mutant actin formed pleomorphic cytoplasmic aggregates whereas wild-type actin appeared in filamentous structures. We conclude that mutations in ACTA1 can cause pathologic features consistent with myofibrillar myopathy, and mutations in ACTA1 should be considered in patients with severe congenital hypotonia associated with muscle weakness and features of myofibrillar myopathy.

  1. Nemaline myopathy: A report of four cases

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    Deepti A

    2007-01-01

    Full Text Available Nemaline myopathies are a group of genetically determined (autosomal dominant/recessive congenital myopathies characterized by the formation of nemaline rods within muscle fibers. Congenital, childhood, and adult forms with hypotonia, proximal muscle and facial weakness, and skeletal deformities have been described. The diagnostic hallmark is the presence of nemaline rods on modified Gomori′s trichrome staining. We report the clinical and morphological features of four patients with nemaline rod myopathy: congenital classic (2, childhood (1, and adult (1, and speculate on the disease′s evolution.

  2. Thyrotoxic Myopathy

    Science.gov (United States)

    ... Information from the National Library of Medicine’s MedlinePlus Hyperthyroidism Neuromuscular Disorders Definition Treatment Prognosis Clinical Trials Organizations Publications Definition Thyrotoxic myopathy ...

  3. Inflammatory Myopathies

    Science.gov (United States)

    ... of chronic, or persistent, inflammatory myopathy are polymyositis, dermatomyositis, and inclusion body myositis. What causes these disorders? ... disorders may affect both adults and children, although dermatomyositis is the most common chronic form in children. ...

  4. Congenital Myopathy

    Science.gov (United States)

    ... evaluate the electrical activity of the muscle, a muscle biopsy, and genetic testing. There are currently seven distinct types of congenital myopathy, with some variation in symptoms, complications, treatment options, and outlook. Nemaline ...

  5. Toxic myopathies.

    Science.gov (United States)

    Pasnoor, Mamatha; Barohn, Richard J; Dimachkie, Mazen M

    2014-08-01

    Muscle tissue is highly sensitive to many substances. Early recognition of toxic myopathies is important, because they potentially are reversible on removal of the offending drug or toxin, with greater likelihood of complete resolution the sooner this is achieved. Clinical features range from mild muscle pain and cramps to severe weakness with rhabdomyolysis, renal failure, and even death. The pathogenic bases can be multifactorial. This article reviews some of the common toxic myopathies and their clinical presentation, histopathologic features, and possible underlying cellular mechanisms.

  6. [Inflammatory myopathies].

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    Maurer, Britta

    2017-02-01

    Inflammatory myopathies comprise heterogeneous, often multisystemic autoimmune diseases with muscle involvement as a common feature. The prognosis largely depends on a timely diagnosis and initiation of therapy. Given the complexity of these rare diseases, when an inflammatory myopathy is suspected patients should be referred to an expert center with established algorithms for the diagnostic work-up. The differential diagnostic exclusion of myositis mimics should ideally be carried out in close collaboration with neurologists and neuropathologists. The choice of immunosuppressive treatment should primarily depend on disease severity and organ involvement but age and comorbidities also have to be taken into account.

  7. Axial myopathy

    DEFF Research Database (Denmark)

    Witting, Nanna; Andersen, Linda K; Vissing, John

    2016-01-01

    musculature involvement in the majority of myopathies in which paraspinal musculature was examined. Even in diseases named after a certain pattern of non-axial muscle affection, such as facioscapulohumeral and limb girdle muscular dystrophies, affection of the axial musculature was often severe and early...

  8. Desmin myopathy.

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    Goldfarb, L G; Vicart, P; Goebel, H H; Dalakas, M C

    2004-04-01

    Desmin myopathy is a recently identified disease associated with mutations in desmin or alphaB-crystallin. Typically, the illness presents with lower limb muscle weakness slowly spreading to involve truncal, neck-flexor, facial, bulbar and respiratory muscles. Skeletal myopathy is often combined with cardiomyopathy manifested by conduction blocks and arrhythmias resulting in premature sudden death. Sections of the affected skeletal and cardiac muscles show abnormal fibre areas containing amorphous eosinophilic deposits seen as granular or granulofilamentous material on electron microscopic examination. Immuno-staining for desmin is positive in each region containing abnormal structures. The inheritance pattern in familial desmin myopathy is autosomal dominant or autosomal recessive, but many cases have no family history. At least some, and probably most, non-familial desmin myopathy cases are associated with de novo desmin mutations. Age of disease onset and rate of progression may vary depending on the type of inheritance and location of the causative mutation. Multiple mutations have been identified in the desmin gene: point substitutions, insertion, small in-frame deletions and a larger exon-skipping deletion. The majority of these mutations are located in conserved alpha-helical segments of desmin. Many of the missense mutations result in changing the original amino acid into proline, which is known as a helix breaker. Studies of transfected cell cultures indicate that mutant desmin is assembly-incompetent and able to disrupt a pre-existing filamentous network in dominant-negative fashion. Disease-associated desmin mutations in humans or transgenic mice cause accumulation of chimeric intracellular aggregates containing desmin and other cytoskeletal proteins. alphaB-crystallin serves in the muscle as a chaperone preventing desmin aggregation under various forms of stress. If mutated, alphaB-crystallin may cause a myopathy similar to those resulting from desmin

  9. Molecular and Genetic Studies of Congenital Myopathies

    Science.gov (United States)

    2016-12-08

    Central Core Disease; Centronuclear Myopathy; Congenital Fiber Type Disproportion; Multiminicore Disease; Myotubular Myopathy; Nemaline Myopathy; Rigid Spine Muscular Dystrophy; Undefined Congenital Myopathy

  10. Inflammatory Myopathies (Myositis)

    Science.gov (United States)

    ... Texas 2 Inflammatory Myopathies • ©2011 MDA Polymyositis and dermatomyositis mostly affect the muscles of the hips and ... matory myopathies in MDA’s program — polymyositis (PM) and dermatomyositis (DM) — effective treatments are avail- able. New research ...

  11. Hypertrophic cardiomyopathy in a neonate associated with nemaline myopathy.

    Science.gov (United States)

    Mir, Arshid; Lemler, Matthew; Ramaciotti, Claudio; Blalock, Shannon; Ikemba, Catherine

    2012-01-01

    Nemaline myopathy is a congenital nonprogressive skeletal muscle disorder with a characteristic rod body formation in the skeletal muscle fibers. Cardiac involvement in nemaline myopathy is rare, although both dilated and hypertrophic cardiomyopathy have been reported. We describe an infant diagnosed with hypertrophic cardiomyopathy and hypotonia on the first day of life. Muscle biopsy confirmed nemaline myopathy at 3 weeks of age. The diagnosis of nemaline myopathy precluded consideration of heart transplantation, thus shifting the focus to comfort care. This is the earliest presentation of hypertrophic cardiomyopathy reported in the literature in the setting of nemaline myopathy. The approach to determining an etiology for hypertrophic cardiomyopathy in an infant is reviewed. © 2011 Wiley Periodicals, Inc.

  12. Sudden cardiac arrest in a child with nemaline myopathy

    OpenAIRE

    Marseglia, Lucia; D’Angelo, Gabriella; Manti, Sara; Salpietro, Vincenzo; Arrigo, Teresa; Cavallari, Vittorio; Gitto, Eloisa

    2015-01-01

    Background Nemaline myopathy is a rare, non progressive congenital skeletal muscle disorder defined by the presence of inclusions known as nemaline rods in muscle fibers. Several clinical subtypes have been described, according to degree of muscle weakness, severity and age at onset. The course of nemaline myopathy is very slowly progressive, and death is usually due to respiratory failure. Cardiac involvement is rare and generally considered to be the result of ACTA1 mutations. Patient We re...

  13. Biallelic Mutations in MYPN, Encoding Myopalladin, Are Associated with Childhood-Onset, Slowly Progressive Nemaline Myopathy

    OpenAIRE

    Miyatake, Satoko; Mitsuhashi, Satomi; Hayashi, Yukiko K.; Purevjav, Enkhsaikhan; Nishikawa, Atsuko; Koshimizu, Eriko; Suzuki, Mikiya; Yatabe, Kana; Tanaka, Yuzo; Ogata, Katsuhisa; Kuru, Satoshi; Shiina, Masaaki; Tsurusaki, Yoshinori; Nakashima, Mitsuko; Mizuguchi, Takeshi

    2016-01-01

    Nemaline myopathy (NM) is a common form of congenital nondystrophic skeletal muscle disease characterized by muscular weakness of proximal dominance, hypotonia, and respiratory insufficiency but typically not cardiac dysfunction. Wide variation in severity has been reported. Intranuclear rod myopathy is a subtype of NM in which rod-like bodies are seen in the nucleus, and it often manifests as a severe phenotype. Although ten mutant genes are currently known to be associated with NM, only ACT...

  14. [Steroid-induced myopathy].

    Science.gov (United States)

    Polunina, A G; Isaev, F V; Dem'ianova, M A

    2012-01-01

    Physiological effects of glucocorticoids include the inhibition of protein synthesis and the increase in catabolic processes in muscles. Consequently, a long-term intake of steroids in high doses causes myopathy. Myopathic effects of glucocorticoids are observed during systemic as well as inhallatory use. Most frequently, steroid myopathy manifests as the weakness and hypotrophy of lower limbs muscles, weakness of respiratory muscles, dysphonia. Prevention and treatment of steroid myopathy include limitation of indications for long-term usage of glucocorticoids, alternating regimens of treatment, adequate physical activity. The current data demonstrate the efficacy of vitamin D and amino acids mixtures in the prevention and treatment of steroid myopathy.

  15. Familial visceral myopathy associated with a mitochondrial myopathy.

    OpenAIRE

    Lowsky, R; Davidson, G.; Wolman, S; Jeejeebhoy, K N; Hegele, R. A.

    1993-01-01

    A 27 year old man with intestinal pseudo-obstruction who developed parenteral nutrition induced hyperlipidaemia and who also had ophthalmoplegia and an undifferentiated myopathy is described. Histological examination of biopsy specimens and molecular analysis show that this patient had both familial visceral myopathy and a mitochondrial myopathy, suggesting that a mitochondrial DNA mutation is the molecular lesion in familial visceral myopathy.

  16. Progressive skeletal myopathy, a phenotypic variant of desmin myopathy associated with desmin mutations.

    Science.gov (United States)

    Dalakas, Marinos C; Dagvadorj, Ayush; Goudeau, Bertrand; Park, Kye-Yoon; Takeda, Kazuyo; Simon-Casteras, Monique; Vasconcelos, Olavo; Sambuughin, Nyamkhishig; Shatunov, Alexey; Nagle, James W; Sivakumar, Kumaraswamy; Vicart, Patrick; Goldfarb, Lev G

    2003-03-01

    Desmin myopathy is a familial or sporadic disorder characterized by the presence of desmin mutations that cause skeletal muscle weakness associated with cardiac conduction block, arrhythmia and heart failure. Distinctive histopathologic features include intracytoplasmic accumulation of desmin-reactive deposits and electron-dense granular aggregates in skeletal and cardiac muscle cells. We describe two families with features of adult-onset slowly progressive skeletal myopathy without cardiomyopathy. N342D point mutation was present in the desmin helical rod domain in patients of family 1, and I451M mutation was found in the non-helical tail domain in patients of family 2. Of interest, the same I451M mutation has previously been reported in patients with cardiomyopathy and no signs of skeletal myopathy. Some carriers of the I451M mutation did not develop any disease, suggesting incomplete penetrance. Expression studies demonstrated inability of the N342D mutant desmin to form cellular filamentous network, confirming the pathogenic role of this mutation, but the network was not affected by the tail-domain I451M mutation. Progressive skeletal myopathy is a rare phenotypic variant of desmin myopathy allelic to the more frequent cardio-skeletal form.

  17. Sporadic late onset nemaline myopathy and immunoglobulin deposition disease.

    Science.gov (United States)

    Doppler, Kathrin; Knop, Stefan; Einsele, Hermann; Sommer, Claudia; Wessig, Carsten

    2013-12-01

    In monoclonal gammopathy, organ dysfunction can occur due to deposition of immunoglobulin fragments. A rare form of acquired myopathy often associated with monoclonal gammopathy is sporadic late onset nemaline myopathy (SLONM), which is characterized by nemaline rods in myofibers. The pathogenetic link between monoclonal gammopathy and SLONM has not yet been elucidated. Case report of a patient with monoclonal gammopathy who developed a progressive myopathy, finally diagnosed as SLONM. A muscle biopsy showed mild myopathic changes. A second biopsy 1 year after clinical onset demonstrated deposition of immunoglobulin light and heavy chains and the presence of nemaline rods. The patient experienced marked improvement of muscle strength after autologous stem cell transplantation and treatment with bortezomib, a therapy that is known to be effective in light chain deposition disease. We speculate that deposition of light and heavy chains, rather than nemaline bodies, has myotoxic effects on skeletal muscle. Copyright © 2013 Wiley Periodicals, Inc.

  18. Institutional strengthening to enable local governments's NRM capacity in Bukidnon Province, Philippines

    OpenAIRE

    Sumbalan, Antonio

    2004-01-01

    This presentation discusses the structure of the Philipppine government and the relatively recent decentralization that has increased the role of local government in NRM. The institutional innovations and policy development from the Bukidnon province are presented, as are the ways in which SANREM CRSP has supported the strengthening of local institutions' capacity to manage their natural resources.

  19. A locus on chromosome 15q for a dominantly inherited nemaline myopathy with core-like lesions.

    NARCIS (Netherlands)

    Gommans, I.M.P.; Davis, M.; Saar, K.; Lammens, M.M.Y.; Mastaglia, F.; Lamont, P.; Duijnhoven, G.C.F. van; Laak, H.J. ter; Reis, A.; Vogels, O.J.M.; Laing, N.G.; Engelen, B.G.M. van; Kremer, J.M.J.

    2003-01-01

    Nemaline myopathy is a congenital neuromuscular disorder characterized by muscle weakness and the presence of nemaline rods. Five genes have now been associated with nemaline myopathy: alpha-tropomyosin-3 (TPM3), alpha-actin (ACTA1), nebulin (NEB), beta-tropomysin (TPM2) and troponin T (TNNT1). In

  20. Nemaline myopathies: State of the art.

    Science.gov (United States)

    Malfatti, E; Romero, N B

    2016-10-01

    Nemaline myopathy (NM) is one of the most common forms of congenital myopathy. The condition is defined by the histopathological finding of nemaline bodies (rods) on muscle biopsy and is associated with hypotonia and muscle weakness. The clinical spectrum encompasses lethal forms presenting in the neonatal period with profound weakness and less severe congenital diseases of later onset. NM is significantly heterogeneous from a genetic point of view, and its inheritance can be autosomal-dominant (AD), sporadic or autosomal-recessive (AR). To date, 11 genes encoding proteins of skeletal muscle thin filaments, Kelch domain-associated proteins and an unconventional myosin have been implicated in NM. The mechanisms leading to nemaline body formation and muscle weakness are still largely unclear. This report reviews the clinical, histopathological and genetic features of NM, with a focus on some of the recently discovered forms. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  1. Inflammatory and toxic myopathies.

    Science.gov (United States)

    Dalakas, M C

    1992-10-01

    The major advances in the immunopathogenesis and treatment of inflammatory myopathies, and the main criteria that distinguish polymyositis (PM) from dermatomyositis (DM) or inclusion-body myositis (IBM) are presented. The origin and implications of the amyloid and ubiquitin deposits found within the vacuolated fibers of patients with IBM are considered. The pathogenesis of human immunodeficiency virus (HIV) and human T-cell lymphotrophic virus (HTLV)-I-associated PM is presented, and the role of retroviruses in triggering PM, even in the absence of detectable viral genome within the muscle fibers, is discussed. In addition, three toxic myopathies with distinct morphologic, biochemical, or molecular characteristics, caused by zidovudine [azidothymidine (AZT) myopathy], the cholesterol-lowering-agent myopathy (CLAM), and the combination of blocking agents with corticosteroids are presented.

  2. Dominantly Inherited Nemaline Myopathy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2003-08-01

    Full Text Available A locus on chromosome 15q21-23 for a dominantly inherited nemaline myopathy with core-like lesions is reported in two unrelated families evaluated at University Medical Center, Nijmegen, The Netherlands.

  3. Sudden cardiac arrest in a child with nemaline myopathy.

    Science.gov (United States)

    Marseglia, Lucia; D'Angelo, Gabriella; Manti, Sara; Salpietro, Vincenzo; Arrigo, Teresa; Cavallari, Vittorio; Gitto, Eloisa

    2015-03-21

    Nemaline myopathy is a rare, non progressive congenital skeletal muscle disorder defined by the presence of inclusions known as nemaline rods in muscle fibers. Several clinical subtypes have been described, according to degree of muscle weakness, severity and age at onset. The course of nemaline myopathy is very slowly progressive, and death is usually due to respiratory failure. Cardiac involvement is rare and generally considered to be the result of ACTA1 mutations. We report the case of a 6 year old boy with typical congenital nemaline myopathy. Nemaline myopathy was confirmed at 3 years of age by muscle biopsy. No mutation of ACTA1, TPM2 and TNNT1 genes was detected. The child died suddenly of cardiac arrest and associated hypoxic-ischemic brain injury, in absence of acute respiratory failure or swallowing difficulties. Nemaline cardiomyopathy was suspected, but post mortem cardiac biopsy did not show findings consistent with nemaline myopathy. Congenital typical nemaline myopathy is not necessarily a static or very slowly progressive disorder and acute cardiac deterioration can lead to early death.

  4. Delayed onset of nemaline myopathy: a case report

    Institute of Scientific and Technical Information of China (English)

    韩燕; 郑惠民; 丁素菊

    2003-01-01

    @@ Nemaline myopathy (NM), first reported by Shy et al1 in 1963, is characterized by the presence of nemaline rods in myofibers and in the nucleus in severe cases. NM is a clinically rare, heterogeneous congenital muscle disorder, displaying dominant or recessive autosomal forms, and in rare cases, sporadic as well. Its chief manifestations are proximal muscle weakness and atrophy followed by further progress to generalized weakness and weakness of facial muscles, tongue muscles and throat muscles. Below is the case of an adult onset nemaline myopathy.

  5. Experimental characterization of negative refractive index material NRM at Ka band

    CERN Document Server

    Chatterjee, Sougata

    2016-01-01

    In this paper, we discuss the experimental characterization of a negative refractive material NRM at Ka band using LR labyrinth Ring and wire array WA. We describe in detail the the LR and wire array characterization separately, and after that the combined experimental results, for NRM are reported. The LRs analytical and simulation study is not new but design in Ka band and different experimental procedure for the characterization of the negative refractive index is the novelty of this paper. For performing a negative refractive index experiment we made prism of 150 Prism angle . We get enhanced transmittance of more than 20 dB from background, at a negative angle of refraction. The values of the negative refractive index in a band of about 1 G Hz around 31 GHz are retrieved from the experimental data.

  6. Missense mutations in desmin associated with familial cardiac and skeletal myopathy.

    Science.gov (United States)

    Goldfarb, L G; Park, K Y; Cervenáková, L; Gorokhova, S; Lee, H S; Vasconcelos, O; Nagle, J W; Semino-Mora, C; Sivakumar, K; Dalakas, M C

    1998-08-01

    Desmin-related myopathy (OMIM 601419) is a familial disorder characterized by skeletal muscle weakness associated with cardiac conduction blocks, arrhythmias and restrictive heart failure, and by intracytoplasmic accumulation of desmin-reactive deposits in cardiac and skeletal muscle cells. The underlying molecular mechanisms are unknown. Involvement of the desmin gene (DES) has been excluded in three families diagnosed with desmin-related myopathy. We report two new families with desmin-related cardioskeletal myopathy associated with mutations in the highly conserved carboxy-terminal end of the desmin rod domain. A heterozygous A337P mutation was identified in a family with an adult-onset skeletal myopathy and mild cardiac involvement. Compound heterozygosity for two other mutations, A360P and N393I, was detected in a second family characterized by childhood-onset aggressive course of cardiac and skeletal myopathy.

  7. STATINS AND MYOPATHY: MOLECULAR MECHANISMS

    Directory of Open Access Journals (Sweden)

    O. M. Drapkina

    2012-01-01

    Full Text Available The safety of statin therapy is considered. In particular the reasons of a complication such as myopathy are discussed in detail. The molecular mechanisms of statin myopathy , as well as its risk factors are presented. The role of coenzyme Q10 in the myopathy development and coenzyme Q10 application for the prevention of this complication are considered. 

  8. Protein aggregate myopathies

    Directory of Open Access Journals (Sweden)

    Sharma M

    2005-01-01

    Full Text Available Protein aggregate myopathies (PAM are an emerging group of muscle diseases characterized by structural abnormalities. Protein aggregate myopathies are marked by the aggregation of intrinsic proteins within muscle fibers and fall into four major groups or conditions: (1 desmin-related myopathies (DRM that include desminopathies, a-B crystallinopathies, selenoproteinopathies caused by mutations in the, a-B crystallin and selenoprotein N1 genes, (2 hereditary inclusion body myopathies, several of which have been linked to different chromosomal gene loci, but with as yet unidentified protein product, (3 actinopathies marked by mutations in the sarcomeric ACTA1 gene, and (4 myosinopathy marked by a mutation in the MYH-7 gene. While PAM forms 1 and 2 are probably based on impaired extralysosomal protein degradation, resulting in the accumulation of numerous and diverse proteins (in familial types in addition to respective mutant proteins, PAM forms 3 and 4 may represent anabolic or developmental defects because of preservation of sarcomeres outside of the actin and myosin aggregates and dearth or absence of other proteins in these actin or myosin aggregates, respectively. The pathogenetic principles governing protein aggregation within muscle fibers and subsequent structural sarcomeres are still largely unknown in both the putative catabolic and anabolic forms of PAM. Presence of inclusions and their protein composition in other congenital myopathies such as reducing bodies, cylindrical spirals, tubular aggregates and others await clarification. The hitherto described PAMs were first identified by immunohistochemistry of proteins and subsequently by molecular analysis of their genes.

  9. Severe congenital nemaline myopathy with primary pulmonary lymphangiectasia: unusual clinical presentation and review of the literature

    OpenAIRE

    Waisayarat, Jariya; Suriyonplengsaeng, Chinnawut; Khongkhatithum, Chaiyos; Rochanawutanon, Mana

    2015-01-01

    Introduction Nemaline myopathy is a rare genetic muscle disorder defined by the presence of nemaline rods in the muscle fibre sarcoplasm. Congenital nemaline myopathy is the most serious form of the disease’s spectrum. Case presentation The affected newborn has no spontaneous movement, fractures at birth and respiratory insufficiency. The present case was a Thai male, floppy at birth with fractures of both humeri and femurs and ventilator-dependent respiration. The patient developed bilateral...

  10. Nemaline myopathy type 2 (NEM2): two novel mutations in the nebulin (NEB) gene.

    Science.gov (United States)

    Gajda, Anna; Horváth, Emese; Hortobágyi, Tibor; Gergev, Gyurgyinka; Szabó, Hajnalka; Farkas, Katalin; Nagy, Nikoletta; Széll, Márta; Sztriha, László

    2015-04-01

    Nemaline myopathy is a type of the heterogeneous group of congenital myopathies. Generalized hypotonia, weakness, and delayed motor development are the main clinical features of the typical congenital form. Histopathology shows characteristic nemaline rods in the muscle biopsy. Mutations in at least 7 genes, including nebulin gene (NEB), proved to be responsible for this muscle disease. We present a boy with nemaline myopathy type 2 (NEM2) caused by compound heterozygosity for 2 novel mutations, a deletion and a duplication in the NEB gene. The deletion was inherited from the father and the duplication from the mother. Testing all family members supports genetic counseling. © The Author(s) 2013.

  11. Mutation Update: The Spectra of Nebulin Variants and Associated Myopathies

    Science.gov (United States)

    Lehtokari, Vilma-Lotta; Kiiski, Kirsi; Sandaradura, Sarah A.; Laporte, Jocelyn; Repo, Pauliina; Frey, Jennifer A.; Donner, Kati; Marttila, Minttu; Saunders, Carol; Barth, Peter G.; den Dunnen, Johan T.; Beggs, Alan H.; Clarke, Nigel F.; North, Kathryn N.; Laing, Nigel G.; Romero, Norma B.; Winder, Thomas L.; Pelin, Katarina; Wallgren-Pettersson, Carina

    2015-01-01

    A mutation update on the nebulin gene (NEB) is necessary because of recent developments in analysis methodology, the identification of increasing numbers and novel types of variants, and a widening in the spectrum of clinical and histological phenotypes associated with this gigantic, 183 exons containing gene. Recessive pathogenic variants in NEB are the major cause of nemaline myopathy (NM), one of the most common congenital myopathies. Moreover, pathogenic NEB variants have been identified in core-rod myopathy and in distal myopathies. In this update, we present the disease-causing variants in NEB in 159 families, 143 families with NM, and 16 families with NM-related myopathies. Eighty-eight families are presented here for the first time. We summarize 86 previously published and 126 unpublished variants identified in NEB. Furthermore, we have analyzed the NEB variants deposited in the Exome Variant Server (http://evs.gs.washington.edu/EVS/), identifying that pathogenic variants are a minor fraction of all coding variants (~7%). This indicates that nebulin tolerates substantial changes in its amino acid sequence, providing an explanation as to why variants in such a large gene result in relatively rare disorders. Lastly, we discuss the difficulties of drawing reliable genotype–phenotype correlations in NEB-associated disease. PMID:25205138

  12. Monoclonal gammopathy with both nemaline myopathy and amyloid myopathy.

    Science.gov (United States)

    Wang, Min; Lei, Lin; Chen, Hai; Di, Li; Pang, Mi; Lu, Yan; Lu, Lu; Shen, Xin-Ming; Da, Yuwei

    2017-10-01

    Monoclonal gammopathies due to plasma cell dyscrasias can induce diverse rare neuromuscular disorders. Deposition of monoclonal antibody light chains in skeletal muscle causes amyloid myopathy. Monoclonal gammopathy is occasionally associated with sporadic late-onset nemaline myopathy. Here we report a monoclonal gammopathy patient with both sporadic late-onset nemaline myopathy and amyloid myopathy. The diagnoses were based on immunofixation electrophoresis of urine, and serum for free light chain assay, Congo red staining and Thioflavin S staining of muscle biopsies, as well as immunohistochemical staining and electron-microscopic observation. Nemaline myopathy and amyloid myopathy can present in the same patient with monoclonal gammopathy. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Anaphase promoting complex-dependent degradation of transcriptional repressors Nrm1 and Yhp1 in Saccharomyces cerevisiae.

    Science.gov (United States)

    Ostapenko, Denis; Solomon, Mark J

    2011-07-01

    The anaphase-promoting complex/cyclosome (APC/C) is an essential ubiquitin ligase that targets cell cycle proteins for proteasome-mediated degradation in mitosis and G1. The APC regulates a number of cell cycle processes, including spindle assembly, mitotic exit, and cytokinesis, but the full range of its functions is still unknown. To better understand cellular pathways controlled by the APC, we performed a proteomic screen to identify additional APC substrates. We analyzed cell cycle-regulated proteins whose expression peaked during the period when other APC substrates were expressed. Subsequent analysis identified several proteins, including the transcriptional repressors Nrm1 and Yhp1, as authentic APC substrates. We found that APC(Cdh1) targeted Nrm1 and Yhp1 for degradation in early G1 through Destruction-box motifs and that the degradation of these repressors coincided with transcriptional activation of MBF and Mcm1 target genes, respectively. In addition, Nrm1 was stabilized by phosphorylation, most likely by the budding yeast cyclin-dependent protein kinase, Cdc28. We found that expression of stabilized forms of Nrm1 and Yhp1 resulted in reduced cell fitness, due at least in part to incomplete activation of G1-specific genes. Therefore, in addition to its known functions, APC-mediated targeting of Nrm1 and Yhp1 coordinates transcription of multiple genes in G1 with other cell cycle events.

  14. Cerebrovascular Accidents In Myopathies

    Directory of Open Access Journals (Sweden)

    Farzad Fatehi

    2017-02-01

    Full Text Available Several types of stroke in myopathies are described: ischemic, metabolic, or cryptogenic. Ischemic stroke may be categorized as cardioembolic, angiopathic, hemodynamic, or thrombophilic. Cardiac involvement in the form of atrial fibrillation/flutter, dilated cardiomyopathy, or non-compaction Cardioembolic could ensue in stroke. Angiopathic stroke occurs provided that there is atherosclerosis or mitochondrial disorders. Thrombophilic stroke may happen in polymyositis or dermatomyositis along with anti-phospholipid syndrome. Metabolic stroke usually manifests as stroke-like episode and is a distinct feature of various mitochondrial disorders, principally MELAS syndrome. The clinical manifestations are as a result of a vasogenic edema, demonstrating as hyperintensity on T2, DWI, and apparent diffusion coefficient mapping. Differentiation between ischemic and metabolic stroke is essential in terms of diagnosis, therapy, and prognosis. In conclusion, ischemic stroke attributable to cardioembolism, arteriopathy, or thrombophilia are occasional events in myopathies, but metabolic stroke is a frequent feature of mitochondrial disorders.

  15. Renormalization constants for $N_{\\rm f}=2+1+1$ twisted mass QCD

    CERN Document Server

    Blossier, Benoit; Guichon, Pierre; Morénas, Vincent; Pène, Olivier; Rodríguez-Quintero, Jose; Zafeiropoulos, Savvas

    2014-01-01

    We summarize recent non-perturbative results obtained for the renormalization constants computed in the RI'-MOM scheme for $N_{\\rm f}=2+1+1$ twisted mass QCD. Our implementation employs the Iwasaki gauge action and four dynamical degenerate twisted mass fermions. Renormalization constants for scalar, pseudo-scalar, vector and axial operators, as well as the quark propagator renormalization, are computed at three different values of the lattice spacing, two different volumes and several values of the twisted mass. Our method allows for a precise cross-check of the running, because of the particular proper treatment of the hypercubic artifacts. Preliminary results for twist-2 operators are also presented.

  16. Spectrum of congenital myopathies: A single centre experience

    Directory of Open Access Journals (Sweden)

    Megha S Uppin

    2013-01-01

    Full Text Available Background: Congenital myopathies (CMs are rare and they are clinically and genetically heterogeneous. Muscle biopsy is characterized by structural abnormality that is diagnostic. There are few studies from India. Materials and Methods: This is a retrospective study of 12 years. The demographic data, clinical features and laboratory data of patients diagnosed as CMs on muscle biopsy were retrieved from medical records. The slides were reviewed for morphological and structural abnormalities using the following stains hematoxylin and eosin, modified Gomori trichrome, masson trichrome, periodic acid schiff, adenosine triphosphatase preincubated at pH 9.4, 4.6 and 4.3, nicotinamide adenine dinucleotide tetrazolium reductase, succinic dehydrogenase and cytochrome c oxidase. Immunohistochemistry was performed with dystrophin, sarcoglycans and desmin wherever necessary. Results: There were 50 patients with CMs: Centronuclear myopathy (23, myotubular myopathy (3 and central core disease (CCD (8, nemaline myopathy (5, congenital fiber type proportion (10 and desmin related myopathy with arrythmogenic right ventricular cardiomyopathy (ARVD (1. Of the 50 patients, 30 (60% presented in the first decade of life. Proximal muscle weakness and hypotonia were the common presenting features. Type 1 atrophy and predominance were seen in most cases on muscle biopsy. CCD had one patient with high creatine phosphokinase levels, biopsy in one patient showed both rods and cores, in the other limb girdle muscular dystrophy like picture and one biopsy showed uniform type 1 fibers. There was one desmin related myopathy with ARVD, who had cardiac transplantation and both skeletal and cardiac muscle showed characteristic rimmed vacuoles and inclusions positive for desmin. Conclusion: CMs are rare and the diagnosis can only be established on muscle biopsy. Defining the specific CMs helps the clinician in counseling the patient and family.

  17. Inherited myopathies and muscular dystrophies

    NARCIS (Netherlands)

    Cardamone, Michael; Darras, Basil T.; Ryan, Monique M.

    The inherited myopathies and muscular dystrophies are a diverse group of muscle diseases presenting with common complaints and physical signs: weakness, motor delay, and respiratory and bulbar dysfunction. The myopathies are caused by genetic defects in the contractile apparatus of muscle, and

  18. Craniofacial Manifestations in Severe Nemaline Myopathy.

    Science.gov (United States)

    Xue, Yunfeng; Magoulas, Pilar L; Wirthlin, John O; Buchanan, Edward P

    2017-05-01

    Nemaline myopathy (NM) is a rare congenital muscular disease characterized by the presence of rod (nemaline) bodies visualized on muscle biopsy. The disease is genetically and clinically heterogeneous, and the age of onset can vary from neonate to adult. Patients typically present initially with diffuse muscle weakness and hypotonia. The disease also afflicts facial musculature and can cause anomalous facial growth and development. The authors report a patient of early onset NM with significant craniofacial abnormalities. The untreated facial growth is discussed and illustrated in this article. The authors reviewed the current knowledge in the literature regarding the molecular and genetic pathogenesis of NM. The roles of both surgical and supportive management are discussed in this particular patient.

  19. Recent advances in nemaline myopathy.

    Science.gov (United States)

    Romero, Norma B; Sandaradura, Sarah A; Clarke, Nigel F

    2013-10-01

    This article reviews recent advances in the understanding of nemaline myopathy, with a focus on the genetic basis of the disorder, histology, and pathogenesis. Pathogenic mutations have been identified in eight genes and there is evidence of further genetic heterogeneity in nemaline myopathy. Clinical presentation, histological features on skeletal muscle biopsy, and pattern of changes on muscle MRI may guide prioritization of molecular genetic testing. It is anticipated that use of new technologies such as whole exome sequencing and comparative genomic hybridization will increase the number of genes associated with nemaline myopathy and the proportion of patients in whom the genetic basis of the disorder is identified. Single fiber studies and animal models continue to add to understanding of the pathogenesis of this disorder. Current management focuses on supportive treatment; however, encouraging advances are emerging for the future. Recent advances in understanding of nemaline myopathy have important implications for clinical practice and for genetic diagnosis of patients with nemaline myopathy.

  20. Muscle regeneration in mitochondrial myopathies

    DEFF Research Database (Denmark)

    Krag, T O; Hauerslev, S; Jeppesen, T D

    2013-01-01

    Mitochondrial myopathies cover a diverse group of disorders in which ragged red and COX-negative fibers are common findings on muscle morphology. In contrast, muscle degeneration and regeneration, typically found in muscular dystrophies, are not considered characteristic features of mitochondrial...... myopathies. We investigated regeneration in muscle biopsies from 61 genetically well-defined patients affected by mitochondrial myopathy. Our results show that the perturbed energy metabolism in mitochondrial myopathies causes ongoing muscle regeneration in a majority of patients, and some were even affected...... by a dystrophic morphology. The results add to the complexity of the pathogenesis underlying mitochondrial myopathies, and expand the knowledge about the impact of energy deficiency on another aspect of muscle structure and function....

  1. Mutations in the nebulin gene can cause severe congenital nemaline myopathy

    NARCIS (Netherlands)

    Wallgren-Pettersson, C; Donner, K; Sewry, C; Lammens, M; Bushby, K; Uzielli, MLG; Lapi, E; Odent, S; Akcoren, Z; Topaloglu, H; Pelin, K; Bijlsma, E.

    2002-01-01

    Previously, we reported results indicating that nebulin was the gene causing the typical form of autosomal recessive nemaline (rod) myopathy. Here we describe the identification of mutations in the nebulin gene in seven offspring of five families affected by the severe congenital form of nemaline

  2. Mutations in the nebulin gene can cause severe congenital nemaline myopathy.

    NARCIS (Netherlands)

    Wallgren-Pettersson, C.; Donner, K.; Sewry, C.A.; Bijlsma, E.; Lammens, M.M.Y.; Bushby, K.; Giovannucci Uzielli, M.L.; Lapi, E.; Odent, S.; Akcoren, Z.; Topaloglu, H.; Pelin, K.

    2002-01-01

    Previously, we reported results indicating that nebulin was the gene causing the typical form of autosomal recessive nemaline (rod) myopathy. Here we describe the identification of mutations in the nebulin gene in seven offspring of five families affected by the severe congenital form of nemaline

  3. Clinical and Histologic Findings in ACTA1-Related Nemaline Myopathy: Case Series and Review of the Literature.

    Science.gov (United States)

    Moreno, Cristiane de Araújo Martins; Abath Neto, Osório; Donkervoort, Sandra; Hu, Ying; Reed, Umbertina Conti; Oliveira, Acary Sousa Bulle; Bönnemann, Carsten; Zanoteli, Edmar

    2017-10-01

    Nemaline myopathy is a rare congenital disease of skeletal muscle characterized by muscle weakness and hypotonia, as well as the diagnostic presence of nemaline rods in skeletal muscle fibers. Nemaline myopathy is genetically and phenotypically heterogeneous and, so far, mutations in 11 different genes have been associated with this disease. Dominant mutations in ACTA1 are the second most frequent genetic cause of nemaline myopathy and can lead to a variety of clinical and histologic phenotypes. We present a series of ACTA1-related cases from a Brazilian cohort of 23 patients with nemaline myopathy, diagnosed after Sanger sequencing the entire coding region of ACTA1, and review the literature on ACTA1-related nemaline myopathy. The study confirmed ACTA1 mutations in four patients, including one with intranuclear rods, one with large intracytoplasmic aggregates, and two with nemaline intracytoplasmic rods. A repeat muscle biopsy in one patient did not show histological progression. Despite the recognized phenotypic variability in ACTA1-related nemaline myopathy, clinical and histological presentations appear to correlate with the position of the mutation, which confirms emerging genotype/phenotype correlations and better predict the prognosis of affected patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Critical illness myopathy.

    Science.gov (United States)

    Latronico, Nicola; Tomelleri, Giuliano; Filosto, Massimiliano

    2012-11-01

    To describe the incidence, major risk factors, and the clinical, electrophysiological, and histological features of critical illness myopathy (CIM). Major pathogenetic mechanisms and long-term consequences of CIM are also reviewed. CIM is frequently associated with critical illness polyneuropathy (CIP), and may have a relevant impact on patients' outcome. CIM has an earlier onset than CIP, and recovery is faster. Loss of myosin filaments on muscle biopsy is important to diagnose CIM, and has a good prognosis. Critical illness, use of steroids, and immobility concur in causing CIM. A rationale diagnostic approach to CIM using clinical, electrophysiological, and muscle biopsy investigations is important to plan adequate therapy and to predict recovery.

  5. Virtual directions in paleomagnetism: A global and rapid approach to evaluate the NRM components.

    Science.gov (United States)

    Ramón, Maria J.; Pueyo, Emilio L.; Oliva-Urcia, Belén; Larrasoaña, Juan C.

    2017-02-01

    We introduce a method and software to process demagnetization data for a rapid and integrative estimation of characteristic remanent magnetization (ChRM) components. The virtual directions (VIDI) of a paleomagnetic site are “all” possible directions that can be calculated from a given demagnetization routine of “n” steps (being m the number of specimens in the site). If the ChRM can be defined for a site, it will be represented in the VIDI set. Directions can be calculated for successive steps using principal component analysis, both anchored to the origin (resultant virtual directions RVD; m * (n2+n)/2) and not anchored (difference virtual directions DVD; m * (n2-n)/2). The number of directions per specimen (n2) is very large and will enhance all ChRM components with noisy regions where two components were fitted together (mixing their unblocking intervals). In the same way, resultant and difference virtual circles (RVC, DVC) are calculated. Virtual directions and circles are a global and objective approach to unravel different natural remanent magnetization (NRM) components for a paleomagnetic site without any assumption. To better constrain the stable components, some filters can be applied, such as establishing an upper boundary to the MAD, removing samples with anomalous intensities, or stating a minimum number of demagnetization steps (objective filters) or selecting a given unblocking interval (subjective but based on the expertise). On the other hand, the VPD program also allows the application of standard approaches (classic PCA fitting of directions a circles) and other ancillary methods (stacking routine, linearity spectrum analysis) giving an objective, global and robust idea of the demagnetization structure with minimal assumptions. Application of the VIDI method to natural cases (outcrops in the Pyrenees and u-channel data from a Roman dam infill in northern Spain) and their comparison to other approaches (classic end-point, demagnetization

  6. Immunohistochemical differentiation of inflammatory myopathies

    Directory of Open Access Journals (Sweden)

    Jayalakshmi B Panicker

    2011-01-01

    Full Text Available Background: Idiopathic inflammatory myopathies are a heterogeneous group of acquired muscle disorders with considerable overlap in the histological features, making histological diagnosis difficult at times. Aims: To determine the immunohistochemical profile of clinically suspected cases of inflammatory myopathies, using monoclonal antibodies to HLA-1 and membrane attack complex (MAC, and to correlate the clinical, serological, and electromyographic profile and the histopathological picture, with the immunohistochemical profile. Settings and Design: This was a retrospective study analyzing the clinical and histopathological features in muscle of clinically suspected cases of inflammatory myopathy and correlating it to their HLA-1 and MAC immunostaining profiles. Material and Methods: The study subjects included 33 cases with suspected inflammatory myopathy and 59 with non-inflammatory muscle disease, as controls. Clinical data, electromyographic findings, serological profile, and details of therapy were obtained from patient records. Statistical Analysis: Student ′T′ test, Pearson′s Chi square test, and Kappa statistics were used appropriately. Results: Although HLA-1 and MAC immunostaining did not help to differentiate the individual subtypes of inflammatory myopathy, when either HLA-1 or MAC was positive, inflammatory myopathy could be ruled in with 86.5% certainty and when both HLA-1 and MAC were negative, it could be ruled out with 95% certainty. Conclusions: A combination of clinical presentation, serological profile, electromyographic and histopathological features, together with the immunoprofile for HLA-1 and MAC, contribute toward making a diagnosis of inflammatory myopathy.

  7. Relapses in inflammatory myopathies

    Directory of Open Access Journals (Sweden)

    Blas J. Larrauri

    2016-12-01

    Full Text Available Most studies about treatment of inflammatory myopathies consist of cross-sectional analyses that do not assess long-term efficacy. In the present study we describe the follow-up of seven patients with inflammatory myopathies, 5 polymyositis and 2 dermatomyositis. We describe their clinical features, follow-up, muscle enzyme levels, and treatment responses. We define the latter as treatment cycles, every one of which end when steroid doses need to be increased or a new immunosuppressive drug has to be added because of clinical worsening or sustained increases in muscle enzyme levels. Treatment can cause remission, partially control, or fail in achieving myositis improvement when it normalizes, stabilizes, or does not affect muscle enzymes or clinical features, respectively. We analyzed 20 cycles, in which remission was achieved in 14 cases, partial control in 5 instances, and treatment failure in one case. Remission occurred after an average of 139 ± 98 days, whereas partial control took place in 160 ± 100 days. Except in one case, all treatment cycles controlled or remitted the symptoms. However, in all patients the illness recurred with time.

  8. Inclusion body myositis and myopathies.

    Science.gov (United States)

    Sivakumar, K; Dalakas, M C

    1997-10-01

    Sporadic inclusion body myositis is a frequent, acquired, adult-onset vacuolar myopathy affecting proximal and distal muscles with a distinct, easily identifiable clinical pattern. Although its primary cause is still unknown, autoimmune, viral, and degenerative processes, alone or in combination, are being considered. A uniform and sustained therapeutic response using the currently available immunomodulatory agents has not yet been achieved. Hereditary, inherited noninflammatory rimmed vacuolar myopathies with similar histologic features, collectively called hereditary inclusion body myopathies, are being redefined with the use of molecular genetics. The implications of the recent advances in clinical and basic sciences are discussed in the present review.

  9. Centronuclear (myotubular myopathy

    Directory of Open Access Journals (Sweden)

    Wallgren-Pettersson Carina

    2008-09-01

    Full Text Available Abstract Centronuclear myopathy (CNM is an inherited neuromuscular disorder characterised by clinical features of a congenital myopathy and centrally placed nuclei on muscle biopsy. The incidence of X-linked myotubular myopathy is estimated at 2/100000 male births but epidemiological data for other forms are not currently available. The clinical picture is highly variable. The X-linked form usually gives rise to a severe phenotype in males presenting at birth with marked weakness and hypotonia, external ophthalmoplegia and respiratory failure. Signs of antenatal onset comprise reduced foetal movements, polyhydramnios and thinning of the ribs on chest radiographs; birth asphyxia may be the present. Affected infants are often macrosomic, with length above the 90th centile and large head circumference. Testes are frequently undescended. Both autosomal-recessive (AR and autosomal-dominant (AD forms differ from the X-linked form regarding age at onset, severity, clinical characteristics and prognosis. In general, AD forms have a later onset and milder course than the X-linked form, and the AR form is intermediate in both respects. Mutations in the myotubularin (MTM1 gene on chromosome Xq28 have been identified in the majority of patients with the X-linked recessive form, whilst AD and AR forms have been associated with mutations in the dynamin 2 (DNM2 gene on chromosome 19p13.2 and the amphiphysin 2 (BIN1 gene on chromosome 2q14, respectively. Single cases with features of CNM have been associated with mutations in the skeletal muscle ryanodine receptor (RYR1 and the hJUMPY (MTMR14 genes. Diagnosis is based on typical histopathological findings on muscle biopsy in combination with suggestive clinical features; muscle magnetic resonance imaging may complement clinical assessment and inform genetic testing in cases with equivocal features. Genetic counselling should be offered to all patients and families in whom a diagnosis of CNM has been made. The

  10. Mitochondrial Myopathy with DNA Deletions

    OpenAIRE

    J Gordon Millichap

    1992-01-01

    Deletions of mitochondrial DNA (mtDNA) are reported in 19 of 56 patients with mitochondrial myopathy examined in the Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, MN.

  11. Genetics Home Reference: Miyoshi myopathy

    Science.gov (United States)

    ... tiptoe. As Miyoshi myopathy slowly worsens, the muscle weakness and atrophy spread up the leg to the muscles in the thigh and buttock and can also involve the upper arm and shoulder muscles. Eventually, affected individuals may have difficulty climbing ...

  12. Adult-onset mitochondrial myopathy.

    Science.gov (United States)

    Fernandez-Sola, J.; Casademont, J.; Grau, J. M.; Graus, F.; Cardellach, F.; Pedrol, E.; Urbano-Marquez, A.

    1992-01-01

    Mitochondrial diseases are polymorphic entities which may affect many organs and systems. Skeletal muscle involvement is frequent in the context of systemic mitochondrial disease, but adult-onset pure mitochondrial myopathy appears to be rare. We report 3 patients with progressive skeletal mitochondrial myopathy starting in adult age. In all cases, the proximal myopathy was the only clinical feature. Mitochondrial pathology was confirmed by evidence of ragged-red fibres in muscle histochemistry, an abnormal mitochondrial morphology in electron microscopy and by exclusion of other underlying diseases. No deletions of mitochondrial DNA were found. We emphasize the need to look for a mitochondrial disorder in some non-specific myopathies starting in adult life. Images Figure 1 Figure 2 PMID:1589382

  13. Sarcomere Dysfunction in Nemaline Myopathy

    OpenAIRE

    de Winter, Josine M.; Ottenheijm, Coen A. C.

    2017-01-01

    Nemaline myopathy (NM) is among the most common non-dystrophic congenital myopathies (incidence 1:50.000). Hallmark features of NM are skeletal muscle weakness and the presence of nemaline bodies in the muscle fiber. The clinical phenotype of NM patients is quite diverse, ranging from neonatal death to normal lifespan with almost normal motor function. As the respiratory muscles are involved as well, severely affected patients are ventilator-dependent. The mechanisms underlying muscle weaknes...

  14. A Patient With Pyruvate Carboxylase Deficiency and Nemaline Rods on Muscle Biopsy.

    Science.gov (United States)

    Unal, Ozlem; Orhan, Diclehan; Ostergaard, Elsebet; Tokatli, Aysegul; Dursun, Ali; Ozturk-Hismi, Burcu; Coskun, Turgay; Wibrand, Flemming; Kalkanoglu-Sivri, H Serap

    2013-11-01

    Nemaline rods are the pathologic hallmark of nemaline myopathy, but they have also been described as a secondary phenomenon in a variety of other disorders. Nemaline rods have not been reported in pyruvate carboxylase deficiency before. Here we present a patient with pyruvate carboxylase deficiency and nemaline rods detected on muscle biopsy. The nemaline rods may be due to cellular energy shortage and altered energy metabolism in pyruvate carboxylase deficiency, similar to that in the previously reported patients. The mechanism of nemaline rod formation may be associated with the role of pyruvate carboxylase in cellular energy pathways.

  15. A Patient With Pyruvate Carboxylase Deficiency and Nemaline Rods on Muscle Biopsy

    DEFF Research Database (Denmark)

    Unal, Ozlem; Orhan, Diclehan; Ostergaard, Elsebet

    2013-01-01

    Nemaline rods are the pathologic hallmark of nemaline myopathy, but they have also been described as a secondary phenomenon in a variety of other disorders. Nemaline rods have not been reported in pyruvate carboxylase deficiency before. Here we present a patient with pyruvate carboxylase deficiency...... and nemaline rods detected on muscle biopsy. The nemaline rods may be due to cellular energy shortage and altered energy metabolism in pyruvate carboxylase deficiency, similar to that in the previously reported patients. The mechanism of nemaline rod formation may be associated with the role of pyruvate...

  16. Genetics Home Reference: idiopathic inflammatory myopathy

    Science.gov (United States)

    ... myopathy have had close relatives with autoimmune disorders. Autoimmune diseases occur when the immune system malfunctions and attacks ... Ollier WE, Cooper RG. An update on the immunogenetics of idiopathic inflammatory myopathies: major histocompatibility complex and ...

  17. [Thyroid myopathy in an aged woman].

    Science.gov (United States)

    Oscuro, F; Antico, C N; Calvanese, A; Chianese, U; Gallo, M

    1994-08-01

    The case is reported of an old woman with a myopathy syndrome. Upon differential diagnosis this myopathy was attributed to hypothyroidism. Treatment with low doses of L-thyroxine lead to complete remission of the clinical and serologic syndrome.

  18. A collaborative resource management workspace and project management application for data collection, analysis and visualization: OpenNRM

    Science.gov (United States)

    Osti, A.

    2013-12-01

    During the process of research and design for OpenNRM, we imagined a place where diverse groups of people and communities could effectively and efficiently collaborate to manage large-scale environmental problems and projects. Our research revealed the need to combine a variety of software components. Users can explore and analyze a topic while simultaneously develop stories and solve problems in a way that the end result is consumable by their colleagues and the general public. To do this we brought together software modules that are typically separate: Document and Asset Management, GIS and Interactive Mapping, WIKI and Information Libraries, Data Catalogs and Services, Project Management Tools and Storytelling templates. These components, along with others are supported by extensive data catalogs (NWIS, Storet, CDEC, Cuahsi), data analysis tools and web services for a turn-key workspace that will allow you to quickly build project communities and data stories. In this presentation we will show you how our investigation into these collaborative efforts are implemented and working for some of our clients, including the State of California's Sacramento San Joaquin Bay-Delta and San Joaquin River Basin. The case study will display the use of the OpenNRM workspace for real time environmental conditions management, data visualization, project operations, environmental restoration, high frequency monitoring and data reporting. We will demonstrate how scientists and policy makers are working together to tell the story of this complicated and divisive system and how they are becoming better managers of that system. Using the genius of web services, we will show you how OpenNRM was designed to allow you to build your own community while easily sharing data stories, project data, monitoring results, document libraries, interactive maps and datasets with others. We will get into more technical detail by presenting how our data interpolation tools can show high frequency

  19. Recessive RYR1 mutations in a patient with severe congenital nemaline myopathy with ophthalomoplegia identified through massively parallel sequencing.

    Science.gov (United States)

    Kondo, Eri; Nishimura, Takafumi; Kosho, Tomoki; Inaba, Yuji; Mitsuhashi, Satomi; Ishida, Takefumi; Baba, Atsushi; Koike, Kenichi; Nishino, Ichizo; Nonaka, Ikuya; Furukawa, Toru; Saito, Kayoko

    2012-04-01

    Nemaline myopathy (NM) is a group of congenital myopathies, characterized by the presence of distinct rod-like inclusions "nemaline bodies" in the sarcoplasm of skeletal muscle fibers. To date, ACTA1, NEB, TPM3, TPM2, TNNT1, and CFL2 have been found to cause NM. We have identified recessive RYR1 mutations in a patient with severe congenital NM, through high-throughput screening of congenital myopathy/muscular dystrophy-related genes using massively parallel sequencing with target gene capture. The patient manifested fetal akinesia, neonatal severe hypotonia with muscle weakness, respiratory insufficiency, swallowing disturbance, and ophthalomoplegia. Skeletal muscle histology demonstrated nemaline bodies and small type 1 fibers, but without central cores or minicores. Congenital myopathies, a molecularly, histopathologically, and clinically heterogeneous group of disorders are considered to be a good candidate for massively parallel sequencing. Copyright © 2012 Wiley Periodicals, Inc.

  20. Morphoelastic rods

    CERN Document Server

    Tiero, Alessandro

    2014-01-01

    We propose a mechanical theory describing elastic rods which, like plant organs, can grow and can change their intrinsic curvature and torsion. The equations ruling accretion and remodeling are obtained by combining balance laws involving non-standard forces with constitutive prescriptions filtered by a dissipation principle that takes into account both standard and non-standard working.

  1. Identification of a novel nemaline myopathy-causing mutation in the troponin T1 (TNNT1) gene: a case outside of the old order Amish.

    Science.gov (United States)

    Marra, Jonathan D; Engelstad, Kristin E; Ankala, Arunkanth; Tanji, Kurenai; Dastgir, Jahannaz; De Vivo, Darryl C; Coffee, Bradford; Chiriboga, Claudia A

    2015-05-01

    Nemaline myopathy (NM) is a congenital neuromuscular disorder often characterized by hypotonia, facial weakness, skeletal muscle weakness, and the presence of rods on muscle biopsy. A rare form of nemaline myopathy known as Amish Nemaline Myopathy has only been seen in a genetically isolated cohort of Old Order Amish patients who may additionally present with tremors in the first 2-3 months of life. We describe an Hispanic male diagnosed with nemaline myopathy histopathologically and subsequently confirmed by next generation gene sequencing. Direct sequencing revealed that he is homozygous for a pathogenic nonsense variant c.323C>G (p.S108X) in exon 9 of the TNNT1 gene. This report describes a novel pathogenic variant in the TNNT1 gene and represents a nemaline myopathy-causing variant in the TNNT1 gene outside of the Old Order Amish and Dutch ancestry. © 2014 Wiley Periodicals, Inc.

  2. Gene Expression Profiles of Inflammatory Myopathies

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2002-11-01

    Full Text Available The simultaneous expression of 10,000 genes was measured, using Affymetrix GeneChip microarrays, in muscle specimens from 45 patients with various myopathies (dystrophy, congenital myopathy, and inflammatory myopathy examined at Brigham and Women’s Hospital, and Children’s Hospital, Harvard Medical School, Boston, MA.

  3. Desmin splice variants causing cardiac and skeletal myopathy.

    Science.gov (United States)

    Park, K Y; Dalakas, M C; Goebel, H H; Ferrans, V J; Semino-Mora, C; Litvak, S; Takeda, K; Goldfarb, L G

    2000-11-01

    Desmin myopathy is a hereditary or sporadic cardiac and skeletal myopathy characterised by intracytoplasmic accumulation of desmin reactive deposits in muscle cells. We have characterised novel splice site mutations in the gene desmin resulting in deletion of the entire exon 3 during the pre-mRNA splicing. Sequencing of cDNA and genomic DNA identified a heterozygous de novo A to G change at the +3 position of the splice donor site of intron 3 (IVS3+3A-->G) in a patient with sporadic skeletal and cardiac myopathy. A G to A transition at the highly conserved -1 nucleotide position of intron 2 affecting the splice acceptor site (IVS2-1G-->A) was found in an unrelated patient with a similar phenotype. Expression of genomic DNA fragments carrying the IVS3+3A-->G and IVS2-1G-->A mutations confirmed that these mutations cause exon 3 deletion. Aberrant splicing leads to an in frame deletion of 32 complete codons and is predicted to result in mutant desmin lacking 32 amino acids from the 1B segment of the alpha helical rod. Functional analysis of the mutant desmin in SW13 (vim-) cells showed aggregation of abnormal coarse clumps of desmin positive material dispersed throughout the cytoplasm. This is the first report on the pathogenic potentials of splice site mutations in the desmin gene.

  4. A Large Deletion Affecting TPM3, Causing Severe Nemaline Myopathy.

    Science.gov (United States)

    Kiiski, K; Lehtokari, V-L; Manzur, A Y; Sewry, C; Zaharieva, I; Muntoni, F; Pelin, K; Wallgren-Pettersson, C

    2015-09-21

    Nemaline myopathy may be caused by pathogenic variants in the TPM3 gene and is then called NEM1. All previously identified disease-causing variants are point mutations including missense, nonsense and splice-site variants. The aim of the study was to identify the disease-causing gene in this patient and verify the NM diagnosis. Mutation analysis methods include our self-designed nemaline myopathy array, The Nemaline Myopathy Comparative Genomic Hybridisation Array (NM-CGH array), whole-genome array-CGH, dHPLC, Sanger sequencing and whole-exome sequencing. The diagnostic muscle biopsy was investigated further by routine histopathological methods. We present here the first large (17-21 kb) aberration in the α-tropomyosinslow gene (TPM3), identified using the NM-CGH array. This homozygous deletion removes the exons 1a and 2b as well as the promoter of the TPM3 isoform encoding Tpm3.12st. The severe phenotype included paucity of movement, proximal and axial weakness and feeding difficulties requiring nasogastric tube feeding. The infant died at the age of 17.5 months. Muscle biopsy showed variation in fibre size and rods in a population of hypotrophic muscle fibres expressing slow myosin, often with internal nuclei, and abnormal immunolabelling revealing many hybrid fibres. This is the only copy number variation we have identified in any NM gene other than nebulin (NEB), suggesting that large deletions or duplications in these genes are very rare, yet possible, causes of NM.

  5. Mild clinical presentation in KLHL40-related nemaline myopathy (NEM 8).

    Science.gov (United States)

    Seferian, Andreea M; Malfatti, Edoardo; Bosson, Caroline; Pelletier, Laurent; Taytard, Jessica; Forin, Veronique; Gidaro, Teresa; Gargaun, Elena; Carlier, Pierre; Fauré, Julien; Romero, Norma B; Rendu, John; Servais, Laurent

    2016-10-01

    Nemaline myopathies are clinically and genetically heterogeneous muscle diseases characterized by the presence of nemaline bodies (rods) in muscle fibers. Mutations in the KLHL40 (kelch-like family member 40) gene (NEM 8) are common cause of severe/lethal nemaline myopathy. We report an 8-year-old girl born to consanguineous Moroccan parents, who presented with hypotonia and poor sucking at birth, delayed motor development, and further mild difficulties in walking and fatigability. A muscle biopsy revealed the presence of nemaline bodies. KLHL40 gene Sanger sequencing disclosed a never before reported pathogenic homozygous mutation which resulted in absent KLHL40 protein expression in the muscle. This further expands the phenotypical spectrum of KLHL40 related nemaline myopathy. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Resveratrol and Myopathy.

    Science.gov (United States)

    Bastin, Jean; Djouadi, Fatima

    2016-04-28

    Resveratrol is a natural polyphenolic compound produced by plants under various stress conditions. Resveratrol has been reported to exhibit antioxidant, anti-inflammatory, and anti-proliferative properties in mammalian cells and animal models, and might therefore exert pleiotropic beneficial effects in different pathophysiological states. More recently, resveratrol has also been shown to potentially target many mitochondrial metabolic pathways, including fatty acid β-oxidation or oxidative phosphorylation, leading to the up-regulation of the energy metabolism via signaling pathways involving PGC-1α, SIRT1, and/or AMP-kinase, which are not yet fully delineated. Some of resveratrol beneficial effects likely arise from its cellular effects in the skeletal muscle, which, surprisingly, has been given relatively little attention, compared to other target tissues. Here, we review the potential for resveratrol to ameliorate or correct mitochondrial metabolic deficiencies responsible for myopathies, due to inherited fatty acid β-oxidation or to respiratory chain defects, for which no treatment exists to date. We also review recent data supporting therapeutic effects of resveratrol in the Duchenne Muscular Dystrophy, a fatal genetic disease affecting the production of muscle dystrophin, associated to a variety of mitochondrial dysfunctions, which likely contribute to disease pathogenesis.

  7. Resveratrol and Myopathy

    Directory of Open Access Journals (Sweden)

    Jean Bastin

    2016-04-01

    Full Text Available Resveratrol is a natural polyphenolic compound produced by plants under various stress conditions. Resveratrol has been reported to exhibit antioxidant, anti-inflammatory, and anti-proliferative properties in mammalian cells and animal models, and might therefore exert pleiotropic beneficial effects in different pathophysiological states. More recently, resveratrol has also been shown to potentially target many mitochondrial metabolic pathways, including fatty acid β-oxidation or oxidative phosphorylation, leading to the up-regulation of the energy metabolism via signaling pathways involving PGC-1α, SIRT1, and/or AMP-kinase, which are not yet fully delineated. Some of resveratrol beneficial effects likely arise from its cellular effects in the skeletal muscle, which, surprisingly, has been given relatively little attention, compared to other target tissues. Here, we review the potential for resveratrol to ameliorate or correct mitochondrial metabolic deficiencies responsible for myopathies, due to inherited fatty acid β-oxidation or to respiratory chain defects, for which no treatment exists to date. We also review recent data supporting therapeutic effects of resveratrol in the Duchenne Muscular Dystrophy, a fatal genetic disease affecting the production of muscle dystrophin, associated to a variety of mitochondrial dysfunctions, which likely contribute to disease pathogenesis.

  8. Dominant mutations in KBTBD13, a member of the BTB/Kelch family, cause nemaline myopathy with cores.

    NARCIS (Netherlands)

    Sambuughin, N.; Yau, K.S.; Olive, M.; Duff, R.M.; Bayarsaikhan, M.; Lu, S.; Gonzalez-Mera, L.; Sivadorai, P.; Nowak, K.J.; Ravenscroft, G.; Mastaglia, F.L.; North, K.N.; Ilkovski, B.; Kremer, J.M.J.; Lammens, M.M.Y.; Engelen, B.G.M. van; Fabian, V.; Lamont, P.; Davis, M.R.; Laing, N.G.; Goldfarb, L.G.

    2010-01-01

    We identified a member of the BTB/Kelch protein family that is mutated in nemaline myopathy type 6 (NEM6), an autosomal-dominant neuromuscular disorder characterized by the presence of nemaline rods and core lesions in the skeletal myofibers. Analysis of affected families allowed narrowing of the

  9. Idiopathic Inflammatory Myopathies: An update

    Directory of Open Access Journals (Sweden)

    Bulent KURT

    2016-06-01

    Full Text Available Idiopathic inflammatory myopathies (IIM are a heterogeneous group of disease with complex clinical features. It has been sub-classified as: (1 Dermatomyositis, (2 Polymyositis, and (3 Inclusion body myositis (IBM. Nowadays, there are some studies in literature suggest necrotizing autoimmune myopathy and immune-mediated necrotizing myopathy should also be added to this group of disease. There is a debate in the diagnosis of IIMs and up until now, about 12 criteria systems have been proposed. Some of the criteria systems have been used widely such as Griggs et al.'s proposal for IBM. Clinical findings, autoantibodies, enzymes, electrophysiological, and muscle biopsy findings are diagnostic tools. Because of diseases' complexity, none of the findings are diagnostic alone. In this study, we discussed the diagnostic criteria of IMMs and described detailed morphological features. [J Interdiscipl Histopathol 2016; 4(2.000: 41-45

  10. Update on idiopathic inflammatory myopathies.

    Science.gov (United States)

    Briani, C; Doria, A; Sarzi-Puttini, P; Dalakas, M C

    2006-05-01

    The inflammatory myopathies are a group of acquired diseases, characterized by an inflammatory infiltrate of the skeletal muscle. On the basis of clinical, immuno-pathological and demographic features, three major diseases can be identified: dermatomyositis (DM); polymyositis (PM); and inclusion body myositis (IBM). New diagnostic criteria have recently been introduced, which are crucial for discriminating between the three different subsets of inflammatory myopathies and for excluding other disorders. DM is a complement-mediated microangiopathy affecting skin and muscle. PM and IBM are T cell-mediated disorders, where CD8-positive cytotoxic T cells invade muscle fibres expressing MHC class I antigens, thus leading to fibre necrosis. In IBM, vacuolar formation with amyloid deposits are also present. This article summarizes the main clinical, laboratory, electrophysiological, immunological and histologic features as well as the therapeutic options of the inflammatory myopathies.

  11. Amyloid myopathy: a diagnostic challenge

    Directory of Open Access Journals (Sweden)

    Heli Tuomaala

    2009-08-01

    Full Text Available Amyloid myopathy (AM is a rare manifestation of primary systemic amyloidosis (AL. Like inflammatory myopathies, it presents with proximal muscle weakness and an increased creatine kinase level. We describe a case of AL with severe, rapidly progressive myopathy as the initial symptom. The clinical manifestation and muscle biopsy were suggestive of inclusion body myositis. AM was not suspected until amyloidosis was seen in the gastric mucosal biopsy. The muscle biopsy was then re-examined more specifically, and Congo red staining eventually showed vascular and interstitial amyloid accumulation, which led to a diagnosis of AM. The present case illustrates the fact that the clinical picture of AM can mimic that of inclusion body myositis.

  12. Current essentials in inflammatory myopathies

    Directory of Open Access Journals (Sweden)

    Maren Breithaupt

    2013-08-01

    Full Text Available Inflammatory myopathies are a heterogeneous group of acquired systemic diseases, which include dermatomyositis (DM, polymyositis (PM, necrotising myopathy (NM and inclusion body myositis (IBM. All four disease entities share certain clinical characteristics, such as progressive muscle weakness and elevated muscle enzymes. Other characteristic-associated features such as skin involvement in DM or the detection of myositis-specific antibodies, may be indicative of a particular subtype. However, muscle biopsy is still essential for the diagnosis and shows distinct histopathological characteristics for each subtype of myositis. Treatment of inflammatory myopathies is still based on clinical experience, since placebo-controlled trials are scarce. While DM, PM and NM respond well to immunosuppressive treatment, IBM is usually resistant to immunotherapy. This review aims to give a concise overview and provide guidance for general management of myositis.

  13. CONTROL ROD

    Science.gov (United States)

    Zinn, W.H.; Ross, H.V.

    1958-11-18

    A control rod is described for a nuclear reactor. In certaln reactor designs it becomes desirable to use a control rod having great width but relatively llttle thickness. This patent is addressed to such a need. The neutron absorbing material is inserted in a triangular tube, leaving volds between the circular insert and the corners of the triangular tube. The material is positioned within the tube by the use of dummy spacers to achleve the desired absorption pattern, then the ends of the tubes are sealed with suitable plugs. The tubes may be welded or soldered together to form two flat surfaces of any desired width, and covered with sheetmetal to protect the tubes from damage. This design provides a control member that will not distort under the action of outside forces or be ruptured by gases generated within the jacketed control member.

  14. Myopathy mutations in alpha-skeletal-muscle actin cause a range of molecular defects.

    Science.gov (United States)

    Costa, Céline F; Rommelaere, Heidi; Waterschoot, Davy; Sethi, Kamaljit K; Nowak, Kristen J; Laing, Nigel G; Ampe, Christophe; Machesky, Laura M

    2004-07-01

    Mutations in the gene encoding alpha-skeletal-muscle actin, ACTA1, cause congenital myopathies of various phenotypes that have been studied since their discovery in 1999. Although much is now known about the clinical aspects of myopathies resulting from over 60 different ACTA1 mutations, we have very little evidence for how mutations alter the behavior of the actin protein and thus lead to disease. We used a combination of biochemical and cell biological analysis to classify 19 myopathy mutants and found a range of defects in the actin. Using in vitro expression systems, we probed actin folding and actin's capacity to interact with actin-binding proteins and polymerization. Only two mutants failed to fold; these represent recessive alleles, causing severe myopathy, indicating that patients produce nonfunctional actin. Four other mutants bound tightly to cyclase-associated protein, indicating a possible instability in the nucleotide-binding pocket, and formed rods and aggregates in cells. Eleven mutants showed defects in the ability to co-polymerize with wild-type actin. Some of these could incorporate into normal actin structures in NIH 3T3 fibroblasts, but two of the three tested also formed aggregates. Four mutants showed no defect in vitro but two of these formed aggregates in cells, indicating functional defects that we have not yet tested for. Overall, we found a range of defects and behaviors of the mutants in vitro and in cultured cells, paralleling the complexity of actin-based muscle myopathy phenotypes.

  15. Pathogenic mechanisms in centronuclear myopathies

    Directory of Open Access Journals (Sweden)

    Heinz eJungbluth

    2014-12-01

    Full Text Available Centronuclear myopathies (CNMs are a genetically heterogeneous group of inherited neuromuscular disorders characterized by clinical features of a congenital myopathy and abundant central nuclei as the most prominent histopathological feature. The most common forms of congenital myopathies with central nuclei have been attributed to X-linked recessive mutations in the MTM1 gene encoding myotubularin (X-linked myotubular myopathy, XLMTM, autosomal-dominant mutations in the DNM2 gene encoding dynamin-2 and the BIN1 gene encoding amphiphysin-2 (also named bridging integrator-1, BIN1, or SH3P9, and autosomal-recessive mutations in BIN1, the RYR1 gene encoding the skeletal muscle ryanodine receptor, and the TTN gene encoding titin. Models to study and rescue the affected cellular pathways are now available in yeast, C. elegans, drosophila, zebrafish, mouse and dog. Defects in membrane trafficking have emerged as a key pathogenic mechanisms, with aberrant T-tubule formation, abnormalities of triadic assembly and disturbance of the excitation-contraction machinery the main downstream effects studied to date. Abnormal autophagy has recently been recognized as another important collateral of defective membrane trafficking in different genetic forms of CNM, suggesting an intriguing link to primary disorders of defective autophagy with overlapping histopathological features.The following review will provide an overview of clinical, histopathological and genetic aspects of the CNMs in the context of the key pathogenic mechanism, outline unresolved questions and indicate promising future lines of enquiry.

  16. Immunopathogenesis of inflammatory myopathies.

    Science.gov (United States)

    Dalakas, M C

    1995-05-01

    Immune-mediated mechanisms appear to play a primary role in the pathogenesis of polymyositis (PM) and dermatomyositis (DM). The serum of patients with active DM has high levels of circulating complement fragments C3b, C4b, and C5b-9 membranolytic attack complex (MAC) and demonstrates a very high C3 uptake in an vitro assay system. The MAC and the immune complex-specific C3bNEO fragment are deposited on the endomysial capillaries early in the disease and lead sequentially to loss of capillaries, muscle ischemia, muscle fiber necrosis, and perifascicular atrophy. In contrast, in PM the muscle fiber injury is initiated by sensitized CD8+ cytotoxic T cells that recognize heretofore unknown and probably endogenous muscle antigens in the context of major histocompatibility complex (MHC) class I expression. A restricted (oligoclonal) pattern of T-cell receptor with prominence of Va1, Vb6, and Vb15 genes is noted within the endomysial infiltrates suggesting that the T-cell response is antigen driven. In both PM and DM, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 are upregulated in the endomysial endothelial cells and function as ligands for the leukocyte integrins leukocyte function-associated antigen (LFA)-1 and very late activating antigen (VLA)-4, allowing activated lymphocytes to adhere to the endothelial cells and migrate to the muscle fibers. Among viruses, only the retroviruses human immunodeficiency virus (HIV) and human T-cell lymphotropic virus (HTLV)-1 have been convincingly shown to trigger PM, which is mediated by nonviral-specific, cytotoxic CD8+ cells. The treatment of inflammatory myopathies remains empirical. Many patients respond to steroids to some degree and for some period of time. Azathioprine, methotrexate, cyclosporine, cyclophosphamide, and plasmapheresis can be of mild to moderate benefit. High-dose intravenous immunoglobulin (IVIg) is a promising therapeutic modality for some patients resistant to

  17. NEUROMUSCULAR DISEASE MIMICKING MYASTHENIA GRAVIS IN A NIGERIAN FEMALE ADOLESCENT: COULD THIS BE NEMALINE ROD DISEASE?

    OpenAIRE

    Oyinlade, O.A.; Lagunju, I.A.; Adebayo, B.E.

    2016-01-01

    Background: Nemaline rod disease is a congenital myopathy, presentation of which may mimic myasthenia gravis. Method: We report a suspected case of nemaline rod disease in a female adolescent who presented with features similar to myasthenia gravis but failed to respond effectively to its conventional management. She had features of respiratory failure and cardiomyopathy. Results: Patient had a turbulent clinical course and finally succumbed to illness on the fifth day of admission. Conclusio...

  18. Stepwise Approach to Myopathy in Systemic Disease

    Directory of Open Access Journals (Sweden)

    Jasvinder eChawla

    2011-08-01

    Full Text Available Muscle diseases can constitute a large variety of both acquired and hereditary disorders. Myopathies in systemic disease results from several different disease processes including endocrine, inflammatory, paraneoplastic, infectious, drug and toxin-induced, critical illness myopathy, metabolic and myopathies with other systemic disorders. Patients with systemic myopathies often present acutely or sub acutely. On the other hand, familial myopathies or dystrophies generally present in a chronic fashion with exceptions of metabolic myopathies where symptoms on occasion can be precipitated acutely. Most of the inflammatory myopathies can have a chance association with malignant lesions; the incidence appears to be specifically increased only in patients with dermatomyositis. In dealing with myopathies associated with systemic illnesses, the focus will be on the acquired causes. Management is beyond the scope of this chapter. Prognosis is based upon the underlying cause and, most of the time, carries a good prognosis. In order to approach a patient with suspected myopathy from systemic disease, a stepwise approach is utilized.

  19. Biallelic Mutations in MYPN, Encoding Myopalladin, Are Associated with Childhood-Onset, Slowly Progressive Nemaline Myopathy.

    Science.gov (United States)

    Miyatake, Satoko; Mitsuhashi, Satomi; Hayashi, Yukiko K; Purevjav, Enkhsaikhan; Nishikawa, Atsuko; Koshimizu, Eriko; Suzuki, Mikiya; Yatabe, Kana; Tanaka, Yuzo; Ogata, Katsuhisa; Kuru, Satoshi; Shiina, Masaaki; Tsurusaki, Yoshinori; Nakashima, Mitsuko; Mizuguchi, Takeshi; Miyake, Noriko; Saitsu, Hirotomo; Ogata, Kazuhiro; Kawai, Mitsuru; Towbin, Jeffrey; Nonaka, Ikuya; Nishino, Ichizo; Matsumoto, Naomichi

    2017-01-05

    Nemaline myopathy (NM) is a common form of congenital nondystrophic skeletal muscle disease characterized by muscular weakness of proximal dominance, hypotonia, and respiratory insufficiency but typically not cardiac dysfunction. Wide variation in severity has been reported. Intranuclear rod myopathy is a subtype of NM in which rod-like bodies are seen in the nucleus, and it often manifests as a severe phenotype. Although ten mutant genes are currently known to be associated with NM, only ACTA1 is associated with intranuclear rod myopathy. In addition, the genetic cause remains unclear in approximately 25%-30% of individuals with NM. We performed whole-exome sequencing on individuals with histologically confirmed but genetically unsolved NM. Our study included individuals with milder, later-onset NM and identified biallelic loss-of-function mutations in myopalladin (MYPN) in four families. Encoded MYPN is a sarcomeric protein exclusively localized in striated muscle in humans. Individuals with identified MYPN mutations in all four of these families have relatively mild, childhood- to adult-onset NM with slowly progressive muscle weakness. Walking difficulties were recognized around their forties. Decreased respiratory function, cardiac involvement, and intranuclear rods in biopsied muscle were observed in two individuals. MYPN was localized at the Z-line in control skeletal muscles but was absent from affected individuals. Homozygous knockin mice with a nonsense mutation in Mypn showed Z-streaming and nemaline-like bodies adjacent to a disorganized Z-line on electron microscopy, recapitulating the disease. Our results suggest that MYPN screening should be considered in individuals with mild NM, especially when cardiac problems or intranuclear rods are present. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  20. Integrated classification of inflammatory myopathies.

    Science.gov (United States)

    Allenbach, Y; Benveniste, O; Goebel, H-H; Stenzel, W

    2017-02-01

    Inflammatory myopathies comprise a multitude of diverse diseases, most often occurring in complex clinical settings. To ensure accurate diagnosis, multidisciplinary expertise is required. Here, we propose a comprehensive myositis classification that incorporates clinical, morphological and molecular data as well as autoantibody profile. This review focuses on recent advances in myositis research, in particular, the correlation between autoantibodies and morphological or clinical phenotypes that can be used as the basis for an 'integrated' classification system.

  1. Evidence-based treatment of metabolic myopathy

    Directory of Open Access Journals (Sweden)

    Yan LIN

    2014-05-01

    Full Text Available Objective To evaluate the current treatments and possible adverse reactions of metabolic myopathy, and to develop the best solution for evidence-based treatment.  Methods Taking metabolic myopathy, mitochondrial myopathy, lipid storage myopathy, glycogen storage diseases, endocrine myopathy, drug toxicity myopathy and treatment as search terms, retrieve in databases such as PubMed, Cochrane Library, ClinicalKey database, National Science and Technology Library (NSTL, in order to collect the relevant literature database including clinical guidelines, systematic reviews (SR, randomized controlled trials (RCT, controlled clinical trials, retrospective case analysis and case study. Jadad Scale was used to evaluate the quality of literature.  Results Twenty-eight related articles were selected, including 6 clinical guidelines, 5 systematic reviews, 10 randomized controlled trials and 7 clinical controlled trials. According to Jadad Scale, 23 articles were evaluated as high-quality literature (≥ 4, and the remaining 5 were evaluated as low-quality literature (< 4. Treatment principles of these clinical trials, efficacy of different therapies and drug safety evaluation suggest that: 1 Acid α-glycosidase (GAA enzyme replacement therapy (ERT is the main treatment for glycogen storage diseases, with taking a high-protein diet, exercising before taking a small amount of fructose orally and reducing the patient's physical activity gradually. 2 Carnitine supplementation is used in the treatment of lipid storage myopathy, with carbohydrate and low fat diet provided before exercise or sports. 3 Patients with mitochondrial myopathy can take coenzyme Q10, vitamin B, vitamin K, vitamin C, etc. Proper aerobic exercise combined with strength training is safe, and it can also enhance the exercise tolerance of patients effectively. 4 The first choice to treat the endocrine myopathy is treating primary affection. 5 Myopathies due to drugs and toxins should

  2. [Sporadic Late-Onset Nemaline Myopathy Associated with MGUS].

    Science.gov (United States)

    Nagai, Taiji; Sunada, Yoshihide

    2015-12-01

    Sporadic late-onset nemaline myopathy is an uncommon disease. Clinically, it is characterized by progressive muscle weakness that can develop in limbs or axial muscles. Asymmetrical distal weakness, facial weakness, dropped head, and dysphagia can also occur. Since the serum creatine kinase level usually remains within the normal range, patients can be misdiagnosed with motor neuron disease. Recognition of nemaline rods on muscle biopsy is crucial for accurate diagnosis. If it is associated with monoclonal gammopathy of undetermined significance, the outcome is known to be unfavorable. In spite of various immunotherapies such as corticosteroids, immunosuppressants, and plasmapheresis, most patients die of respiratory failure within 5 years. Since the efficacy of autologous stem cell transplantation following high-dose melphalan was first reported in 2008, there have been accumulating reports that showed the positive effect of this therapy for the disease.

  3. Two novel nebulin variants in an adult patient with congenital nemaline myopathy.

    Science.gov (United States)

    Güttsches, Anne K; Dekomien, Gabriele; Claeys, Kristl G; von der Hagen, Maja; Huebner, Angela; Kley, Rudolf A; Kirschner, Janbernd; Vorgerd, Matthias

    2015-05-01

    Congenital myopathies are clinically and genetically heterogeneous disorders, which often remain genetically undiagnosed for many years. Here we present a 40-year old patient with an almost lifelong history of a congenital myopathy of unknown cause. Muscle biopsy in childhood revealed mild myopathic features and rods. Clinical examination on presentation at the age of 40 revealed a facial weakness, atrophy and weakness of the arm muscles and distal leg muscles with mild contractures of the foot flexors and the right elbow. Subsequently, the nebulin gene was identified as a putative candidate gene by linkage analyses, but sequence analysis only revealed one heterozygous splice site mutation in intron 73 (c.10872+1G>T). Therefore, "Next Generation Sequencing" was performed, which revealed a second pathogenic variant in exon 145 (c.21622A>C). Compound-heterozygous carrier status was confirmed via sequence analysis of the index patient's parents. Whole body muscle MRI showed a muscle involvement as previously described in nebulin-associated myopathies. Based on biopsy material, genetic analyses and muscle MRI, we identified two novel, compound-heterozygous variants in the nebulin gene after a 30 year clinical history, which cause a classical childhood type of nemaline myopathy. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Severe congenital nemaline myopathy with primary pulmonary lymphangiectasia: unusual clinical presentation and review of the literature.

    Science.gov (United States)

    Waisayarat, Jariya; Suriyonplengsaeng, Chinnawut; Khongkhatithum, Chaiyos; Rochanawutanon, Mana

    2015-04-16

    Nemaline myopathy is a rare genetic muscle disorder defined by the presence of nemaline rods in the muscle fibre sarcoplasm. Congenital nemaline myopathy is the most serious form of the disease's spectrum. The affected newborn has no spontaneous movement, fractures at birth and respiratory insufficiency. The present case was a Thai male, floppy at birth with fractures of both humeri and femurs and ventilator-dependent respiration. The patient developed bilateral chylothorax two weeks later and died at the age of 6 weeks. Whole-body postmortem examination with informed consent and genetic analysis of ACTA1 mutation were performed. A skeletal muscle biopsy examined by light and transmission electron microscopy showed the features of nemaline myopathy. ACTA 1 heterozygous missense mutation (c.1127G > C) was identified. Histological examination of both lungs revealed primary pulmonary lymphangiectasia. To the best of our knowledge, congenital nemaline myopathy with primary pulmonary lymphangiectasia causing bilateral chylothrax has never been previously reported. Considering chylothorax as a poor prognostic index and an unusual clinical presentation of severe congenital NM are proposed. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9710506431489501 .

  5. Clinical and pathological features of patients with nemaline myopathy.

    Science.gov (United States)

    Yin, Xi; Pu, Chuan Qiang; Wang, Qian; Liu, Jie Xiao; Mao, Yan Ling

    2014-07-01

    Nemaline myopathy (NM) is a rare congenital myopathy of great heterogeneity, characterized by the presence of rods in the cytoplasm of muscle fibers. This study aimed to summarize and analyze retrospectively the clinicopathological features of 28 patients with NM. Among the 28 patients, 15 were classified as of the typical congenital type, manifested as lower- or four-limb weakness as the first symptom and slowly progressive course. Six patients were classified as of childhood onset type, with lower-limb weakness and progressive course. Seven patients were classified as of the adult onset type, with rapidly progressive course and obvious muscle atrophy. Patient's 1, 16 and 23 had rapid clinical progression. On follow up, the three patients showed respiratory failure. Limb weakness in all patients was proximal‑dominant. Hypotonia was observed in most patients. High arched feet were also observed as dysmorfic features. In all patients, the creatine kinase (CK) level was normal or mildly elevated, and electromyography revealed myogenic changes. Nemaline bodies were observed under a light microscope in more than half of the patients' muscle fibers, and especially in type I fibers. All patients showed fiber type I predominance and atrophy. Modified Gömöri trichrome staining showed characteristic purple‑colored rods. Muscle electron microscopy revealed the presence of high electron‑dense nemaline bodies around the nucleus, and of a disorganized myofibrillar apparatus, with broken myofilaments and irregular myofibrils and Z lines. The 28 patients with NM shared a number of clinical features, such as proximal limb weakness, reduced deep tendon reflex and dysmorfic features. Differences were also observed between the three types of patients, with regards to course progression, disease severity and respiratory failure. In conclusion, patients with NM showed great clinical heterogeneity. The diagnosis of NM was mainly based on the muscle biopsy.

  6. Mitochondrial myopathy and myoclonic epilepsy

    Directory of Open Access Journals (Sweden)

    Walter O. Arruda

    1990-03-01

    Full Text Available The authors describe a family (mother, son and two daughters with mitochondrial myopathy. The mother was asymptomatic. Two daughters had lactic acidosis and myoclonic epilepsy, mild dementia, ataxia, weakness and sensory neuropathy. The son suffered one acute hemiplegic episode due to an ischemic infarct in the right temporal region. All the patients studied had hypertension. EEG disclosed photomyoclonic response in the proband patient. Muscle biopsy disclosed ragged-red fibers and abnormal mitochondria by electron microscopy. Biochemical analysis showed a defect of cytochrome C oxidase in mitochondria isolated from skeletal muscle. Several clinical and genetic aspects of the mitochondrial encephalomyopathies are discussed.

  7. Cellular and Molecular Mechanisms Underlying Congenital Myopathy-related Weakness

    OpenAIRE

    Lindqvist, Johan

    2014-01-01

    Congenital myopathies are a rare and heterogeneous group of diseases. They are primarily characterised by skeletal muscle weakness and disease-specific pathological features. They harshly limit ordinary life and in severe cases, these myopathies are associated with early death of the affected individuals. The congenital myopathies investigated in this thesis are nemaline myopathy and myofibrillar myopathy. These diseases are usually caused by missense mutations in genes encoding myofibrillar ...

  8. Adult-onset nemaline myopathy in a dog presenting with persistent atrial standstill and primary hypothyroidism.

    Science.gov (United States)

    Nakamura, R K; Russell, N J; Shelton, G D

    2012-06-01

    A nine-year-old neutered female mixed breed dog presented for evaluation following a five-day history of lethargy, inappetence, weakness, abdominal distension and generalised muscle atrophy. Persistent vatrial standstill with a junctional rhythm was identified on electrocardiogram. Echocardiogram identified moderate dilation of all cardiac chambers and mild thickening of the mitral and tricuspid valves. Serology was negative for Neospora caninum and Toxoplasma gondii. Permanent pacemaker implantation was performed in addition to endomyocardial and skeletal muscle biopsies. Cryosections from the biceps femoris muscle showed numerous nemaline rod bodies while endomyocardial biopsies were possibly consistent with end-stage myocarditis. Rod bodies have rarely been reported in the veterinary literature. To the authors' knowledge, this is the first report of adult-onset nemaline rod myopathy and hypothyroidism with concurrent cardiac disease in a dog. © 2012 British Small Animal Veterinary Association.

  9. Actin nemaline myopathy mouse reproduces disease, suggests other actin disease phenotypes and provides cautionary note on muscle transgene expression.

    Directory of Open Access Journals (Sweden)

    Gianina Ravenscroft

    Full Text Available Mutations in the skeletal muscle α-actin gene (ACTA1 cause congenital myopathies including nemaline myopathy, actin aggregate myopathy and rod-core disease. The majority of patients with ACTA1 mutations have severe hypotonia and do not survive beyond the age of one. A transgenic mouse model was generated expressing an autosomal dominant mutant (D286G of ACTA1 (identified in a severe nemaline myopathy patient fused with EGFP. Nemaline bodies were observed in multiple skeletal muscles, with serial sections showing these correlated to aggregates of the mutant skeletal muscle α-actin-EGFP. Isolated extensor digitorum longus and soleus muscles were significantly weaker than wild-type (WT muscle at 4 weeks of age, coinciding with the peak in structural lesions. These 4 week-old mice were ~30% less active on voluntary running wheels than WT mice. The α-actin-EGFP protein clearly demonstrated that the transgene was expressed equally in all myosin heavy chain (MHC fibre types during the early postnatal period, but subsequently became largely confined to MHCIIB fibres. Ringbinden fibres, internal nuclei and myofibrillar myopathy pathologies, not typical features in nemaline myopathy or patients with ACTA1 mutations, were frequently observed. Ringbinden were found in fast fibre predominant muscles of adult mice and were exclusively MHCIIB-positive fibres. Thus, this mouse model presents a reliable model for the investigation of the pathobiology of nemaline body formation and muscle weakness and for evaluation of potential therapeutic interventions. The occurrence of core-like regions, internal nuclei and ringbinden will allow analysis of the mechanisms underlying these lesions. The occurrence of ringbinden and features of myofibrillar myopathy in this mouse model of ACTA1 disease suggests that patients with these pathologies and no genetic explanation should be screened for ACTA1 mutations.

  10. Acute myopathy associated with liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Ok-Jae Lee; Jee-Hyang Yoon; Eun-Jeong Lee; Hyun-Jin Kim; Tae-Hyo Kim

    2006-01-01

    AIM: Many cirrhotic patients have muscular symptoms and rhabdomyolysis. However, myopathy associated with liver cirrhosis has not been established as a disease entity. We evaluated the clinical significance of acute myopathy associated with liver cirrhosis.METHODS: We retrospectively reviewed the medical records of 5440 cirrhotic patients who had been admitted to Gyeongsang National University Hospital from August 1997 to January 2003. Among these, 99 developed acute myopathies, and they were analyzed with respect to clinical and laboratory parameters, and outcomes.RESULTS: The Child-Pugh classification at the time of myopathy onset was A in 3(3.1%) cases, B in 33(33.3%), and C in 63 (63.6%). Infection was identified as the most predisposing factor to myopathy. Fifty percent of 18 idiopathic cases who were tested for influenza antibody were positive. Forty-two of the 99 cases were complicated by acute renal failure, and 25 (59.5%) of these expired. Apart from 6 cases lost to follow-up, 64 of 93 recovered, giving a mortality rate of 31.2%. Mortality was higher in Child-Pugh class C than in B or A.CONCLUSION: Acute myopathy can develop as a serious complication in liver cirrhosis. Its frequency, severity and mortality depend on underlying liver function, and are higher in decompensated liver cirrhosis. Influenza should be considered as an etiologic factor in idiopathic cases. It is proposed that acute myopathy associated with liver cirrhosis be called 'hepatic myopathy', and that careful monitoring for hepatic myopathy is necessary in the patients with advanced liver cirrhosis.

  11. Sarcomere Dysfunction in Nemaline Myopathy.

    Science.gov (United States)

    de Winter, Josine M; Ottenheijm, Coen A C

    2017-01-01

    Nemaline myopathy (NM) is among the most common non-dystrophic congenital myopathies (incidence 1:50.000). Hallmark features of NM are skeletal muscle weakness and the presence of nemaline bodies in the muscle fiber. The clinical phenotype of NM patients is quite diverse, ranging from neonatal death to normal lifespan with almost normal motor function. As the respiratory muscles are involved as well, severely affected patients are ventilator-dependent. The mechanisms underlying muscle weakness in NM are currently poorly understood. Therefore, no therapeutic treatment is available yet.Eleven implicated genes have been identified: ten genes encode proteins that are either components of thin filament, or are thought to contribute to stability or turnover of thin filament proteins. The thin filament is a major constituent of the sarcomere, the smallest contractile unit in muscle. It is at this level of contraction - thin-thick filament interaction - where muscle weakness originates in NM patients.This review focusses on how sarcomeric gene mutations directly compromise sarcomere function in NM. Insight into the contribution of sarcomeric dysfunction to muscle weakness in NM, across the genes involved, will direct towards the development of targeted therapeutic strategies.

  12. Actin-Interacting Protein 1 Contributes to Intranuclear Rod Assembly in Dictyostelium discoideum

    Science.gov (United States)

    Ishikawa-Ankerhold, Hellen C.; Daszkiewicz, Wioleta; Schleicher, Michael; Müller-Taubenberger, Annette

    2017-01-01

    Intranuclear rods are aggregates consisting of actin and cofilin that are formed in the nucleus in consequence of chemical or mechanical stress conditions. The formation of rods is implicated in a variety of pathological conditions, such as certain myopathies and some neurological disorders. It is still not well understood what exactly triggers the formation of intranuclear rods, whether other proteins are involved, and what the underlying mechanisms of rod assembly or disassembly are. In this study, Dictyostelium discoideum was used to examine appearance, stages of assembly, composition, stability, and dismantling of rods. Our data show that intranuclear rods, in addition to actin and cofilin, are composed of a distinct set of other proteins comprising actin-interacting protein 1 (Aip1), coronin (CorA), filactin (Fia), and the 34 kDa actin-bundling protein B (AbpB). A finely tuned spatio-temporal pattern of protein recruitment was found during formation of rods. Aip1 is important for the final state of rod compaction indicating that Aip1 plays a major role in shaping the intranuclear rods. In the absence of both Aip1 and CorA, rods are not formed in the nucleus, suggesting that a sufficient supply of monomeric actin is a prerequisite for rod formation. PMID:28074884

  13. Ultrastructural characteristics and DNA immunocytochemistry in human immunodeficiency virus and zidovudine-associated myopathies.

    Science.gov (United States)

    Pezeshkpour, G; Illa, I; Dalakas, M C

    1991-12-01

    Electron microscopic features of muscle biopsies from 13 human immunodeficiency (HIV)-positive patients who had myopathy while receiving zidovudine (AZT) were compared with biopsies from five patients with HIV-induced myopathy who were not treated with AZT. All specimens showed disorganization of the myofibrillar structures, along with a varying degree of nemaline (rod) bodies, vacuolization, inflammation, and endothelial tubuloreticular profiles. One untreated and all AZT-treated patients had cytoplasmic bodies, which in the latter were abundant, large, and irregular. Two untreated patients had a peculiar osmiophilic destruction of the muscle fibers, with numerous tubuloreticular profiles in the endothelial cells and brisk inflammation that included lymphoplasmatoid cells. The AZT-treated group had ubiquitous abnormal mitochondria that complemented the presence of ragged red fibers seen by light microscopy. There was subsarcolemmal proliferation of mitochondria, with marked variation in size and shape and proliferation or disorganization of their cristae. Paracrystalline inclusions were seen in one patient. Blind re-examination of the electron micrographs showed abnormal mitochondria that readily distinguished patients with AZT-associated myopathy from those with untreated HIV-induced myopathy. Immunocytochemistry using antibodies to single- and double-stranded DNA revealed severe reduction of mitochondrial DNA compared with the normal nuclear DNA. Although the myopathies associated with HIV and AZT share common myopathologic features, the mitochondrial abnormalities are unique to the AZT-treated patients. Since mitochondrial DNA is specifically reduced, the structural changes noted on electron microscopy are probably associated with mitochondrial dysfunction. Zidovudine, a DNA chain terminator that inhibits the mitochondrial gamma-DNA polymerase, is toxic to muscle mitochondria.

  14. Vitelliform macular degeneration associated with mitochondrial myopathy.

    OpenAIRE

    Modi, G; Heckman, J M; Saffer, D

    1992-01-01

    A patient with mitochondrial myopathy is described. Examination of his fundus revealed bilateral vitelliform degeneration of the maculae. This lesion is a focal abnormality of the retinal pigment epithelium and may be a manifestation of the underlying mitochondrial disease.

  15. Mitochondrial abnormalities in the myofibrillar myopathies.

    Science.gov (United States)

    Jackson, S; Schaefer, J; Meinhardt, M; Reichmann, H

    2015-11-01

    Myofibrillar myopathies are a genetically diverse group of skeletal muscle disorders, with distinctive muscle histopathology. Causative mutations have been identified in the genes MYOT, LDB3, DES, CRYAB, FLNC, BAG3, DNAJB6, FHL1, PLEC and TTN, which encode proteins which either reside in the Z-disc or associate with the Z-disc. Mitochondrial abnormalities have been described in muscle from patients with a myofibrillar myopathy. We reviewed the literature to determine the extent of mitochondrial dysfunction in each of the myofibrillar myopathy subtypes. Abnormal mitochondrial distribution is a frequent finding in each of the subtypes, but a high frequency of COX-negative or ragged red fibres, a characteristic finding in some of the conventional mitochondrial myopathies, is a rare finding. Few in vitro studies of mitochondrial function have been performed in affected patients.

  16. Idiopathic inflammatory myopathies: diagnosis, treatment and outcome

    NARCIS (Netherlands)

    van de Vlekkert, J.

    2015-01-01

    The idiopathic inflammatory myopathies (IIM) in adults are a heterogenic group of disorders characterized by muscle inflammation and progressive muscle weakness. This group consists of five subacute-onset disorders: polymyositis (PM) which is extremely rare, (clinically amyopathic) dermatomyositis (

  17. Nemaline myopathy with dilated cardiomyopathy in childhood.

    Science.gov (United States)

    Gatayama, Ryohei; Ueno, Kentaro; Nakamura, Hideaki; Yanagi, Sadamitsu; Ueda, Hideaki; Yamagishi, Hiroyuki; Yasui, Seiyo

    2013-06-01

    We present a case of a 9-year-old boy with nemaline myopathy and dilated cardiomyopathy. The combination of nemaline myopathy and cardiomyopathy is rare, and this is the first reported case of dilated cardiomyopathy associated with childhood-onset nemaline myopathy. A novel mutation, p.W358C, in ACTA1 was detected in this patient. An unusual feature of this case was that the patient's cardiac failure developed during early childhood with no delay of gross motor milestones. The use of a β-blocker did not improve his clinical course, and the patient died 6 months after diagnosis of dilated cardiomyopathy. Congenital nonprogressive nemaline myopathy is not necessarily a benign disorder: deterioration can occur early in the course of dilated cardiomyopathy with neuromuscular disease, and careful clinical evaluation is therefore necessary.

  18. Lipid storage myopathies with unusual clinical manifestations

    Directory of Open Access Journals (Sweden)

    Uppin Megha

    2008-01-01

    Full Text Available We describe the clinical presentation, course and pathologic findings found in three adult patients with lipid storage myopathy. Excessive lipid storage was found in Type 1 fibers of muscle. Clinical improvement on oral levo-carnitine therapy suggests the possibility of carnitine deficiency as the most likely etiology in two of the patients and one had mitochondrial myopathy confirmed on genetic analysis.

  19. Tie rod insertion test

    CERN Multimedia

    B. LEVESY

    2002-01-01

    The superconducting coil is inserted in the outer vaccum tank and supported by a set of tie rods. These tie rods are made of titanium alloy. This test reproduce the final insertion of the tie rods inside the outer vacuum tank.

  20. Review of Cardiac Disease in Nemaline Myopathy.

    Science.gov (United States)

    Finsterer, Josef; Stöllberger, Claudia

    2015-12-01

    Little is known about the type, frequency, severity, treatment, and outcome of cardiac disease in nemaline myopathy. This review summarizes and discusses findings concerning the type, prevalence, diagnosis, treatment, and outcome of cardiac involvement in nemaline myopathy. Review of publications about nemaline myopathy and cardiac disease. Altogether, 35 patients with nemaline myopathy with cardiac disease were identified. Age at presentation ranged from 0 to 62 years. In 30 individuals whose gender was described, 22 were male and eight were female. Onset was congenital in 16 patients, infantile in five, and adult in four. Nine patients presented with dilated cardiomyopathy, six with hypertrophic cardiomyopathy, and one with nonspecific cardiomyopathy. Among those with cardiomyopathy, four developed heart failure. One patient experienced sudden cardiac death. A ventricular septal defect was described in two patients. Cardiac treatment included drugs for heart failure (eight patients), implantable cardioverter-defibrillator implantation (one patient), and heart transplant (three patients). Four patients received noninvasive positive-pressure ventilation and two continuous positive-pressure ventilation. The outcome was fatal in 11 patients. Cardiac disease in nemaline myopathy manifests as cardiomyopathy leading to heart failure. If respiratory muscles are affected, the right side of the heart may be secondarily involved. Early detection of cardiac involvement is essential since effective treatment for cardiac disease in nemaline myopathy may be available. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Mitochondrial dysfunction in myofibrillar myopathy.

    Science.gov (United States)

    Vincent, Amy E; Grady, John P; Rocha, Mariana C; Alston, Charlotte L; Rygiel, Karolina A; Barresi, Rita; Taylor, Robert W; Turnbull, Doug M

    2016-10-01

    Myofibrillar myopathies (MFM) are characterised by focal myofibrillar destruction and accumulation of myofibrillar elements as protein aggregates. They are caused by mutations in the DES, MYOT, CRYAB, FLNC, BAG3, DNAJB6 and ZASP genes as well as other as yet unidentified genes. Previous studies have reported changes in mitochondrial morphology and cellular positioning, as well as clonally-expanded, large-scale mitochondrial DNA (mtDNA) deletions and focal respiratory chain deficiency in muscle of MFM patients. Here we examine skeletal muscle from patients with desmin (n = 6), ZASP (n = 1) and myotilin (n = 2) mutations and MFM protein aggregates, to understand how mitochondrial dysfunction may contribute to the underlying mechanisms causing disease pathology. We have used a validated quantitative immunofluorescent assay to study respiratory chain protein levels, together with oxidative enzyme histochemistry and single cell mitochondrial DNA analysis, to examine mitochondrial changes. Results demonstrate a small number of clonally-expanded mitochondrial DNA deletions, which we conclude are due to both ageing and disease pathology. Further to this we report higher levels of respiratory chain complex I and IV deficiency compared to age matched controls, although overall levels of respiratory deficient muscle fibres in patient biopsies are low. More strikingly, a significantly higher percentage of myofibrillar myopathy patient muscle fibres have a low mitochondrial mass compared to controls. We concluded this is mechanistically unrelated to desmin and myotilin protein aggregates; however, correlation between mitochondrial mass and muscle fibre area is found. We suggest this may be due to reduced mitochondrial biogenesis in combination with muscle fibre hypertrophy.

  2. Equine metabolic myopathies with emphasis on the diagnostic approach - Comparison with human myopathies - A review

    NARCIS (Netherlands)

    Westermann, C. M.; Dorland, L.; Wijnberg, I. D.; van der Kolk, J. H.

    2007-01-01

    This review gives an overview of the presently known human and equine metabolic myopathies with emphasis on the diagnostic approach. Metabolic myopathies are muscle disorders caused by a biochemical defect of the skeletal muscle energy system, which results in inefficient muscle performance. Myopath

  3. Equine metabolic myopathies with emphasis on the diagnostic approach - Comparison with human myopathies - A review

    NARCIS (Netherlands)

    Westermann, C. M.; Dorland, L.; Wijnberg, I. D.; van der Kolk, J. H.

    2007-01-01

    This review gives an overview of the presently known human and equine metabolic myopathies with emphasis on the diagnostic approach. Metabolic myopathies are muscle disorders caused by a biochemical defect of the skeletal muscle energy system, which results in inefficient muscle performance. Myopath

  4. Myopathies in critical illness: characterization and nutritional aspects.

    Science.gov (United States)

    Burnham, Ellen L; Moss, Marc; Ziegler, Thomas R

    2005-07-01

    Myopathies related to critical illness have received increasing recognition over the past decade and are common in patients even after a brief period in the intensive care unit. Recent studies have revealed that myopathies in the critically ill may in fact be more prevalent than neuropathies and that morbidity and mortality may be greater. Protein catabolism, an increase in urinary nitrogen loss, and muscle wasting are observed in critical illness myopathy. Muscle biopsies in critically ill patients demonstrate low glutamine levels, low protein/DNA levels, and high concentrations of extracellular water. The increased flux of glutamine in muscle in these patients is thought to be insufficient to meet the body's requirement for glutamine, and thus in critical illness this amino acid may be classified as "conditionally essential." Three subtypes of critical illness myopathy have been described that are often grouped together as acute quadriplegic myopathy: thick-filament myopathy, critical illness myopathy, and necrotizing myopathy. These can be differentiated based on clinical features and muscle biopsy. Treatments for critical illness myopathies range from primary prevention, i.e., avoiding myopathy-inducing drugs, to novel nutritional therapies, such as glutamine and glutathione supplementation. One should be particularly vigilant for the development of myopathies in critically ill alcoholic patients, who may have a chronic alcoholic myopathy at baseline. In the past decade, advances have been made in characterizing and identifying patients with myopathies due to critical illness. However, additional studies must be performed in order to develop appropriate therapies for this potentially devastating disorder.

  5. Clinical and Pathological Features of Childhood-Onset Nemaline Myopathy: A Report of Four Cases

    Directory of Open Access Journals (Sweden)

    Chao Jiang

    2012-01-01

    Full Text Available We examined whether immunological abnormalities can be found in the specimens of four childhood-onset nemaline myopathy (NM patients without autoimmune diseases. Pathological examination revealed that nemaline rods were found in all specimens. The immunohistochemical results showed that CD4 positive cells and some other cells were gathered among the necrotic muscle fibers. We conclude that immunological abnormalities are present in the specimens of certain childhood-onset NM patients without autoimmune diseases. Further evaluation of the immunological changes is warranted in childhood-onset NM patients.

  6. Glucocorticoid-induced myopathy: Pathophysiology, diagnosis, and treatment

    Directory of Open Access Journals (Sweden)

    Anu Gupta

    2013-01-01

    Full Text Available Glucocorticoid-induced myopathy is the most common type of drug-induced myopathy. Nearly 60% of patients with Cushing′s syndrome have muscle weakness. Glucocorticoid-induced muscle atrophy affects mainly fast-twitch glycolytic muscle fibers (type IIb fibers. This brief review will discuss the pathophysiology behind glucocorticoid-induced myopathy, along with diagnostic features and treatment.

  7. Hypovitaminosis D myopathy without biochemical signs of osteomalacic bone involvement

    DEFF Research Database (Denmark)

    Glerup, H; Mikkelsen, K; Poulsen, L

    2000-01-01

    The aims of this study were to investigate myopathy in relation to vitamin D status, and to study the muscular effects of vitamin D treatment on vitamin D-deficient individuals. Further, hypovitaminosis D myopathy was investigated in relation to alkaline phosphatase (ALP), the most commonly used...... disease develop. Full normalization of hypovitaminosis D myopathy demands high...

  8. Nemaline body myopathy caused by a novel mutation in troponin T1 (TNNT1).

    Science.gov (United States)

    Abdulhaq, Ulla Najwa; Daana, Mohannad; Dor, Talia; Fellig, Yakov; Eylon, Sharon; Schuelke, Markus; Shaag, Avraham; Elpeleg, Orly; Edvardson, Simon

    2016-04-01

    Nemaline myopathy is a rare disorder characterized by skeletal muscle weakness of varying severity and onset, with the presence of nemaline rods on muscle biopsy. Congenital nemaline body myopathy due to mutations in TNNT1 has hitherto only been described as a result of a single founder mutation in patients of Amish origin and in 2 other individuals with different recessive mutations. Autozygosity mapping and whole exome sequencing were applied after we identified 9 Palestinian patients from 7 unrelated families who have nemaline myopathy. All patients were homozygous for a novel complex rearrangement of the TNNT1 gene (c.574_577delinsTAGTGCTGT | NM_003283) leading to C-terminal truncation of the protein (p.L203* | NP_003274.3). Their clinical course was remarkable for early respiratory failure and striking stiffness of the cervical spine. This report exemplifies the utility of combining autozygosity mapping and whole exome sequencing and expands the phenotype associated with TNNT1 mutations. © 2015 Wiley Periodicals, Inc.

  9. An integrated diagnosis strategy for congenital myopathies.

    Directory of Open Access Journals (Sweden)

    Johann Böhm

    Full Text Available Congenital myopathies are severe muscle disorders affecting adults as well as children in all populations. The diagnosis of congenital myopathies is constrained by strong clinical and genetic heterogeneity. Moreover, the majority of patients present with unspecific histological features, precluding purposive molecular diagnosis and demonstrating the need for an alternative and more efficient diagnostic approach. We used exome sequencing complemented by histological and ultrastructural analysis of muscle biopsies to identify the causative mutations in eight patients with clinically different skeletal muscle pathologies, ranging from a fatal neonatal myopathy to a mild and slowly progressive myopathy with adult onset. We identified RYR1 (ryanodine receptor mutations in six patients and NEB (nebulin mutations in two patients. We found novel missense and nonsense mutations, unraveled small insertions/deletions and confirmed their impact on splicing and mRNA/protein stability. Histological and ultrastructural findings of the muscle biopsies of the patients validated the exome sequencing results. We provide the evidence that an integrated strategy combining exome sequencing with clinical and histopathological investigations overcomes the limitations of the individual approaches to allow a fast and efficient diagnosis, accelerating the patient's access to a better healthcare and disease management. This is of particular interest for the diagnosis of congenital myopathies, which involve very large genes like RYR1 and NEB as well as genetic and phenotypic heterogeneity.

  10. Vaccines as a trigger for myopathies.

    Science.gov (United States)

    Orbach, H; Tanay, A

    2009-11-01

    Vaccines are considered to be among the greatest medical discoveries, credited with the virtual eradication of some diseases and the consequent improved survival and quality of life of the at-risk population. With that, vaccines are among the environmental factors implicated as triggers for the development of inflammatory myopathies. The sporadic reports on vaccine-induced inflammatory myopathies include cases of hepatitis B virus, bacillus Calmette-Guérin, tetanus, influenza, smallpox, polio, diphtheria, diphtheria-pertussis-tetanus, combination of diphtheria with scarlet fever and diphtheria-pertussis-tetanus with polio vaccines. However, a significant increase in the incidence of dermatomyositis or polymyositis after any massive vaccination campaign has not been reported in the literature. In study patients with inflammatory myopathies, no recent immunization was recorded in any of the patients. Moreover, after the 1976 mass flu vaccination, no increase in the incidence of inflammatory myopathies was observed. Although rare, macrophagic myofasciitis has been reported following vaccination and is attributed to the aluminium hydroxide used as an adjuvant in some vaccines. Prospective multicenter studies are needed to identify potential environmental factors, including vaccines, as potential triggers for inflammatory myopathies.

  11. Novel deletion of lysine 7 expands the clinical, histopathological and genetic spectrum of TPM2-related myopathies

    Science.gov (United States)

    Davidson, Ann E.; Carlson, Heather A.; Moore, Brian E.; Love, Seth; Born, Donald E.; Roper, Helen; Majumdar, Anirban; Jayadev, Suman; Underhill, Hunter R.; Smith, Corrine O.; von der Hagen, Maja; Hubner, Angela; Jardine, Philip; Merrison, Andria; Curtis, Elizabeth; Cullup, Thomas; Jungbluth, Heinz; Cox, Mary O.; Winder, Thomas L.; Abdel Salam, Hossam; Li, Jun Z.; Moore, Steven A.; Dowling, James J.

    2013-01-01

    The β-tropomyosin gene encodes a component of the sarcomeric thin filament. Rod-shaped dimers of tropomyosin regulate actin-myosin interactions and β-tropomyosin mutations have been associated with nemaline myopathy, cap myopathy, Escobar syndrome and distal arthrogryposis types 1A and 2B. In this study, we expand the allelic spectrum of β-tropomyosin-related myopathies through the identification of a novel β-tropomyosin mutation in two clinical contexts not previously associated with β-tropomyosin. The first clinical phenotype is core-rod myopathy, with a β-tropomyosin mutation uncovered by whole exome sequencing in a family with autosomal dominant distal myopathy and muscle biopsy features of both minicores and nemaline rods. The second phenotype, observed in four unrelated families, is autosomal dominant trismus-pseudocamptodactyly syndrome (distal arthrogryposis type 7; previously associated exclusively with myosin heavy chain 8 mutations). In all four families, the mutation identified was a novel 3-bp in-frame deletion (c.20_22del) that results in deletion of a conserved lysine at the seventh amino acid position (p.K7del). This is the first mutation identified in the extreme N-terminus of β-tropomyosin. To understand the potential pathogenic mechanism(s) underlying this mutation, we performed both computational analysis and in vivo modelling. Our theoretical model predicts that the mutation disrupts the N-terminus of the α-helices of dimeric β-tropomyosin, a change predicted to alter protein–protein binding between β-tropomyosin and other molecules and to disturb head-to-tail polymerization of β-tropomyosin dimers. To create an in vivo model, we expressed wild-type or p.K7del β-tropomyosin in the developing zebrafish. p.K7del β-tropomyosin fails to localize properly within the thin filament compartment and its expression alters sarcomere length, suggesting that the mutation interferes with head-to-tail β-tropomyosin polymerization and with

  12. Telescopic drilling rod

    Energy Technology Data Exchange (ETDEWEB)

    Kagan, I.L.; Berezov, S.I.; Gavrilov, G.A.; Goykhman, Ya.A.; Makushkin, D.O.; Rachev, M.P.; Voynich, L.K.

    1981-09-07

    The telescopic drilling rod includes an inner section of the rod, in whose center cable has been passed and is attached a bearing assembly connecting it to the winch, outer section of rod along which there is pipeline connecting the working cavity formed by the inner section of rod and the housing, installed on the lower end of the outer section of rod, with cavity formed by framework of the guide swivel and end piece and connected to the hydraulic system of the machine by pipeline, as well as clamping elements. In order to drill wells to a depth greater than the length of the outer sectrion of the rod, the latter jointly with the inner section of rod is lowered into the extreme lower position until swivel rests on the feed mechanism. With further slipping of cable and the absence of pressure in the hydraulic system, clamping elements do not have an effect on the inner section of rod. It has the opportunity to freely move along the outer section of rod downwards to the face. When pressure is supplied on pipeline into cavity and further through pipeline into working cavity, the inner section of rod is clamped with feed of the outer section in the process of drilling, both sections move jointly. Because of the link between working cavity of sleeve installed on the lower end of the outer section of rod, and the hydraulic system of the machine through the swivel cavity, it is possible to fix the drilling rod in any mutual axial position of the section.

  13. Muscle weakness in respiratory and peripheral skeletal muscles in a mouse model for nebulin-based nemaline myopathy.

    Science.gov (United States)

    Joureau, Barbara; de Winter, Josine M; Stam, Kelly; Granzier, Henk; Ottenheijm, Coen A C

    2017-01-01

    Nemaline myopathy is among the most common non-dystrophic congenital myopathies, and is characterized by the presence of nemaline rods in skeletal muscles fibers, general muscle weakness, and hypotonia. Although respiratory failure is the main cause of death in nemaline myopathy, only little is known regarding the contractile strength of the diaphragm, the main muscle of inspiration. To investigate diaphragm contractility, in the present study we took advantage of a mouse model for nebulin-based nemaline myopathy that we recently developed. In this mouse model, exon 55 of Neb is deleted (Neb(ΔExon55)), a mutation frequently found in patients. Diaphragm contractility was determined in permeabilized muscle fibers and was compared to the contractility of permeabilized fibers from three peripheral skeletal muscles: soleus, extensor digitorum longus, and gastrocnemius. The force generating capacity of diaphragm muscle fibers of Neb(ΔExon55) mice was reduced to 25% of wildtype levels, indicating severe contractile weakness. The contractile weakness of diaphragm fibers was more pronounced than that observed in soleus muscle, but not more pronounced than that observed in extensor digitorum longus and gastrocnemius muscles. The reduced muscle contractility was at least partly caused by changes in cross-bridge cycling kinetics which reduced the number of bound cross-bridges. The severe diaphragm weakness likely contributes to the development of respiratory failure in Neb(ΔExon55) mice and might explain their early, postnatal death. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. [Pathogenesis of the idiopathic inflammatory myopathies].

    Science.gov (United States)

    Riebeling-Navarro, Carlos; Nava, Arnulfo

    2009-11-01

    The inflammatory myopathies, commonly described as idiopathic, are a group of acquired diseases characterized by an inflammatory infiltrate of the skeletal muscle. On the basis of clinical and immuno-pathological features, three major diseases can be identified: dermatomiositis (DM), polymyositis (PM) and inclusion body myositis (IBM). Immunopathogenesis mechanisms are crucial for discriminating between the three different subsets of inflammatory myopathies. DM is a complement-mediated microangiopathy affecting skin and muscle. PM and IBM are T cell-mediated disorders, where CD8-positive cytotoxic T cells invade muscle fibres expressing MHC class I antigens. This article summarizes the main immunopathological markers. The impact of this new knowledge must be defined in relation to potential therapeutic targets for idiopathic inflammatory myopathies.

  15. [Progressive external ophthalmoplegia and distal myopathy].

    Science.gov (United States)

    Damian, C

    1993-01-01

    A patient, 58 years old, presents progressive blepharoptosis, in both eyes and external ophthalmoplegia. The general somatic examination, shows, at the level of the higher limbs, distal myopathy with muscular hypotony and articular deformities fibrosis and tendinous retraction. On examining the eye bottom we found colloid degeneration in the muscle region. Within the same family a ten-year-old nephew presents congenital ptosis. The muscular biopsy from the levator palpebrae shows muscular degenerative lesions with the reduction of nuclei and the proliferation of conjunctive tissue. It is shown that progressive external ophthalmoplegia must be interpreted as an ocular myopathy. The association with the distal myopathy at the level of the higher limbs, in the presented observation, upholds this pathogeny.

  16. Adult-onset nemaline myopathy presenting as respiratory failure.

    LENUS (Irish Health Repository)

    Kelly, Emer

    2008-11-01

    Nemaline myopathy is a rare congenital myopathy that generally presents in childhood. We report a case of a 44-year-old man who presented with severe hypoxic hypercapnic respiratory failure as the initial manifestation of nemaline myopathy. After starting noninvasive ventilation, his pulmonary function test results improved substantially, and over the 4 years since diagnosis his respiratory function remained stable. There are few reported cases of respiratory failure in patients with adult-onset nemaline myopathy, and the insidious onset in this case is even more unusual. This case highlights the varied presenting features of adult-onset nemaline myopathy and that noninvasive ventilation improves respiratory function.

  17. Zebrafish models for nemaline myopathy reveal a spectrum of nemaline bodies contributing to reduced muscle function.

    Science.gov (United States)

    Sztal, Tamar E; Zhao, Mo; Williams, Caitlin; Oorschot, Viola; Parslow, Adam C; Giousoh, Aminah; Yuen, Michaela; Hall, Thomas E; Costin, Adam; Ramm, Georg; Bird, Phillip I; Busch-Nentwich, Elisabeth M; Stemple, Derek L; Currie, Peter D; Cooper, Sandra T; Laing, Nigel G; Nowak, Kristen J; Bryson-Richardson, Robert J

    2015-09-01

    Nemaline myopathy is characterized by muscle weakness and the presence of rod-like (nemaline) bodies. The genetic etiology of nemaline myopathy is becoming increasingly understood with mutations in ten genes now known to cause the disease. Despite this, the mechanism by which skeletal muscle weakness occurs remains elusive, with previous studies showing no correlation between the frequency of nemaline bodies and disease severity. To investigate the formation of nemaline bodies and their role in pathogenesis, we generated overexpression and loss-of-function zebrafish models for skeletal muscle α-actin (ACTA1) and nebulin (NEB). We identify three distinct types of nemaline bodies and visualize their formation in vivo, demonstrating these nemaline bodies not only exhibit different subcellular origins, but also have distinct pathological consequences within the skeletal muscle. One subtype is highly dynamic and upon breakdown leads to the accumulation of cytoplasmic actin contributing to muscle weakness. Examination of a Neb-deficient model suggests this mechanism may be common in nemaline myopathy. Another subtype results from a reduction of actin and forms a more stable cytoplasmic body. In contrast, the final type originates at the Z-disk and is associated with myofibrillar disorganization. Analysis of zebrafish and muscle biopsies from ACTA1 nemaline myopathy patients demonstrates that nemaline bodies also possess a different protein signature. In addition, we show that the ACTA1(D286G) mutation causes impaired actin incorporation and localization in the sarcomere. Together these data provide a novel examination of nemaline body origins and dynamics in vivo and identifies pathological changes that correlate with muscle weakness.

  18. NEUROMUSCULAR DISEASE MIMICKING MYASTHENIA GRAVIS IN A NIGERIAN FEMALE ADOLESCENT: COULD THIS BE NEMALINE ROD DISEASE?

    Science.gov (United States)

    Oyinlade, O A; Lagunju, I A; Adebayo, B E

    2016-12-01

    Nemaline rod disease is a congenital myopathy, presentation of which may mimic myasthenia gravis. We report a suspected case of nemaline rod disease in a female adolescent who presented with features similar to myasthenia gravis but failed to respond effectively to its conventional management. She had features of respiratory failure and cardiomyopathy. Patient had a turbulent clinical course and finally succumbed to illness on the fifth day of admission. This report is meant to sensitize child neurologists and general paediatricians on the need to have a broad spectrum of considerations in the management of suspected myasthenia gravis, especially when response to anticholinesterase is poor.

  19. Exome sequencing reveals a nebulin nonsense mutation in a dog model of nemaline myopathy.

    Science.gov (United States)

    Evans, Jacquelyn M; Cox, Melissa L; Huska, Jonathan; Li, Frank; Gaitero, Luis; Guo, Ling T; Casal, Margaret L; Granzier, Henk L; Shelton, G Diane; Clark, Leigh Anne

    2016-10-01

    Nemaline myopathy (NM) is a congenital muscle disorder associated with muscle weakness, hypotonia, and rod bodies in the skeletal muscle fibers. Mutations in 10 genes have been implicated in human NM, but spontaneous cases in dogs have not been genetically characterized. We identified a novel recessive myopathy in a family of line-bred American bulldogs (ABDs); rod bodies in muscle biopsies established this as NM. Using SNP profiles from the nuclear family, we evaluated inheritance patterns at candidate loci and prioritized TNNT1 and NEB for further investigation. Whole exome sequencing of the dam, two affected littermates, and an unaffected littermate revealed a nonsense mutation in NEB (g.52734272 C>A, S8042X). Whole tissue gel electrophoresis and western blots confirmed a lack of full-length NEB in affected tissues, suggesting nonsense-mediated decay. The pathogenic variant was absent from 120 dogs of 24 other breeds and 100 unrelated ABDs, suggesting that it occurred recently and may be private to the family. This study presents the first molecularly characterized large animal model of NM, which could provide new opportunities for therapeutic approaches.

  20. Research progress of electrophysiology for the diagnosis of metabolic myopathy

    Directory of Open Access Journals (Sweden)

    Lei ZHAO

    2014-06-01

    Full Text Available Metabolic myopathies comprise a group of diverse disorders characterized by defects ofn energy metabolism in skeletal muscle cells, including glycogen storage disease (GSD, lipid storage myopathy (LSM and mitochondrial myopathy. The diagnosis of metabolic myopathies is often challenging due to the clinical and etiological heterogeneity between different metabolic myopathies. Generally, the diagnosis of metabolic myopathies is mainly based on the age of onset, family history, clinical manifestation, electrophysiological examinations, serological screening of metabolic markers, muscle biopsy and the DNA testing for specific mutations. The classical electrophysiological diagnostic methods and the corresponding manifestation of metabolic myopathies were reviewed and some new diagnostic techniques, including new motor unit potential (MUP parameters were introduced in this article. doi: 10.3969/j.issn.1672-6731.2014.06.002

  1. A Premature Stop Codon in MYO18B is Associated with Severe Nemaline Myopathy with Cardiomyopathy.

    Science.gov (United States)

    Malfatti, Edoardo; Böhm, Johann; Lacène, Emmanuelle; Beuvin, Maud; Romero, Norma B; Laporte, Jocelyn

    2015-09-02

    Nemaline myopathies (NM) are rare and severe muscle diseases characterized by the presence of nemaline bodies (rods) in muscle fibers. Although ten genes have been implicated in the etiology of NM, an important number of patients remain without a molecular diagnosis. Here we describe the clinical and histopathological features of a sporadic case presenting with severe NM and cardiomyopathy. Using exome sequencing, we aimed to identify the causative gene. We identified a homozygous nonsense mutation in the last exon of MYO18B, leading to a truncated protein lacking the most C-terminal part. MYO18B codes for an unconventional myosin protein and it is mainly expressed in skeletal and cardiac muscles, two tissues severely affected in the patient. We showed that the mutation does not impact on mRNA stability. Immunostaining and Western blot confirmed the absence of the full-length protein. We propose MYO18B as a novel gene associated with nemaline myopathy and cardiomyopathy.

  2. Aerobic Training in Patients with Congenital Myopathy

    DEFF Research Database (Denmark)

    Hedermann, Gitte; Vissing, Christoffer Rasmus; Jensen, Karen

    2016-01-01

    INTRODUCTION: Congenital myopathies (CM) often affect contractile proteins of the sarcomere, which could render patients susceptible to exercise-induced muscle damage. We investigated if exercise is safe and beneficial in patients with CM. METHODS: Patients exercised on a stationary bike for 30 m...

  3. Corticosteroid myopathy: a clinical and pathological study.

    Science.gov (United States)

    Khaleeli, A A; Edwards, R H; Gohil, K; McPhail, G; Rennie, M J; Round, J; Ross, E J

    1983-02-01

    In six patients with Cushing's syndrome and three with steroid myopathy, the clinical, functional, biochemical and structural characteristics of myopathy are described. Proximal muscle weakness occurred in all the patients, preferentially affected the lower limbs and was accompanied by muscle wasting in all but one patient. Force measurements confirmed quadriceps weakness in every patient. Vastus lateralis muscle biopsies showed light microscopic abnormalities in two of three patients with steroid myopathy and one of five patients with Cushing's syndrome. Type II fibre atrophy was the commonest abnormality. Reduced type II mean fibre areas occurred in all the patients with steroid myopathy and were common in Cushing's syndrome patients. Type I mean fibre areas were also reduced in two of the former group and one of the latter group and two further patients in this group had areas at the lower end of the normal range. Abnormalities in electron microscopy, mitochondrial function tests and chemical content of skeletal muscle were frequent and are described and discussed. A plasma creatine kinase activity (CK) at the lower end of the normal range, a myopathic electromyogram (EMG) and a raised 24-h urinary 3-methylhistidine/creatinine ratio on a creatine free diet were other characteristic findings in both groups of patients.

  4. Congenital myopathy with fiber type disproportion

    DEFF Research Database (Denmark)

    Gerdes, A M; Petersen, M B; Schrøder, H D

    1994-01-01

    A patient with myopathy and congenital fiber type disproportion presented at birth with arthrogryposis multiplex congenita, dislocation of the hips and mild scoliosis. Later in life she developed marked muscle weakness. A balanced chromosomal translocation t(10;17) (p11.2;q25), transmitted by the...

  5. Sporadic late-onset nemaline myopathy: clinico-pathological characteristics and review of 76 cases.

    Science.gov (United States)

    Schnitzler, Lukas J; Schreckenbach, Tobias; Nadaj-Pakleza, Aleksandra; Stenzel, Werner; Rushing, Elisabeth J; Van Damme, Philip; Ferbert, Andreas; Petri, Susanne; Hartmann, Christian; Bornemann, Antje; Meisel, Andreas; Petersen, Jens A; Tousseyn, Thomas; Thal, Dietmar R; Reimann, Jens; De Jonghe, Peter; Martin, Jean-Jacques; Van den Bergh, Peter Y; Schulz, Jörg B; Weis, Joachim; Claeys, Kristl G

    2017-05-11

    Sporadic late-onset nemaline myopathy (SLONM) is a rare, late-onset muscle disorder, characterized by the presence of nemaline rods in muscle fibers. Phenotypic characterization in a large cohort and a comprehensive overview of SLONM are lacking. We studied the clinico-pathological features, treatment and outcome in a large cohort of 76 patients with SLONM, comprising 10 new patients and 66 cases derived from a literature meta-analysis (PubMed, 1966-2016), and compared these with 15 reported HIV-associated nemaline myopathy (HIV-NM) cases. In 6 SLONM patients, we performed a targeted next-generation sequencing (NGS) panel comprising 283 myopathy genes. SLONM patients had a mean age at onset of 52 years. The predominant phenotype consisted of weakness and atrophy of proximal upper limbs in 84%, of proximal lower limbs in 80% and both in 67%. Other common symptoms included axial weakness in 68%, as well as dyspnea in 55% and dysphagia in 47% of the patients. In 53% a monoclonal gammopathy of unknown significance (MGUS) was detected in serum. The mean percentage of muscle fibers containing rods was 28% (range 1-63%). In 2 cases ultrastructural analysis was necessary to detect the rods. The most successful treatment in SLONM patients (all with MGUS) was autologous peripheral blood stem cell therapy. A targeted NGS gene panel in 6 SLONM patients (without MGUS) did not reveal causative pathogenic variants. In a comparison of SLONM patients with and without MGUS, the former comprised significantly more males, had more rapid disease progression, and more vacuolar changes in muscle fibers. Interestingly, the muscle biopsy of 2 SLONM patients with MGUS revealed intranuclear rods, whereas this feature was not seen in any of the biopsies from patients without paraproteinemia. Compared to the overall SLONM cohort, significantly more HIV-NM patients were male, with a lower age at onset (mean 34 years). In addition, immunosuppression was more frequently applied with more

  6. Nemaline myopathy: clinical, histochemical and immunohistochemical features Miopatia nemalínica: achados clínicos, histoquímicos e imuno-histoquímicos

    OpenAIRE

    Nazah Cherif Mohamad Youssef; Rosana Herminia Scola; Paulo José Lorenzoni; Lineu César Werneck

    2009-01-01

    Nemaline myopathy (NM) is a congenital disease that leads to hypotonia and feeding difficulties in neonates. Some cases have a more benign course, with skeletal abnormalities later in life. We analyzed a series of eight patients with NM obtained from a retrospective analysis of 4300 muscle biopsies. Patients were classified as having the typical form in five cases, intermediate form in two cases and severe form in one case. Histochemical analysis showed mixed rods distribution in all cases an...

  7. Muscle histopathology in nebulin-related nemaline myopathy: ultrastrastructural findings correlated to disease severity and genotype.

    Science.gov (United States)

    Malfatti, Edoardo; Lehtokari, Vilma-Lotta; Böhm, Johann; De Winter, Josine M; Schäffer, Ursula; Estournet, Brigitte; Quijano-Roy, Susana; Monges, Soledad; Lubieniecki, Fabiana; Bellance, Remi; Viou, Mai Thao; Madelaine, Angéline; Wu, Bin; Taratuto, Ana Lía; Eymard, Bruno; Pelin, Katarina; Fardeau, Michel; Ottenheijm, Coen A C; Wallgren-Pettersson, Carina; Laporte, Jocelyn; Romero, Norma B

    2014-04-12

    Nemaline myopathy (NM) is a rare congenital myopathy characterised by hypotonia, muscle weakness, and often skeletal muscle deformities with the presence of nemaline bodies (rods) in the muscle biopsy. The nebulin (NEB) gene is the most commonly mutated and is thought to account for approximately 50% of genetically diagnosed cases of NM. We undertook a detailed muscle morphological analysis of 14 NEB-mutated NM patients with different clinical forms to define muscle pathological patterns and correlate them with clinical course and genotype. Three groups were identified according to clinical severity. Group 1 (n = 5) comprises severe/lethal NM and biopsy in the first days of life. Group 2 (n = 4) includes intermediate NM and biopsy in infancy. Group 3 (n = 5) comprises typical/mild NM and biopsy in childhood or early adult life. Biopsies underwent histoenzymological, immunohistochemical and ultrastructural analysis. Fibre type distribution patterns, rod characteristics, distribution and localization were investigated. Contractile performance was studied in muscle fibre preparations isolated from seven muscle biopsies from each of the three groups. G1 showed significant myofibrillar dissociation and smallness with scattered globular rods in one third of fibres; there was no type 1 predominance. G2 presented milder sarcomeric dissociation, dispersed or clustered nemaline bodies, and type 1 predominance/uniformity. In contrast, G3 had well-delimited clusters of subsarcolemmal elongated rods and type 1 uniformity without sarcomeric alterations. In accordance with the clinical and morphological data, functional studies revealed markedly low forces in muscle bundles from G1 and a better contractile performance in muscle bundles from biopsies of patients from G2, and G3.In conclusion NEB-mutated NM patients present a wide spectrum of morphological features. It is difficult to establish firm genotype phenotype correlation. Interestingly, there was a correlation

  8. Autosomal Dominant Centronuclear Myopathy with Unique Clinical Presentations

    OpenAIRE

    Lee, Jee-Young; Min, Ju-Hong; Hong, Yoon-Ho; Sung, Jung-Joon; Park, Sung-Hye; Park, Seong-Ho; Lee, Kwang-Woo; Park, Kyung Seok

    2007-01-01

    Centronuclear myopathies are clinically and genetically heterogenous diseases with common histological findings, namely, centrally located nuclei in muscle fibers with a predominance and hypotrophy of type 1 fibers. We describe two cases from one family with autosomal dominant centronuclear myopathy with unusual clinical features that had initially suggested distal myopathy. Clinically, the patients presented with muscle weakness and atrophy localized mainly to the posterior compartment of th...

  9. Glucocorticoid-induced apoptosis and cellular mechanisms of myopathy.

    Science.gov (United States)

    Dirks-Naylor, Amie J; Griffiths, Carrie L

    2009-10-01

    Glucocorticoid-induced myopathy is a common side effect of chronic glucocorticoid therapy. Several mechanisms are currently being examined as ways in which glucocorticoid-induced myopathy occurs. These include apoptotic signaling through mitochondrial-mediated and Fas-mediated apoptosis, the role of the proteosome, the suppression of the IGF-1 signaling, and the role of ceramide in glucocorticoid-induced apoptosis and myopathy. It is difficult to differentiate which mechanism may be the initiating event responsible for the induction of apoptosis; however, all of the mechanisms play a vital role in glucocorticoid-induced myopathy.

  10. Autosomal dominant centronuclear myopathy with unique clinical presentations.

    Science.gov (United States)

    Lee, Jee Young; Min, Ju Hong; Hong, Yoon Ho; Sung, Jung Joon; Park, Sung Hye; Park, Seong Ho; Lee, Kwang Woo; Park, Kyung Seok

    2007-12-01

    Centronuclear myopathies are clinically and genetically heterogenous diseases with common histological findings, namely, centrally located nuclei in muscle fibers with a predominance and hypotrophy of type 1 fibers. We describe two cases from one family with autosomal dominant centronuclear myopathy with unusual clinical features that had initially suggested distal myopathy. Clinically, the patients presented with muscle weakness and atrophy localized mainly to the posterior compartment of the distal lower extremities. Magnetic resonance imaging revealed predominant atrophy and fatty changes of bilateral gastrocnemius and soleus muscles. This report demonstrates the expanding clinical heterogeneity of autosomal dominant centronuclear myopathy.

  11. MITOCHONDRIAL MYOPATHY: A NEW THERAPEUTIC APPROACH.

    Science.gov (United States)

    Hagiu, B A; Mungiu, C

    2016-01-01

    Restoration of deoxyribonucleic acid in mitochondrial myopathies may occur after a mechanical or chemical injury of striated muscle or by endurance training. Therapies with enzymes, gene therapies, or treatments with substances that stimulate mitochondrial biogenesis are used at the moment. Genesis of mitochondria may also come from myonuclei by releasing the nuclear respiratory factor-1/2 during muscle contractions. Multiplying of myonuclei depends on muscle satellite cell activation. Since the electromyostimulation increase the number of circulating stem cells that may participate in the genesis of new muscle fibers (adding to the deposit of specific stem cells of the muscle), and intermittent hypoxia stimulates the proliferation of muscle satellite cells, we propose to combine the two processes for the treatment of mitochondrial myopathies. Respective combined therapy may be useful for restoring damaged mitochondria by drug side effects.

  12. Presumed isotretinoin-induced extraocular myopathy

    Directory of Open Access Journals (Sweden)

    Md. Shahid Alam

    2016-01-01

    Full Text Available Isotretinoin a synthetic analogue of vitamin A is primarily used for cystic acne not responding to conventional treatment. Several ocular side effects including blurring of vision, decreased dark adaptation, corneal opacities and meibomian gland atrophy have been reported with prolonged use of isotretinoin. There have been reports of muscular damage caused by isotretinoin. Extra ocular myopathy as an adverse effect of long term used of isotretinoin has never been mentioned in literature. We report a case of a young male who presented to us with complaints of diplopia after using isotretinoin for a prolonged period. He was diagnosed as a case of presumed isotretinoin extraocular myopathy after imaging and other blood investigations.

  13. Miopatia ocular descendente Descending ocular myopathy

    Directory of Open Access Journals (Sweden)

    Nunjo Finkel

    1972-06-01

    Full Text Available São relatados 4 casos de miopatia ocular descendente (MOD com história familial levantada em três gerações. Biópsia musculares e eletromiografia em um caso confirmaram o caráter miogênico da doença. A MOD nada mais seria do que uma forma clínica especial de distrofia muscular, de início tardio.Four cases of the so-called descending ocular myopathy with a family history in three generations are reported. In the first case muscular biopsy and electromyographic studies proved the myogenic nature of the process. Descending ocular myopathy seems to be just a clinical form of muscular distrophy of late onset.

  14. Muscle biopsy findings in inflammatory myopathies.

    Science.gov (United States)

    Dalakas, Marinos C

    2002-11-01

    The inflammatory myopathies encompass a heterogeneous group of acquired muscle diseases characterized clinically, by muscle weakness, and histologically, by inflammatory infiltrates within the skeletal muscles. The group of these myopathies comprise three major and discrete subsets: polymyositis (PM), dermatomyositis (DM), and inclusion body myositis (IBM). Each subset retains its characteristic clinical, immunopathologic, and morphologic features regardless of whether it occurs separately or in connection with other systemic diseases. Although the diagnosis of these disorders is based on the combination of clinical examination, electromyographic data, serum muscle enzyme levels, various autoantibodies, and the muscle biopsy findings, the muscle biopsy offers the most definitive diagnostic information in the majority of the cases. This article summarizes the main histologic features that characterize PM, DM, or IBM and emphasizes the main pitfalls associated with interpretation of the biopsies.

  15. Centronuclear myopathy in a Border collie dog.

    Science.gov (United States)

    Eminaga, S; Cherubini, G B; Shelton, G D

    2012-10-01

    A two-year old, male entire Border collie was presented with a one-year history of exercise-induced collapsing on the pelvic limbs. Physical examination revealed generalised muscle atrophy. Neurological examination supported a generalised neuromuscular disorder. Electromyography revealed spontaneous electrical activity in almost all muscles. Unfixed and formaldehyde-fixed biopsy samples were collected from the triceps brachii, longissimus and vastus lateralis muscles. Histopathological, histochemical and ultrastructural examinations of biopsy specimens were consistent with either centronuclear or myotubular myopathy. The dog clinically improved with supportive treatment with L-carnitine, co-enzyme Q10 and vitamin B compound. To the authors' knowledge, this is the first report of centronuclear/myotubular myopathy in a Border collie.

  16. Bethlem myopathy: An autosomal dominant myopathy with flexion contractures, keloids, and follicular hyperkeratosis

    Directory of Open Access Journals (Sweden)

    Aralikatte Onkarappa Saroja

    2013-01-01

    Full Text Available Bethlem myopathy and Ullrich congenital muscular dystrophy form a spectrum of collagenopathies caused by genetic mutations encoding for any of the three subunits of collagen VI. Bethlem phenotype is relatively benign and is characterized by proximal dominant myopathy, keloids, contractures, distal hyperextensibility, and follicular hyperkeratosis. Three patients from a single family were diagnosed to have Bethlem myopathy based on European Neuromuscular Centre Bethlem Consortium criteria. Affected father and his both sons had slowly progressive proximal dominant weakness and recurrent falls from the first decade. Both children aged 18 and 20 years were ambulant at presentation. All had flexion contractures, keloids, and follicular hyperkeratosis without muscle hypertrophy. Creatinine kinase was mildly elevated and electromyography revealed myopathic features. Muscle imaging revealed severe involvement of glutei and vasti with "central shadow" in rectus femoris. Muscle biopsy in the father showed dystrophic changes with normal immmunostaining for collagen VI, sarcoglycans, and dysferlin.

  17. Therapeutic approaches in patients with inflammatory myopathies.

    Science.gov (United States)

    Dalakas, Marinos C

    2003-06-01

    Among the group of inflammatory myopathies, dermatomyositis (DM) remains the most treatable subset responding, in the majority of the cases, to steroids, intravenous immunoglobulin (IVIg), or immunosuppressants. Inclusion-body myositis (IBM) remains the most difficult disease to treat; in uncontrolled studies immunosuppressants and steroids have not helped, and controlled trials with IVIg have been disappointing. Polymyositis (PM) is a very uncommon, although still overdiagnosed, disorder and its rarity poses difficulties in performing large-scale therapeutic studies; based on small series, however, PM seems to variably respond to immunotherapeutic interventions. The most consistent problem in the treatment of inflammatory myopathies remains the distinction of true PM from the difficult-to-treat cases of IBM, or from necrotizing myopathies and dystrophic processes where secondary endomysial inflammation may be prominent. The future in the management of PM, DM, and IBM seems promising because of the availability of new agents directed at T-cell activation molecules, cytokines, chemokines, and adhesion receptors. In IBM, the use of such immunomodulatory drugs may be combined with agents that block cytokine-enhancing amyloid or with agents that inhibit the formation and polymerization of amyloid fibrils.

  18. Current treatment of the inflammatory myopathies.

    Science.gov (United States)

    Dalakas, M C

    1994-11-01

    Among the main concerns regarding the current therapy for the inflammatory myopathies are a lack of adequate controlled trials, a lack of objective means to reliably measure muscle strength, lack of natural history data, consideration of polymyositis, dermatomyositis, and inclusion-body myositis as a homogeneous group of inflammatory myopathies, and reliance on nonspecific markers for determining prognosis and assessing response to therapies. Prednisone remains the drug of choice in treating these disorders, although a controlled trial has never been undertaken to study its efficacy. Among the steroid-sparing agents, azathioprine, methotrexate, cyclosporine, and chlorambucil are used with invariably low to moderate success. There are no results of controlled trials to indicate whether one of these drugs is superior to another. Intravenous immunoglobulin, which is very expensive, was shown in a controlled trial to be effective in steroid-resistant dermatomyositis not only in dramatically improving muscle strength and skin rash but also in resolving the underlying immunopathology. Controlled trials of intravenous immunoglobulin in patients with polymyositis and inclusion-body myositis are under way. Inclusion-body myositis has emerged as a common inflammatory myopathy that is predictably disabling and resistant to most therapies.

  19. Toxic and drug-induced myopathies.

    Science.gov (United States)

    Dalakas, M C

    2009-08-01

    Drugs used for therapeutic interventions either alone or in combination may sometimes cause unexpected toxicity to the muscles, resulting in a varying degree of symptomatology, from mild discomfort and inconvenience to permanent damage and disability. The clinician should suspect a toxic myopathy when a patient without a pre-existing muscle disease develops myalgia, fatigue, weakness or myoglobinuria, temporally connected to the administration of a drug or exposure to a myotoxic substance. This review provides an update on the drugs with well-documented myocytoxicity and cautions the clinicians to be alert for the potential toxicity of newly marketed drugs; highlights the clinical features and pathomechanisms of the induced muscle disease; and offers guidance on how best to treat and distinguish toxic myopathies from other acquired or hereditary muscle disorders. Practical issues regarding the diagnosis and management of statin-induced myopathies are emphasized. Myotoxicity resulting from direct insertion of transgenes to the muscle, an exciting new tool currently tested for treatment of muscular dystrophies, is also discussed.

  20. Fundamentos teóricos de la formación de imágenes por resonancia magnética nuclear NRM

    OpenAIRE

    Yapur, Miguel; Correa, José

    1990-01-01

    El diagnóstico médico ha sido beneficiado por los avances tecnológicos logrados con los avances recientes. La tecnología mejorada de Rayos - X. La tomografía computarizada (CT) y el ultrasonido han sido las principales técnicas de imágenes. Hoy en día, esta progresión tecnológica han dado un paso adelante con la introducción de la Resonancia Magnética Nuclear (NRM). Las imágenes obtenidas por este método proveeen imágenes de alto contraste sin radiación ionizante. Debido a lo nuevo del tema y...

  1. Mitochondrial processes are impaired in hereditary inclusion body myopathy.

    NARCIS (Netherlands)

    Eisenberg, I.; Novershtern, N.; Itzhaki, Z.; Becker-Cohen, M.; Sadeh, M.; Willems, P.H.G.M.; Friedman, N.; Koopman, W.J.H.; Mitrani-Rosenbaum, S.

    2008-01-01

    Hereditary inclusion body myopathy (HIBM) is an adult onset, slowly progressive distal and proximal myopathy. Although the causing gene, GNE, encodes for a key enzyme in the biosynthesis of sialic acid, its primary function in HIBM remains unknown. To elucidate the pathological mechanisms leading fr

  2. Mitochondrial myopathy with respiratory muscle involvement: a case report

    Directory of Open Access Journals (Sweden)

    J. A. Levy

    1983-03-01

    Full Text Available A case of a 10-year-old patient with a benign congenital myopathy, suddenly aggravated because of an accentuated deficit in respiratory muscles is reported. The institution of assisted respiration at night allowed the patient to return to her daily activities. Examination of muscular biopsy with ultra-microscope permitted the diagnosis of mitochondrial myopathy.

  3. Morphological differential diagnosis of the main types of inflammatory myopathies

    Directory of Open Access Journals (Sweden)

    S. G. Radenska-Lopovok

    2012-01-01

    Full Text Available The review provides an update on the diagnosis of the main subtypes of inflammatory myopathies. Proper choice of biopsied muscle and histological methods of investigation are presented. Histochemical and immunohistochemical characteristic of tissue markers in inflammatory myopathies are given. Some dilemmas, as well as the most common errors of histological diagnostics are discussed.

  4. Clinical course correlates poorly with muscle pathology in nemaline myopathy

    NARCIS (Netherlands)

    Ryan, MM; Ilkovski, B; Strickland, CD; Schnell, C; Sanoudou, D; Midgett, C; Houston, R; Muirhead, D; Dermett, [No Value; Shield, LK; De Girolami, U; Iannaccone, ST; Laing, NG; North, KN; Beggs, AH

    2003-01-01

    Objective: To report pathologic findings in 124 Australian and North American cases of primary nemaline myopathy. Methods: Results of 164 muscle biopsies from 124 Australian and North American patients with primary nemaline myopathy were reviewed, including biopsies from 19 patients with nemaline

  5. A new phenotype of autosomal dominant nemaline myopathy.

    NARCIS (Netherlands)

    Gommans, I.M.P.; Engelen, B.G.M. van; Laak, H.J. ter; Brunner, H.G.; Kremer, H.P.H.; Lammens, M.M.Y.; Vogels, O.J.M.

    2002-01-01

    We present a five-generation family with a novel phenotype of autosomal dominant nemaline myopathy not linked to the three genes known to be causative for nemaline myopathy (alpha-tropomyosin-3, nebulin, and alpha-actin). Although there was muscle weakness in the neck flexors and proximal muscles of

  6. Genetics Home Reference: early-onset myopathy with fatal cardiomyopathy

    Science.gov (United States)

    ... called sarcomeres . Sarcomeres are the basic units of muscle contraction; they are made of proteins that generate the mechanical force needed for muscles to contract. Titin has several functions within sarcomeres. One of this protein's most ... CMD Salih congenital muscular dystrophy Salih myopathy titinopathy & early-onset myopathy with ...

  7. Nemaline myopathy caused byTNNT1 mutations in a Dutch pedigree.

    Science.gov (United States)

    van der Pol, W Ludo; Leijenaar, Jolien F; Spliet, Wim G M; Lavrijsen, Selma W; Jansen, Nicolaas J G; Braun, Kees P J; Mulder, Marcel; Timmers-Raaijmakers, Brigitte; Ratsma, Kimberly; Dooijes, Dennis; van Haelst, Mieke M

    2014-03-01

    Nemaline myopathy (NM) is genetically heterogeneous disorder characterized by early onset muscular weakness and sarcoplasmatic or intranuclear inclusions of rod-shaped Z-disk material in muscle fibers. Thus far, mutations in seven genes have been identified as cause of NM. Only one singleTNNT1 nonsense mutation has been previously described that causes autosomal recessive NM in the old order Amish with a very specific clinical phenotype including rapidly progressive contractures. Here, we report a patient who is compound heterozygous for a c.309+1G>A mutation and an exon 14 deletion in theTNNT1 gene. This report confirms the specific clinical phenotype ofTNNT1 NM and documents two newTNNT1 mutations outside the old order Amish.

  8. Critical illness polyneuropathy and myopathy: a systematic review.

    Science.gov (United States)

    Zhou, Chunkui; Wu, Limin; Ni, Fengming; Ji, Wei; Wu, Jiang; Zhang, Hongliang

    2014-01-01

    Critical illness polyneuropathy and critical illness myopathy are frequent complications of severe illness that involve sensorimotor axons and skeletal muscles, respectively. Clinically, they manifest as limb and respiratory muscle weakness. Critical illness polyneuropathy/myopathy in isolation or combination increases intensive care unit morbidity via the inability or difficulty in weaning these patients off mechanical ventilation. Many patients continue to suffer from decreased exercise capacity and compromised quality of life for months to years after the acute event. Substantial progress has been made lately in the understanding of the pathophysiology of critical illness polyneuropathy and myopathy. Clinical and ancillary test results should be carefully interpreted to differentiate critical illness polyneuropathy/myopathy from similar weaknesses in this patient population. The present review is aimed at providing the latest knowledge concerning the pathophysiology of critical illness polyneuropathy/myopathy along with relevant clinical, diagnostic, differentiating, and treatment information for this debilitating neurological disease.

  9. Necrotising myopathy, an unusual presentation of a steroid-responsive myopathy

    NARCIS (Netherlands)

    Bronner, IM; Hoogendijk, JE; Wintzen, AR; van der Meulen, MFG; Linssen, WHJP; Wokke, JHJ; de Visser, M

    2003-01-01

    Objective To evaluate the clinical features, muscle pathology and response to treatment in patients with a necrotising myopathy, without mononuclear cell infiltrates. Background Mononuclear cell infiltrates in the muscle biopsy specimen are the diagnostic hallmark of the immune-mediated idiopathic i

  10. Congenital myopathy caused by a novel missense mutation in the CFL2 gene.

    NARCIS (Netherlands)

    Ockeloen, C.W.; Gilhuis, H.J.; Pfundt, R.; Kamsteeg, E.J.; Agrawal, P.B.; Beggs, A.H.; Hama-Amin, A.D.; Diekstra, A.; Knoers, N.V.A.M.; Lammens, M.M.; Alfen, N. van

    2012-01-01

    Nemaline myopathy and myofibrillar myopathy are heterogeneous myopathies that both comprise early-onset forms. We present two sisters from a consanguineous Iraqi Kurdish family with predominant axial and limb girdle weakness. Muscle biopsies showed features of both nemaline myopathy and myofibrillar

  11. Mitochondrial myopathy caused by long-term zidovudine therapy.

    Science.gov (United States)

    Dalakas, M C; Illa, I; Pezeshkpour, G H; Laukaitis, J P; Cohen, B; Griffin, J L

    1990-04-19

    Both infection with the human immunodeficiency virus type 1 (HIV) and zidovudine (formerly called azidothymidine [AZT]) cause myopathy. To identify criteria for distinguishing zidovudine-induced myopathy from that caused by primary HIV infection, we reviewed the histochemical, immunocytochemical, and electron-microscopical features of muscle-biopsy specimens from 20 HIV-positive patients with myopathy (15 of whom had been treated with zidovudine) and compared the findings with the patients' clinical course and response to various therapies. Among the zidovudine-treated patients, the myopathy responded to prednisone in four, to the discontinuation of zidovudine in eight, and to nonsteroidal anti-inflammatory drugs in two. Numerous "ragged-red" fibers, indicative of abnormal mitochondria with paracrystalline inclusions, were found in the biopsy specimens from the zidovudine-treated patients but not in those from the other patients. The number of these fibers appeared to correlate with the severity of the myopathy. All the patients, regardless of whether they had been treated with zidovudine, had inflammatory myopathy characterized by degenerating fibers, cytoplasmic bodies, and endomysial infiltrates consisting of CD8+ cells (mean +/- SD, 60.7 +/- 6.4 percent) and macrophages (39.2 +/- 6.4 percent) associated with Class I major histocompatibility complex (MHC-I) antigens (HLA-A, -B, and -C antigens) in the muscle fibers. The numbers and percentages of CD8+ cells and macrophages were similar in both the zidovudine-treated and the untreated HIV-positive patients. Specimens obtained on repeat muscle biopsy from two patients in whom the myopathy responded to the discontinuation of zidovudine showed remarkable histologic improvement. We conclude that long-term therapy with zidovudine can cause a toxic mitochondrial myopathy, which coexists with a T-cell-mediated inflammatory myopathy that is restricted to MHC-I antigen, and is indistinguishable from the myopathy

  12. Myopathy in Patients Taking Atorvastatin: A Pilot Study.

    Science.gov (United States)

    Manoj, K; Jain, N; Madhu, S V

    2017-01-01

    This study aims to investigate the prevalence and risk factors of statin-induced myopathy. A total of 200 patients aged ≥ 40 years and taking atorvastatin 10 mg/day or more for at least 2 weeks were recruited in the study. A detailed history of participants and anthropometry of study participants was recorded, and features of myopathy were explained. Biochemical investigations along with thyroid stimulating hormone (TSH) and Vitamin D were done in all patients. Mean age of study population was 54.81 ± 9.10 years. Sixty-five percent (65.5%) of atorvastatin users had coronary heart disease, 62.5% were hypertensive, 38% had diabetes. Thirty-five percent (35.5%) patients were taking 10 mg/day atorvastatin, 45% were taking 20 mg/day, and 19.5% were taking 40 mg/day. The overall frequency of myopathy among statin users was 7.5% which was significantly higher with increasing dose of atorvastatin (1.4% in 10 mg/day group, 10% in 20 mg/day group, and 12.8% in 40 mg/day, P < 0.05). The frequency of atorvastatin-related myopathy was higher in females 8.65% compared to 6.25% in males. Serum TSH levels in patients with myopathy were 4.05 ± 7.76 μIU/ml while in those without myopathy were 3.13 ± 2.88 μIU/ml (P = 0.649). Serum 25-hydroxy Vitamin D levels were measured in 66 patients randomly. Mean levels in patients with myopathy were 15.98 ± 12.94 ng/ml and without myopathy were 10.20 ± 5.64 ng/ml (P = 0.285). The present study demonstrates that a significantly higher number of patients taking atorvastatin develop myopathy in real life clinical condition. The frequency of myopathy increases with increase in atorvastatin dose.

  13. [Myopathy in acromegaly. Report of two cases].

    Science.gov (United States)

    Abe, M; Tabuchi, K; Fujii, K; Oda, K; Ishimoto, S

    1990-10-01

    Acromegaly is often associated with neuromuscular disorders. Most of them are caused by compression of nerves with hypertrophic bone and soft tissues or complications of diabetes mellitus. Myopathy has rarely been reported in the Japanese literature. We report two cases with myopathy out of 14 cases of acromegaly. Case 1 is a 62-year-old woman who developed muscle weakness and atrophy in the shoulder girdle, pelvic girdle and femoral regions after a 10-year history of acromegaly. She showed positive Gowers' sign and normal DTRs. Basal growth hormone (GH) level in plasma was 1076 ng/ml. Electromyograms (EMG) obtained from the deltoid and rectus femoris muscles revealed typical myopathic abnormalities; an excess of small-amplitude, short-duration, polyphasic motor unit potentials. Histological examinations of the rectus femoris muscle showed diffuse atrophy of both type I and type II fibers. She also had bilateral carpal tunnel syndrome and bilateral tarsal tunnel syndrome, which were confirmed by nerve conduction studies of median nerves and posterior tibial nerves. A cranial computed tomography (CT) scan demonstrated sellar mass with suprasellar extension. She underwent transsphenoidal adenomectomy and radiation therapy. GH level lowered to 29 ng/ml, however, myopathy remained unchanged for 3 years after the surgery. Case 2 is a 38-year-old woman who had undergone partial removal of a pituitary adenoma 9 years after the onset of acromegaly. Basal GH level in plasma before the surgery had been 1694 ng/ml and was still high after the surgery (100-505 ng/ml). The patient developed proximal muscle weakness and atrophy 4 years after the surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Morphoelastic rods. Part I: A single growing elastic rod

    KAUST Repository

    Moulton, D.E.

    2013-02-01

    A theory for the dynamics and statics of growing elastic rods is presented. First, a single growing rod is considered and the formalism of three-dimensional multiplicative decomposition of morphoelasticity is used to describe the bulk growth of Kirchhoff elastic rods. Possible constitutive laws for growth are discussed and analysed. Second, a rod constrained or glued to a rigid substrate is considered, with the mismatch between the attachment site and the growing rod inducing stress. This stress can eventually lead to instability, bifurcation, and buckling. © 2012 Elsevier Ltd. All rights reserved.

  15. Learning with Rods: One Account.

    Science.gov (United States)

    Cherry, Donald Esha

    This paper discusses one English as a Second Language (ESL) teacher's attempts to use cuisenaire rods as a language learning tool. Cuisenaire rods (sometimes called algebricks) vary in size from 1 x 1 x 10 centimeter sticks to 1 x 1 x 1 centimeter cubes, with each of the 10 sizes a different color. Although such rods have been used to teach…

  16. Two novel MYH7 proline substitutions cause Laing Distal Myopathy-like phenotypes with variable expressivity and neck extensor contracture.

    Science.gov (United States)

    Feinstein-Linial, Miora; Buvoli, Massimo; Buvoli, Ada; Sadeh, Menachem; Dabby, Ron; Straussberg, Rachel; Shelef, Ilan; Dayan, Daniel; Leinwand, Leslie Anne; Birk, Ohad S

    2016-08-12

    Human skeletal muscles express three major myosin heavy chain (MyHC) isoforms: MyHCIIx (MYH1) in fast type 2B muscle fibers, MyHCIIa (MYH2) in fast type 2A fibers and MyHCI/β-cardiac MyHC (MYH7) in slow type I skeletal fibers and cardiac ventricles. In line with its expression pattern, MYH7 mutations have been reported in association with hypertrophic or dilated cardiomyopathy, skeletal myopathies or a combination of both. We analyzed the clinical and molecular phenotype of two unrelated families of Jewish Moroccan ancestry that presented with apparently autosomal dominant inheritance of progressive Laing-like distal myopathy with non-specific myopathic changes, but uncommon marked contractures and wasting of the neck extensors. Clinical phenotyping, whole exome sequencing and restriction analysis, generation of mutants followed by cell culture transfection and imaging. Using whole exome sequencing we identified in both families two novel heterozygous proline substitutions located in exon 31 of MYH7 within its rod domain: c.4309G>C (p.Ala1437Pro) and c.4301G>C (p.Arg1434Pro). Here we show that the phenotype caused by these mutations includes marked cervical muscle contracture, and report that the severity of the phenotype varies significantly, to the extent of non-penetrance in one of the families. Finally, we provide evidence that both proline substitutions impair myosin self-assembly in non-muscle cells transfected with β-myosin constructs carrying the mutations, but do not prevent incorporation of the mutant molecules into the sarcomere. This study expands our clinical and molecular knowledge of MYH7 rod mutations causing skeletal myopathies, and underscores the importance of discussing disease penetrance during genetic counseling.

  17. Bethlem myopathy is not allelic to limb-girdle muscular dystrophy type 1A

    Energy Technology Data Exchange (ETDEWEB)

    Speer, M.C.; Yamaoka, L.H.; Stajich, J.; Lewis, K. [and others

    1995-08-28

    The Bethlem myopathy, an autosomal-dominant myopathy, shows a distribution of proximal muscle weakness similar to that observed in dominant limb-girdle muscular dystrophy (LGMD). Yet the Bethlem myopathy differs from most limb-girdle dystrophies in two important regards. First, the Bethlem myopathy presents with joint contractures most commonly observed at the elbows, ankles, and neck. Secondly, disease onset in the Bethlem myopathy is in early childhood, while most dominant LGMDs present with adult onset. 6 refs., 1 fig.

  18. Retroviruses and inflammatory myopathies in humans and primates.

    Science.gov (United States)

    Dalakas, M C

    1993-11-01

    The human immunodeficiency virus (HIV), the human T cell lymphotropic virus (HTLV-1), the human foamy retrovirus and the simian immunodeficiency viruses have been associated with the development of an inflammatory myopathy in humans and primates. The myopathy caused by HIV and HTLV-1 is not due to direct infection of the muscle by these viruses, but rather due to an immunopathologic process triggered by the viruses, mediated by autoaggressive CD8+ cells in the context of MHC-class I antigen expression. This has been based on a series of studies utilizing immunocytochemistry, in situ hybridization, polymerase chain reaction, and co-cultivation of human myotubes with the viruses or with HIV-1 and HTLV-1-infected homologous lymphoid cells. Because the clinical, histological and immunological picture of patients with retroviral-associated inflammatory myopathies is identical to that of patients with retroviral-negative inflammatory myopathy, there is a reasonable possibility that retroviruses may be candidate viruses in triggering inflammatory myopathies. In recent years, the antiretroviral drug AZT (Zidovudine), commonly used for the treatment of AIDS, has been shown to cause a distinct mitochondrial myopathy characterized by depletion of the muscle mitochondrial DNA due to AZT's ability to inhibit the gamma-DNA polymerase of the mitochondrial matrix. Distinction of the AZT-myopathy is clinically important because it responds to discontinuation of AZT and to administration of another antiretroviral agent such as ddI or ddC.

  19. Safety rod latch inspection

    Energy Technology Data Exchange (ETDEWEB)

    Leader, D.R.

    1992-02-01

    During an attempt to raise control rods from the 100 K reactor in December, one rod could not be withdrawn. Subsequent investigation revealed that a small button'' in the latch mechanism had broken off of the lock plunger'' and was wedged in a position that prevented rod withdrawal. Concern that this failure may have resulted from corrosion or some other metallurgical problem resulted in a request that SRL examine six typical latch mechanisms from the 100 L reactor by use of radiography and metallography. During the examination of the L-Area latches, a failed latch mechanism from the 100 K reactor was added to the investigation. Fourteen latches that had a history of problems were removed from K-Area and sent to SRL for inclusion in this study the week after the original seven assemblies were examined, bringing the total of latch assemblies discussed in this report to twenty one. Results of the examination of the K-Area latch that initiated this study is not included in this report.

  20. Safety rod latch inspection

    Energy Technology Data Exchange (ETDEWEB)

    Leader, D.R.

    1992-02-01

    During an attempt to raise control rods from the 100 K reactor in December, one rod could not be withdrawn. Subsequent investigation revealed that a small ``button`` in the latch mechanism had broken off of the ``lock plunger`` and was wedged in a position that prevented rod withdrawal. Concern that this failure may have resulted from corrosion or some other metallurgical problem resulted in a request that SRL examine six typical latch mechanisms from the 100 L reactor by use of radiography and metallography. During the examination of the L-Area latches, a failed latch mechanism from the 100 K reactor was added to the investigation. Fourteen latches that had a history of problems were removed from K-Area and sent to SRL for inclusion in this study the week after the original seven assemblies were examined, bringing the total of latch assemblies discussed in this report to twenty one. Results of the examination of the K-Area latch that initiated this study is not included in this report.

  1. Pathophysiology of inflammatory and autoimmune myopathies.

    Science.gov (United States)

    Dalakas, Marinos C

    2011-04-01

    The main subtypes of inflammatory myopathies include dermatomyositis (DM), polymyositis (PM), necrotizing autoimmune myositis (NAM) and sporadic inclusion-body myositis (sIBM). The review provides an update on the main clinical characteristics unique to each subset, including fundamental aspects on muscle pathology helpful to assure accurate diagnosis, underlying immunopathomechanisms and therapeutic strategies. DM is a complement-mediated microangiopathy leading to destruction of capillaries, distal hypoperfusion and inflammatory cell stress on the perifascicular regions. NAM is an increasingly recognized subacute myopathy triggered by statins, viral infections, cancer or autoimmunity with macrophages as the final effector cells mediating fiber injury. PM and IBM are characterized by cytotoxic CD8-positive T cells which clonally expand in situ and invade MHC-I-expressing muscle fibers. In IBM, in addition to autoimmunity, there is vacuolization and intrafiber accumulation of degenerative and stressor molecules. Pro-inflammatory mediators, such as gamma interferon and interleukin IL1-β, seem to enhance the accumulation of stressor and amyloid-related misfolded proteins. Current therapies using various immunosuppressive and immunomodulating drugs are discussed for PM, DM and NAM, and the principles for effective treatment strategies in IBM are outlined.

  2. Cardiac involvement in adult and juvenile idiopathic inflammatory myopathies

    DEFF Research Database (Denmark)

    Schwartz, TThomas W; Diederichsen, L. P.; Lundberg, Ingrid E.

    2016-01-01

    Idiopathic inflammatory myopathies (IIM) include the main subgroups polymyositis (PM), dermatomyositis (DM), inclusion body myositis (IBM) and juvenile DM ( JDM). The mentioned subgroups are characterised by inflammation of skeletal muscles leading to muscle weakness and other organs can also...

  3. Mechanisms of zidovudine-induced mitochondrial toxicity and myopathy.

    Science.gov (United States)

    Scruggs, Erin R; Dirks Naylor, Amie J

    2008-01-01

    Zidovudine (3-azido-3'-deoxythymidine), also referred to as azidothymidine (AZT), has become an integral component in highly active antiretroviral therapy, and has also been used in the treatment of cancer. The clinical effectiveness of AZT is constrained due to its association with increased adverse effects, such as myopathy. There are numerous potential mechanisms that may contribute to AZT-induced myopathy. The first hypothesized mechanism to explain AZT-induced toxicity was mtDNA depletion due to inhibition of DNA polymerase gamma. Although mtDNA depletion is present in patients with myopathy, current data suggests that alternative mechanisms may play a more direct role in the myotoxicity. These mechanisms include AZT-induced oxidative stress, direct inhibition of mitochondrial bioenergetic machinery, and mitochondrial depletion of L-carnitine. Furthermore, we hypothesize that apoptosis may play a role in AZT-induced myopathy.

  4. Genetics Home Reference: X-linked myotubular myopathy

    Science.gov (United States)

    ... Lagier-Tourenne C, Buj-Bello A, Romero NB, Mandel JL. Characterisation of mutations in 77 patients with ... Laguna A, Biancalana V, Böhm J, Tranchant C, Mandel JL, Laporte J. Adult centronuclear myopathies: A hospital- ...

  5. Statin Induced Myopathy a Patient with Multiple Systemic Diseases

    Directory of Open Access Journals (Sweden)

    Özgül Uçar

    2011-04-01

    Full Text Available Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins are the most successful class of drugs for the treatment of hypercholesterolaemia and dyslipidaemia. However, the popular profile of statins in terms of efficacy has been maligned by theiradverse effects. Statin induced myopathy, which can be seen at any time during the course of therapy, is a clinically important cause of statin intolerance and discontinuation. When a patient with multiple systemic diseases who use numerous medications represent with myalgia and muscle cramps, statin induced myopathy may not be remembered at first. We present a patient with multiple systemic diseases, alcohol and morphine abuse in whom myopathy developed. After exclusion of other etiologies, we concluded that myopathy was related to statin therapy.

  6. Cone rod dystrophies

    Directory of Open Access Journals (Sweden)

    Hamel Christian P

    2007-02-01

    Full Text Available Abstract Cone rod dystrophies (CRDs (prevalence 1/40,000 are inherited retinal dystrophies that belong to the group of pigmentary retinopathies. CRDs are characterized by retinal pigment deposits visible on fundus examination, predominantly localized to the macular region. In contrast to typical retinitis pigmentosa (RP, also called the rod cone dystrophies (RCDs resulting from the primary loss in rod photoreceptors and later followed by the secondary loss in cone photoreceptors, CRDs reflect the opposite sequence of events. CRD is characterized by primary cone involvement, or, sometimes, by concomitant loss of both cones and rods that explains the predominant symptoms of CRDs: decreased visual acuity, color vision defects, photoaversion and decreased sensitivity in the central visual field, later followed by progressive loss in peripheral vision and night blindness. The clinical course of CRDs is generally more severe and rapid than that of RCDs, leading to earlier legal blindness and disability. At end stage, however, CRDs do not differ from RCDs. CRDs are most frequently non syndromic, but they may also be part of several syndromes, such as Bardet Biedl syndrome and Spinocerebellar Ataxia Type 7 (SCA7. Non syndromic CRDs are genetically heterogeneous (ten cloned genes and three loci have been identified so far. The four major causative genes involved in the pathogenesis of CRDs are ABCA4 (which causes Stargardt disease and also 30 to 60% of autosomal recessive CRDs, CRX and GUCY2D (which are responsible for many reported cases of autosomal dominant CRDs, and RPGR (which causes about 2/3 of X-linked RP and also an undetermined percentage of X-linked CRDs. It is likely that highly deleterious mutations in genes that otherwise cause RP or macular dystrophy may also lead to CRDs. The diagnosis of CRDs is based on clinical history, fundus examination and electroretinogram. Molecular diagnosis can be made for some genes, genetic counseling is

  7. Diagnostic challenges in combined multiple sclerosis and centronuclear myopathy

    DEFF Research Database (Denmark)

    Olsen, D.B.; Langkilde, Annika Reynberg; Schmalbruch, H

    2000-01-01

    The first case of combined centronuclear myopathy and multiple sclerosis is reported. The difficulties of diagnosing multiple sclerosis in patients with muscular disorders associated with the central nervous system involvement are discussed......The first case of combined centronuclear myopathy and multiple sclerosis is reported. The difficulties of diagnosing multiple sclerosis in patients with muscular disorders associated with the central nervous system involvement are discussed...

  8. Modern Therapies for Idiopathic Inflammatory Myopathies (IIMs): Role of Biologics

    OpenAIRE

    Moghadam-Kia, Siamak; Oddis, Chester V.; Aggarwal, Rohit

    2017-01-01

    Despite the lack of placebo-controlled trials, glucocorticoids are considered the mainstay of initial treatment for idiopathic inflammatory myopathy (IIMs) and myositis-associated ILD (MA-ILD). Glucocorticoid-sparing agents are often given concomitantly with other immunosuppressive agents, particularly in patients with moderate or severe disease. As treatment of refractory cases of idiopathic inflammatory myopathies has been challenging, there is growing interest in evaluating newer therapies...

  9. [Treatability of sporadic late onset nemaline myopathy].

    Science.gov (United States)

    Hanisch, F; Schneider, I; Müller, T; Romeike, B F; Stoltenburg, G; Holzhausen, H J; Zierz, S

    2013-08-01

    Sporadic late onset nemaline myopathy (SLONM) is an extremely rare disorder which can be associated with monoclonal gammopathy of unclear significance (MGUS). Clinically SLONM appears mostly after the fourth decade of life as rapidly progressing tetraparesis, respiratory insufficiency and features, such as dropped head syndrome, facial and bulbar involvement. Diagnosis is confirmed by muscle biopsy with detection of nemaline bodies and also frequently lobulated fibres. Immunosuppressant and immunomodulating therapies have been shown to be ineffective but clinical improvement accompanied by disappearance of monoclonal gammopathy and even nemaline bodies was reported following autologous stem cell transplantation and chemotherapy with melphalan. This article presents the case of a 53-year-old man with a 4-year history of SLOMN with MGUS in which administration of intravenous immunoglobulin therapy (IVIG) was not successful in reversing gammopathy, histopathological changes or clinical symptoms.

  10. Active Brownian rods

    Science.gov (United States)

    Peruani, Fernando

    2016-11-01

    Bacteria, chemically-driven rods, and motility assays are examples of active (i.e. self-propelled) Brownian rods (ABR). The physics of ABR, despite their ubiquity in experimental systems, remains still poorly understood. Here, we review the large-scale properties of collections of ABR moving in a dissipative medium. We address the problem by presenting three different models, of decreasing complexity, which we refer to as model I, II, and III, respectively. Comparing model I, II, and III, we disentangle the role of activity and interactions. In particular, we learn that in two dimensions by ignoring steric or volume exclusion effects, large-scale nematic order seems to be possible, while steric interactions prevent the formation of orientational order at large scales. The macroscopic behavior of ABR results from the interplay between active stresses and local alignment. ABR exhibit, depending on where we locate ourselves in parameter space, a zoology of macroscopic patterns that ranges from polar and nematic bands to dynamic aggregates.

  11. Control of Rod-Rod Interactions in Poly(3-alkylthiophenes)

    Science.gov (United States)

    Ho, Victor; Boudouris, Bryan W.; Segalman, Rachel A.

    2010-03-01

    Poly(3-hexylthiophene) is a commonly used semiconducting polymer because of its relatively high charge transport ability, low band gap, and solution processiblity. Strong intermolecular interactions lead to the formation of nanofibers during crystallization, which prevents long-range microstructural ordering. We show rod-rod interactions, parameterized by the Maier-Saupe parameter, can be controlled by rational polythiophene side chain design. Effects of side chain passivation are evidenced by a depressed melting temperature and the presence of a liquid crystalline region. Additionally, the Maier-Saupe parameters are estimated for poly(3-dodecylthiophene) and poly(3-ethylhexylthiophene); the relative magnitudes of each are related to the interchain spacings obtained by x-ray diffraction experiments. The systematic tuning of the rod-rod interactions in polythiophenes allows for manipulation of the ratio of Maier-Saupe to the Flory-Huggins parameter, a crucial value in obtaining long-range order in rod-coil block copolymer morphologies.

  12. Cuisenaire Rods Go to College.

    Science.gov (United States)

    Chinn, Phyllis; And Others

    1992-01-01

    Presents examples of questions and answers arising from a hands-on and exploratory approach to discrete mathematics using cuisenaire rods. Combinatorial questions about trains formed of cuisenaire rods provide the setting for discovering numerical patterns by experimentation and organizing the results using induction and successive differences.…

  13. Acute liver failure after recommended doses of acetaminophen in patients with myopathies

    NARCIS (Netherlands)

    I. Ceelie (Ilse); L.P. James (Laura); V.M.G.J. Gijsen (Violette); R.A.A. Mathôt (Ron); S. Ito (Shinya); C.D. Tesselaar (Coranne); D. Tibboel (Dick); G. Koren (Gideon); S.N. de Wildt (Saskia)

    2011-01-01

    textabstractObjective: To determine the likelihood that recommended doses of acetaminophen are associated with acute liver failure in patients with myopathies. Design: Retrospective analysis. Setting: Level III pediatric intensive care unit. Patients: Two pediatric patients with myopathies and acute

  14. Acute liver failure after recommended doses of acetaminophen in patients with myopathies

    NARCIS (Netherlands)

    I. Ceelie (Ilse); L.P. James (Laura); V.M.G.J. Gijsen (Violette); R.A.A. Mathot (Ron); S. Ito (Shinya); C.D. Tesselaar (Coranne); D. Tibboel (Dick); G. Koren (Gideon); S.N. de Wildt (Saskia)

    2011-01-01

    textabstractObjective: To determine the likelihood that recommended doses of acetaminophen are associated with acute liver failure in patients with myopathies. Design: Retrospective analysis. Setting: Level III pediatric intensive care unit. Patients: Two pediatric patients with myopathies and acute

  15. Genetics Home Reference: inclusion body myopathy with early-onset Paget disease and frontotemporal dementia

    Science.gov (United States)

    ... myopathy with early-onset Paget disease and frontotemporal dementia Enable Javascript to view the expand/collapse boxes. ... myopathy with early-onset Paget disease and frontotemporal dementia ( IBMPFD ) is a condition that can affect the ...

  16. Metabolic myopathy presenting with polyarteritis nodosa: a case report

    Directory of Open Access Journals (Sweden)

    Elbalkhi Amro

    2011-06-01

    Full Text Available Abstract Introduction To the best of our knowledge, we describe for the first time a patient in whom an unusual metabolic myopathy was identified after failure to respond to curative therapy for a systemic vasculitis, polyarteritis nodosa. We hope this report will heighten awareness of common metabolic myopathies that may present later in life. It also speculates on the potential relationship between metabolic myopathy and systemic vasculitis. Case presentation A 78-year-old African-American woman with a two-year history of progressive fatigue and exercise intolerance presented to our facility with new skin lesions and profound muscle weakness. Skin and muscle biopsies demonstrated a medium-sized artery vasculitis consistent with polyarteritis nodosa. Biochemical studies of the muscle revealed diminished cytochrome C oxidase activity (0.78 μmol/minute/g tissue; normal range 1.03 to 3.83 μmol/minute/g tissue, elevated acid maltase activity (23.39 μmol/minute/g tissue; normal range 1.74 to 9.98 μmol/minute/g tissue and elevated neutral maltase activity (35.89 μmol/minute/g tissue; normal range 4.35 to 16.03 μmol/minute/g tissue. Treatment for polyarteritis nodosa with prednisone and cyclophosphamide resulted in minimal symptomatic improvement. Additional management with a diet low in complex carbohydrates and ubiquinone, creatine, carnitine, folic acid, α-lipoic acid and ribose resulted in dramatic clinical improvement. Conclusions Our patient's initial symptoms of fatigue, exercise intolerance and progressive weakness were likely related to her complex metabolic myopathy involving both the mitochondrial respiratory chain and glycogen storage pathways. Management of our patient required treatment of both the polyarteritis nodosa as well as metabolic myopathy. Metabolic myopathies are common and should be considered in any patient with exercise intolerance. Metabolic myopathies may complicate the management of various disease states.

  17. Absence of upregulated genes associated with protein accumulations in desmin myopathy.

    Science.gov (United States)

    Raju, Raghavan; Dalakas, Marinos C

    2007-03-01

    In desmin myopathy but not hereditary inclusion-body myopathy (hIBM), there is accumulation of myofibrillar proteins including desmin, myotilin, dystrophin, gelsolin, actin, and CDC kinase. To assess the cause of protein excess, we studied the genes coding the accumulated proteins in desmin myopathy, hIBM, and controls. No differences were found among them. In desmin myopathy, protein accumulation is not due to upregulation of genes triggered by mutant desmin, but rather to posttranslational disassembly of intermediate filaments.

  18. Pharmacogenomic insights into treatment and management of statin-induced myopathy

    OpenAIRE

    Peters, Bas JM; Klungel, Olaf H.; Visseren, Frank L.; de Boer, Anthonius; Maitland-van der Zee, Anke-Hilse

    2009-01-01

    Although statins are generally well tolerated, the most common adverse drug reaction from statin therapy is myopathy. This article reviews the current pharmacogenomic knowledge of statin-induced myopathy. Furthermore, we will discuss the importance of recent pharmacogenetic advances for the treatment and management of statin-induced myopathy. Variation in the SLCO1B1 gene is associated with increased incidence of statin-induced myopathy, particularly with simvastatin and less so with other st...

  19. K7del is a common TPM2 gene mutation associated with nemaline myopathy and raised myofibre calcium sensitivity.

    Science.gov (United States)

    Mokbel, Nancy; Ilkovski, Biljana; Kreissl, Michaela; Memo, Massimiliano; Jeffries, Cy M; Marttila, Minttu; Lehtokari, Vilma-Lotta; Lemola, Elina; Grönholm, Mikaela; Yang, Nan; Menard, Dominique; Marcorelles, Pascale; Echaniz-Laguna, Andoni; Reimann, Jens; Vainzof, Mariz; Monnier, Nicole; Ravenscroft, Gianina; McNamara, Elyshia; Nowak, Kristen J; Laing, Nigel G; Wallgren-Pettersson, Carina; Trewhella, Jill; Marston, Steve; Ottenheijm, Coen; North, Kathryn N; Clarke, Nigel F

    2013-02-01

    Mutations in the TPM2 gene, which encodes β-tropomyosin, are an established cause of several congenital skeletal myopathies and distal arthrogryposis. We have identified a TPM2 mutation, p.K7del, in five unrelated families with nemaline myopathy and a consistent distinctive clinical phenotype. Patients develop large joint contractures during childhood, followed by slowly progressive skeletal muscle weakness during adulthood. The TPM2 p.K7del mutation results in the loss of a highly conserved lysine residue near the N-terminus of β-tropomyosin, which is predicted to disrupt head-to-tail polymerization of tropomyosin. Recombinant K7del-β-tropomyosin incorporates poorly into sarcomeres in C2C12 myotubes and has a reduced affinity for actin. Two-dimensional gel electrophoresis of patient muscle and primary patient cultured myotubes showed that mutant protein is expressed but incorporates poorly into sarcomeres and likely accumulates in nemaline rods. In vitro studies using recombinant K7del-β-tropomyosin and force measurements from single dissected patient myofibres showed increased myofilament calcium sensitivity. Together these data indicate that p.K7del is a common recurrent TPM2 mutation associated with mild nemaline myopathy. The p.K7del mutation likely disrupts head-to-tail polymerization of tropomyosin, which impairs incorporation into sarcomeres and also affects the equilibrium of the troponin/tropomyosin-dependent calcium switch of muscle. Joint contractures may stem from chronic muscle hypercontraction due to increased myofibrillar calcium sensitivity while declining strength in adulthood likely arises from other mechanisms, such as myofibre decompensation and fatty infiltration. These results suggest that patients may benefit from therapies that reduce skeletal muscle calcium sensitivity, and we highlight late muscle decompensation as an important cause of morbidity.

  20. Mutation Update and Genotype–Phenotype Correlations of Novel and Previously Described Mutations in TPM2 and TPM3 Causing Congenital Myopathies

    Science.gov (United States)

    Marttila, Minttu; Lehtokari, Vilma-Lotta; Marston, Steven; Nyman, Tuula A.; Barnerias, Christine; Beggs, Alan H.; Bertini, Enrico; Ceyhan-Birsoy, OÖzge; Cintas, Pascal; Gerard, Marion; Gilbert-Dussardier, Brigitte; Hogue, Jacob S.; Longman, Cheryl; Eymard, Bruno; Frydman, Moshe; Kang, Peter B.; Klinge, Lars; Kolski, Hanna; Lochmüller, Hans; Magy, Laurent; Manel, Véronique; Mayer, Michèle; Mercuri, Eugenio; North, Kathryn N.; Peudenier-Robert, Sylviane; Pihko, Helena; Probst, Frank J.; Reisin, Ricardo; Stewart, Willie; Taratuto, Ana Lia; de Visser, Marianne; Wilichowski, Ekkehard; Winer, John; Nowak, Kristen; Laing, Nigel G.; Winder, Tom L.; Monnier, Nicole; Clarke, Nigel F.; Pelin, Katarina; Grönholm, Mikaela; Wallgren-Pettersson, Carina

    2014-01-01

    Mutations affecting skeletal muscle isoforms of the tropomyosin genes may cause nemaline myopathy, cap myopathy, core-rod myopathy, congenital fiber-type disproportion, distal arthrogryposes, and Escobar syndrome. We correlate the clinical picture of these diseases with novel (19) and previously reported (31) mutations of the TPM2 and TPM3 genes. Included are altogether 93 families: 53 with TPM2 mutations and 40 with TPM3 mutations. Thirty distinct pathogenic variants of TPM2 and 20 of TPM3 have been published or listed in the Leiden Open Variant Database (http://www.dmd.nl/). Most are heterozygous changes associated with autosomal-dominant disease. Patients with TPM2 mutations tended to present with milder symptoms than those with TPM3 mutations, DA being present only in the TPM2 group. Previous studies have shown that five of the mutations in TPM2 and one in TPM3 cause increased Ca2+ sensitivity resulting in a hypercontractile molecular phenotype. Patients with hypercontractile phenotype more often had contractures of the limb joints (18/19) and jaw (6/19) than those with nonhypercontractile ones (2/22 and 1/22), whereas patients with the non-hypercontractile molecular phenotype more often (19/22) had axial contractures than the hypercontractile group (7/19). Our in silico predictions show that most mutations affect tropomyosin–actin association or tropomyosin head-to-tail binding. PMID:24692096

  1. Mitochondrial myopathy presenting as fibromyalgia: a case report

    Directory of Open Access Journals (Sweden)

    Abdullah Mishal

    2012-02-01

    Full Text Available Abstract Introduction To the best of our knowledge, we describe for the first time the case of a woman who met the diagnostic criteria for fibromyalgia, did not respond to therapy for that disorder, and was subsequently diagnosed by biochemical and genetic studies with a mitochondrial myopathy. Treatment of the mitochondrial myopathy resulted in resolution of symptoms. This case demonstrates that mitochondrial myopathy may present in an adult with a symptom complex consistent with fibromyalgia. Case presentation Our patient was a 41-year-old Caucasian woman with symptoms of fatigue, exercise intolerance, headache, and multiple trigger points. Treatment for fibromyalgia with a wide spectrum of medications including non-steroidal anti-inflammatory drugs, antidepressants, gabapentin and pregabalin had no impact on her symptoms. A six-minute walk study demonstrated an elevated lactic acid level (5 mmol/L; normal Conclusions This case demonstrates that adults diagnosed with fibromyalgia may have their symptom complex related to an adult onset mitochondrial myopathy. This is an important finding since treatment of mitochondrial myopathy resulted in resolution of symptoms.

  2. Myofibrillar myopathies: State of the art, present and future challenges.

    Science.gov (United States)

    Béhin, A; Salort-Campana, E; Wahbi, K; Richard, P; Carlier, R-Y; Carlier, P; Laforêt, P; Stojkovic, T; Maisonobe, T; Verschueren, A; Franques, J; Attarian, S; Maues de Paula, A; Figarella-Branger, D; Bécane, H-M; Nelson, I; Duboc, D; Bonne, G; Vicart, P; Udd, B; Romero, N; Pouget, J; Eymard, B

    2015-10-01

    Myofibrillar myopathies (MFM) have been described in the mid-1990s as a group of diseases sharing common histological features, including an abnormal accumulation of intrasarcoplasmic proteins, the presence of vacuoles and a disorganization of the intermyofibrillar network beginning at the Z-disk. The boundaries of this concept are still uncertain, and whereas six genes (DES, CRYAB, LDB3/ZASP, MYOT, FLNC and BAG3) are now classically considered as responsible for MFM, other entities such as FHL1 myopathy or Hereditary Myopathy with Early Respiratory Failure linked to mutations of titin can now as well be included in this group. The diagnosis of MFM is not always easy; as histological lesions can be focal, and muscle biopsy may be disappointing; this has led to a growing importance of muscle imaging, and the selectivity of muscle involvement has now been described in several disorders. Due to the rarity of these myopathies, if some clinical patterns (such as distal myopathy associated with cardiomyopathy due to desmin mutations) are now well known, surprises remain possible and should lead to systematic testing of the known genes in case of a typical histological presentation. In this paper, we aim at reviewing the data acquired on the six main genes listed above as well as presenting the experience from two French reference centres, Paris and Marseilles.

  3. Ultrastructural mitochondrial alterations in equine myopathies of unknown origin.

    Science.gov (United States)

    Van Driessche, K; Ducatelle, R; Chiers, K; Van Coster, R; van der Kolk, J H; van der Kolk, H

    2015-03-01

    Very few mitochondrial myopathies have been described in horses. To examine the ultrastructure of muscle mitochondria in equine cases of myopathy of unknown origin. Biopsies of vastus lateralis of the Musculus quadriceps femoris were taken predominantly immediately post mortem and processed for transmission electron microscopy. As a result, electron micrographs of 90 horses in total were available for analysis comprising 4 control horses, 16 horses suffering from myopathy and 70 otherwise diseased horses. Following a thorough clinical and laboratory work-up, four out of five patients that did not fit into the usual algorithm to detect known causes of myopathy showed ultrastructural mitochondrial alterations. Small mitochondria with zones with complete disruption of cristae associated with lactic acidemia were detected in a 17-year-old pony mare, extremely long and slender mitochondria with longitudinal cristae in a 5-year-old Quarter horse stallion, a mixture of irregular extremely large mitochondria (measuring 2500 by 800 nm) next to smaller ones in an 8-year-old Hanoverian mare and round mitochondria with only few cristae in a 11-year-old pony gelding. It remains uncertain whether the subsarcolemmal mitochondrial accumulations observed in the fifth patient have any pathological significance. Ultrastructural alterations in mitochondria were detected in at least four horses. To conclude that these are due to mitochondrial dysfuntions, biochemical tests should be performed. The possibility of a mitochondrial myopathy should be included in the differential diagnosis of muscle weakness.

  4. Eulerian formulation of elastic rods

    Science.gov (United States)

    Huynen, Alexandre; Detournay, Emmanuel; Denoël, Vincent

    2016-06-01

    In numerous biological, medical and engineering applications, elastic rods are constrained to deform inside or around tube-like surfaces. To solve efficiently this class of problems, the equations governing the deflection of elastic rods are reformulated within the Eulerian framework of this generic tubular constraint defined as a perfectly stiff normal ringed surface. This reformulation hinges on describing the rod-deformed configuration by means of its relative position with respect to a reference curve, defined as the axis or spine curve of the constraint, and on restating the rod local equilibrium in terms of the curvilinear coordinate parametrizing this curve. Associated with a segmentation strategy, which partitions the global problem into a sequence of rod segments either in continuous contact with the constraint or free of contact (except for their extremities), this re-parametrization not only trivializes the detection of new contacts but also transforms these free boundary problems into classic two-points boundary-value problems and suppresses the isoperimetric constraints resulting from the imposition of the rod position at the extremities of each rod segment.

  5. Status of rod consolidation, 1988

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, W.J.

    1989-01-01

    It is estimated that the spent fuel storage pools at some domestic light-water reactors will run out of space before 2003, the year that the US Department of Energy currently predicts it will have a repository available. Of the methods being studied to alleviate the problem, rod consolidation is one of the leading candidates for achieving more efficient use of existing space in spent fuel storage pools. Rod consolidation involves mechanically removing all the fuel rods from the fuel assembly hardware (i.e., the structural components) and placing the fuel rods in a close-packed array in a canister without space grids. A typical goal of rod consolidation systems is to insert the fuel rods from two fuel assemblies into a canister that has the same exterior dimensions as one standard fuel assembly (i.e., to achieve a consolidation or compaction ratio of 2:1) and to compact the nonfuel-bearing structural components from those two fuel assemblies by a factor of 10 to 20. This report provides an overview of the current status of rod consolidation in the United States and a small amount of information on related activities in other countries. 85 refs., 36 figs., 5 tabs.

  6. Zellweger syndrome and secondary mitochondrial myopathy.

    Science.gov (United States)

    Salpietro, Vincenzo; Phadke, Rahul; Saggar, Anand; Hargreaves, Iain P; Yates, Robert; Fokoloros, Christos; Mankad, Kshitij; Hertecant, Jozef; Ruggieri, Martino; McCormick, David; Kinali, Maria

    2015-04-01

    Defects in peroxisomes such as those associated with Zellweger syndrome (ZS) can influence diverse intracellular metabolic pathways, including mitochondrial functioning. We report on an 8-month-old female infant and a 6-month-old female infant with typical clinical, radiological and laboratory features of Zellweger syndrome; light microscopic and ultrastructural evidence of mitochondrial pathology in their muscle biopsies; and homozygous pathogenic mutations of the PEX16 gene (c.460 + 5G > A) and the PEX 12 gene (c.888_889 del p.Leu297Thrfs*12), respectively. Additionally, mitochondrial respiratory chain enzymology analysis in the first girl showed a mildly low activity in complexes II-III and IV. We also review five children previously reported in the literature with a presumptive diagnosis of ZS and additional mitochondrial findings in their muscle biopsies. In conclusion, this is the first study of patients with a molecularly confirmed peroxisomal disorder with features of a concomitant mitochondrial myopathy and underscores the role of secondary mitochondrial dysfunction in Zellweger syndrome, potentially contributing to the clinical phenotype.

  7. Myopathy in patients with Hashimoto's disease.

    Science.gov (United States)

    Villar, Jaqueline; Finol, Héctor J; Torres, Sonia H; Roschman-González, Antonio

    2015-03-01

    Hashimoto thyroiditis (HT) is an autoimmune disease of the thyroid gland. Patients may present or not a hypothyroid state, and frequently have manifestations of myopathy. The present work was aimed to assess the clinical symptoms and signs of skeletal muscle alterations in HT, describe the muscular pathological changes and relate them to the functional thyroid status and to the autoimmune condition of the patient. Clinical and laboratory studies were performed in ten HT patients and three control subjects (hormonal levels and electromyography). Biopsies from their vastus lateralis of quadriceps femoris muscle were analyzed under light (histochemistry and immunofluorescense) and electron microscopy. All patients showed muscle focal alterations, ranging from moderate to severe atrophy, necrosis, activation of satellite cells, presence of autophagosomes, capillary alterations and macrophage and mast cell infiltration, common to autoimmune diseases. The intensity of clinical signs and symptoms was not related to the morphological muscle findings, the electromyography results, or to the state of the thyroid function. Reactions for immunoglobulin in muscle fibers were positive in 80% of the patients. Fiber type II proportion was increased in all patients, with the exception of those treated with L-thyroxine. In conclusion, autoimmune processes in several of the patients may be associated to the skeletal muscle alterations, independently of the functional state of the thyroid gland; however, fiber II type proportion could have been normalized by L-thyroxine treatment.

  8. Distal vacuolar myopathy in nephropathic cystinosis.

    Science.gov (United States)

    Charnas, L R; Luciano, C A; Dalakas, M; Gilliatt, R W; Bernardini, I; Ishak, K; Cwik, V A; Fraker, D; Brushart, T A; Gahl, W A

    1994-02-01

    Nephropathic cystinosis is a lysosomal storage disorder leading to renal failure by age 10 years. Prolonged patient survival following renal transplantation has allowed the development of previously unknown long-term complications. Muscle involvement has been reported in a single posttransplant cystinosis patient, but the range of clinical, electrophysiologic, and histologic features has not been fully described. Thirteen of 54 post-renal-transplant patients that we examined developed weakness and wasting in the small hand muscles, with or without facial weakness and dysphagia. Tendon reflexes were preserved and sensory examinations were normal. Electrophysiologic studies in 11 affected patients showed normal nerve conduction velocities and preserved sensory action potentials. The voluntary motor units in the affected distal muscles had reduced amplitude and brief duration, confirmed with quantitative electromyography in 4 patients. Biopsy of the severely affected abductor digiti minimi or extensor carpi radialis brevis muscles in 2 patients revealed marked fiber size variability, prominent acid phosphatase-positive vacuoles, and absence of fiber type grouping or inflammatory cells. Crystals of cystine were detected in perimysial cells but not within the muscle cell vacuoles. The muscle cystine content of clinically affected muscles was markedly elevated. We conclude that a distal vacuolar myopathy is a common late complication of untreated nephropathic cystinosis. Although the cause is unclear, the general lysosomal defect in this disease may also affect the lysosomes within muscle fibers.

  9. Muscle MR imaging in tubular aggregate myopathy.

    Directory of Open Access Journals (Sweden)

    Valeria Beltrame

    Full Text Available PURPOSE: To evaluate with Magnetic Resonance (MR the degree of fatty replacement and edematous involvement in skeletal muscles in patients with Tubular Aggregate Myopathy (TAM. To asses the inter-observer agreement in evaluating muscle involvement and the symmetry index of fatty replacement. MATERIALS AND METHODS: 13 patients were evaluated by MR to ascertain the degree of fatty replacement (T1W sequences according to Mercuri's scale, and edema score (STIR sequences according to extent and site. RESULTS: Fatty replacement mainly affects the posterior superficial compartment of the leg; the anterior compartment is generally spared. Edema was generally poor and almost only in the superficial compartment of the leg. The inter-observer agreement is very good with a Krippendorff's coefficient >0.9. Data show a total symmetry in the muscular replacement (McNemar-Bowker test with p = 1. CONCLUSIONS: MR reveals characteristic muscular involvement, and is a reproducible technique for evaluation of TAM. There may also be a characteristic involvement of the long and short heads of the biceps femoris. It is useful for aimed biopsies, diagnostic hypotheses and evaluation of disease progression.

  10. Antiangiogenic VEGF Isoform in Inflammatory Myopathies

    Directory of Open Access Journals (Sweden)

    Nila Volpi

    2013-01-01

    Full Text Available Objective. To investigate expression of vascular endothelial growth factor (VEGF antiangiogenic isoform A-165b on human muscle in idiopathic inflammatory myopathies (IIM and to compare distribution of angiogenic/antiangiogenic VEGFs, as isoforms shifts are described in other autoimmune disorders. Subjects and Methods. We analyzed VEGF-A165b and VEGF-A by western blot and immunohistochemistry on skeletal muscle biopsies from 21 patients affected with IIM (polymyositis, dermatomyositis, and inclusion body myositis and 6 control muscle samples. TGF-β, a prominent VEGF inductor, was analogously evaluated. Intergroup differences of western blot bands density were statistically examined. Endomysial vascularization, inflammatory score, and muscle regeneration, as pathological parameters of IIM, were quantitatively determined and their levels were confronted with VEGF expression. Results. VEGF-A165b was significantly upregulated in IIM, as well as TGF-β. VEGF-A was diffusely expressed on unaffected myofibers, whereas regenerating/atrophic myofibres strongly reacted for both VEGF-A isoforms. Most inflammatory cells and endomysial vessels expressed both isoforms. VEGF-A165b levels were in positive correlation to inflammatory score, endomysial vascularization, and TGF-β. Conclusions. Our findings indicate skeletal muscle expression of antiangiogenic VEGF-A165b and preferential upregulation in IIM, suggesting that modulation of VEGF-A isoforms may occur in myositides.

  11. A Case Report of Inflammatory Myopathy and Sideroblastic Anemia

    Directory of Open Access Journals (Sweden)

    F Binesh

    2007-01-01

    Full Text Available Mitochondrial myopathy, lactic acidosis, and siderobastic anemia (MLA SA syndrome is one of the newly reported mitochondrial diseases, seven cases of which have been reported. We report a child with inflammatory myopathy, sideroblastic anemia and lactic acidosis .The patient is a 8.5 year old boy with normal cognitive function suffering from chronic progressive weakness in lower extremities, inability to walk since four months and pallor. In paraclinical evaluation, sideroblastic anemia, mild lactic acidosis and elevated muscle enzymes were seen. Inflammatory myopathy (myositis in muscle biopsy was detected as well .The patient was administered oral prednisolone, folic acid, B6 and underwent regular physiotherapy. He ambulated after four months and resumed education and schooling.

  12. [Inflammatory myopathy with initial respiratory muscles involvement and rheumatoid arthritis].

    Science.gov (United States)

    Hunter, Martín; Telias, Irene; Collado, Victoria; Sarano, Judith; Alvarez, Clarisa; Suárez, Juan Pablo

    2014-01-01

    Inflammatory myopathies comprise a heterogeneous group of subacute, chronic and sometimes acute acquired muscle diseases. The most common inflammatory myopathies seen in practice can be separated into four distinct subsets: polymyositis, dermatomyositis, necrotizing autoimmune myositis and inclusion body myositis. These disorders present as proximal and symmetric muscle weakness but rarely respiratory muscles may also be affected. We report the case of a 39 year-old female with inflammatory myopathy with acute respiratory failure due to alveolar hypoventilation secondary to respiratory muscle dysfunction that required mechanical ventilation. The treatment with steroids, methotrexate and intravenous immune globulin was successful as well as the implementation of non-invasive ventilation as an alternative to endotracheal intubation.

  13. An unusual case of glipizide-induced proximal myopathy

    Directory of Open Access Journals (Sweden)

    Saibal Das

    2016-01-01

    Full Text Available This case report outlines a very rare case of glipizide-induced severe proximal myopathy in a 61-year-old diabetic man. After taking 10 mg glipizide for 5 months, diabetes was well controlled but the patient presented with progressive proximal muscle weakness in all the four limbs. Clinical examination and relevant investigations suggested it to be a case of proximal myopathy and might be drug induced. De-challenge was done and was treated resulting in reversal of the diseased state. After 3 more months, controlled re-challenge was done and there was recurrence of proximal muscle weakness. There were no evidences of any other possible metabolic, infective, organic or other pathologic causes giving rise to that condition and Naranjo adverse drug reaction probability scale suggested that it was "probable" that glipizide was responsible for the development of myopathy in this patient.

  14. Inflammatory myopathy as the initial presentation of cryoglobulinaemic vasculitis.

    Science.gov (United States)

    Rodríguez-Pérez, Noelia; Rodríguez-Navedo, Yerania; Font, Yvonne M; Vilá, Luis M

    2013-06-03

    Cryoglobulinaemic vasculitis is characterised by immunoglobulin deposition at low temperatures. The most common manifestations are cutaneous involvement, arthralgias, Raynaud's phenomenon, peripheral neuropathy and renal disease. Myopathy is unusual and only a few cases have been reported. Here, we present a 31-year-old woman who developed progressive muscle weakness involving upper and lower extremities, dysphagia, paraesthesias and palpable purpura. Diagnostic studies revealed elevated creatine kinase, diffuse myopathic and sensorimotor axonal neuropathy on electromyography and nerve conduction studies, and inflammatory myopathy on muscle biospsy. Cryoglobulin levels were elevated on two occasions. She responded favourably to cyclophosphamide and high-dose corticosteroids. Cyclophosphamide was continued for 1 year followed by methotrexate. Prednisone was gradually tapered and discontinued 1 year later. She remained in clinical remission after 4 years of follow-up. This case suggests that cryoglobulinaemia should be considered in the differential diagnosis of a patient presenting with inflammatory myopathy.

  15. Adult-onset Nemaline Myopathy Coexisting With Myasthenia Gravis

    Science.gov (United States)

    Cao, Lingling; Wang, Yanling; Liu, Xiaofeng; Hu, Yanxia; Li, Nianchun; Qiu, Guoping; Luo, Yun; Li, Weidong

    2016-01-01

    Abstract Myasthenia gravis (MG) is an autoimmune neuromuscular junction disorder which is characterized by fluctuating muscle fatigue. However, the association of MG with nemaline myopathy is rarely reported. Here we report a case of MG coexisting with adult-onset nemaline myopathy. A 55-year-old man endured fluctuating muscle weakness with positive acetylcholine receptor and titin antibodies. After the patient was administrated cholinergic drugs and immunosuppression, the muscle weakness of the patient had mildly been alleviated. Electromyography showed a progressive decrement in the amplitude of muscle action potential at low frequency. Muscle biopsy showed numerous nemalines in the muscle fibers. This is the first reported case of nemalines present in the muscle fibers of adult patient with MG. The pathogenesis of nemaline may be related to titin antibody in adult-onset nemaline myopathy with MG. PMID:26825889

  16. Topological mixing with ghost rods

    Science.gov (United States)

    Gouillart, Emmanuelle; Thiffeault, Jean-Luc; Finn, Matthew D.

    2006-03-01

    Topological chaos relies on the periodic motion of obstacles in a two-dimensional flow in order to form nontrivial braids. This motion generates exponential stretching of material lines, and hence efficient mixing. Boyland, Aref, and Stremler [J. Fluid Mech. 403, 277 (2000)] have studied a specific periodic motion of rods that exhibits topological chaos in a viscous fluid. We show that it is possible to extend their work to cases where the motion of the stirring rods is topologically trivial by considering the dynamics of special periodic points that we call “ghost rods”, because they play a similar role to stirring rods. The ghost rods framework provides a new technique for quantifying chaos and gives insight into the mechanisms that produce chaos and mixing. Numerical simulations for Stokes flow support our results.

  17. Dynamin 2 mutations cause sporadic centronuclear myopathy with neonatal onset.

    Science.gov (United States)

    Bitoun, Marc; Bevilacqua, Jorge A; Prudhon, Bernard; Maugenre, Svetlana; Taratuto, Ana Lia; Monges, Soledad; Lubieniecki, Fabiana; Cances, Claude; Uro-Coste, Emmanuelle; Mayer, Michèle; Fardeau, Michel; Romero, Norma B; Guicheney, Pascale

    2007-12-01

    We report four heterozygous dynamin 2 (DNM2) mutations in five centronuclear myopathy patients aged 1 to 15 years. They all presented with neonatal hypotonia with weak suckling. Thereafter, their phenotype progressively improved. All patients demonstrated muscle weakness prominent in the lower limbs, and most of them also presented with facial weakness, open mouth, arched palate, ptosis, and ophthalmoparesis. Electrophysiology showed only myopathic changes, and muscle biopsies showed central nuclei and type 1 fiber hypotrophy and predominance. Our results expand the phenotypic spectrum of dynamin 2-related centronuclear myopathy from the classic mild form to the more severe neonatal phenotype.

  18. Hoffmann's disease: MR imaging of hypothyroid myopathy

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Jeewon; Ahn, Kyung-Sik; Kang, Chang Ho [Korea University Anam Hospital, Korea University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Hong, Suk-Joo [Korea University Guro Hospital, Korea University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Kim, Beak Hyun [Korea University Ansan Hospital, Korea University College of Medicine, Department of Radiology, Gyeonggi-do (Korea, Republic of)

    2015-11-15

    Hoffmann's syndrome is a hypothyroid myopathy presenting as muscle stiffness and hypertrophy. It is a rare complication of hypothyroidism. MRI features of this syndrome have seldom been described in the literature. We present a case of Hoffmann's syndrome in a 34-year-old man who underwent lower extremity contrast-enhanced MRI. MRI can demonstrate the hypertrophic configuration, T2 hyperintensity, and enhancement of the involved muscles in Hoffmann's syndrome. Along with clinical, laboratory, and electromyography findings, MRI may be helpful in distinguishing between inflammatory myopathy, myonecrosis, subacute muscle denervation, and infectious myositis. (orig.)

  19. Renal Involvement in Idiopathic Inflammatory Myopathies.

    Science.gov (United States)

    Cucchiari, David; Angelini, Claudio

    2017-02-01

    Renal involvement in idiopathic inflammatory myopathies is not as uncommon as was previously thought, as it develops in about one fifth of patients. Clinical presentation includes either acute kidney injury or chronic glomerulonephritis. The former usually develops abruptly during acute phases of rhabdomyolysis: in this case, kidney injury is caused by the toxic effects that myoglobinuria has on the kidney tubules, including cast formation and iron-induced oxidative stress and the development of a third space into the injured muscles. The latter instead has an autoimmune nature, a pleomorphic histological picture, and a more indolent course, with the exception of crescentic glomerulonephritis. Accurate diagnosis and management is crucial for these patients, as timely evaluation and treatment can prevent most of the complications. In the setting of rhabdomyolysis-induced acute kidney injury, the necessity of dialysis can be avoided through aggressive hydration and alkalinization, in order to force diuresis and avoid acidosis and hyperkalemia. In immune-mediated glomerulonephritis, renal biopsy is of undoubtedly value in the diagnostic process and can add prognostic and therapeutic information. In these forms, the development of chronic kidney disease can be prevented or at least delayed by the institution or modification of immunosuppressive treatment. Moreover, the use of drugs that inhibit the renin-angiotensin-aldosterone system and some lifestyle modifications, such as smoking cessation, weight loss, and salt restriction have also value in reducing proteinuria and the progression of kidney damage. In this review, we have summarized the currently available evidence and the different case series in an attempt to provide the readers with the most complete and practical notions that are needed to handle these delicate patients.

  20. DNAJB6 myopathies: Focused review on an emerging and expanding group of myopathies

    Directory of Open Access Journals (Sweden)

    Alessandra Ruggieri

    2016-09-01

    Full Text Available Mutations in the DNAJB6 gene have been associated with the autosomal dominant limb girdle muscular dystrophy type 1D (LGMD1D, a disorder characterized by abnormal protein aggregates and rimmed vacuoles in muscle fibers. DNAJB6 is a ubiquitously expressed Hsp40 co-chaperone characterized by a J domain that specifies Hsp70 functions in the cellular environment. DNAJB6 is also a potent inhibitor of expanded polyglutamine (polyQ aggregation preventing aggregate toxicity in cells. In DNAJB6-mutated patients this anti-aggregation property is significantly reduced, albeit not completely lost. To elucidate the pathogenetic mechanisms underlying the DNAJB6-related myopathy, animal models have been created showing that, indeed, conditional muscular expression of a DNAJB6 mutant in the mouse causes a LGMD1D myofibrillary muscle tissue phenotype. Both mutations and phenotypes reported until recently were rather homogeneous, being exclusively missense mutations of a few amino acids of the protein G/F domain, and with a phenotype characterized by adult-onset slowly progressive muscular dystrophy predominantly affecting proximal muscles. Lately, several novel mutations and new phenotypes of DNAJB6 have been described. These mutations once more affect the G/F domain of DNAJB6 with missense changes and a splice site mutation; and the phenotypes include childhood onset and distal involvement of muscles, or childhood-onset LGMD1D with loss of ambulation in early adulthood and respiratory involvement. Thus, the spectrum of DNAJB6-related phenotypes is widening. Although our knowledge about the role of DNAJB6 in the pathogenesis of muscle diseases has made great progression, several questions remain unsolved, including why a ubiquitous protein affects only, or predominantly, skeletal muscle; why only the G/F domain is involved; and what is the possible role of the DNAJB6a isoform. Clarification of these issues will provide clues to implement possible therapeutic

  1. Occurrence of disabling myopathy secondary to hypovitaminosis D

    Directory of Open Access Journals (Sweden)

    Utkarsha Chandrashekhar Narone

    2013-04-01

    Full Text Available We report a case of severe proximal muscle weakness caused by vitamin D deficiency. Hypovitaminosis D myopathy (HDM is often misdiagnosed, as the symptoms are non-specific. However, the disease is easily treatable and complete recovery is possible if diagnosed on time.

  2. Eosinophilic fasciitis in a child mimicking a myopathy.

    NARCIS (Netherlands)

    Pillen, S.; Engelen, B.G.M. van; Hoogen, F.H.J. van den; Fiselier, T.J.W.; Vossen, P. van der; Drost, G.

    2006-01-01

    A 14-year-old boy was suspected of having a myopathy with joint contractures. He presented with progressive painless joint contractures of his right wrist and fingers, and reduced muscle strength of his right arm, without obvious skin changes. Laboratory investigation showed a normal CK,

  3. A possible new inherited myopathy in a young Labrador retriever

    OpenAIRE

    Cosford, Kevin L.; Taylor, Susan M.; Thompson, Logan; Shelton, G. Diane

    2008-01-01

    A 5-month-old, male, Labrador retriever was evaluated for progressive weakness and muscle atrophy. Histologic evaluation of fresh frozen muscle revealed distinct cytoarchitectural changes and central mitochondrial accumulations indistinguishable from those found in the inherited myopathy described in Great Danes. Multiple male littermates and half-siblings were similarly affected.

  4. Rituximab treatment in patients with refractory inflammatory myopathies

    NARCIS (Netherlands)

    Mahler, E.A.; Blom, M.; Voermans, N.C.; Engelen, B.G. van; Riel, P.L. van; Vonk, M.C.

    2011-01-01

    Objective. To assess the efficacy of rituximab on disease activity and muscle strength in patients with inflammatory myopathies refractory to conventional therapy. Methods. Thirteen patients were treated with rituximab 1000 mg i.v., twice, with a 2-week interval and followed for a median of 27 month

  5. Treatment of the inflammatory myopathies: update and practical recommendations.

    NARCIS (Netherlands)

    Hengstman, G.J.D.; Hoogen, F.H.J. van den; Engelen, B.G.M. van

    2009-01-01

    BACKGROUND: The inflammatory myopathies are a heterogeneous group of diseases including dermatomyositis, polymyositis, and inclusion body myositis. Clinical trials in myositis are rare, making it difficult to make clear recommendations on the treatment of these rare disorders. OBJECTIVE: To give an

  6. Muscle slowness in a family with nemaline myopathy.

    NARCIS (Netherlands)

    Gommans, I.M.P.; Gerrits, K.H.; Haan, A. de; Engelen, B.G.M. van

    2006-01-01

    All patients of a large family with nemaline myopathy complained of slowness in movement. We confirmed this clinical complaint physiologically by showing lower contractile speed in quadriceps muscle. Electrically evoked contractions of the quadriceps muscle elicited a lower rate of relaxation and a

  7. Zidovudine-induced mitochondrial myopathy is associated with muscle carnitine deficiency and lipid storage.

    Science.gov (United States)

    Dalakas, M C; Leon-Monzon, M E; Bernardini, I; Gahl, W A; Jay, C A

    1994-04-01

    The use of zidovudine (AZT) for the treatment of acquired immunodeficiency syndrome (AIDS) induces a DNA-depleting mitochondrial myopathy, which is histologically characterized by the presence of muscle fibers with "ragged-red"-like features, red-rimmed or empty cracks, granular degeneration, and rods (AZT fibers). Because dysfunctioning muscle mitochondria may lead to defects of beta-oxidation of fatty acids, we examined the degree of neutral fat accumulation and muscle carnitine levels in the muscle biopsy specimens from 21 patients with AZT-induced myopathic symptoms of varying severity. Six patients with no AZT fibers had normal endomyofibrillar lipid deposits and muscle carnitine levels; 7 patients with fewer than 5 AZT fibers per field had a mild (+) to moderate (++) increase in lipid droplets, and reduced muscle carnitine levels (3 patients); and 8 patients with more than 5 AZT fibers had severe muscle changes, a ++ to marked ( ) increase in lipid droplets, and reduced muscle carnitine levels (6 patients). Serial sections showed lipid globules often within "cracks" or vacuoles of the abnormal muscle fibers. We conclude that the muscle mitochondrial impairment caused by AZT results in (1) accumulation of lipid within the muscle fibers owing to poor utilization of long-chain fatty acids, (2) reduction of muscle carnitine levels probably due to decreased carnitine uptake by the muscle, and (3) depletion of energy stores within the muscle fibers. The findings may have potential therapeutic implications in the treatment of AZT-induced myopathic symptoms using oral carnitine supplementation.

  8. The Third ATLAS ROD Workshop

    CERN Multimedia

    Poggioli, L.

    A new-style Workshop After two successful ATLAS ROD Workshops dedicated to the ROD hardware and held at the Geneva University in 1998 and in 2000, a new style Workshop took place at LAPP in Annecy on November 14-15, 2002. This time the Workshop was fully dedicated to the ROD-TDAQ integration and software in view of the near future integration activities of the final RODs for the detector assembly and commissioning. More precisely, the aim of this workshop was to get from the sub-detectors the parameters needed for T-DAQ, as well as status and plans from ROD builders. On the other hand, what was decided and assumed had to be stated (like EB decisions and URDs), and also support plans. The Workshop gathered about 70 participants from all ATLAS sub-detectors and the T-DAQ community. The quite dense agenda allowed nevertheless for many lively discussions, and for a dinner in the old town of Annecy. The Sessions The Workshop was organized in five main sessions: Assumptions and recommendations Sub-de...

  9. Clinical, immunopathologic, and therapeutic considerations of inflammatory myopathies.

    Science.gov (United States)

    Dalakas, M C

    1992-10-01

    The inflammatory myopathies encompass a group of heterogenous muscle diseases which have in common an acquired myopathy with histological signs of endomysial inflammation. We present evidence based on recently emerged clinical, histologic, immunopathologic, demographic and therapeutic observations that these myopathies comprise three major and distinct groups: polymyositis (PM), dermatomyositis (DM), and inclusion-body myositis (IBM). Immune-mediated mechanisms characteristic for each group appear to play a primary role in the pathogenesis of these diseases. In DM there is an intramuscular microangiopathy mediated by the C5b-9 membranolytic attack complex, leading sequentially to loss of capillaries, muscle ischemia, muscle fiber necrosis and perifascicular atrophy. In contrast, in PM and IBM the muscle fiber injury is initiated by sensitized CD8+ cytotoxic T cells that recognize MHC-I restricted muscle antigens, leading to phagocytosis and fiber necrosis. Among the viruses implicated in the cause of inflammatory myopathies, only the retroviruses, HIV, HTLV-1 and simian retroviruses, have been convincingly associated with PM. Retroviruses, therefore, appear to be the leading group of viruses capable of triggering these diseases. The treatment of inflammatory myopathies has been largely empirical. A detailed therapeutic plan based on our experience with a large number of patients is presented. Patients with bona fide PM or DM respond to steroids to some degree and for some period of time. In contrast, patients with IBM do not respond to any therapy and the disease should be suspected when a patient with presumed PM has failed treatment. Methotrexate and cyclophosphamide are disappointing. Cyclosporine and Azathioprine are commonly used but they are of uncertain benefit. Plasmapheresis is ineffective. High-dose intravenous immunoglobulin is a promising new therapeutic modality.

  10. REV-ERB and ROR: therapeutic targets for treating myopathies

    Science.gov (United States)

    Welch, Ryan D.; Flaveny, Colin A.

    2017-08-01

    Muscle is primarily known for its mechanical roles in locomotion, maintenance of posture, and regulation of cardiac and respiratory function. There are numerous medical conditions that adversely affect muscle, myopathies that disrupt muscle development, regeneration and protein turnover to detrimental effect. Skeletal muscle is also a vital secretory organ that regulates thermogenesis, inflammatory signaling and directs context specific global metabolic changes in energy substrate preference on a daily basis. Myopathies differ in the causative factors that drive them but share common features including severe reduction in quality of life and significantly increased mortality all due irrefutably to the loss of muscle mass. Thus far clinically viable approaches for preserving muscle proteins and stimulating new muscle growth without unwanted side effects or limited efficacy has been elusive. Over the last few decades, evidence has emerged through in vitro and in vivo studies that suggest the nuclear receptors REV-ERB and ROR might modulate pathways involved in myogenesis and mitochondrial biogenesis. Hinting that REV-ERB and ROR might be targeted to treat myopathies. However there is still a need for substantial investigation into the roles of these nuclear receptors in in vivo rodent models of degenerative muscle diseases and acute injury. Although exciting, REV-ERB and ROR have somewhat confounding roles in muscle physiology and therefore more studies utilizing in vivo models of skeletal muscle myopathies are needed. In this review we highlight the molecular forces driving some of the major degenerative muscular diseases and showcase two promising molecular targets that may have the potential to treat myopathies: ROR and REV-ERB.

  11. Topological Optimization of Rod Mixers

    Science.gov (United States)

    Finn, Matthew D.; Thiffeault, Jean-Luc

    2006-11-01

    Stirring of fluid with moving rods is necessary in many practical applications to achieve homogeneity. These rods are topological obstacles that force stretching of fluid elements. The resulting stretching and folding is commonly observed as filaments and striations, and is a precursor to mixing. In a space-time diagram, the trajectories of the rods form a braid [1], and the properties of this braid impose a minimal complexity in the flow. We discuss how optimal mixing protocols can be obtained by a judicious choice of braid, and how these protocols can be implemented using simple gearing [2].[12pt] [1] P. L. Boyland, H. Aref, and M. A. Stremler, JFM 403, 277 (2000).[8pt] [2] J.-L. Thiffeault and M. D. Finn, http://arxiv.org/nlin/0603003

  12. Advanced gray rod control assembly

    Energy Technology Data Exchange (ETDEWEB)

    Drudy, Keith J; Carlson, William R; Conner, Michael E; Goldenfield, Mark; Hone, Michael J; Long, Jr., Carroll J; Parkinson, Jerod; Pomirleanu, Radu O

    2013-09-17

    An advanced gray rod control assembly (GRCA) for a nuclear reactor. The GRCA provides controlled insertion of gray rod assemblies into the reactor, thereby controlling the rate of power produced by the reactor and providing reactivity control at full power. Each gray rod assembly includes an elongated tubular member, a primary neutron-absorber disposed within the tubular member said neutron-absorber comprising an absorber material, preferably tungsten, having a 2200 m/s neutron absorption microscopic capture cross-section of from 10 to 30 barns. An internal support tube can be positioned between the primary absorber and the tubular member as a secondary absorber to enhance neutron absorption, absorber depletion, assembly weight, and assembly heat transfer characteristics.

  13. 刺激大鼠海马后PAG、NRM和脊髓背角5-HT的变化%Change of PAG, NRM and dosal horn 5-HT after stimulating hippocampus in rats

    Institute of Scientific and Technical Information of China (English)

    高艳; 吴爱群; 张静; 方智慧

    2002-01-01

    目的:探讨刺激大鼠海马后导水管周围灰质(Periaqueductal central gray matter,PAG)、中缝大核(Nueleus raphesmagnus,NRM)和脊髓背角5-HT的变化,分析海马在镇痛中的作用机制.方法:健康成年Wistar大鼠40只,随机分为4组.A组:正常对照组;B组:疼痛组;C组:谷氨酸钠组;D组:生理盐水组.四组动物均于2小时后处死,常规灌注冰冻连续切片,采用SABC免疫组化和计算机图像分析技术,检测PAG、NRM5-HT神经元阳性细胞个数及光密度及脊髓背角5-HT阳性纤维及终未的积分光密度等均值.结果:疼痛刺激后,PAG、NRM、脊髓背角内5-HT水平较正常显著增高(P<0.05),谷氨酸钠组则较疼痛组进一步增加.结论:海马兴奋后,激活内源性镇痛系统,使5-HT大量释放,参与镇痛.

  14. Polymyositis without Beneficial Response to Steroid Therapy:Should Miyoshi Myopathy be a Differential Diagnosis?

    OpenAIRE

    Scalco,Renata Siciliani; Lorenzoni,Paulo José; David S Lynch; Martins, William Alves; Jungbluth, Heinz; Quinlivan, Ros; Becker, Jefferson; Houlden, Henry

    2017-01-01

    Patient: Male, 16 Final Diagnosis: Miyoshi myopathy Symptoms: HyperCKemia • myalgia • weakness Medication: — Clinical Procedure: — Specialty: Neurology Objective: Rare disease Background: Miyoshi myopathy (MM) is an autosomal-recessive muscle disorder caused by mutations in the DYSF gene. Clinical features and histopathological changes in dysferlinopathies may mimic inflammatory myopathies and a high degree of clinical suspicion is required to guide the genetic investigation. Case Report: We ...

  15. Control rods in LMFBRs: a physics assessment

    Energy Technology Data Exchange (ETDEWEB)

    McFarlane, H.F.; Collins, P.J.

    1982-08-01

    This physics assessment is based on roughly 300 control rod worth measurements in ZPPR from 1972 to 1981. All ZPPR assemblies simulated mixed-oxide LMFBRs, representing sizes of 350, 700, and 900 MWe. Control rod worth measurements included single rods, various combinations of rods, and Ta and Eu rods. Additional measurements studied variations in B/sub 4/C enrichment, rod interaction effects, variations in rod geometry, neutron streaming in sodium-filled channels, and axial worth profiles. Analyses were done with design-equivalent methods, using ENDF/B Version IV data. Some computations for the sensitivities to approximations in the methods have been included. Comparisons of these analyses with the experiments have allowed the status of control rod physics in the US to be clearly defined.

  16. A CASE REPORT OF AMIODARONE INDUCED MYOPATHY IN A PATIENT OF VENTRICULAR ARRHYTHMIA

    Directory of Open Access Journals (Sweden)

    Rajat

    2014-09-01

    Full Text Available Myopathies are disorders with structural changes or functional impairment of muscle. Voluntary muscle is subject to a range of hereditary and acquired disorders affecting either its structure, or the biochemical processes which convert the chemical energy derived from cell metabolism into mechanical energy in a controlled manner. These disorders present in a limited number of ways, most commonly a symmetrical weakness of the large, power-generating proximal muscles. Drug induced myopathy comes under acquired causes of myopathy. Here we shall be presenting a case of Amiodarone induced myopathy in a 40 years old male patient of ventricular arrhythmia. We shall also discuss the further management of this presentation.

  17. Solid-state-laser-rod holder

    Science.gov (United States)

    Gettemy, D.J.; Barnes, N.P.; Griggs, J.E.

    1981-08-11

    The disclosure relates to a solid state laser rod holder comprising Invar, copper tubing, and epoxy joints. Materials and coefficients of expansion of the components of the holder combine with the rod to produce a joint which will give before the rod itself will. The rod may be lased at about 70 to 80/sup 0/K and returned from such a temperature to room temperature repeatedly without its or the holder's destruction.

  18. Lamellar magnetism and exchange bias in billion-year-old metamorphic titanohematite with nanoscale ilmenite exsolution lamellae: II. Exchange-bias at 5 K after field-free cooling of NRM and after cooling in a +5 T field

    Science.gov (United States)

    Robinson, Peter; McEnroe, Suzanne A.; Jackson, M.

    2016-11-01

    This is the second of three papers investigating properties of titanohematite-bearing quartzo-feldspathic rocks that create a significant remanent magnetic anomaly in the Modum District, South Norway. The first paper provided initial magnetic results, mineralogical characterization and evidence for the presence of lamellar magnetism. In this paper, knowledge of lamellar magnetic properties is explored through experiments where ilmenite lamellae were magnetized below 57 K, and interact magnetically along interfaces with the titanohematite host. Samples with known NRM directions were placed in specific orientations in an MPMS then cooled in zero field to 5 K, where hysteresis loops were measured in fields up to 5 Tesla. This assured that results were ultimately related to the natural lamellar magnetism produced during cooling ˜ 1 billion years ago. In a second set of experiments the same oriented samples, were subjected to a +5 Tesla field then field cooled to 5 K before hysteresis experiments. The first experiments consistently produced asymmetric shifted hysteresis loops with two loop separations, one in a positive field and one in a negative field. Without exception, when the NRM was oriented toward the negative field end of the MPMS, the bimodal loop showed a dominant loop separation in a positive field. By contrast, when the NRM was oriented toward the positive field end of the MPMS, the bimodal loop showed a dominant loop separation in a negative field. Both observations are consistent with antiferromagnetic coupling between the hard magnetization of ilmenite and the more easily shifted lamellar magnetism of the hematite. The bimodal nature of the loops indicates that the NRMs are vector sums of natural lamellar moments, which are oriented both positively and negatively, and that these opposite moments control the orientations of ilmenite magnetizations when cooling through 57 K. Here, extreme exchange biases up to 1.68 Tesla were measured. The second set of

  19. Lamellar magnetism and exchange bias in billion-year-old metamorphic titanohematite with nanoscale ilmenite exsolution lamellae - II: exchange-bias at 5 K after field-free cooling of NRM and after cooling in a +5 T field

    Science.gov (United States)

    Robinson, Peter; McEnroe, Suzanne A.; Jackson, Mike

    2017-02-01

    This is the second of three papers investigating properties of titanohematite-bearing quartzo-feldspathic rocks that create a significant remanent magnetic anomaly in the Modum District, South Norway. The first paper provided initial magnetic results, mineralogical characterization and evidence for the presence of lamellar magnetism. In this paper, knowledge of lamellar magnetic properties is explored through experiments where ilmenite lamellae were magnetized below 57 K, and interact magnetically along interfaces with the titanohematite host. Samples with known NRM directions were placed in specific orientations in an MPMS then cooled in zero field to 5 K, where hysteresis loops were measured in fields up to 5 Tesla. This assured that results were ultimately related to the natural lamellar magnetism produced during cooling ˜1 billion years ago. In a second set of experiments the same oriented samples, were subjected to a +5 Tesla (T) field then field cooled to 5 K before hysteresis experiments. The first experiments consistently produced asymmetric shifted hysteresis loops with two loop separations, one in a positive field and one in a negative field. Without exception, when the NRM was oriented toward the negative field end of the MPMS, the bimodal loop showed a dominant loop separation in a positive field. By contrast, when the NRM was oriented toward the positive field end of the MPMS, the bimodal loop showed a dominant loop separation in a negative field. Both observations are consistent with antiferromagnetic coupling between the hard magnetization of ilmenite and the more easily shifted lamellar magnetism of the hematite. The bimodal nature of the loops indicates that the NRMs are vector sums of natural lamellar moments, which are oriented both positively and negatively, and that these opposite moments control the orientations of ilmenite magnetizations when cooling through 57 K. Here, extreme exchange biases up to 1.68 T were measured. The second set of

  20. Chronic primary intestinal pseudo-obstruction from visceral myopathy

    Directory of Open Access Journals (Sweden)

    M. T. Muñoz-Yagüe

    Full Text Available Chronic intestinal pseudo-obstruction is an uncommon syndrome characterized by relapsing episodes suggesting intestinal obstruction during which no mechanical causes are identified to account for symptoms. Etiologic factors may be manifold. Among them a number of neurologic conditions, gastrointestinal smooth muscle myopathies, endocrino-metabolic and autoimmune diseases, and the use of selected drugs stand out. We report a case of chronic intestinal pseudo-obstruction originating in a sporadic, primary intestinal myopathy that corresponds to no type thus far described. A histological study of the intestinal wall showed disrupted muscle bundles and the presence of interstitial edema. Myocytes had severe degenerative changes, and no alterations were seen in submucosal and myenteric plexus neurons. The activity of enzyme complexes in the mitochondrial respiratory chain, and of thymidine phosphorylase was normal. No mitochondrial DNA changes were seen.

  1. Chronic primary intestinal pseudo-obstruction from visceral myopathy.

    Science.gov (United States)

    Muñoz-Yagüe, M T; Marín, J C; Colina, F; Ibarrola, C; López-Alonso, G; Martín, M A; Solís-Herruzo, J A

    2006-04-01

    Chronic intestinal pseudo-obstruction is an uncommon syndrome characterized by relapsing episodes suggesting intestinal obstruction during which no mechanical causes are identified to account for symptoms. Etiologic factors may be manifold. Among them a number of neurologic conditions, gastrointestinal smooth muscle myopathies, endocrino-metabolic and autoimmune diseases, and the use of selected drugs stand out. We report a case of chronic intestinal pseudo-obstruction originating in a sporadic, primary intestinal myopathy that corresponds to no type thus far described. A histological study of the intestinal wall showed disrupted muscle bundles and the presence of interstitial edema. Myocytes had severe degenerative changes, and no alterations were seen in submucosal and myenteric plexus neurons. The activity of enzyme complexes in the mitochondrial respiratory chain, and of thymidine phosphorylase was normal. No mitochondrial DNA changes were seen.

  2. An unusual myopathy: speckled muscle fibers due to enlarged mitochondria.

    Science.gov (United States)

    Jeffree, Rosalind L; Wills, Edward J; Harper, Clive

    2007-07-01

    We report a 52-year-old woman who presented with a 6-month history of proximal muscle weakness, elevated serum creatine kinase, and myopathic pattern on electromyography (EMG). Histology of the muscle shows a speckled pattern due to clustering of enlarged mitochondria. The pathology resembles that of selenium deficiency. The patient was found to have borderline low serum selenium and also low vitamin D and thyroid-stimulating hormone. The cause of this unusual myopathy is probably multifactorial. This case is important because the unusual pathological picture represents a potentially treatable myopathy. In addition, we hope that publication of the complex clinical and biochemical abnormalities of this case, in conjunction with other case reports, may facilitate future elucidation of muscle mitochondrial function and dysfunction.

  3. Sarcoidosis Presenting as Löfgren’s Syndrome with Myopathy

    Directory of Open Access Journals (Sweden)

    Şenol Kobak

    2013-01-01

    Full Text Available A 34-year-old female patient, who had proximal muscle weakness for 8 months, presented with erythema nodosum lesions on the pretibial region in addition to pain, swelling, and movement restriction in both ankles for the last one month. Thoracic CT demonstrated hilar and mediastinal lymphadenopathy. She underwent mediastinoscopic lymph node biopsy; biopsy result was consistent with noncaseating granuloma. Serum angiotensin converting enzyme level and muscle enzymes have been elevated. Muscular MRI and EMG findings were consistent with myositis. Muscle biopsy was done, and myopathy was found. The patient was diagnosed with sarcoidosis, Löfgren's syndrome, and sarcoid myopathy. The patient displayed remarkable clinical and radiological regression after 6-month corticosteroid and MTX therapy.

  4. Molecular basis of infantile reversible cytochrome c oxidase deficiency myopathy.

    Science.gov (United States)

    Horvath, Rita; Kemp, John P; Tuppen, Helen A L; Hudson, Gavin; Oldfors, Anders; Marie, Suely K N; Moslemi, Ali-Reza; Servidei, Serenella; Holme, Elisabeth; Shanske, Sara; Kollberg, Gittan; Jayakar, Parul; Pyle, Angela; Marks, Harold M; Holinski-Feder, Elke; Scavina, Mena; Walter, Maggie C; Coku, Jorida; Günther-Scholz, Andrea; Smith, Paul M; McFarland, Robert; Chrzanowska-Lightowlers, Zofia M A; Lightowlers, Robert N; Hirano, Michio; Lochmüller, Hanns; Taylor, Robert W; Chinnery, Patrick F; Tulinius, Mar; DiMauro, Salvatore

    2009-11-01

    Childhood-onset mitochondrial encephalomyopathies are usually severe, relentlessly progressive conditions that have a fatal outcome. However, a puzzling infantile disorder, long known as 'benign cytochrome c oxidase deficiency myopathy' is an exception because it shows spontaneous recovery if infants survive the first months of life. Current investigations cannot distinguish those with a good prognosis from those with terminal disease, making it very difficult to decide when to continue intensive supportive care. Here we define the principal molecular basis of the disorder by identifying a maternally inherited, homoplasmic m.14674T>C mt-tRNA(Glu) mutation in 17 patients from 12 families. Our results provide functional evidence for the pathogenicity of the mutation and show that tissue-specific mechanisms downstream of tRNA(Glu) may explain the spontaneous recovery. This study provides the rationale for a simple genetic test to identify infants with mitochondrial myopathy and good prognosis.

  5. Magnetic resonance imaging in the idiopathic inflammatory myopathies.

    Science.gov (United States)

    Fraser, D D; Frank, J A; Dalakas, M; Miller, F W; Hicks, J E; Plotz, P

    1991-11-01

    We examined the usefulness of magnetic resonance imaging (MRI) in detecting active muscle disease in 40 patients with idiopathic inflammatory myopathies (IIM). Ten patients without evidence of an inflammatory neuromuscular disease were also studied. The fat-suppressive (STIR) image signal intensity correlated with clinical disease activity and, in most cases, with the presence of inflammation on muscle biopsy. Increased STIR signal intensity paralleled disease activity in 3 patients followed serially. MRI provided a detailed anatomic view of the extent of muscle changes in these diseases. Because of inherent limitations of other measures of disease in these disorders, MRI may prove to be a useful complimentary test for assessing disease activity and guiding therapeutic decisions and biopsy in the idiopathic inflammatory myopathies.

  6. Nemaline myopathy in a newborn infant: a rare muscle disorder.

    Science.gov (United States)

    Olukman, O; Calkavur, S; Diniz, G; Unalp, A; Atlihan, F

    2013-01-01

    Nemaline myopathy (NM) is a genetically and clinically heterogeneous muscle disorder, defined by the presence of characteristic nemaline bodies on muscle biopsy. The disease has a wide spectrum of phenotypes, ranging from forms with neonatal onset and fatal outcome to asymptomatic forms. The neonatal form is severe and usually fatal. The clinical variability, with differing age of onset and severity of symptoms makes the diagnosis difficult during infancy. There is no curative treatment. L-tyrosine may prevent aspiration by reducing pharyngeal secretions and drooling. Most of the patients die from respiratory and cardiac failure. This article discusses a newborn infant who presented with generalized weakness and respiratory failure. Partial response to L-tyrosine treatment was noted. The case is worth presenting to remind clinicians of congenital myopathies in the differential diagnosis of floppy infant during neonatal period and to emphasize the importance of muscle biopsy in diagnosis.

  7. 21 CFR 876.4270 - Colostomy rod.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Colostomy rod. 876.4270 Section 876.4270 Food and... GASTROENTEROLOGY-UROLOGY DEVICES Surgical Devices § 876.4270 Colostomy rod. (a) Identification. A colostomy rod is a device used during the loop colostomy procedure. A loop of colon is surgically brought out...

  8. Solitary waves on nonlinear elastic rods. II

    DEFF Research Database (Denmark)

    Sørensen, Mads Peter; Christiansen, Peter Leth; Lomdahl, P. S.

    1987-01-01

    In continuation of an earlier study of propagation of solitary waves on nonlinear elastic rods, numerical investigations of blowup, reflection, and fission at continuous and discontinuous variation of the cross section for the rod and reflection at the end of the rod are presented. The results...

  9. Phase behavior of colloidal silica rods

    NARCIS (Netherlands)

    Kuijk, A.; Byelov, D.; Petukhov, A.V.; van Blaaderen, A.; Imhof, A.

    2012-01-01

    Recently, a novel colloidal hard-rod-like model system was developed which consists of silica rods [Kuijk et al., JACS, 2011, 133, 2346]. Here, we present a study of the phase behavior of these rods, for aspect ratios ranging from 3.7 to 8.0. By combining real-space confocal laser scanning microscop

  10. Hydraulic Actuator for Ganged Control Rods

    Science.gov (United States)

    Thompson, D. C.; Robey, R. M.

    1986-01-01

    Hydraulic actuator moves several nuclear-reactor control rods in unison. Electromagnetic pump pushes liquid lithium against ends of control rods, forcing them out of or into nuclear reactor. Color arrows show lithium flow for reactor startup and operation. Flow reversed for shutdown. Conceived for use aboard spacecraft, actuator principle applied to terrestrial hydraulic machinery involving motion of ganged rods.

  11. C4d staining as immunohistochemical marker in inflammatory myopathies.

    Science.gov (United States)

    Pytel, Peter

    2014-10-01

    The diagnosis of an inflammatory myopathy is often established based on basic histologic studies. Additional immunohistochemical studies are sometimes required to support the diagnosis and the classification of inflammatory myopathies. Staining for major histocompatibility complex 1 (MHC1) often shows increased sarcolemmal labeling in inflammatory myopathies. Endomysial capillary staining C5b-9 (membrane attack complex) is a feature that is reported as frequently associated with dermatomyositis. Immunohistochemical staining for C4d is widely used for various applications including the assessment of antibody-mediated rejection after solid organ transplantation. In the context of dermatomyositis, C4d staining has been described in skin biopsies but not in muscle biopsies. A total of 32 muscle biopsy specimens were examined. The hematoxylin and eosin-stained slides were reviewed, and immunohistochemical studies for MHC1, C5b-9, and C4d were conducted. The staining observed for C5b-9 and C4d was compared. Overall, the staining pattern for C4d mirrored the one observed for C5b-9 in the examined muscle biopsy specimens. There was high and statistically significant (P<0.0001) correlation between the staining seen with these 2 antibodies. Both antibodies labeled the cytoplasm of degenerating necrotic myofibers. In addition, both antibodies showed distinct endomysial capillary labeling in a subset of dermatomyositis. Areas with perifascicular atrophy often exhibited the most prominent vascular labeling for C4d and C5b-9. In conclusion, C4d and C5b-9 show similar expression patterns in muscle biopsies of patients with inflammatory myopathies and both highlight the presence of vascular labeling associated with dermatomyositis. C4d antibodies are widely used and may offer an alternative for C5b-9 staining.

  12. Statin Induced Myopathy a Patient with Multiple Systemic Diseases

    OpenAIRE

    Özgül Uçar; İbrahim Kocaoğlu; Ahmet Karagöz; Serkan Gökaslan

    2011-01-01

    Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) are the most successful class of drugs for the treatment of hypercholesterolaemia and dyslipidaemia. However, the popular profile of statins in terms of efficacy has been maligned by theiradverse effects. Statin induced myopathy, which can be seen at any time during the course of therapy, is a clinically important cause of statin intolerance and discontinuation. When a patient with multiple systemic diseases who use numerous medi...

  13. [Communication and language problems in children with nemaline myopathy].

    Science.gov (United States)

    Cervera-Merida, J F; Villa-Garcia, I; Ygual-Fernandez, A

    2017-02-24

    Nemaline myopathy is a rare disease with an incidence of 1 in every 50,000 live births. It is the most prevalent of the congenital myopathies, a heterogeneous set of neuromuscular disorders present at birth or manifesting at a very early age, which affect the skeletal muscles and give rise to weakness, hypotonia and psychomotor retardation, although cognitive development remains normal. To review the studies conducted to date on the communication difficulties and dysphagia of children with nemaline myopathy and their possible management based on speech therapy. All the children presented dysphagia, with severe feeding problems during the first three years of life that nevertheless are somewhat mitigated as time goes by. In 50% of cases a gastrostomy will be used, although some oral ingestion is maintained in many of them. Nemaline myopathy gives rise to a clearly dysarthric pattern. The weakness of the muscles involved in ventilation and of the face, with a limited ability to close the mouth, leads to hypophonia, nasality and marked unintelligibility. Studies conducted on treatments based on speech therapy suggest that, in the most disabling cases of dysarthria, alternative systems of communication should be used in the first years of life so as to eliminate the frustration caused by the lack of meaningful expression. Later, communicators based on written language can be used. In the remaining cases, the aim must be to improve speech intelligibility. Speech therapy can contribute to improve the quality of life of these children with two types of treatment: management of their dysphagia and improvement of their communication problems through speech or technical aids. These is insufficient scientific evidence of the effectiveness of these treatments.

  14. Integrative Data Mining Highlights Candidate Genes for Monogenic Myopathies

    Science.gov (United States)

    Neto, Osorio Abath; Tassy, Olivier; Biancalana, Valérie; Zanoteli, Edmar; Pourquié, Olivier; Laporte, Jocelyn

    2014-01-01

    Inherited myopathies are a heterogeneous group of disabling disorders with still barely understood pathological mechanisms. Around 40% of afflicted patients remain without a molecular diagnosis after exclusion of known genes. The advent of high-throughput sequencing has opened avenues to the discovery of new implicated genes, but a working list of prioritized candidate genes is necessary to deal with the complexity of analyzing large-scale sequencing data. Here we used an integrative data mining strategy to analyze the genetic network linked to myopathies, derive specific signatures for inherited myopathy and related disorders, and identify and rank candidate genes for these groups. Training sets of genes were selected after literature review and used in Manteia, a public web-based data mining system, to extract disease group signatures in the form of enriched descriptor terms, which include functional annotation, human and mouse phenotypes, as well as biological pathways and protein interactions. These specific signatures were then used as an input to mine and rank candidate genes, followed by filtration against skeletal muscle expression and association with known diseases. Signatures and identified candidate genes highlight both potential common pathological mechanisms and allelic disease groups. Recent discoveries of gene associations to diseases, like B3GALNT2, GMPPB and B3GNT1 to congenital muscular dystrophies, were prioritized in the ranked lists, suggesting a posteriori validation of our approach and predictions. We show an example of how the ranked lists can be used to help analyze high-throughput sequencing data to identify candidate genes, and highlight the best candidate genes matching genomic regions linked to myopathies without known causative genes. This strategy can be automatized to generate fresh candidate gene lists, which help cope with database annotation updates as new knowledge is incorporated. PMID:25353622

  15. Capture myopathy in an endangered sandhill crane (Grus canadensis pulla)

    Science.gov (United States)

    Carpenter, J.W.; Thomas, N.J.; Reeves, S.

    1991-01-01

    Despite precautions to protect cranes, a 3-year-old endangered Mississippi sandhill crane (Grus canadensis pulla) was found caught in a leghold trap in Gautier, Mississippi, on 11 November 1987. The bird could have been in the trap for up to 16 hr and was standing and struggling to escape when it was discovered. Serum chemistries of the crane on 12 November revealed elevated lactic dehydrogenase (2,880 IU/L), alanine aminotransferase (ALT) (152 IU/L), and aspartate aminotransferase (AST) (>1,000 IU/L) values. Following surgical amputation of a fractured toe, the bird never attempted to stand and was unable to stand even when manually supported. Radiographic and physical examination of both legs did not reveal any anatomical abnormalities. Despite medical care, including supportive therapy, no improvement was observed in the bird's ability to stand and to support itself, and the bird died on 19 November. Serum chemistries and the postmortem and histopathologic findings were compatible with capture myopathy described in other species. Because of the possible susceptibility of long-legged birds such as the Mississippi sandhill crane to capture myopathy, special care must be taken when trapping, handling, chemically immobilizing, and transporting these species. In addition, precautions must be taken when conducting a predator-control program to ensure that nontarget wildlife are unlikely to encounter traps. Capture myopathy has only rarely been observed in wild birds, and this case represents the first report in a Mississippi sandhill crane.

  16. Morphologic imaging in muscular dystrophies and inflammatory myopathies

    Energy Technology Data Exchange (ETDEWEB)

    Degardin, Adrian; Lacour, Arnaud; Vermersch, Patrick [CHU de Lille, Clinique neurologique, Lille (France); Morillon, David; Cotten, Anne [CHRU de Lille, Service de Radiologie Osteoarticulaire, Hopital Roger Salengro, Lille (France); Stojkovic, Tanya [G-H Pitie-Salpetriere, Institut de Myologie, Paris (France)

    2010-12-15

    To determine if magnetic resonance imaging (MR imaging) is useful in the diagnostic workup of muscular dystrophies and idiopathic inflammatory myopathies for describing the topography of muscle involvement. MR imaging was performed in 31 patients: 8 with dystrophic myotony types 1 (n = 4) or 2 (n = 4); 11 with limb-girdle muscular dystrophy, including dysferlinopathy, calpainopathy, sarcoglycanopathy, and dystrophy associated with fukutin-related protein mutation; 3 with Becker muscular dystrophy; and 9 with idiopathic inflammatory myopathies, including polymyositis, dermatomyositis, and sporadic inclusion body myositis. Analysis of T1 images enabled us to describe the most affected muscles and the muscles usually spared for each muscular disease. In particular, examination of pelvis, thigh, and leg muscles demonstrated significant differences between the muscular diseases. On STIR images, hyperintensities were present in 62% of our patients with muscular dystrophies. A specific pattern of muscular involvement was established for each muscular disease. Hyperintensities observed on STIR images precede fatty degeneration and are not specific for inflammatory myopathies. (orig.)

  17. Dermatomyositis, polymyositis and immune-mediated necrotising myopathies.

    Science.gov (United States)

    Luo, Yue-Bei; Mastaglia, Frank L

    2015-04-01

    Dermatomyositis, polymyositis and immune-mediated necrotising myopathy are major forms of idiopathic inflammatory myopathy. We review here recent developments in understanding the pathology and pathogenesis of these diseases, and characterisation of autoantibody biomarkers. Dermatomyositis is traditionally considered to be due to a complement-mediated microangiopathy but the factors responsible for complement activation remain uncertain. Recent studies have emphasised the importance of the type I interferon pathway in the pathogenesis of the disease and have identified autoantibodies with specificities for different clinical subgroups of patients. Polymyositis is characterised by a cytotoxic T cell response targeting as yet unidentified muscle antigens presented by MHC Class I molecules, and can occur in isolation but is more often part of a multi-systemic overlap syndrome. The immune-mediated necrotising myopathies are heterogeneous and are distinguished from polymyositis by the sparseness of inflammatory infiltrates and recognition of an association with specific autoantibodies such as anti-SRP and anti-HMGCR in many cases. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis.

  18. Undiagnosed myopathy before surgery and safe anaesthesia table.

    Science.gov (United States)

    Trevisan, Carlo P; Accorsi, Alma; Morandi, Lucia O; Mongini, Tiziana; Savoia, Gennaro; Gravino, Elvira; Angelini, Corrado; Tegazzin, Vincenzo

    2013-10-01

    Patients with muscle pathology are a challenge for anaesthesiologists because of possible life-threatening general anaesthesia complications. A review of the current medical literature on the issue clearly indicates that increasing awareness by anaesthesiologists in recent years has led to a reduction in the occurrence of adverse events in patients with diagnostically well-defined muscle disease. On the other hand, the current emerging aspect is that the great majority of complications concern subjects with clinically non-overt (silent to mildly symptomatic) and thus undiagnosed myopathy. With a view to improving prevention of possible critical anaesthesia complications in such patients, we present a "Safe Anaesthesia Table", listing both the anaesthetic drugs to be avoided and those considered harmless for myopathic patients, irrespective of age and type of pathology. In addition, a brief outline about the clinical aspects suggestive of a possible muscle pathology is also provided. Using "safe drugs" during routine surgical procedures in subjects with suspected undiagnosed myopathy will enable the anaesthesiologist to avoid delaying surgery, while protecting them from anaesthesia complications. By following this approach the presumed myopathy can be properly investigated after surgery.

  19. Zidovudine-induced myopathy: A study in Indian patients

    Directory of Open Access Journals (Sweden)

    Amitabh Sagar

    2010-01-01

    Full Text Available Context: Literature is replete with studies on zidovudine-induced myopathy after prolonged use (use beyond 270 days on an average. However, all these studies have been done on patients of Caucasian, American and African ethnic origin. No such study has been carried out in Indian patients to our knowledge. Aims: To determine the correlation of zidovudine usage with serum creatine phosphokinase (CK levels, clinical muscular weakness and muscle histology in Indian patients, we studied 147 physically active, Human Immunodeficiency Virus infected men on prolonged zidovudine-based antiretroviral therapy (ART. Settings and Design: Cross-sectional study on hospital follow-up patients of HIV infection. Materials and Methods: All cases on ART who reported to our canter during a period of 18 months were evaluated for symptoms (muscle fatigue, myalgia, objective muscle strength (testing clinically and serum CK levels, and a select group was evaluated by muscle biopsy. These patients were on zidovudine for 1 to 7 years. Results: None of the patients studied had significant symptoms or objective muscle weakness and only a small fraction (10.8% of cases had marginally raised serum CK levels. All muscle biopsies were normal on light microscopy. Conclusions: Zidovudine myopathy may be a constraint for use of the drug in the western population; however, it is a well-tolerated drug as regards myopathy in our study on Indian patients.

  20. Two cases of refractory polymyositis accompanied with steroid myopathy.

    Science.gov (United States)

    Izumi, Yasumori; Miyashita, Taiichiro; Kitajima, Tsubasa; Yoshimura, Shunsuke; Takeoka, Atsushi; Eguchi, Katsumi; Motomura, Masakatsu; Kawakami, Atsushi; Migita, Kiyoshi

    2015-01-01

    Polymyositis (PM) is an inflammatory muscle disease characterized by chronic inflammation in skeletal muscle. Although most patients with PM respond to corticosteroids, some cases show an unsatisfactory response and other therapeutic options must be considered. Furthermore, glucocorticosteroid (GC) toxicity leads to a significant disability known as steroid myopathy, particularly in elderly patients. Here we report two patients with refractory PM. Combined treatment with high-dose GCs, tacrolimus, and intravenous immunoglobulin resulted in beneficial effects against myositis. However, muscle weakness and the disability progressed due to steroid myopathy, and subsequent oral intake became impossible because of swallowing disturbance in these two patients. Nutritional intervention, including branched-chain amino acids (BCAAs) and rehabilitation, was undertaken in addition to treatment against myositis. These treatments finally improved the muscle weakness and activities of daily living, and the two patients were discharged after recovery. The high-dose GC treatment caused elevation of serum levels of amino acids, including BCAAs, but these amino acids subsequently declined during BCAA replacement therapy. These findings suggest that the catabolic effects of the glucocorticoid treatment impair the balance of amino acids, including BCAAs, within the muscle, leading to steroid myopathy.

  1. Assessment of Sonoelastography as Diagnosis Tool of Inflammatory Myopathies

    Directory of Open Access Journals (Sweden)

    Carolina BOTAR-JID

    2010-12-01

    Full Text Available Background: Inflammatory myopathies represent a special group of pathology. Establishing the correct diagnosis in the early phase and a better follow-up are the main objective for improving the life quality of these patients. Objective: The aim of this research was to assess the usefulness of sonoelastography in diagnosis of inflammatory myopathies. Material and Method: A prospective longitudinal study with a control group was carried out in the Radio-Imaging Department, Cluj-Napoca District University Hospital, Romania, from May 2007 to July 2010. Measurements: Image Processing 2.8 software was used to analyze the elastographic images in correlation with clinical and biochemical data was used. Results: Analysis of Receiver Operating Characteristic curves statistics for elastography parameters showed significant values for the following parameters: average green color, average blue color, average intensity of color, dispersion of red, dispersion of green, and dispersion of hue. Conclusions: Our study highlighted the utility of some elastography parameters in the diagnosis of inflammatory myopathies; the parameter proved to be statistically different in case group compared to control. Anyway, standardization of sonoelastography and larger studies are required to ensure accurate diagnosis, reproductibility and reliability.

  2. ELECTROMAGNETIC APPARATUS FOR MOVING A ROD

    Science.gov (United States)

    Young, J.N.

    1958-04-22

    An electromagnetic apparatus for moving a rod-like member in small steps in either direction is described. The invention has particular application in the reactor field where the reactor control rods must be moved only a small distance and where the use of mechanical couplings is impractical due to the high- pressure seals required. A neutron-absorbing rod is mounted in a housing with gripping uaits that engage the rod, and coils for magnetizing the gripping units to make them grip, shift, and release the rod are located outside the housing.

  3. Exploiting rod technology. Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1990-06-01

    ROD development was proceeding apace until recent budgetary decisions caused funding support for ROD development to be drastically reduced. The funding which was originally provided by DARPA and the Balanced Technology Initiative (BTI) Office has been cut back to zero from $800K. To determine the aeroballistic coefficients of a candidate dart, ARDEC is currently supporting development out of its own 6.2 funds at about $100K. ARDEC has made slow progress toward achieving this end because of failures in the original dart during testing. It appears that the next dart design to be tested will diverge from the original concept visualized by DARPA and Science and Technology Associates (STA). STA, the design engineer, takes exception to these changes on the basis of inappropriate test conditions and insufficient testing. At this time, the full resolution of this issue will be difficult because of the current management structure, which separates the developer (ARDEC) from the designer (STA).

  4. X-linked myotubular myopathy due to a complex rearrangement involving a duplication of MTM1 exon 10

    NARCIS (Netherlands)

    Trump, N.; Cullup, T.; Verheij, J. B. G. M.; Manzur, A.; Muntoni, F.; Abbs, S.; Jungbluth, H.

    2012-01-01

    X-linked myotubular myopathy is a predominantly severe congenital myopathy with central nuclei on muscle biopsy due to mutations in the MTM1 gene encoding myotubularin. We report a boy with typical features of X-linked myotubular myopathy. Sequencing of the MTM1 gene did not reveal any causative mut

  5. Isotretinoin-induced acute severe myopathy involving pelvic girdle muscles: A case report

    Science.gov (United States)

    Sameem, Farah; Semira

    2016-01-01

    Oral isotretinoin has been in widespread use for more than three decades. It causes numerous side effects; skin and mucous membrane being commonly involved. Musculoskeletal adverse effects are also known to occur, but pelvic girdle myopathy is rarely reported. We report myopathy involving pelvic girdle muscles in a young male who received oral isotretinoin for folliculitis decalvans.

  6. Isotretinoin-induced acute severe myopathy involving pelvic girdle muscles: A case report

    Directory of Open Access Journals (Sweden)

    Farah Sameem

    2016-01-01

    Full Text Available Oral isotretinoin has been in widespread use for more than three decades. It causes numerous side effects; skin and mucous membrane being commonly involved. Musculoskeletal adverse effects are also known to occur, but pelvic girdle myopathy is rarely reported. We report myopathy involving pelvic girdle muscles in a young male who received oral isotretinoin for folliculitis decalvans.

  7. Polymyositis without Beneficial Response to Steroid Therapy: Should Miyoshi Myopathy be a Differential Diagnosis?

    Science.gov (United States)

    Scalco, Renata Siciliani; Lorenzoni, Paulo José; Lynch, David S.; Martins, William Alves; Jungbluth, Heinz; Quinlivan, Ros; Becker, Jefferson; Houlden, Henry

    2017-01-01

    Patient: Male, 16 Final Diagnosis: Miyoshi myopathy Symptoms: HyperCKemia • myalgia • weakness Medication: — Clinical Procedure: — Specialty: Neurology Objective: Rare disease Background: Miyoshi myopathy (MM) is an autosomal-recessive muscle disorder caused by mutations in the DYSF gene. Clinical features and histopathological changes in dysferlinopathies may mimic inflammatory myopathies and a high degree of clinical suspicion is required to guide the genetic investigation. Case Report: We report the case of a 16-year-old male who presented with severe bilateral calf pain and elevated CK levels (15 000 IU/l) who was on prolonged steroid therapy prompted by the clinical suspicion of inflammatory myopathy. Three years into his illness, he was referred for neuromuscular evaluation presenting with untreatable muscle pain and progressive weakness. The diagnosis of “refractory polymyositis” was revisited. Targeted exome sequencing revealed homozygous pathogenic mutations in the DYSF gene, confirming a diagnosis of Miyoshi myopathy. Conclusions: Our case illustrates that severe muscle pain may be the initial feature of Miyoshi myopathy and should be considered in the differential diagnosis of inflammatory myopathies. Although the described patient reported partial clinical improvement in muscle pain, steroid treatment is not an effective therapy for dysferlinopathy patients and it did not prevent disease progression. In addition, we confirm the utility of next-generation sequencing approaches to myopathies, particularly in complex or unusual cases when muscle biopsy is not available. PMID:28053302

  8. Phenotypes of Myopathy-related Actin Mutants in differentiated C2C12 Myotubes

    Directory of Open Access Journals (Sweden)

    Machesky Laura M

    2007-01-01

    Full Text Available Abstract Background About 20 % of nemaline myopathies are thus far related to skeletal muscle alpha-actin. Seven actin mutants located in different parts of the actin molecule and linked to different forms of the disease were selected and expressed as EGFP-tagged constructs in differentiated C2C12 mytoubes. Results were compared with phenotypes in patient skeletal muscle fibres and with previous expression studies in fibroblasts and C2C12 myoblasts/myotubes. Results Whereas EGFP wt-actin nicely incorporated into endogenous stress fibres and sarcomeric structures, the mutants showed a range of phenotypes, which generally changed upon differentiation. Many mutants appeared delocalized in myoblasts but integrated into endogenous actin structures after 4–6 days of differentiation, demonstrating a poor correlation between the appearance in myotubes and the severity of the disease. However, for some mutants, integration into stress fibres induced aberrant structures in differentiated cells, like thickening or fragmentation of stress fibres. Other mutants almost failed to integrate but formed huge aggregates in the cytoplasm of myotubes. Those did not co-stain with alpha-actinin, a main component of nemaline bodies found in patient muscle. Interestingly, nuclear aggregates as formed by two of the mutants in myoblasts were found less frequently or not at all in differentiated cells. Conclusion Myotubes are a suitable system to study the capacity of a mutant to incorporate into actin structures or to form or induce pathological changes. Some of the phenotypes observed in undifferentiated myoblasts may only be in vitro effects. Other phenotypes, like aberrant stress fibres or rod formation may be more directly correlated with disease phenotypes. Some mutants did not induce any changes in the cellular actin system, indicating the importance of additional studies like functional assays to fully characterize the pathological impact of a mutant.

  9. A de novo dominant mutation in ACTA1 causing congenital nemaline myopathy associated with a milder phenotype: expanding the spectrum of dominant ACTA1 mutations.

    Science.gov (United States)

    Levesque, L; Del Bigio, M R; Krawitz, S; Mhanni, A A

    2013-03-01

    We describe the presentation and six-year follow up of a child with nemaline myopathy due to a de novo mutation in the skeletal muscle α-actin gene (ACTA1) characterized by dramatic improvement during the early childhood years. The presentation in this female patient was infantile-onset weakness in the facial, bulbar, respiratory and neck flexor muscles. A six-year follow-up revealed continued progressive improvement in her muscle strength. Based upon the histopathologic and ultrastructural features of nemaline rod disease, ACTA1 was sequenced. This revealed a mutation in exon 4 of ACTA1 (c.557A>G). Our report further expands the phenotypic spectrum associated with ACTA1 mutations. Although it is difficult to infer any genotype-phenotype correlation, this report stimulates the discussion regarding the pathophysiologic mechanism of the clinical improvement seen in some patients with ACTA1 mutations. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Limb girdle muscular dystrophy type 2L presenting as necrotizing myopathy.

    Science.gov (United States)

    Schneider, Ilka; Stoltenburg, Gisela; Deschauer, Marcus; Winterholler, Martin; Hanisch, Frank

    2014-05-01

    Recessive mutations in the ANO5 gene, encoding anoctamin 5, cause proximal limb girdle muscular dystrophy (LGMD2L), Miyoshi-type distal myopathy (MM3) and asymptomatic hyper- CKemia. We report a woman with exertion-induced myalgia and weakness in the hip girdle manifesting at the age of 40. Creatine kinase (CK) was increased 20-fold. Histologically the dominating feature was necrotizing myopathy, but long-term immunosuppressive therapy did not change CK level or myopathic symptoms. Molecular genetic investigation led to the finding of the homozygous ANO5 c.191dupA mutation. This is a report of a muscular dystrophy due to ANO5 mutation presenting histologically as necrotizing myopathy. For this reason our finding extends the histological spectrum of myopathies due to ANO5 mutations as well as the possible differential diagnoses for necrotizing myopathy.

  11. Study of cognitive sphere in children and adolescents with congenital myopathy (theoretical review

    Directory of Open Access Journals (Sweden)

    V. A. Erokhina

    2013-08-01

    Full Text Available This paper presents an analysis of current approaches to the study of states of higher mental functions in children and adolescents suffering from various forms of hereditary myopathies. The aim of this work is to study the theoretical rationale and the possibility of specific disorders of mental function in children and adolescents with congenital myopathies. To achieve this objective during the study it was necessary to solve the following problems: give a description of the various groups and forms of congenital myopathies, their clinical characteristics; justify the possibility of considering the hereditary myopathies as a factor in the formation of changes in visual-spatial activities and thinking; evaluate the possibility to use complex neuropsychological psycho-diagnostic techniques for investigating the state of the higher mental functions of children with congenital myopathies. The possibility of neuropsychological correction for this category of patients is discussed also.

  12. High temperature control rod assembly

    Energy Technology Data Exchange (ETDEWEB)

    Vollman, Russell E. (Solana Beach, CA)

    1991-01-01

    A high temperature nuclear control rod assembly comprises a plurality of substantially cylindrical segments flexibly joined together in succession by ball joints. The segments are made of a high temperature graphite or carbon-carbon composite. The segment includes a hollow cylindrical sleeve which has an opening for receiving neutron-absorbing material in the form of pellets or compacted rings. The sleeve has a threaded sleeve bore and outer threaded surface. A cylindrical support post has a threaded shaft at one end which is threadably engaged with the sleeve bore to rigidly couple the support post to the sleeve. The other end of the post is formed with a ball portion. A hollow cylindrical collar has an inner threaded surface engageable with the outer threaded surface of the sleeve to rigidly couple the collar to the sleeve. the collar also has a socket portion which cooperates with the ball portion to flexibly connect segments together to form a ball and socket-type joint. In another embodiment, the segment comprises a support member which has a threaded shaft portion and a ball surface portion. The threaded shaft portion is engageable with an inner threaded surface of a ring for rigidly coupling the support member to the ring. The ring in turn has an outer surface at one end which is threadably engageably with a hollow cylindrical sleeve. The other end of the sleeve is formed with a socket portion for engagement with a ball portion of the support member. In yet another embodiment, a secondary rod is slidably inserted in a hollow channel through the center of the segment to provide additional strength. A method for controlling a nuclear reactor utilizing the control rod assembly is also included.

  13. Topological Mixing with Ghost Rods

    OpenAIRE

    2005-01-01

    Topological chaos relies on the periodic motion of obstacles in a two-dimensional flow in order to form nontrivial braids. This motion generates exponential stretching of material lines, and hence efficient mixing. Boyland et al. [P. L. Boyland, H. Aref, and M. A. Stremler, J. Fluid Mech. 403, 277 (2000)] have studied a specific periodic motion of rods that exhibits topological chaos in a viscous fluid. We show that it is possible to extend their work to cases where the motion of the stirring...

  14. Reactor control rod timing system. [LMFBR

    Science.gov (United States)

    Wu, P.T.K.

    1980-03-18

    A fluid driven jet-edge whistle timing system is described for control rods of a nuclear reactor for producing real-time detection of the timing of each control rod in its scram operation. An important parameter in reactor safety, particularly for liquid metal fast breeder reactors (LMFBR), is the time deviation between the time the control rod is released and the time the rod actually reaches the down position. The whistle has a nearly pure tone signal with center frequency (above 100 kHz) far above the frequency band in which the energy of the background noise is concentrated. Each control rod can be fitted with a whistle with a different frequency so that there is no ambiguity in differentiating the signal from each control rod.

  15. Automatic safety rod for reactors. [LMFBR

    Science.gov (United States)

    Germer, J.H.

    1982-03-23

    An automatic safety rod for a nuclear reactor containing neutron absorbing material and designed to be inserted into a reactor core after a loss-of-flow. Actuation is based upon either a sudden decrease in core pressure drop or the pressure drop decreases below a predetermined minimum value. The automatic control rod includes a pressure regulating device whereby a controlled decrease in operating pressure due to reduced coolant flow does not cause the rod to drop into the core.

  16. [Myopathy and rhabdomyolysis after treatment with simvastatin, amlodipine, and roxithromycin].

    Science.gov (United States)

    Skovbølling, Sara Lyngby; Lindelof, Mette

    2014-10-06

    This is a case report of a 71-year-old male with known diabetes, hypertension and diabetic nephropaty who over the course of one year developed an unrecognized myopathy due to concomitant treatment with high-dose simvastatin and amlodipin. Due to rhabdomyolysis he was after seven days of treatment with roxithromycin admitted to hospital with loss of the ability to walk. We wish to raise awareness of the potentially severe side effects of simvastatin and to emphasize that these can be limited by increased attention to patients with risk factors and to interactions with other drugs.

  17. Muscle structural changes in mitochondrial myopathy relate to genotype

    DEFF Research Database (Denmark)

    Olsen, David B.; Langkilde, Annika Reynberg; Ørngreen, Mette C.

    2003-01-01

    It is well known that morphological changes at the cellular level occur in muscle of patients with mitochondrial myopathy (MM), but changes in muscle structure with fat infiltration and gross variation of muscle fiber size with giant fibers, normally encountered in the muscular dystrophies, have...... typically not been associated with mitochondrial disease. We investigated gross and microscopic muscle morphology in thigh muscles by muscle biopsy and MRI in 16 patients with MM, and compared findings with those obtained in muscular dystrophy patients and healthy subjects. Changes of muscle architecture...

  18. Acoustic loading effects on oscillating rod bundles

    Energy Technology Data Exchange (ETDEWEB)

    Lin, W.H.

    1980-01-01

    An analytical study of the interaction between an infinite acoustic medium and a cluster of circular rods is described. The acoustic field due to oscillating rods and the acoustic loading on the rods are first solved in a closed form. The acoustic loading is then used as a forcing function for rod responses, and the acousto-elastic couplings are solved simultaneously. Numerical examples are presented for several cases to illustrate the effects of various system parameters on the acoustic reaction force coefficients. The effect of the acoustic loading on the coupled eigenfrequencies are discussed.

  19. Polymyositis without Beneficial Response to Steroid Therapy: Should Miyoshi Myopathy be a Differential Diagnosis?

    Science.gov (United States)

    Scalco, Renata Siciliani; Lorenzoni, Paulo José; Lynch, David S; Martins, William Alves; Jungbluth, Heinz; Quinlivan, Ros; Becker, Jefferson; Houlden, Henry

    2017-01-05

    BACKGROUND Miyoshi myopathy (MM) is an autosomal-recessive muscle disorder caused by mutations in the DYSF gene. Clinical features and histopathological changes in dysferlinopathies may mimic inflammatory myopathies and a high degree of clinical suspicion is required to guide the genetic investigation. CASE REPORT We report the case of a 16-year-old male who presented with severe bilateral calf pain and elevated CK levels (15 000 IU/l) who was on prolonged steroid therapy prompted by the clinical suspicion of inflammatory myopathy. Three years into his illness, he was referred for neuromuscular evaluation presenting with untreatable muscle pain and progressive weakness. The diagnosis of "refractory polymyositis" was revisited. Targeted exome sequencing revealed homozygous pathogenic mutations in the DYSF gene, confirming a diagnosis of Miyoshi myopathy. CONCLUSIONS Our case illustrates that severe muscle pain may be the initial feature of Miyoshi myopathy and should be considered in the differential diagnosis of inflammatory myopathies. Although the described patient reported partial clinical improvement in muscle pain, steroid treatment is not an effective therapy for dysferlinopathy patients and it did not prevent disease progression. In addition, we confirm the utility of next-generation sequencing approaches to myopathies, particularly in complex or unusual cases when muscle biopsy is not available.

  20. Scoliosis in mitochondrial myopathy: case report and review of the literature.

    Science.gov (United States)

    Li, Zheng; Shen, Jianxiong; Liang, Jinqian

    2015-02-01

    The mitochondrial myopathies include a diverse group of disorders characterized by morphological abnormalities of muscle mitochondria. Little is reported about spinal deformity associated with this syndrome.This study presents a case of scoliosis occurring in the setting of mitochondrial myopathies and explores the possible mechanisms between the 2 diseases.A previously unreported scoliosis in mitochondrial myopathies is described. The patient was a 16-year-old Chinese adolescent boy undergoing a posterior correction at thoracic 2-lumbar 3 (T2-L3) levels using the Moss-SI spinal system. At 48-month follow-up, the patient was clinically pain free and well balanced. Plain radiographs showed solid spine fusion with no loss of deformity correction. After evaluating 60 mitochondrial myopathies, patients referred to Peking Union Medical College Hospital from February 2009 to May 2013, the prevalence of scoliosis among patients with mitochondrial myopathies was 5% (3/60), much higher than that among general population (2%).The scoliosis in mitochondrial myopathies is usually extensive and progressively aggravated and the correction of the associated spinal deformities is generally difficult. Therefore, the exact role of mitochondrial myopathy in the development of scoliosis requires further study for a better understanding of the disease, as well as adequate and effective patient care.

  1. Cancer association as a risk factor for anti-HMGCR antibody-positive myopathy

    Science.gov (United States)

    Kadoya, Masato; Hida, Ayumi; Hashimoto Maeda, Meiko; Taira, Kenichiro; Ikenaga, Chiseko; Uchio, Naohiro; Kubota, Akatsuki; Kaida, Kenichi; Miwa, Yusuke; Kurasawa, Kazuhiro; Shimada, Hiroyuki; Sonoo, Masahiro; Chiba, Atsuro; Shiio, Yasushi; Uesaka, Yoshikazu; Sakurai, Yasuhisa; Izumi, Toru; Inoue, Manami; Kwak, Shin; Tsuji, Shoji

    2016-01-01

    Objective: To show cancer association is a risk factor other than statin exposure for anti-3-hydroxy-3-methylglutaryl coenzyme A reductase autoantibody-positive (anti-HMGCR Ab+) myopathy. Methods: We analyzed the clinical features and courses of 33 patients (23 female and 10 male) with anti-HMGCR Ab+ myopathy among 621 consecutive patients with idiopathic inflammatory myopathies. Results: Among the 33 patients, 7 (21%) were statin-exposed and 26 were statin-naive. In relation with cancer, there were 12 patients (statin-exposed, n = 4) with cancers detected within 3 years of myopathy diagnosis (cancer association), 3 patients (all statin-naive) with cancers detected more than 3 years before myopathy diagnosis (cancer history), 10 cancer-free patients followed up for more than 3 years (all statin-naive), and 8 patients without cancer detection but followed up for less than 3 years (statin-exposed, n = 3). Therefore, 12 patients with cancer association (36%) formed a larger group than that of 7 statin-exposed patients (21%). Among 12 patients with cancer association, 92% had cancer detection within 1 year of myopathy diagnosis (after 1.3 years in the remaining patient), 83% had advanced cancers, and 75% died of cancers within 2.7 years. Of interest, 1 patient with cancer history had sustained increase in creatine kinase level over 12 years from cancer removal to the development of weakness. Conclusions: Patients with cancer association formed a large group with poor prognosis in our series of patients with anti-HMGCR Ab+ myopathy. The close synchronous occurrence of cancers and myopathies suggested that cancer association is one of the risk factors for developing anti-HMGCR Ab+ myopathy. PMID:27761483

  2. The proteomic profile of hereditary inclusion body myopathy.

    Directory of Open Access Journals (Sweden)

    Ilan Sela

    Full Text Available Hereditary inclusion body myopathy (HIBM is an adult onset, slowly progressive distal and proximal myopathy. Although the causing gene, GNE, encodes for a key enzyme in the biosynthesis of sialic acid, its primary function in HIBM remains unknown. The goal of this study was to unravel new clues on the biological pathways leading to HIBM by proteomic comparison. Muscle cultures and biopsies were analyzed by two dimensional gel electrophoresis (2-DE and the same biopsy extracts by isobaric tag for relative and absolute quantitation (iTRAQ. Proteins that were differentially expressed in all HIBM specimens versus all controls in each analysis were identified by mass spectrometry. The muscle cultures 2-DE analysis yielded 41 such proteins, while the biopsies 2-DE analysis showed 26 differentially expressed proteins. Out of the 400 proteins identified in biopsies by iTRAQ, 41 showed altered expression. In spite of the different nature of specimens (muscle primary cultures versus muscle biopsies and of the different methods applied (2D gels versus iTRAQ the differentially expressed proteins identified in each of the three analyses where related mainly to the same pathways, ubiquitination, stress response and mitochondrial processes, but the most robust cluster (30% was assigned to cytoskeleton and sarcomere organization. Taken together, these findings indicate a possible novel function of GNE in the muscle filamentous apparatus that could be involved in the pathogenesis of HIBM.

  3. Mitochondrial myopathy induces a starvation-like response.

    Science.gov (United States)

    Tyynismaa, Henna; Carroll, Christopher J; Raimundo, Nuno; Ahola-Erkkilä, Sofia; Wenz, Tina; Ruhanen, Heini; Guse, Kilian; Hemminki, Akseli; Peltola-Mjøsund, Katja E; Tulkki, Valtteri; Oresic, Matej; Moraes, Carlos T; Pietiläinen, Kirsi; Hovatta, Iiris; Suomalainen, Anu

    2010-10-15

    Mitochondrial respiratory chain (RC) deficiency is among the most common causes of inherited metabolic disease, but its physiological consequences are poorly characterized. We studied the skeletal muscle gene expression profiles of mice with late-onset mitochondrial myopathy. These animals express a dominant patient mutation in the mitochondrial replicative helicase Twinkle, leading to accumulation of multiple mtDNA deletions and progressive subtle RC deficiency in the skeletal muscle. The global gene expression pattern of the mouse skeletal muscle showed induction of pathways involved in amino acid starvation response and activation of Akt signaling. Furthermore, the muscle showed induction of a fasting-related hormone, fibroblast growth factor 21 (Fgf21). This secreted regulator of lipid metabolism was also elevated in the mouse serum, and the animals showed widespread changes in their lipid metabolism: small adipocyte size, low fat content in the liver and resistance to high-fat diet. We propose that RC deficiency induces a mitochondrial stress response, with local and global changes mimicking starvation, in a normal nutritional state. These results may have important implications for understanding the metabolic consequences of mitochondrial myopathies.

  4. Mitochondrial myopathy in Senna occidentalis-seed-fed chicken.

    Science.gov (United States)

    Cavaliere, M J; Calore, E E; Haraguchi, M; Górniak, S L; Dagli, M L; Raspantini, P C; Calore, N M; Weg, R

    1997-07-01

    Plants of the genus Senna (formerly Cassia) have been recognized as the cause of a natural and experimental syndrome of muscle degeneration frequently leading to death in animals. Histologically, it demonstrated skeletal and cardiac muscle necrosis, with floccular degeneration and proliferation of sarcolemmal nuclei. Recently, it was described as an experimental model of mitochondrial myopathy in hens chronically treated with Senna occidentalis. Currently, skeletal muscles of chicks intoxicated with seeds of the poisonous plant S. occidentalis were studied by histochemistry and electron microscopy. Since birth, the birds were fed ground dried seeds of this plant with a regular chicken ration at a dose of 4% for 11 days. Microscopic examination revealed, besides muscle-fiber atrophy, lipid storage in most fibers and a moderate amount of cytochrome oxidase-negative fibers. By electron microscopy, enlarged mitochondria with disrupted or excessively branched cristae were seen. This picture was characteristic of mitochondrial myopathy. These findings have hitherto remained unnoticed in skeletal muscle of young birds treated with S. occidentalis.

  5. Review: An update on inflammatory and autoimmune myopathies.

    Science.gov (United States)

    Dalakas, M C

    2011-04-01

    The review provides an update on the diagnosis of the main subtypes of inflammatory myopathies including dermatomyositis (DM), polymyositis (PM), necrotizing autoimmune myositis (NAM) and sporadic inclusion body myositis (sIBM). The fundamental aspects on muscle pathology and the unique pathomechanisms of each subset are outlined and the diagnostic dilemmas concerning the distinction of PM from sIBM and NAM are addressed. Dermatomyositis is a complement-mediated microangiopathy leading to destruction of capillaries, hypoperfusion and inflammatory cell stress on the perifascicular regions. NAM, is an increasingly recognized subacute myopathy triggered by statins, viral infections, cancer or autoimmuity with macrophages as the final effector cells causing fibre injury. In PM and sIBM cytotoxic CD8-positive T cells clonally expand in situ and invade major histocompatibility-I-expressing muscle fibres. The pathology of sporadic inclusion body myositis is complex because, in addition to the inflammatory mechanisms, there are degenerative features characterized by vacuolization and the accumulation of stressor and amyloid-related misfolded proteins. Inducible pro-inflammatory molecules, such as interleukin 1-β, may enhance the accumulation of stressor proteins. The principles for more effective treatment strategies are discussed.

  6. Desmin-related myopathy: Report of a rare case

    Directory of Open Access Journals (Sweden)

    Sridhar E

    2005-01-01

    Full Text Available The Protein Surplus Myopathies (PSM are characterized by accumulation of protein aggregates, identifiable ultrastructurally, resulting due to mutations of the encoding genes. Desmin-related myopathies (DRM are a form of PSM characterized by mutations of the desmin gene resulting in the formation of protein aggregates comprising mutant protein desmin and disturbance of the regular desmin intermediate network in the muscle fibers. We describe a rare case of DRM in a 23-year-old man who presented with complaints of difficulty in climbing stairs and running since the age of 5 years. EMG studies revealed a myopathic pattern. Muscle biopsy showed the features of muscular dystrophy with bluish rimmed vacuoles and sarcoplasmic inclusions, which were immunoreactive to desmin. Ultrastructural examination showed sarcoplasmic bodies and granulofilamentous inclusions. Although rare, the possibility of DRM/desminopathy should be considered in the presence of bluish rimmed vacuoles on light microscopy and characteristic ultrastructural inclusions. To the best of our knowledge this is the first case of DRM/desminopathy reported from India.

  7. Idiopathic Inflammatory Myopathies and Malignancy: a Comprehensive Review.

    Science.gov (United States)

    Tiniakou, Eleni; Mammen, Andrew L

    2017-02-01

    The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of autoimmune diseases (collectively known as myositis) affecting the skeletal muscles as well as other organ systems such as skin, lungs, and joints. The primary forms of myositis include polymyositis (PM), dermatomyositis (PM), and immune-mediated necrotizing myopathy (IMNM). Patients with these diseases experience progressive proximal muscle weakness, have characteristic muscle biopsy findings, and produce autoantibodies that are associated with unique clinical features. One distinguishing feature of these patients is that they are also known to have an increased risk of cancer. Since the first description of the association in 1916, it has been extensively reported in the medical literature. However, there have been significant variations between the different studies with regard to the degree of cancer risk in patients with IIM. These discrepancies can, in part, be attributed to differences in the definition of malignancy-associated myositis used in different studies. In recent years, significant advances have been made in defining specific features of IIM that are associated with the development of malignancy. One of these has been myositis-specific antibodies (MSAs), which are linked to distinct clinical phenotypes and categorize patients into groups with more homogeneous features. Indeed, patients with certain MSAs seem to be at particularly increased risk of malignancy. This review attempts a systematic evaluation of research regarding the association between malignancy and myositis.

  8. Novel mutations in NEB cause abnormal nebulin expression and markedly impaired muscle force generation in severe nemaline myopathy

    Directory of Open Access Journals (Sweden)

    Lawlor Michael W

    2011-06-01

    Full Text Available Abstract Background Nemaline myopathy (NM is a congenital muscle disease associated with weakness and the presence of nemaline bodies (rods in muscle fibers. Mutations in seven genes have been associated with NM, but the most commonly mutated gene is nebulin (NEB, which is thought to account for roughly 50% of cases. Results We describe two siblings with severe NM, arthrogryposis and neonatal death caused by two novel NEB mutations: a point mutation in intron 13 and a frameshift mutation in exon 81. Levels of detectable nebulin protein were significantly lower than those in normal control muscle biopsies or those from patients with less severe NM due to deletion of NEB exon 55. Mechanical studies of skinned myofibers revealed marked impairment of force development, with an increase in tension cost. Conclusions Our findings demonstrate that the mechanical phenotype of severe NM is the consequence of mutations that severely reduce nebulin protein levels and suggest that the level of nebulin expression may correlate with the severity of disease.

  9. Fibrous Myopathy as a Complication of Repeated Intramuscular Injections for Chronic Headache

    Directory of Open Access Journals (Sweden)

    R Burnham

    2006-01-01

    Full Text Available Two cases of fibrous myopathy associated with repeated, long-term intramuscular injections for treatment of chronic temporomandibular joint pain and chronic headache, respectively, are described. Both patients developed severe, function-limiting contractures in upper and lower extremity muscles used as injection sites. In one of the cases, the contractures were painful. Electrophysiological testing, magnetic resonance imaging and muscle biopsy results were all consistent with myopathy and replacement of skeletal muscle with noncontractile fibrous tissue. These cases are presented to increase awareness of fibrous myopathy and to promote surveillance for this serious potential complication of long-term intramuscular injections in chronic headache and other pain patients.

  10. Viscoelasticity of suspensions of long, rigid rods

    NARCIS (Netherlands)

    Dhont, Jan K.G.; Briels, W.J.

    2003-01-01

    A microscopic theory for the viscoelastic behaviour of suspensions of rigid rods with excluded volume interactions is presented, which is valid in the asymptotic limit of very long and thin rods. Stresses arising from translational and rotational Brownian motion and direct interactions are calculate

  11. Study of the rod style SFRFQ structure

    CERN Document Server

    Yan Xue Qing; Chen J

    2002-01-01

    There is a problem about upper limit of energy in the RFQ structure, although it is a wonderful low-energy-suited high current accelerating structure. After proposing an improved rod style SFRFQ structure without reversed field, the author studies its energy gain and transverse motion. The rod style SFRFQ structure is roughly compared with diaphragm SFRFQ structure

  12. Nrl is required for rod photoreceptor development.

    Science.gov (United States)

    Mears, A J; Kondo, M; Swain, P K; Takada, Y; Bush, R A; Saunders, T L; Sieving, P A; Swaroop, A

    2001-12-01

    The protein neural retina leucine zipper (Nrl) is a basic motif-leucine zipper transcription factor that is preferentially expressed in rod photoreceptors. It acts synergistically with Crx to regulate rhodopsin transcription. Missense mutations in human NRL have been associated with autosomal dominant retinitis pigmentosa. Here we report that deletion of Nrl in mice results in the complete loss of rod function and super-normal cone function, mediated by S cones. The photoreceptors in the Nrl-/- retina have cone-like nuclear morphology and short, sparse outer segments with abnormal disks. Analysis of retinal gene expression confirms the apparent functional transformation of rods into S cones in the Nrl-/- retina. On the basis of these findings, we postulate that Nrl acts as a 'molecular switch' during rod-cell development by directly modulating rod-specific genes while simultaneously inhibiting the S-cone pathway through the activation of Nr2e3.

  13. Human congenital myopathy actin mutants cause myopathy and alter Z-disc structure in Drosophila flight muscle.

    Science.gov (United States)

    Sevdali, Maria; Kumar, Vikash; Peckham, Michelle; Sparrow, John

    2013-03-01

    Over 190 mutations in the human skeletal muscle α-actin gene, ACTA1 cause congenital actin myopathies. We transgenically expressed six different mutant actins, G15R, I136M, D154N, V163L, V163M and D292V in Drosophila indirect flight muscles and investigated their effects in flies that express one wild type and one mutant actin copy. All the flies were flightless, and the IFMs showed incomplete Z-discs, disorganised actin filaments and 'zebra bodies'. No differences in levels of sarcomeric protein expression were observed, but tropomodulin staining was somewhat disrupted in D164N, V163L, G15R and V163M heterozygotes. A single copy of D292V mutant actin rescued the hypercontractile phenotypes caused by TnI and TnT mutants, suggesting that the D292V mutation interferes with thin filament regulation. Our results show that expression of actin mutations homologous to those in humans in the indirect flight muscles of Drosophila disrupt sarcomere organisation, with somewhat similar phenotypes to those observed in humans. Using Drosophila to study actin mutations may help aid our understanding of congential myopathies caused by actin mutations.

  14. Study of idiopathic inflammatory myopathies with special reference to borderland between idiopathic inflammatory myopathies and muscular dystrophies

    Directory of Open Access Journals (Sweden)

    Khadilkar Satish

    2008-01-01

    Full Text Available Background: Idiopathic inflammatory myopathies (IIMs form important treatable myopathies, hence it is important to recognize and categorize them. In some cases, the differential diagnosis between IIM and muscular dystrophies can be difficult. Aim: To study the clinical and laboratory features of patients with IIMs and compare and contrast this group with limb girdle muscular dystrophies (LGMDs. Setting and Design: A prospective study for the period of five years [1999-2004] was undertaken at a tertiary neuromuscular center. Materials and Methods: Bohan and Peter criteria were used for the diagnosis of IIM and Bushby criteria were used for the diagnosis of LGMD. Patients underwent history, clinical examination, hematological tests, electrophysiological studies and muscle biopsy. The biopsies were studied for histology and immunocytochemistry. A clinical scoring system was evolved to differentiate IIM from LGMD and was validated in a blinded manner. Receiver operator curves were used as the statistical method to analyze the sensitivity and specificity. Results and Conclusions: In the IIM group, dermatomyositis was most common, followed by polymyositis, occurring in young females. Overlap group was less common. In patients with polymyositis, onset in upper girdle was associated with adverse outcome. The scoring system helped to differentiate IIM from LGMD, mainly using clinical pointers. This was particularly valuable in chronic cases.

  15. Phase behavior and structure formation of hairy-rod supramolecules

    NARCIS (Netherlands)

    Subbotin, A; Stepanyan, R; Knaapila, M; Ikkala, O; ten Brinke, G

    2003-01-01

    Phase behavior and microstructure formation of rod and coil molecules, which can associate to form hairy-rod polymeric supramolecules, are addressed theoretically. Association induces considerable compatibility enhancement between the rod and coil molecules and various microscopically ordered struct

  16. Eulerian Formulation of Spatially Constrained Elastic Rods

    Science.gov (United States)

    Huynen, Alexandre

    Slender elastic rods are ubiquitous in nature and technology. For a vast majority of applications, the rod deflection is restricted by an external constraint and a significant part of the elastic body is in contact with a stiff constraining surface. The research work presented in this doctoral dissertation formulates a computational model for the solution of elastic rods constrained inside or around frictionless tube-like surfaces. The segmentation strategy adopted to cope with this complex class of problems consists in sequencing the global problem into, comparatively simpler, elementary problems either in continuous contact with the constraint or contact-free between their extremities. Within the conventional Lagrangian formulation of elastic rods, this approach is however associated with two major drawbacks. First, the boundary conditions specifying the locations of the rod centerline at both extremities of each elementary problem lead to the establishment of isoperimetric constraints, i.e., integral constraints on the unknown length of the rod. Second, the assessment of the unilateral contact condition requires, in principle, the comparison of two curves parametrized by distinct curvilinear coordinates, viz. the rod centerline and the constraint axis. Both conspire to burden the computations associated with the method. To streamline the solution along the elementary problems and rationalize the assessment of the unilateral contact condition, the rod governing equations are reformulated within the Eulerian framework of the constraint. The methodical exploration of both types of elementary problems leads to specific formulations of the rod governing equations that stress the profound connection between the mechanics of the rod and the geometry of the constraint surface. The proposed Eulerian reformulation, which restates the rod local equilibrium in terms of the curvilinear coordinate associated with the constraint axis, describes the rod deformed configuration

  17. Analysis on clinical features of necrotizing autoimmune myopathy

    Directory of Open Access Journals (Sweden)

    Yi LI

    2016-10-01

    Full Text Available Objective To investigate the clinical manifestations and auxiliary examination features of necrotizing autoimmune myopathy (NAM. Methods According to the inclusion criteria from European Neuromuscular Center (ENMC International Workshop on idiopathic inflammatory myopathies published in 2004, 57 patients were diagnosed as NAM from 107 patients with necrotizing myopathy (NM. The risk factors, clinical symptoms, laboratory tests, electrocardiography (ECG, electromyography (EMG, skeletal muscle MRI and muscle pathology were retrospectively analyzed. Results There were more female patients than male patients (male∶female = 1.00∶1.59, with the peak onset age during 40 to 59 years old (43.86% , 25/57 in this study. Clinical types included idiopathic NAM, NAM with connective tissue disease, statin-associated NAM and NAM with cancer. Muscle weakness mainly affected proximal muscle, while it may simultaneously affect distal muscle (28.07% , 16/57. Serum creatine kinase (CK elevated apparently (420-15 320 U/L. Serum anti-signal recognition particle (SRP antibodies were detected in 24 out of 44 patients (54.55%. A total of 41 in 45 patients (91.11% were detected myogenic damage on EMG, and 15 patients (33.33%, 15/45 also had spontaneous potentials. Thigh muscle MRI showed edema in 25 out of 27 patients (92.59% and fatty infiltration in 16 out of 27 patients (59.26% . Other than necrotic fibers, major histocompatibility complex-1 (MHC-1 on sarcolemma were positive in 98.25% (56/57 cases, and membrane attack complex (MAC deposition on capillary walls was detected in 92.98% (53/57 cases. Conclusions NAM can happen in all ages, mainly during 40 to 59 years old. Idiopathic NAM is the main type. Its main manifestation involves weakness of proximal muscle, sometimes with distal muscle. Extra-muscle symptoms are rare. Serum anti-SRP antibodies are common in NAM and edema is prominent change in thigh MRI. DOI: 10.3969/j.issn.1672-6731.2016.10.009

  18. Natural history of pulmonary function in collagen VI-related myopathies

    National Research Council Canada - National Science Library

    Foley, A Reghan; Quijano-Roy, Susana; Collins, James; Straub, Volker; McCallum, Michelle; Deconinck, Nicolas; Mercuri, Eugenio; Pane, Marika; D'Amico, Adele; Bertini, Enrico; North, Kathryn; Ryan, Monique M; Richard, Pascale; Allamand, Valérie; Hicks, Debbie; Lamandé, Shireen; Hu, Ying; Gualandi, Francesca; Auh, Sungyoung; Muntoni, Francesco; Bönnemann, Carsten G

    2013-01-01

    .... To further define the clinical course of these variants, we studied the natural history of pulmonary function in correlation to motor abilities in the collagen VI-related myopathies by analysing...

  19. Systematic protein-protein interaction and pathway analyses in the idiopathic inflammatory myopathies

    NARCIS (Netherlands)

    Parkes, Joanna E.; Rothwell, Simon; Day, Philip J.; McHugh, Neil J.; Betteridge, Zoë E.; Cooper, Robert G.; Ollier, William E.; Chinoy, Hector; Lamb, Janine A.; Lundberg, Ingrid E.; Miller, Frederick W.; Gregersen, Peter K.; Vencovsky, Jiri; Danko, Katalin; Limaye, Vidya; Selva-O'Callaghan, Albert; Machado, Pedro M.; Hanna, Michael G.; Pachman, Lauren M.; Reed, Ann M.; Rider, Lisa G.; Platt, Hazel; Molberg, Øyvind; Benveniste, Olivier; Mathiesen, Pernille; Radstake, Timothy; Doria, Andrea; Bleecker, Jan De; Paepe, Boel De; Maurer, Britta; Padyukov, Leonid; O'Hanlon, Terrance P.; Lee, Annette; Amos, Christopher I.; Gieger, Christian; Meitinger, Thomas; Winkelmann, Juliane; Wedderburn, Lucy R.; Denton, Christopher; Mann, Herman; Hilton-Jones, David; Kiely, Patrick; Plotz, Paul H.; Gourley, Mark; Rouster-Stevens, Kelly; Huber, Adam M.; Marder, Galina; Dimachkie, Mazen

    2016-01-01

    Background: The idiopathic inflammatory myopathies (IIM) are autoimmune diseases characterised by acquired proximal muscle weakness, inflammatory cell infiltrates in muscle and myositis-specific/associated autoantibodies. It is unclear which pathways are involved in IIM, and the functional

  20. Diagnostic value of MHC class I staining in idiopathic inflammatory myopathies.

    NARCIS (Netherlands)

    Pas, J. van der; Hengstman, G.J.D.; Laak, H.J. ter; Borm, G.F.; Engelen, B.G.M. van

    2004-01-01

    BACKGROUND: Identification of mononuclear cellular infiltrates in skeletal muscle tissue is the histological cornerstone of the diagnosis of idiopathic inflammatory myopathy (IIM). However, these infiltrates are not always present. OBJECTIVE: To determine whether MHC class I antigen expression on th

  1. Oculopharyngeal Weakness, Hypophrenia, Deafness, and Impaired Vision: A Novel Autosomal Dominant Myopathy with Rimmed Vacuoles

    Directory of Open Access Journals (Sweden)

    Ting Chen

    2016-01-01

    Conclusions: We reported a novel autosomal dominant myopathy with rimmed vacuoles characterized by dysarthria, dysphagia, external ophthalmoplegia, limb weakness, hypophrenia, deafness, and impaired vision, but the causative gene has not been found and needs further study.

  2. Systematic protein-protein interaction and pathway analyses in the idiopathic inflammatory myopathies

    NARCIS (Netherlands)

    Parkes, Joanna E.; Rothwell, Simon; Day, Philip J.; McHugh, Neil J.; Betteridge, Zoë E.; Cooper, Robert G.; Ollier, William E.; Chinoy, Hector; Lamb, Janine A.; Lundberg, Ingrid E.; Miller, Frederick W.; Gregersen, Peter K.; Vencovsky, Jiri; Danko, Katalin; Limaye, Vidya; Selva-O'Callaghan, Albert; Machado, Pedro M.; Hanna, Michael G.; Pachman, Lauren M.; Reed, Ann M.; Rider, Lisa G.; Platt, Hazel; Molberg, Øyvind; Benveniste, Olivier; Mathiesen, Pernille; Radstake, Timothy; Doria, Andrea; Bleecker, Jan De; Paepe, Boel De; Maurer, Britta; Padyukov, Leonid; O'Hanlon, Terrance P.; Lee, Annette; Amos, Christopher I.; Gieger, Christian; Meitinger, Thomas; Winkelmann, Juliane; Wedderburn, Lucy R.; Denton, Christopher; Mann, Herman; Hilton-Jones, David; Kiely, Patrick; Plotz, Paul H.; Gourley, Mark; Rouster-Stevens, Kelly; Huber, Adam M.; Marder, Galina; Dimachkie, Mazen

    2016-01-01

    Background: The idiopathic inflammatory myopathies (IIM) are autoimmune diseases characterised by acquired proximal muscle weakness, inflammatory cell infiltrates in muscle and myositis-specific/associated autoantibodies. It is unclear which pathways are involved in IIM, and the functional relations

  3. Morphoelastic rods Part II: Growing birods

    Science.gov (United States)

    Lessinnes, Thomas; Moulton, Derek E.; Goriely, Alain

    2017-03-01

    The general problem of determining the shape and response of two attached growing elastic Kirchhoff rods is considered. A description of the kinematics of the individual interacting rods is introduced. Each rod has a given intrinsic shape and constitutive laws, and a map associating points on the two rods is defined. The resulting filamentary structure, a growing birod, can be seen as a new filamentary structure. This kinematic description is used to derive the general equilibrium equations for the shape of the rods under loads, or equivalently, for the new birod. It is shown that, in general, the birod is not simply a Kirchhoff rod but rather, due to the internal constraints, new effects can appear. The two-dimensional restriction is then considered explicitly and the limit for small deformation is shown to be equivalent to the classic Timsohenko bi-metallic strip problem. A number of examples and applications are presented. In particular, the problem of two attached rods with intrinsic helical shape and uniform growth is computed in detail and a host of new interesting solutions and bifurcations are observed.

  4. Granular materials interacting with thin flexible rods

    Science.gov (United States)

    Neto, Alfredo Gay; Campello, Eduardo M. B.

    2017-04-01

    In this work, we develop a computational model for the simulation of problems wherein granular materials interact with thin flexible rods. We treat granular materials as a collection of spherical particles following a discrete element method (DEM) approach, while flexible rods are described by a large deformation finite element (FEM) rod formulation. Grain-to-grain, grain-to-rod, and rod-to-rod contacts are fully permitted and resolved. A simple and efficient strategy is proposed for coupling the motion of the two types (discrete and continuum) of materials within an iterative time-stepping solution scheme. Implementation details are shown and discussed. Validity and applicability of the model are assessed by means of a few numerical examples. We believe that robust, efficiently coupled DEM-FEM schemes can be a useful tool to the simulation of problems wherein granular materials interact with thin flexible rods, such as (but not limited to) bombardment of grains on beam structures, flow of granular materials over surfaces covered by threads of hair in many biological processes, flow of grains through filters and strainers in various industrial segregation processes, and many others.

  5. Magnetically controlled growing rods for scoliosis surgery.

    Science.gov (United States)

    Metkar, Umesh; Kurra, Swamy; Quinzi, David; Albanese, Stephen; Lavelle, William F

    2017-02-01

    Early onset scoliosis can be both a disfiguring as well as a life threatening condition. When more conservative treatments fail, pediatric spinal surgeons are forced to consider operative interventions. Traditionally, these interventions have involved the insertion of a variety of implants into the patient with a limited number of anchor points controlling the spine. In the past, these pediatric patients have had multiple surgeries for elective lengthening of these devices to facilitate their growth while attempting to control the scoliosis. These patients often experience a physical and emotional toll from their multiple repeated surgeries. Growing spine techniques have also had a noted high complication rate due to implant dislodgement and infections. Recently, the development of non-invasively, self-lengthening growing rods has occurred. These devices have the potential to allow for the devices to be lengthened magnetically in a conscious patient in the surgeon's office. Areas covered: This review summarized previously published articles in the English literature using a key word search in PubMed for: 'magnetically controlled growing rods', 'Magec rods', 'magnetic growing rods' and 'growing rods'. Expert commentary: Magnetically controlled growing rods have an advantage over growing rods in lengthening the growing spine in the absence of repetitive surgeries.

  6. Control Rod Malfunction at the NRAD Reactor

    Energy Technology Data Exchange (ETDEWEB)

    Thomas L. Maddock

    2010-05-01

    The neutron Radiography Reactor (NRAD) is a training, research, and isotope (TRIGA) reactor located at the INL. The reactor is normally shut down by the insertion of three control rods that drop into the core when power is removed from electromagnets. During a routine shutdown, indicator lights on the console showed that one of the control rods was not inserted. It was initially thought that the indicator lights were in error because of a limit switch that was out of adjustment. Through further testing, it was determined that the control rod did not drop when the scram switch was initially pressed. The control rod anomaly led to a six month shutdown of the reactor and an in depth investigation of the reactor protective system. The investigation looked into: scram switch operation, console modifications, and control rod drive mechanisms. A number of latent issues were discovered and corrected during the investigation. The cause of the control rod malfunction was found to be a buildup of corrosion in the control rod drive mechanism. The investigation resulted in modifications to equipment, changes to both operation and maintenance procedures, and additional training. No reoccurrences of the problem have been observed since corrective actions were implemented.

  7. Estimation of irradiated control rod worth

    Energy Technology Data Exchange (ETDEWEB)

    Varvayanni, M., E-mail: melina@ipta.demokritos.g [NCSR ' DEMOKRITOS' , PO Box 60228, 15310 Aghia Paraskevi (Greece); Catsaros, N. [NCSR ' DEMOKRITOS' , PO Box 60228, 15310 Aghia Paraskevi (Greece); Antonopoulos-Domis, M. [School of Electrical and Computer Engineering, Aristotle University of Thessaloniki, Thessaloniki (Greece)

    2009-11-15

    When depleted control rods are planned to be used in new core configurations, their worth has to be accurately predicted in order to deduce key design and safety parameters such as the available shutdown margin. In this work a methodology is suggested for the derivation of the distributed absorbing capacity of a depleted rod, useful in the case that the level of detail that is known about the irradiation history of the control rod does not allow an accurate calculation of the absorber's burnup. The suggested methodology is based on measurements of the rod's worth carried out in the former core configuration and on corresponding calculations based on the original (before first irradiation) absorber concentration. The methodology is formulated for the general case of the multi-group theory; it is successfully tested for the one-group approximation, for a depleted control rod of the Greek Research Reactor, containing five neutron absorbers. The computations reproduce satisfactorily the irradiated rod worth measurements, practically eliminating the discrepancy of the total rod worth, compared to the computations based on the nominal absorber densities.

  8. Granular materials interacting with thin flexible rods

    Science.gov (United States)

    Neto, Alfredo Gay; Campello, Eduardo M. B.

    2016-01-01

    In this work, we develop a computational model for the simulation of problems wherein granular materials interact with thin flexible rods. We treat granular materials as a collection of spherical particles following a discrete element method (DEM) approach, while flexible rods are described by a large deformation finite element (FEM) rod formulation. Grain-to-grain, grain-to-rod, and rod-to-rod contacts are fully permitted and resolved. A simple and efficient strategy is proposed for coupling the motion of the two types (discrete and continuum) of materials within an iterative time-stepping solution scheme. Implementation details are shown and discussed. Validity and applicability of the model are assessed by means of a few numerical examples. We believe that robust, efficiently coupled DEM-FEM schemes can be a useful tool to the simulation of problems wherein granular materials interact with thin flexible rods, such as (but not limited to) bombardment of grains on beam structures, flow of granular materials over surfaces covered by threads of hair in many biological processes, flow of grains through filters and strainers in various industrial segregation processes, and many others.

  9. Mitochondrial depletion causes neonatal-onset leigh syndrome, myopathy, and renal tubulopathy.

    Science.gov (United States)

    Lee, Inn-Chi; Lee, Ni-Chung; Lu, Jang-Jih; Su, Pen-Hua

    2013-03-01

    The authors describe a newborn with postnatal myopathy who subsequently developed feeding difficulties, ophthalmoplegia, ptosis, encephalopathy, and seizures. She became ventilator dependent after sudden apnea. The myopathy was without ragged red fibers in the muscle biopsy. An electron transport chain study showed a markedly generalized low level of enzyme activity, particularly in complexes I, I + III, and IV. An initial electroencephalogram finding was normal; subsequent electroencephalograms showed suppression bursts. The mitochondrial copy number in skeletal muscle was 2% of normal.

  10. Calcium homeostasis alterations in a mouse model of the Dynamin 2-related centronuclear myopathy

    OpenAIRE

    Fraysse, Bodvaël; Guicheney, Pascale; Bitoun, Marc

    2016-01-01

    ABSTRACT Autosomal dominant centronuclear myopathy (CNM) is a rare congenital myopathy characterized by centrally located nuclei in muscle fibers. CNM results from mutations in the gene encoding dynamin 2 (DNM2), a large GTPase involved in endocytosis, intracellular membrane trafficking, and cytoskeleton regulation. We developed a knock-in mouse model expressing the most frequent DNM2-CNM mutation; i.e. the KI-Dnm2 R465W model. Heterozygous (HTZ) KI-Dnm2 mice progressively develop muscle atro...

  11. Calcium homeostasis alterations in a mouse model of the Dynamin 2-related centronuclear myopathy

    OpenAIRE

    Bodvaël Fraysse; Pascale Guicheney; Marc Bitoun

    2016-01-01

    International audience; Autosomal dominant centronuclear myopathy (CNM) is a rare congenital myopathy characterized by centrally located nuclei in muscle fibers. CNM results from mutations in the gene encoding dynamin 2 (DNM2), a large GTPase involved in endocytosis, intracellular membrane trafficking, and cytoskeleton regulation. We developed a knock-in mouse model expressing the most frequent DNM2-CNM mutation; i.e. the KI-Dnm2 R465W model. Heterozygous (HTZ) KI-Dnm2 mice progressively deve...

  12. Prominent subcutaneous oedema as a masquerading symptom of an underlying inflammatory myopathy.

    Science.gov (United States)

    Anantharajah, Anthea; Vucic, Steve; Tarafdar, Surjit; Vongsuvanh, Roslyn; Wilcken, Nicholas; Swaminathan, Sanjay

    2017-02-01

    The inflammatory myopathies are a group of immune-mediated inflammatory muscle disorders that typically present with marked proximal muscle weakness. We report four cases of inflammatory myopathies with marked subcutaneous oedema as their main complaint. Three of the four patients had normal or low levels of creatine kinase, an enzyme often markedly elevated in these disorders. Magnetic resonance imaging of the muscles, followed by a muscle biopsy were used to make a definitive diagnosis.

  13. Loss of myotubularin function results in T-tubule disorganization in zebrafish and human myotubular myopathy.

    Science.gov (United States)

    Dowling, James J; Vreede, Andrew P; Low, Sean E; Gibbs, Elizabeth M; Kuwada, John Y; Bonnemann, Carsten G; Feldman, Eva L

    2009-02-01

    Myotubularin is a lipid phosphatase implicated in endosomal trafficking in vitro, but with an unknown function in vivo. Mutations in myotubularin cause myotubular myopathy, a devastating congenital myopathy with unclear pathogenesis and no current therapies. Myotubular myopathy was the first described of a growing list of conditions caused by mutations in proteins implicated in membrane trafficking. To advance the understanding of myotubularin function and disease pathogenesis, we have created a zebrafish model of myotubular myopathy using morpholino antisense technology. Zebrafish with reduced levels of myotubularin have significantly impaired motor function and obvious histopathologic changes in their muscle. These changes include abnormally shaped and positioned nuclei and myofiber hypotrophy. These findings are consistent with those observed in the human disease. We demonstrate for the first time that myotubularin functions to regulate PI3P levels in a vertebrate in vivo, and that homologous myotubularin-related proteins can functionally compensate for the loss of myotubularin. Finally, we identify abnormalities in the tubulo-reticular network in muscle from myotubularin zebrafish morphants and correlate these changes with abnormalities in T-tubule organization in biopsies from patients with myotubular myopathy. In all, we have generated a new model of myotubular myopathy and employed this model to uncover a novel function for myotubularin and a new pathomechanism for the human disease that may explain the weakness associated with the condition (defective excitation-contraction coupling). In addition, our findings of tubuloreticular abnormalities and defective excitation-contraction coupling mechanistically link myotubular myopathy with several other inherited muscle diseases, most notably those due to ryanodine receptor mutations. Based on our findings, we speculate that congenital myopathies, usually considered entities with similar clinical features but very

  14. Loss of myotubularin function results in T-tubule disorganization in zebrafish and human myotubular myopathy.

    Directory of Open Access Journals (Sweden)

    James J Dowling

    2009-02-01

    Full Text Available Myotubularin is a lipid phosphatase implicated in endosomal trafficking in vitro, but with an unknown function in vivo. Mutations in myotubularin cause myotubular myopathy, a devastating congenital myopathy with unclear pathogenesis and no current therapies. Myotubular myopathy was the first described of a growing list of conditions caused by mutations in proteins implicated in membrane trafficking. To advance the understanding of myotubularin function and disease pathogenesis, we have created a zebrafish model of myotubular myopathy using morpholino antisense technology. Zebrafish with reduced levels of myotubularin have significantly impaired motor function and obvious histopathologic changes in their muscle. These changes include abnormally shaped and positioned nuclei and myofiber hypotrophy. These findings are consistent with those observed in the human disease. We demonstrate for the first time that myotubularin functions to regulate PI3P levels in a vertebrate in vivo, and that homologous myotubularin-related proteins can functionally compensate for the loss of myotubularin. Finally, we identify abnormalities in the tubulo-reticular network in muscle from myotubularin zebrafish morphants and correlate these changes with abnormalities in T-tubule organization in biopsies from patients with myotubular myopathy. In all, we have generated a new model of myotubular myopathy and employed this model to uncover a novel function for myotubularin and a new pathomechanism for the human disease that may explain the weakness associated with the condition (defective excitation-contraction coupling. In addition, our findings of tubuloreticular abnormalities and defective excitation-contraction coupling mechanistically link myotubular myopathy with several other inherited muscle diseases, most notably those due to ryanodine receptor mutations. Based on our findings, we speculate that congenital myopathies, usually considered entities with similar

  15. Overt hypothyroidism with rhabdomyolysis and myopathy: a case report

    Institute of Scientific and Technical Information of China (English)

    KUO Hsu-tung; JENG Chii-yuan

    2010-01-01

    @@ Muscle involvement in adults with hypothyroidism is common.At least 79% of patients with hypothyroidism have muscle weakness,cramps,and myalgia complaints~1.The patients with hypothyroidism do have myopathy rather than functional muscle diseases~2.Nonspecific muscle stiffness related to myalgia may be associated with serum muscle enzyme elevations.Serum creatine kinase (CK) elevation can be observed in 57%-90% of patients with hypothyroidism.Skeletal muscle is affected more profoundly in cases of overt hypothyroidism,less so when subclinical hypothyroidism is present~1.However,clinical muscular symptoms are not usually the chief complaint at presentation.More than 40% of patients with hypothyroidism also had neuromuscular complaints at the time of diagnosis~2.

  16. Multiple mitochondrial alterations in a case of myopathy.

    Science.gov (United States)

    Fujioka, H; Tandler, B; Cohen, M; Koontz, D; Hoppel, C L

    2014-05-01

    Mitochondrial alterations are the most common feature of human myopathies. A biopsy of quadriceps muscle from a 50-year-old woman exhibiting myopathic symptoms was examined by transmission electron microscopy. Biopsied fibers from quadriceps muscle displayed numerous subsarcolemmal mitochondria that contained crystalloids. Numbering 1-6 per organelle, these consisted of rows of punctuate densities measuring ∼0.34 nm; the parallel rows of these dots had a periodicity of ∼0.8 nm. The crystalloids were ensconced within cristae or in the outer compartment. Some mitochondria without crystalloids had circumferential cristae, leaving a membrane-free center that was filled with a farinaceous material. Other scattered fibrocyte defects included disruption of the contractile apparatus or its sporadic replacement by a finely punctuate material in some myofibers. Intramitochondrial crystalloids, although morphologically striking, do not impair organelle physiology to a significant degree, so the muscle weakness of the patient must originate elsewhere.

  17. Muscle structural changes in mitochondrial myopathy relate to genotype

    DEFF Research Database (Denmark)

    Olsen, David B.; Langkilde, Annika Reynberg; Ørngreen, Mette C.

    2003-01-01

    It is well known that morphological changes at the cellular level occur in muscle of patients with mitochondrial myopathy (MM), but changes in muscle structure with fat infiltration and gross variation of muscle fiber size with giant fibers, normally encountered in the muscular dystrophies, have...... typically not been associated with mitochondrial disease. We investigated gross and microscopic muscle morphology in thigh muscles by muscle biopsy and MRI in 16 patients with MM, and compared findings with those obtained in muscular dystrophy patients and healthy subjects. Changes of muscle architecture......, similar to those found in the group of muscular dystrophy patients occurred consistently in patients with a high mutation load for single, largescale deletions of mtDNA, but were absent in all patients with the 3243A-->G mtDNA point mutation. Dystrophic changes of muscle architecture were also present...

  18. Restrictive extraocular myopathy: A presenting feature of acromegaly

    Directory of Open Access Journals (Sweden)

    Steven Heireman

    2011-01-01

    Full Text Available A 45-year-old man presented with binocular diplopia in primary gaze for 1 year. Orthoptic evaluation showed 10-prism diopter right eye hypotropia and 6-prism diopter right eye esotropia. The elevation and abduction of the right eye were mechanically restricted. This was associated with systemic features suggestive of acromegaly. Magnetic resonance imaging (MRI of the brain demonstrated a pituitary macroadenoma. An elevated serum insulin-like growth factor I level and the failure of growth hormone suppression after an oral glucose load biochemically confirmed the diagnosis of acromegaly. Computed tomography (CT of the orbit demonstrated bilateral symmetrical enlargement of the medial rectus and inferior rectus muscle bellies. All tests regarding Graves-Basedow disease were negative. Although rare, diplopia due to a restrictive extraocular myopathy could be the presenting symptom of acromegaly.

  19. Rituximab in the treatment of inflammatory myopathies: a review.

    Science.gov (United States)

    Fasano, Serena; Gordon, Patrick; Hajji, Raouf; Loyo, Esthela; Isenberg, David A

    2017-01-01

    Several uncontrolled studies have encouraged the use of rituximab (RTX) in patients with myositis. Unfortunately, the first placebo-phase trial to assess the efficacy of RTX in refractory myositis did not show a significant difference between the two treatment groups, and doubts have been expressed about its study design. In this review we present an up-to-date overview of the reported experiences of RTX therapy in myositis. A PubMed search was performed to find all the available cases of refractory myositis patients treated with RTX up to July 2015. The following terms were assessed: inflammatory myopathies OR anti-synthetase syndrome OR polymyositis OR dermatomyositis AND RTX. A total of 48 studies were included. We identified 458 patients with myositis treated with RTX. We found a rate of response to RTX of 78.3%. RTX can play a role in the management of patients with myositis, at least in those with positive myositis-specific autoantibodies.

  20. A case of congenital myopathy masquerading as paroxysmal dyskinesia

    Directory of Open Access Journals (Sweden)

    Harsh Patel

    2014-01-01

    Full Text Available Gastroesophageal reflux (GER disease is a significant comorbidity of neuromuscular disorders. It may present as paroxysmal dyskinesia, an entity known as Sandifer syndrome. A 6-week-old neonate presented with very frequent paroxysms of generalized stiffening and opisthotonic posture since day 22 of life. These were initially diagnosed as seizures and he was started on multiple antiepileptics which did not show any response. After a normal video electroencephalogram (VEEG was documented, possibility of dyskinesia was kept. However, when he did not respond to symptomatic therapy, Sandifer syndrome was thought of and GER scan was done, which revealed severe GER. After his symptoms got reduced to some extent, a detailed clinical examination revealed abnormal facies with flaccid quadriparesis. Muscle biopsy confirmed the diagnosis of a specific congenital myopathy. On antireflux measures, those episodic paroxysms reduced to some extent. Partial response to therapy in GER should prompt search for an underlying secondary etiology.

  1. Tipping time of a quantum rod

    Energy Technology Data Exchange (ETDEWEB)

    Parrikar, Onkar [Birla Institute of Technology and Science-Pilani, Goa campus, Zuarinagar, Goa 4032726 (India)], E-mail: onkarsp@gmail.com

    2010-03-15

    The behaviour of a quantum rod, pivoted at its lower end on an impenetrable floor and restricted to moving in the vertical plane under the gravitational potential, is studied analytically under the approximation that the rod is initially localized to a 'small-enough' neighbourhood around the point of classical unstable equilibrium. It is shown that the rod evolves out of this neighbourhood. The time required for this to happen, i.e. the tipping time, is calculated using the semi-classical path integral. It is shown that equilibrium is recovered in the classical limit, and that our calculations are consistent with the uncertainty principle.

  2. Signal recognition particle immunoglobulin g detected incidentally associates with autoimmune myopathy

    Science.gov (United States)

    Apiwattanakul, Metha; Milone, Margherita; Pittock, Sean J.; Kryzer, Thomas J.; Fryer, James P.; O'toole, Orna; Mckeon, Andrew

    2016-01-01

    ABSTRACT Introduction: Paraneoplastic autoantibody screening of 150,000 patient sera by tissue‐based immunofluorescence incidentally revealed 170 with unsuspected signal recognition particle (SRP) immunoglobulin G (IgG), which is a recognized biomarker of autoimmune myopathy. Of the 77 patients with available information, 54 had myopathy. We describe the clinical/laboratory associations. Methods: Distinctive cytoplasm‐binding IgG (mouse tissue substrate) prompted western blot, enzyme‐linked immunoassay, and immunoprecipitation analyses. Available histories were reviewed. Results: The immunostaining pattern resembled rough endoplasmic reticulum, and mimicked Purkinje‐cell cytoplasmic antibody type 1 IgG/anti‐Yo. Immunoblotting revealed ribonucleoprotein reactivity. Recombinant antigens confirmed the following: SRP54 IgG specificity alone (17); SRP72 IgG specificity alone (3); both (32); or neither (2). Coexisting neural autoantibodies were identified in 28% (low titer). Electromyography revealed myopathy with fibrillation potentials; 78% of biopsies had active necrotizing myopathy with minimal inflammation, and 17% had inflammatory myopathy. Immunotherapy responsiveness was typically slow and incomplete, and relapses were frequent on withdrawal. Histologically confirmed cancers (17%) were primarily breast and hematologic, with some others. Conclusions: Autoimmune necrotizing SRP myopathy, both idiopathic and paraneoplastic, is underdiagnosed in neurological practice. Serological screening aids early diagnosis. Cancer surveillance and appropriate immunosuppressant therapy may improve outcome. Muscle Nerve 53: 925–932, 2016 PMID:26561982

  3. Abnormal distribution of calcium-handling proteins: a novel distinctive marker in core myopathies.

    Science.gov (United States)

    Herasse, Muriel; Parain, Karine; Marty, Isabelle; Monnier, Nicole; Kaindl, Angela M; Leroy, Jean-Paul; Richard, Pascale; Lunardi, Jöel; Romero, Norma B; Ferreiro, Ana

    2007-01-01

    Central core disease (CCD) and multi-minicore disease (MmD) are muscle disorders characterized by foci of mitochondria depletion and sarcomere disorganization ("cores") in muscle fibers. Although core myopathies are the most frequent congenital myopathies, their pathogenesis remains elusive and specific diagnostic markers are lacking. Core myopathies are mostly caused by mutations in 2 sarcoplasmic reticulum proteins: the massive Ca-release channel RyR1 or the selenoprotein N (SelN) of unknown function. To search for distinctive markers and to obtain further pathophysiological insight, we identified the molecular defects in 12 core myopathy patients and analyzed the immunolocalization of 6 proteins of the Ca-release complex in their muscle biopsies. In 7 cases with RYR1 mutations (6 CCD, one MmD), RyR1 was depleted from the cores; in contrast, the other proteins of the sarcoplasmic reticulum (calsequestrin, SERCA1/2, and triadin) and the T-tubule (dihydropyridine receptor-alpha1subunit) accumulated within or around the lesions, suggesting an original modification of the Ca-release complex protein arrangement. Conversely, all Ca-related proteins were distributed normally in 5 MmD cases with SelN mutations. Our results provide an appropriate tool to orientate the differential and molecular diagnosis of core myopathies and suggest that different pathophysiological mechanisms lead to core formation in SelN- and in RyR1-related core myopathies.

  4. Troponin activator augments muscle force in nemaline myopathy patients with nebulin mutations.

    Science.gov (United States)

    de Winter, Josine Marieke; Buck, Danielle; Hidalgo, Carlos; Jasper, Jeffrey R; Malik, Fady I; Clarke, Nigel F; Stienen, Ger J M; Lawlor, Michael W; Beggs, Alan H; Ottenheijm, Coen A C; Granzier, Henk

    2013-06-01

    Nemaline myopathy-the most common non-dystrophic congenital myopathy-is caused by mutations in thin filament genes, of which the nebulin gene is the most frequently affected one. The nebulin gene codes for the giant sarcomeric protein nebulin, which plays a crucial role in skeletal muscle contractile performance. Muscle weakness is a hallmark feature of nemaline myopathy patients with nebulin mutations, and is caused by changes in contractile protein function, including a lower calcium-sensitivity of force generation. To date no therapy exists to treat muscle weakness in nemaline myopathy. Here, we studied the ability of the novel fast skeletal muscle troponin activator, CK-2066260, to augment force generation at submaximal calcium levels in muscle cells from nemaline myopathy patients with nebulin mutations. Contractile protein function was determined in permeabilised muscle cells isolated from frozen patient biopsies. The effect of 5 μM CK-2066260 on force production was assessed. Nebulin protein concentrations were severely reduced in muscle cells from these patients compared to controls, while myofibrillar ultrastructure was largely preserved. Both maximal active tension and the calcium-sensitivity of force generation were lower in patients compared to controls. Importantly, CK-2066260 greatly increased the calcium-sensitivity of force generation-without affecting the cooperativity of activation-in patients to levels that exceed those observed in untreated control muscle. Fast skeletal troponin activation is a therapeutic mechanism to augment contractile protein function in nemaline myopathy patients with nebulin mutations and with other neuromuscular diseases.

  5. KLHL40-related nemaline myopathy with a sustained, positive response to treatment with acetylcholinesterase inhibitors.

    Science.gov (United States)

    Natera-de Benito, D; Nascimento, A; Abicht, A; Ortez, C; Jou, C; Müller, J S; Evangelista, T; Töpf, A; Thompson, R; Jimenez-Mallebrera, C; Colomer, J; Lochmüller, H

    2016-03-01

    Congenital myopathies are a group of inherited muscle disorders characterized by hypotonia, weakness and a non-dystrophic muscle biopsy with the presence of one or more characteristic histological features. Neuromuscular transmission defects have recently been reported in several patients with congenital myopathies (CM). Mutations in KLHL40 are among the most common causes of severe forms of nemaline myopathy. Clinical features of affected individuals include fetal akinesia or hypokinesia, respiratory failure, and swallowing difficulties at birth. Muscle weakness is usually severe and nearly half of the individuals have no spontaneous antigravity movement. The average age of death has been reported to be 5 months in a recent case series. Herein we present a case of a patient with a nemaline myopathy due to KLHL40 mutations (c.604delG, p.Ala202Argfs*56 and c.1513G>C, p.Ala505Pro) with an impressive and prolonged beneficial response to treatment with high-dose pyridostigmine. Myasthenic features or response to ACEI have not previously been reported as a characteristic of nemaline myopathy or KLHL40-related myopathy.

  6. Novel TPM3 mutation in a family with cap myopathy and review of the literature.

    Science.gov (United States)

    Schreckenbach, T; Schröder, J M; Voit, T; Abicht, A; Neuen-Jacob, E; Roos, A; Bulst, S; Kuhl, C; Schulz, J B; Weis, J; Claeys, K G

    2014-02-01

    Cap myopathy is a rare congenital myopathy characterized by the presence of caps within muscle fibres and caused by mutations in ACTA1, TPM2 or TPM3. Thus far, only three cases with TPM3-related cap myopathy have been described. Here, we report on the first autosomal dominant family with cap myopathy in three-generations, caused by a novel heterozygous mutation in the alpha-tropomyosin-slow-encoding gene (TPM3; exon 4; c.445C>A; p.Leu149Ile). The three patients experienced first symptoms of muscle weakness in childhood and followed a slowly progressive course. They presented generalized hypotrophy and mild muscle weakness, elongated face, high arched palate, micrognathia, scoliosis and respiratory involvement. Intrafamilial variability of skeletal deformities, respiratory involvement and mild cardiac abnormalities was noted. Muscle MRI revealed a recognizable pattern of fatty muscle infiltration and masseter muscle hypertrophy. Subsarcolemmal caps were present in 6-10% of the fibres and immunoreactive with anti-tropomyosin antibodies. We conclude that the MRI-pattern of muscle involvement and the presence of masseter muscle hypertrophy in cap myopathy may guide molecular genetic diagnosis towards a mutation in TPM3. Regular respiratory examinations are important, even if patients have no anamnestic clues. We compare our findings to all cases of cap myopathy with identified mutations (n=11), thus far reported in the literature. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Deep RNA profiling identified CLOCK and molecular clock genes as pathophysiological signatures in collagen VI myopathy.

    Science.gov (United States)

    Scotton, Chiara; Bovolenta, Matteo; Schwartz, Elena; Falzarano, Maria Sofia; Martoni, Elena; Passarelli, Chiara; Armaroli, Annarita; Osman, Hana; Rodolico, Carmelo; Messina, Sonia; Pegoraro, Elena; D'Amico, Adele; Bertini, Enrico; Gualandi, Francesca; Neri, Marcella; Selvatici, Rita; Boffi, Patrizia; Maioli, Maria Antonietta; Lochmüller, Hanns; Straub, Volker; Bushby, Katherine; Castrignanò, Tiziana; Pesole, Graziano; Sabatelli, Patrizia; Merlini, Luciano; Braghetta, Paola; Bonaldo, Paolo; Bernardi, Paolo; Foley, Reghan; Cirak, Sebahattin; Zaharieva, Irina; Muntoni, Francesco; Capitanio, Daniele; Gelfi, Cecilia; Kotelnikova, Ekaterina; Yuryev, Anton; Lebowitz, Michael; Zhang, Xiping; Hodge, Brian A; Esser, Karyn A; Ferlini, Alessandra

    2016-04-15

    Collagen VI myopathies are genetic disorders caused by mutations in collagen 6 A1, A2 and A3 genes, ranging from the severe Ullrich congenital muscular dystrophy to the milder Bethlem myopathy, which is recapitulated by collagen-VI-null (Col6a1(-/-)) mice. Abnormalities in mitochondria and autophagic pathway have been proposed as pathogenic causes of collagen VI myopathies, but the link between collagen VI defects and these metabolic circuits remains unknown. To unravel the expression profiling perturbation in muscles with collagen VI myopathies, we performed a deep RNA profiling in both Col6a1(-/-)mice and patients with collagen VI pathology. The interactome map identified common pathways suggesting a previously undetected connection between circadian genes and collagen VI pathology. Intriguingly, Bmal1(-/-)(also known as Arntl) mice, a well-characterized model displaying arrhythmic circadian rhythms, showed profound deregulation of the collagen VI pathway and of autophagy-related genes. The involvement of circadian rhythms in collagen VI myopathies is new and links autophagy and mitochondrial abnormalities. It also opens new avenues for therapies of hereditary myopathies to modulate the molecular clock or potential gene-environment interactions that might modify muscle damage pathogenesis.

  8. Whole-body muscle MRI to detect myopathies in non-extrapyramidal bent spine syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Ohana, Mickael [Nouvel Hopital Civil - Hopitaux Universitaires de Strasbourg, Service de Radiologie B, Strasbourg (France); Durand, Marie-Christine [AP-HP - Hopital Raymond Poincare, Service de Neurologie, Garches (France); Marty, Catherine; Lazareth, Jean-Philippe [AP-HP - Hopital Raymond Poincare, Service de Rhumatologie, Garches (France); Maisonobe, Thierry [APH-HP - Hopital de la Pitie-Salpetriere, Service de Neuropathologie, Paris (France); Mompoint, Dominique; Carlier, Robert-Yves [AP-HP - Hopital Raymond Poincare, Service de Radiologie, Garches (France)

    2014-08-15

    Bent spine syndrome (BSS), defined as an abnormal forward flexion of the trunk resolving in supine position, is usually related to parkinsonism, but can also be encountered in myopathies. This study evaluates whole-body muscle MRI (WB-mMRI) as a tool for detecting underlying myopathy in non-extrapyramidal BSS. Forty-three patients (90 % women; 53-86 years old) with a non-extrapyramidal BSS were prospectively included. All underwent a 1.5-T WB-mMRI and a nerve conduction study. Muscle biopsy was performed if a myopathy could not be eliminated based on clinical examination and all tests. Systematic MRI interpretation focused on peripheral and axial muscle injury; spinal posture and incidental findings were also reported. WB-mMRI was completed for all patients, with 13 muscle biopsies ultimately needed and myopathy revealed as the final etiological diagnosis in five cases (12 %). All biopsy-proven myopathies were detected by the WB-mMRI. Relevant incidental MRI findings were made in seven patients. This study supports WB-mMRI as a sensitive and feasible tool for detecting myopathy in BSS patients. Associated with electroneuromyography, it can better indicate when a muscle biopsy is needed and guide it when required. Rigorous radiological interpretation is mandatory, so as not to miss incidental findings of clinical consequence. (orig.)

  9. CHANGES OF SINGLE FIBER ELECTROMYOGRAPHY IN PATIENTS WITH INFLAMMATORY MYOPATHIES

    Institute of Scientific and Technical Information of China (English)

    Fan Jian; Li-ying Cui; Ben-hong Li; Hua Du

    2005-01-01

    Objective To assess the significance of single fiber electromyography (SFEMG) in diagnosis of inflammatory myopathies and the correlation with other assistant examination findings.Methods SFEMG were recorded from the extensor digitorum communis of 34 patients with polymyositis or dermatomyositis and compared with the fmdings of routine electromyography (EMG), serum creatine kinase (CK) determination,and muscle biopsy.Results SFEMG recordings in 34 patients were all abnormal. The prominent feature was markedly increased fiber density (FD) with normally or mildly increased jitter. FD ranged from 1.0 to 6.0 (2.34±0.43). Jitter ranged from 5 to 78μs (41.6±10.3 μs). The potential pairs with jitter values greater than 55 μs ranged from 0% to 55% (7.7% ± 11.8%). Block was detected at one recording site in only one patient. Routine EMG demonstrated myogenic lesions in only 24 patients (70.6%). FD was a little higher in the normal-EMG subgroup or the neurogenic-EMG subgroup than myogenic-EMG subgroup but without statistical significance. Elevated CK levels were found in 75% patients (24/32). FD in the normal CK subgroup was significantly higher than that in the elevated CK subgroup (2.62±0.40 vs. 2.28±0.40, P < 0.05). Muscle pathologies were consistent with the diagnosis of myositis in 75% (15/20).Conclusion SFEMG is of great value in the diagnosis and disease process understanding of inflammatory myopathies for the clinically suspected patients with normal routine EMG, CK levels, and muscle biopsies.

  10. Motor unit reorganization in progressive muscular dystrophies and congenital myopathies.

    Science.gov (United States)

    Szmidt-Sałkowska, Elżbieta; Gaweł, Małgorzata; Lipowska, Marta

    2015-01-01

    The aim of this study was to analyze motor unit reorganization in different types of progressive muscular dystrophies and congenital myopathies. The study population consisted of patients with genetically verified progressive muscular dystrophies: Duchenne (DMD) (n=54), Becker (BMD) (n=30), facio-scapulo-humeral (FSHD) (n=37), and Emery-Dreifuss (E-DD) (n=26). Patients with probable limb-girdle dystrophy (L-GD) (n=58) and congenital myopathies (n=35) were also included in the study. Quantitative EMG recordings were obtained from 469 muscles. Muscle activity at rest and during slight voluntary and maximal muscle contraction was analyzed. The motor unit activity potential (MUAP) duration, amplitude, area, size index (SI), polyphasicity, and the presence of "outliers" were evaluated. Diminished values of MUAP parameters and decreased maximal amplitude of maximal muscle contraction were recorded most frequently in DMD and mainly in the biceps brachii muscles. SI was the most frequently changed EMG parameter. "Outliers" with amplitude below the normal range were recorded more frequently then a decreased mean MUAP amplitude (what could indicate a very high sensitivity of this EMG parameter). Pathological interference pattern was recorded in 34.7% of biceps brachii and in 21.2% of rectus femoris muscles. In FSHD, decreased MUAP duration and SI and pathological interference pattern with low amplitude were recorded most frequently in the tibial anterior and deltoid muscles. The presence of potentials with reduced parameters is a result of decreasing motor unit area (reduced number and size of muscle fibers), while high amplitude potentials recorded in BMD and E-DD could indicate a slow and mild course of disease and muscle regeneration.

  11. Mechanisms of disease: signaling pathways and immunobiology of inflammatory myopathies.

    Science.gov (United States)

    Dalakas, Marinos C

    2006-04-01

    The signaling pathways involved in the immunobiology of polymyositis, dermatomyositis, and inclusion-body myositis are outlined in this Review, which is based on research performed during the past 10 years. In dermatomyositis, the complement cascade is activated and the expression of cytokines and chemokines is upregulated. In polymyositis and inclusion-body myositis, autoinvasive CD8+ T cells are clonally expanded. This T-cell subset possesses conserved amino-acid sequences in complementarity-determining region 3 of the T-cell receptor and, via the perforin pathway, exerts a myotoxic effect on muscle fibers that express major histocompatibility complex (MHC) class I molecules. In all inflammatory myopathies, molecules associated with T-cell transmigration and cytokine signaling, as well as chemokines and their receptors, are strongly expressed by endothelial and inflammatory cells. Early in the pathogenesis of polymyositis and inclusion-body myositis, expression of MHC class I molecules on muscle fibers is upregulated, even in the absence of autoinvasive CD8+ T cells. Emerging data indicate that such continuous upregulation of the expression of MHC class I molecules on muscle fibers leads to an endoplasmic reticulum stress response, intracellular accumulation of misfolded glycoproteins, and activation of nuclear factor kappaB pathways, which can further stimulate formation of MHC class I-CD8 complexes, resulting in a self-sustaining inflammatory response. Advances in our understanding of the signaling pathways involved in the pathogenesis of these inflammatory myopathies are expected to result in the identification of novel therapeutic targets for these diseases.

  12. The occurrence of deep pectoral myopathy in roaster chickens.

    Science.gov (United States)

    Bianchi, M; Petracci, M; Franchini, A; Cavani, C

    2006-10-01

    A study was conducted to determine the incidence of deep pectoral myopathy (DPM) in male roaster chickens reared under intensive conditions, processed at different ages (from 47 to 65 d of age), and belonging to 2 commercial genotypes (Ross 508 and Cobb 500). The study was carried out in a major Italian processing plant on a total of 120,700 male roaster chickens chosen at random from 151 flocks during a 6-mo period. The evaluation of DPM was performed on pectoralis minor muscles and consisted of a visual assessment of the presence or absence of the myopathy as well as the scoring of muscle damage level as being in an "early" (hemorrhagic appearance) or "old" (gray or green discoloration) developing stage. The average incidence of carcasses affected by DPM was found to be 0.84% (0.62 and 0.22% in early and old stages, respectively). The range in the incidence of total DPM was fairly large and varied from 0 to 16.7%. Considerable variations were also observed for early (range: 0 to 12.0%) and old (range: 0 to 5.6%) developing stages. Considering the effect of genotype, Ross 508 exhibited a higher incidence of DPM in respect to Cobb 500 (1.27 vs. 0.35%; P < or = 0.01). This result was due to the higher incidence of carcasses affected by both early (0.94 vs. 0.26%; P < or = 0.01) and old (0.33 vs. 0.09%; P < or = 0.01) developing stages of DPM in Ross 508 birds.

  13. Modern Therapies for Idiopathic Inflammatory Myopathies (IIMs): Role of Biologics.

    Science.gov (United States)

    Moghadam-Kia, Siamak; Oddis, Chester V; Aggarwal, Rohit

    2017-02-01

    Despite the lack of placebo-controlled trials, glucocorticoids are considered the mainstay of initial treatment for idiopathic inflammatory myopathy (IIMs) and myositis-associated ILD (MA-ILD). Glucocorticoid-sparing agents are often given concomitantly with other immunosuppressive agents, particularly in patients with moderate or severe disease. As treatment of refractory cases of idiopathic inflammatory myopathies has been challenging, there is growing interest in evaluating newer therapies including biologics that target various pathways involved in the pathogenesis of IIMs. In a large clinical trial of rituximab in adult and juvenile myositis, the primary outcome was not met, but the definition of improvement was met by most of this refractory group of myositis patients. Rituximab use was also associated with a significant glucocorticoid-sparing effect. Intravenous immune globulin (IVIg) can be used for refractory IIMs or those with severe dysphagia or concomitant infections. Anti-tumor necrosis factor (anti-TNF) utility in IIMs is generally limited by previous negative studies along with recent reports suggesting their potential for inducing myositis. Further research is required to assess the role of new therapies such as tocilizumab (anti-IL6), ACTH gel, sifalimumab (anti-IFNα), and abatacept (inhibition of T cell co-stimulation) given their biological plausibility and encouraging small case series results. Other potential novel therapies include alemtuzumab (a humanized monoclonal antibody which binds CD52 on B and T lymphocytes), fingolimod (a sphingosine 1-phosphate receptor modulator that traps T lymphocytes in the lymphoid organs), eculizumab, and basiliximab. The future investigations in IIMs will depend on well-designed controlled clinical trials using validated consensus core set measures and improvements in myositis classification schemes based on serologic and histopathologic features.

  14. The Clinical and Histological Spectrum of Idiopathic Inflammatory Myopathies.

    Science.gov (United States)

    Cavazzana, Ilaria; Fredi, Micaela; Selmi, Carlo; Tincani, Angela; Franceschini, Franco

    2017-02-01

    Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of myositis, characterised by chronic muscle weakness, cutaneous features, different extra-muscular manifestations and circulating autoantibodies. IIMs included classical polymyositis (PM), dermatomyositis (DM) and other different types of myositis with a wide range of muscle involvement. A complete autoantibody profile and a muscle biopsy are mandatory to correctly diagnose different clinical entities and to define their different prognosis. Bohan and Peter's criteria included five items to diagnose adult onset PM and DM. The sensitivity was 74-100 %, while the specificity is low, due to a poor ability to differentiate PM from neuromuscular diseases. Other criteria included a more accurate histological definition of PM, DM or amyopathic DM, obtaining a higher specificity. Autoantibodies' association, interstitial lung disease and clinical cardiac involvement represent the main items that could define the prognosis of these patients. On the other hand, inclusion body myositis is a different myopathy characterised by a peculiar muscle mass involvement, muscle atrophy and progressive loss of function, due to complete failure to all immunosuppressive drugs used. Treatment of IIMs is based on corticosteroids (CS), which show rapid clinical response and functional improvement. Different immunosuppressant drugs are given to obtain a better control of the disease during CS tapering dose. No controlled double blind trials demonstrated the superiority of one immunesuppressant on another. The occurrence of interstitial lung involvement requires the immediate introduction of immunosuppressants in addiction to CS. Severe dysphagia seems to improve with intravenous immunoglobulins (Ig). Physical therapy could be started after the acute phase of diseases and seems to have a beneficial role in muscle strength recovery.

  15. High temperature control rod assembly

    Energy Technology Data Exchange (ETDEWEB)

    Vollman, R.E.

    1991-12-24

    This patent describes a control rod assembly for use in nuclear reactor control. It comprises segments, each the segment being made of a graphite composite material, each the segment having a chamber for containing neutron-absorbing material, wherein the chamber compromises a hollow cylindrical sleeve having a first end formed with an opening for receiving the neutron-absorbing material, and having a second end formed with a sleeve bore and an outer sleeve surface; a cylindrical weight-bearing support post positioned substantially centrally of the sleeve, the support post having a first end formed as a ball surface portion and a second end formed as a ball surface portion and a second end formed as a shaft, the shaft being engageable with the sleeve bore for rigidly coupling the support post axially within the hollow sleeve, a hollow cylindrical collar having a socket lip portion correspondingly shaped to receive the ball surface portion of an adjacent support post, and having an inner surface for engaging the outer sleeve surface on the second end of the sleeve to rigidly couple the collar to the sleeve.

  16. Centronuclear myopathy related to dynamin 2 mutations: Clinical, morphological, muscle imaging and genetic features of an Italian cohort

    OpenAIRE

    Catteruccia, Michela; Fattori, Fabiana; Codemo, Valentina; Ruggiero, Lucia; Maggi, Lorenzo; Tasca, Giorgio; Fiorillo, Chiara; Pane, Marika; Berardinelli, Angela; Verardo, Margherita; BRAGATO, CINZIA; Mora, Marina; MORANDI, LUCIA; Bruno, Claudio; Santoro, Lucio

    2013-01-01

    Mutations in dynamin 2 (DNM2) gene cause autosomal dominant centronuclear myopathy and occur in around 50% of patients with centronuclear myopathy. We report clinical, morphological, muscle imaging and genetic data of 10 unrelated Italian patients with centronuclear myopathy related to DNM2 mutations. Our results confirm the clinical heterogeneity of this disease, underlining some peculiar clinical features, such as severe pulmonary impairment and jaw contracture that should be considered in ...

  17. On a case of respiratory failure due to diaphragmatic paralysis and dilated cardiomyopathy in a patient with nemaline myopathy

    OpenAIRE

    Taglia, Antonella; D'Ambrosio, Paola; PALLADINO, ALBERTO; Politano, Luisa

    2012-01-01

    Nemaline myopathy is a rare congenital disease that generally occurs in childhood. We report a case of a 50-year-old man who presented with severe heart failure as the initial manifestation of nemaline myopathy. Soon after he developed acute restrictive respiratory failure due to the diaphragmatic paralysis. The diagnosis of "nemaline myopathy" was obtained on muscle biopsy performed one year later. After starting appropriate cardiological treatment and non-invasive ventilation, his cardiac a...

  18. Impact of AD995 alumina rods

    Energy Technology Data Exchange (ETDEWEB)

    Chhabildas, L.C.; Furnish, M.D.; Reinhart, W.D. [Sandia National Labs., Albuquerque, NM (United States); Grady, D.E. [Applied Research Associates, Inc., Albuquerque, NM (United States)

    1997-10-01

    Gas guns and velocity interferometric techniques have been used to determine the loading behavior of an AD995 alumina rod 19 mm in diameter by 75 mm and 150 mm long, respectively. Graded-density materials were used to impact both bare and sleeved alumina rods while the velocity interferometer was used to monitor the axial-velocity of the free end of the rods. Results of these experiments demonstrate that (1) a time-dependent stress pulse generated during impact allows an efficient transition from the initial uniaxial strain loading to a uniaxial stress state as the stress pulse propagates through the rod, and (2) the intermediate loading rates obtained in this configuration lie between split Hopkinson bar and shock-loading techniques.

  19. Computer simulation of rod-sphere mixtures

    CERN Document Server

    Antypov, D

    2003-01-01

    Results are presented from a series of simulations undertaken to investigate the effect of adding small spherical particles to a fluid of rods which would otherwise represent a liquid crystalline (LC) substance. Firstly, a bulk mixture of Hard Gaussian Overlap particles with an aspect ratio of 3:1 and hard spheres with diameters equal to the breadth of the rods is simulated at various sphere concentrations. Both mixing-demixing and isotropic-nematic transition are studied using Monte Carlo techniques. Secondly, the effect of adding Lennard-Jones particles to an LC system modelled using the well established Gay-Berne potential is investigated. These rod-sphere mixtures are simulated using both the original set of interaction parameters and a modified version of the rod-sphere potential proposed in this work. The subject of interest is the internal structure of the binary mixture and its dependence on density, temperature, concentration and various parameters characterising the intermolecular interactions. Both...

  20. Bouncing Balls and Hot Rod Races.

    Science.gov (United States)

    Tibbs, Peggy; Sherrill, Donna

    This paper presents the Bouncing Ball Experiment which models quadratic and exponential functions, and the Hot Rod Races activity that explores velocity and acceleration. Activities include directions for the use of TI-82 and TI-83 calculators. (YDS)

  1. Double-clad nuclear fuel safety rod

    Science.gov (United States)

    McCarthy, William H.; Atcheson, Donald B.; Vaidyanathan, Swaminathan

    1984-01-01

    A device for shutting down a nuclear reactor during an undercooling or overpower event, whether or not the reactor's scram system operates properly. This is accomplished by double-clad fuel safety rods positioned at various locations throughout the reactor core, wherein melting of a secondary internal cladding of the rod allows the fuel column therein to shift from the reactor core to place the reactor in a subcritical condition.

  2. Microelectrophoresis of Silica Rods Using Confocal Microscopy.

    Science.gov (United States)

    Bakker, Henriëtte E; Besseling, Thijs H; Wijnhoven, Judith E G J; Helfferich, Peter H; van Blaaderen, Alfons; Imhof, Arnout

    2017-01-31

    The electrophoretic mobility and the zeta potential (ζ) of fluorescently labeled colloidal silica rods, with an aspect ratio of 3.8 and 6.1, were determined with microelectrophoresis measurements using confocal microscopy. In the case where the colloidal particles all move at the same speed parallel to the direction of the electric field, we record a xyz-stack over the whole depth of the capillary. This method is faster and more robust compared to taking xyt-series at different depths inside the capillary to obtain the parabolic flow profile, as was done in previous work from our group. In some cases, rodlike particles do not move all at the same speed in the electric field, but exhibit a velocity that depends on the angle between the long axis of the rod and the electric field. We measured the orientation-dependent velocity of individual silica rods during electrophoresis as a function of κa, where κ(-1) is the double layer thickness and a is the radius of the rod associated with the diameter. Thus, we determined the anisotropic electrophoretic mobility of the silica rods with different sized double layers. The size of the double layer was tuned by suspending silica rods in different solvents at different electrolyte concentrations. We compared these results with theoretical predictions. We show that even at already relatively high κa when the Smoluchowski limiting law is assumed to be valid (κa > 10), an orientation dependent velocity was measured. Furthermore, we observed that at decreasing values of κa the anisotropy in the electrophoretic mobility of the rods increases. However, in low polar solvents with κa < 1, this trend was reversed: the anisotropy in the electrophoretic mobility of the rods decreased. We argue that this decrease is due to end effects, which was already predicted theoretically. When end effects are not taken into account, this will lead to strong underestimation of the experimentally determined zeta potential.

  3. High Power Performance of Rod Fiber Amplifiers

    DEFF Research Database (Denmark)

    Johansen, Mette Marie; Michieletto, Mattia; Kristensen, Torben

    2015-01-01

    An improved version of the DMF rod fiber is tested in a high power setup delivering 360W of stable signal power. Multiple testing degrades the fiber and transverse modal instability threshold from >360W to ~290W.......An improved version of the DMF rod fiber is tested in a high power setup delivering 360W of stable signal power. Multiple testing degrades the fiber and transverse modal instability threshold from >360W to ~290W....

  4. IMPACT CONICAL ROD ON HARD LIMITER

    Directory of Open Access Journals (Sweden)

    Ulitin G.

    2014-12-01

    Full Text Available The problem is considered of longitudinal impact conical rod in article. A recommendation on the use of the approximate method of calculation is based on an analysis of the influence of design parameters on the value of the main oscillation frequency. There was obtained an equation of the displacement and stress of the rod. Engineering dependence has been proposed to determine the maximum force in the impact section.

  5. Self-diagnosing braided composite rod

    OpenAIRE

    Fangueiro, Raúl; Zdraveva, E.; Pereira, Cristiana Gonilho; Ferreira, A; Lanceros-Méndez, S.

    2010-01-01

    This paper presents the development of a braided reinforced composite rod (BCR) able to both reinforce and monitor the stress state of concrete structures. Carbon fibers have been used as sensing and reinforcing materials along with glass fiber. Various composites rods have been produced using an author patented technique based on a modified conventional braiding machine. The materials investigated were prepared with different carbon fiber content as follows: BCR2 (77% glass/23...

  6. Measurements of control rod efficiency in RBMK critical assembly upon dropping of the rods

    Energy Technology Data Exchange (ETDEWEB)

    Zhitarev, V. E., E-mail: vejitarev@nnrd.kiae.su; Kachanov, V. M.; Sergevnin, A. Yu.; Lebedev, G. V., E-mail: lgv2004@mail.ru [National Research Center Kurchatov Institute (Russian Federation)

    2014-12-15

    The efficiency of control rods in the RBMK critical assembly was measured in the case where one manual-control rod (MCR) is dropped from a steady critical state, and several other MCRs were additionally dropped after 44 s. The measured number of neutrons in the assembly during and after dropping of the rods was used to calculate the efficiency values of the rods by solution of the system of point kinetics equations. A series of methods of the initial data treatment for determination of the desired values of reactivity without the calculated corrections were used.

  7. Measurements of control rod efficiency in RBMK critical assembly upon dropping of the rods

    Science.gov (United States)

    Zhitarev, V. E.; Kachanov, V. M.; Sergevnin, A. Yu.; Lebedev, G. V.

    2014-12-01

    The efficiency of control rods in the RBMK critical assembly was measured in the case where one manual-control rod (MCR) is dropped from a steady critical state, and several other MCRs were additionally dropped after 44 s. The measured number of neutrons in the assembly during and after dropping of the rods was used to calculate the efficiency values of the rods by solution of the system of point kinetics equations. A series of methods of the initial data treatment for determination of the desired values of reactivity without the calculated corrections were used.

  8. High-throughput rod-induced electrospinning

    Science.gov (United States)

    Wu, Dezhi; Xiao, Zhiming; Teh, Kwok Siong; Han, Zhibin; Luo, Guoxi; Shi, Chuan; Sun, Daoheng; Zhao, Jinbao; Lin, Liwei

    2016-09-01

    A high throughput electrospinning process, directly from flat polymer solution surfaces induced by a moving insulating rod, has been proposed and demonstrated. Different rods made of either phenolic resin or paper with a diameter of 1-3 cm and a resistance of about 100-500 MΩ, has been successfully utilized in the process. The rod is placed approximately 10 mm above the flat polymer solution surface with a moving speed of 0.005-0.4 m s-1 this causes the solution to generate multiple liquid jets under an applied voltage of 15-60 kV for the tip-less electrospinning process. The local electric field induced by the rod can boost electrohydrodynamic instability in order to generate Taylor cones and liquid jets. Experimentally, it is found that a large rod diameter and a small solution-to-rod distance can enhance the local electrical field to reduce the magnitude of the applied voltage. In the prototype setup with poly (ethylene oxide) polymer solution, an area of 5 cm  ×  10 cm and under an applied voltage of 60 kV, the maximum throughput of nanofibers is recorded to be approximately144 g m-2 h-1.

  9. Rigid rod anchored to infinite membrane.

    Science.gov (United States)

    Guo, Kunkun; Qiu, Feng; Zhang, Hongdong; Yang, Yuliang

    2005-08-15

    We investigate the shape deformation of an infinite membrane anchored by a rigid rod. The density profile of the rod is calculated by the self-consistent-field theory and the shape of the membrane is predicted by the Helfrich membrane elasticity theory [W. Helfrich, Z. Naturforsch. 28c, 693 (1973)]. It is found that the membrane bends away from the rigid rod when the interaction between the rod and the membrane is repulsive or weakly attractive (adsorption). However, the pulled height of the membrane at first increases and then decreases with the increase of the adsorption strength. Compared to a Gaussian chain with the same length, the rigid rod covers much larger area of the membrane, whereas exerts less local entropic pressure on the membrane. An evident gap is found between the membrane and the rigid rod because the membrane's curvature has to be continuous. These behaviors are compared with that of the flexible-polymer-anchored membranes studied by previous Monte Carlo simulations and theoretical analysis. It is straightforward to extend this method to more complicated and real biological systems, such as infinite membrane/multiple chains, protein inclusion, or systems with phase separation.

  10. Long-Rod Moving-Plate Interaction

    Science.gov (United States)

    Partom, Y.

    2002-07-01

    Understanding the mechanics of interaction of a long rod projectile with a forward moving plate at an angle is essential to understanding long rod interaction with an explosive reactive armor cassette. To investigate the mechanics of such an interaction we use AUTODIN2D/EULER in plane geometry, although the problem is 3D. We assume that this is a satisfactory approximation, as we're only interested in the main features, and are not comparing fine details to experimental results. From the simulations we learn that the interaction never reaches steady state. Initially each material splits into two streams, and the interaction plane is perpendicular to the rod. But with time the interaction plane rotates slowly, until it becomes parallel to the rod, which is then able to continue moving forward without interruption. During this process interacting rod material of length DeltaL is diverted at an angle and becomes ineffective for penetrating the main target. We made many such runs to determine the dependence of DeltaL on the parameters of the problem. This dependence makes it possible to predict DeltaL for a variety of rod-plate situations.

  11. Topological optimisation of rod-stirring devices

    CERN Document Server

    Finn, Matthew D

    2011-01-01

    There are many industrial situations where rods are used to stir a fluid, or where rods repeatedly stretch a material such as bread dough or taffy. The goal in these applications is to stretch either material lines (in a fluid) or the material itself (for dough or taffy) as rapidly as possible. The growth rate of material lines is conveniently given by the topological entropy of the rod motion. We discuss the problem of optimising such rod devices from a topological viewpoint. We express rod motions in terms of generators of the braid group, and assign a cost based on the minimum number of generators needed to write the braid. We show that for one cost function -- the topological entropy per generator -- the optimal growth rate is the logarithm of the golden ratio. For a more realistic cost function,involving the topological entropy per operation where rods are allowed to move together, the optimal growth rate is the logarithm of the silver ratio, $1+\\sqrt{2}$. We show how to construct devices that realise th...

  12. International symposium on fuel rod simulators: development and application

    Energy Technology Data Exchange (ETDEWEB)

    McCulloch, R.W. (comp.)

    1981-05-01

    Separate abstracts are included for each of the papers presented concerning fuel rod simulator operation and performance; simulator design and evaluation; clad heated fuel rod simulators and fuel rod simulators for cladding investigations; fuel rod simulator components and inspection; and simulator analytical modeling. Ten papers have previously been input to the Energy Data Base.

  13. Local Fuel Rod Crud Prediction Tool Applications

    Energy Technology Data Exchange (ETDEWEB)

    Krammen, Michael A.; Karoutas, Zeses E.; Wang, Guoqiang; Young, Michael Y

    2009-06-15

    A code system with attendant methods has been developed for modeling local fuel rod crud. This tool is used to perform the Crud Induced Localized Corrosion (CILC) risk assessment recommended by the EPRI crud and corrosion guidelines, which were developed in response to the INPO zero fuel failures by 2010 initiatives. The methodology is in production use. This paper will describe the range of problems the methodology has already been applied to and the especial pertinence to low duty fuel applications. The methodology begins with Computational Fluid Dynamics (CFD) computations over a fuel assembly grid span. The CFD results provide detailed relative variations in local heat transfer coefficient over the grid span. These very local relative variations are used to determine very local thermal hydraulic conditions over the entire axial length of every fuel rod in a reactor core over the life of the rod in reactor. The expansion using the local relative variations is currently accomplished with the HIDUTYDRV code. The very local thermal hydraulic conditions are combined with reactor coolant crud concentrations derived from EPRI BOA analysis as input to models for predicting very local fuel rod crud deposition. The reactor coolant crud concentrations are determined over each reactor cycle by reactor system wide crud mass balance calculations. The reactor coolant crud concentrations are used to calculate local crud thickness using mass transfer models which are a function of the local thermal conditions. The advanced crud deposition models also include models for calculating local crud dryout. Local crud deposition and crud dryout are strongly dependent on very local boiling or steaming, which are predicted through the translation of the CFD results. The local crud thickness and degree of local crud dryout are key factors in determining the margin or risk for local fuel rod cladding crud induced fuel failure. The development and first application of these methods was in

  14. Regulatory perspective on incomplete control rod insertions

    Energy Technology Data Exchange (ETDEWEB)

    Chatterton, M.

    1997-01-01

    The incomplete control rod insertions experienced at South Texas Unit 1 and Wolf Creek are of safety concern to the NRC staff because they represent potential precursors to loss of shutdown margin. Even before it was determined if these events were caused by the control rods or by the fuel there was an apparent correlation of the problem with high burnup fuel. It was determined that there was also a correlation between high burnup and high drag forces as well as with rod drop time histories and lack of rod recoil. The NRC staff initial actions were aimed at getting a perspective on the magnitude of the problem as far as the number of plants and the amount of fuel that could be involved, as well as the safety significance in terms of shutdown margin. As tests have been performed and data has been analyzed the focus has shifted more toward understanding the problem and the ways to eliminate it. At this time the staff`s understanding of the phenomena is that it was a combination of factors including burnup, power history and temperature. The problem appears to be very sensitive to these factors, the interaction of which is not clearly understood. The model developed by Westinghouse provides a possible explanation but there is not sufficient data to establish confidence levels and sensitivity studies involving the key parameters have not been done. While several fixes to the problem have been discussed, no definitive fixes have been proposed. Without complete understanding of the phenomena, or fixes that clearly eliminate the problem the safety concern remains. The safety significance depends on the amount of shutdown margin lost due to incomplete insertion of the control rods. Were the control rods to stick high in the core, the reactor could not be shutdown by the control rods and other means such as emergency boration would be required.

  15. Diagnostic criteria for idiopathic inflammatory myopathies. Problems of their optimization

    Directory of Open Access Journals (Sweden)

    O. A. Antelava

    2014-01-01

    Full Text Available The paper deals with the problems of optimizing the diagnostic criteria for idiopathic inflammatory myopathies (IIM, a group of heterogeneous rare autoimmune diseases characterized by inflammatory lesion in the skeletal muscles. The representatives of this group are traditionally considered to be polymyositis (PM, dermatomyositis (DM, and inclusion-body myositis. The authors detail the history of classification criteria for IIM from those proposed by T.A. Medsger et al. (1970 relying on its clinical picture, laboratory data and instrumental findings, as well as the criteria (including the first introduced exclusion ones elaborated by A. Bohan and J.B. Peter in 1975, which remain fundamental in both clinical practice and researches. The basis for the clinical and serological criteria proposed by Y. Troyanov et al. (2005 for IIM is the identification of myositis-overlap syndromes. The classificational (subtype identification and therapeutic value of the criteria based on clinical and serological characteristics was supported by the Hungarian investigators A. Vancsa et al. (2010 who investigated the relationship between the clinical and therapeutic characteristics of IIM and positivity for myositis-specific and myositis-associated antibodies. The criteria developed by M.C. Dalakas (1991, 2003 are based on the specific immunopathological features of a histological pattern, which allow the differentiation of DM, PM, and inclusion-body myositis from other myopathic syndromes. The 2004 European Neuromuscular Center (ENMC criteria first identify necrotizing autoimmune myopathy and nonspecific myositis as individual subtypes. The serological classification of IIM, which is based onthe assessment of autoantibodies that play an important role in the pathogenesis of the disease, is of indubitable interest. There is an obvious need for the correct and timely diagnosis of both IIM as a whole and its subtypes in particular, which is complicated by

  16. The Clinical Phenotypes of the Juvenile Idiopathic Inflammatory Myopathies

    Science.gov (United States)

    Shah, Mona; Mamyrova, Gulnara; Targoff, Ira N.; Huber, Adam M.; Malley, James D.; Rice, Madeline Murguia; Miller, Frederick W.; Rider, Lisa G.

    2013-01-01

    Abstract The juvenile idiopathic inflammatory myopathies (JIIM) are systemic autoimmune diseases characterized by skeletal muscle weakness, characteristic rashes, and other systemic features. Although juvenile dermatomyositis (JDM), the most common form of JIIM, has been well studied, the other major clinical subgroups of JIIM, including juvenile polymyositis (JPM) and juvenile myositis overlapping with another autoimmune or connective tissue disease (JCTM), have not been well characterized, and their similarity to the adult clinical subgroups is unknown. We enrolled 436 patients with JIIM, including 354 classified as JDM, 33 as JPM, and 49 as JCTM, in a nationwide registry study. The aim of the study was to compare demographics; clinical features; laboratory measures, including myositis autoantibodies; and outcomes among these clinical subgroups, as well as with published data on adult patients with idiopathic inflammatory myopathies (IIM) enrolled in a separate natural history study. We used random forest classification and logistic regression modeling to compare clinical subgroups, following univariate analysis. JDM was characterized by typical rashes, including Gottron papules, heliotrope rash, malar rash, periungual capillary changes, and other photosensitive and vasculopathic skin rashes. JPM was characterized by more severe weakness, higher creatine kinase levels, falling episodes, and more frequent cardiac disease. JCTM had more frequent interstitial lung disease, Raynaud phenomenon, arthralgia, and malar rash. Differences in autoantibody frequency were also evident, with anti-p155/140, anti-MJ, and anti-Mi-2 seen more frequently in patients with JDM, anti-signal recognition particle and anti-Jo-1 in JPM, and anti-U1-RNP, PM-Scl, and other myositis-associated autoantibodies more commonly present in JCTM. Mortality was highest in patients with JCTM, whereas hospitalizations and wheelchair use were highest in JPM patients. Several demographic and clinical

  17. Bent Telescopic Rods in Patients With Osteogenesis Imperfecta.

    Science.gov (United States)

    Lee, R Jay; Paloski, Michael D; Sponseller, Paul D; Leet, Arabella I

    2016-09-01

    Telescopic rods require alignment of 2 rods to enable lengthening. A telescopic rod converts functionally into a solid rod if either rod bends, preventing proper engagement. Our goal was to characterize implant bending as a mode of failure of telescopic rods used in the treatment of osteogenesis imperfecta in children. We conducted a retrospective review of our osteogenesis imperfecta database for patients treated with intramedullary telescopic rods at our institution from 1992 through 2010 and identified 12 patients with bent rods. The 6 boys and 6 girls had an average age at the time of initial surgery of 3.1 years (range, 1.8 to 8.3 y) and a total of 51 telescoping rods. Clinic notes, operative reports, and radiographs were reviewed. The rods were analyzed for amount of lengthening, characteristics of bending, presence of cut out, or disengagement from an anchor point. Bends in the rods were characterized by their location on the implant component. The bent and straight rods were compared. Data were analyzed with the Mann-Whitney test (statistical significance set at P≤0.05). Of the 51 telescoping rods, 17 constructs (33%) bent. The average interval between surgery and rod bending was 4.0 years (range, 0.9 to 8.2 y). Before bending, 11 of 17 telescoping rods had routine follow-up radiographs for review. In 10 of the rods, bending was present when early signs of rod failure were first detected. Rod bending did not seem to be related to rod size. There was no area on the rod itself that seemed more susceptible to bending. Rod bending can be an early sign of impending rod failure. When rod bending is first noted, it may predispose the rod to other subsequent failures such as loss of proximal and distal fixation and cut out. Rod bending should be viewed as an indicator for closer monitoring of the patient and discussions regarding future need for rod exchange. Level III-retrospective review.

  18. Potassium dependent rescue of a myopathy with core-like structures in mouse.

    Science.gov (United States)

    Hanson, M Gartz; Wilde, Jonathan J; Moreno, Rosa L; Minic, Angela D; Niswander, Lee

    2015-01-07

    Myopathies decrease muscle functionality. Mutations in ryanodine receptor 1 (RyR1) are often associated with myopathies with microscopic core-like structures in the muscle fiber. In this study, we identify a mouse RyR1 model in which heterozygous animals display clinical and pathological hallmarks of myopathy with core-like structures. The RyR1 mutation decreases sensitivity to activated calcium release and myoplasmic calcium levels, subsequently affecting mitochondrial calcium and ATP production. Mutant muscle shows a persistent potassium leak and disrupted expression of regulators of potassium homeostasis. Inhibition of KATP channels or increasing interstitial potassium by diet or FDA-approved drugs can reverse the muscle weakness, fatigue-like physiology and pathology. We identify regulators of potassium homeostasis as biomarkers of disease that may reveal therapeutic targets in human patients with myopathy of central core disease (CCD). Altogether, our results suggest that amelioration of potassium leaks through potassium homeostasis mechanisms may minimize muscle damage of myopathies due to certain RyR1 mutations.

  19. Deleterious mutation in FDX1L gene is associated with a novel mitochondrial muscle myopathy.

    Science.gov (United States)

    Spiegel, Ronen; Saada, Ann; Halvardson, Jonatan; Soiferman, Devorah; Shaag, Avraham; Edvardson, Simon; Horovitz, Yoseph; Khayat, Morad; Shalev, Stavit A; Feuk, Lars; Elpeleg, Orly

    2014-07-01

    Isolated metabolic myopathies encompass a heterogeneous group of disorders, with mitochondrial myopathies being a subgroup, with depleted skeletal muscle energy production manifesting either by recurrent episodes of myoglobinuria or progressive muscle weakness. In this study, we investigated the genetic cause of a patient from a consanguineous family who presented with adolescent onset autosomal recessive mitochondrial myopathy. Analysis of enzyme activities of the five respiratory chain complexes in our patients' skeletal muscle showed severely impaired activities of iron sulfur (Fe-S)-dependent complexes I, II and III and mitochondrial aconitase. We employed exome sequencing combined with homozygosity mapping to identify a homozygous mutation, c.1A>T, in the FDX1L gene, which encodes the mitochondrial ferredoxin 2 (Fdx2) protein. The mutation disrupts the ATG initiation translation site resulting in severe reduction of Fdx2 content in the patient muscle and fibroblasts mitochondria. Fdx2 is the second component of the Fe-S cluster biogenesis machinery, the first being IscU that is associated with isolated mitochondrial myopathy. We suggest adding genetic analysis of FDX1L in cases of mitochondrial myopathy especially when associated with reduced activity of the respiratory chain complexes I, II and III.

  20. Risk of Colchicine-Associated Myopathy in Gout: Influence of Concomitant Use of Statin.

    Science.gov (United States)

    Kwon, Oh Chan; Hong, Seokchan; Ghang, Byeongzu; Kim, Yong-Gil; Lee, Chang-Keun; Yoo, Bin

    2017-05-01

    The purpose of this study was to investigate the risk of myopathy when statins are coadministered with colchicine in patients with gout. In gout patients who received colchicine with or without statin, clinical data collected included medications and history of hypertension, chronic kidney disease, and liver cirrhosis. Myopathy was defined as the presence of muscle symptoms with elevated creatine kinase or myoglobin. Multivariate analysis was performed to identify risk factors for myopathy. Inverse probability of treatment weighting (IPTW)-adjusted analysis was used to evaluate the influence of concomitant colchicine and statin use on myopathy. Of 674 patients, 486 received colchicine alone and 188 also received statin. The incidence of myopathy was not significantly higher in those on both drugs than in those on colchicine alone (2.7% vs 1.4%, P = .330). On multivariate analysis, chronic kidney disease (hazard ratio [HR] 29.056; 95% confidence interval [CI], 4.387-192.450; P gout patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Osteopathic approach to sacroiliac dysfunction in a patient with steroid myopathy: case report and literature review.

    Science.gov (United States)

    Kohns, David J; Fitch, David S

    2014-06-01

    Long-term steroid use has a well-documented risk of myopathy that imposes functional limitations for patients and challenges for health care providers. Proximal weakness from steroid myopathy affects support structures around the pelvic girdle and likely predisposes patients to somatic dysfunction. To the authors' knowledge, there are no prior reports in the literature that describe an osteopathic manipulative medicine (OMM) approach for patients with steroid myopathy. In the present case report, a 59-year-old woman with acute myeloid leukemia received a blood stem cell transplantation and developed gastrointestinal graft-versus-host disease. High-dose steroids were prescribed, and she developed proximal weakness from steroid myopathy. The patient's acute inpatient rehabilitation was impacted by new onset left sacroiliac dysfunction. A patient-focused OMM approach was used to assist the patient in maximizing her sacroiliac function. The proximal weakness seen with steroid myopathy necessitates special considerations for an OMM approach to address somatic dysfunction associated with this disease.

  2. Neb: a zebrafish model of nemaline myopathy due to nebulin mutation.

    Science.gov (United States)

    Telfer, William R; Nelson, Darcee D; Waugh, Trent; Brooks, Susan V; Dowling, James J

    2012-05-01

    Nemaline myopathy is one of the most common and severe non-dystrophic muscle diseases of childhood. Patients typically present in infancy with hypotonia, weakness, delayed motor development, and bulbar and respiratory difficulties. Mutations in six different genes are associated with nemaline myopathy, with nebulin mutations being the most common. No treatments or disease-modifying therapies have been identified for this disease. One of the major barriers to treatment development is the lack of models amenable to rapid and coordinated testing of potential therapeutic strategies. To overcome this barrier, we have characterized the first zebrafish model of nemaline myopathy. This model, termed neb, harbors a recessive mutation in the nebulin gene that results in decreased Nebulin protein levels, a severe motor phenotype and premature lethality. In addition to impaired motor function, neb zebrafish exhibit many of the features associated with human nemaline myopathy. These include impaired force generation, altered thin filament length and the presence of specific histopathological changes, including the formation of nemaline bodies. In summary, neb zebrafish mirror the genetic, clinical and pathological aspects of nemaline myopathy due to NEB mutation, and thus are an excellent model for future therapy development for this devastating disorder.

  3. neb: a zebrafish model of nemaline myopathy due to nebulin mutation

    Directory of Open Access Journals (Sweden)

    William R. Telfer

    2012-05-01

    Nemaline myopathy is one of the most common and severe non-dystrophic muscle diseases of childhood. Patients typically present in infancy with hypotonia, weakness, delayed motor development, and bulbar and respiratory difficulties. Mutations in six different genes are associated with nemaline myopathy, with nebulin mutations being the most common. No treatments or disease-modifying therapies have been identified for this disease. One of the major barriers to treatment development is the lack of models amenable to rapid and coordinated testing of potential therapeutic strategies. To overcome this barrier, we have characterized the first zebrafish model of nemaline myopathy. This model, termed neb, harbors a recessive mutation in the nebulin gene that results in decreased Nebulin protein levels, a severe motor phenotype and premature lethality. In addition to impaired motor function, neb zebrafish exhibit many of the features associated with human nemaline myopathy. These include impaired force generation, altered thin filament length and the presence of specific histopathological changes, including the formation of nemaline bodies. In summary, neb zebrafish mirror the genetic, clinical and pathological aspects of nemaline myopathy due to NEB mutation, and thus are an excellent model for future therapy development for this devastating disorder.

  4. Axial Vibration Confinement in Nonhomogenous Rods

    Directory of Open Access Journals (Sweden)

    S. Choura

    2005-01-01

    Full Text Available A design methodology for the vibration confinement of axial vibrations in nonhomogenous rods is proposed. This is achieved by a proper selection of a set of spatially dependent functions characterizing the rod material and geometric properties. Conditions for selecting such properties are established by constructing positive Lyapunov functions whose derivative with respect to the space variable is negative. It is shown that varying the shape of the rod alone is sufficient to confine the vibratory motion. In such a case, the vibration confinement requires that the eigenfunctions be exponentially decaying functions of space, where the notion of spatial domain stability is introduced as a concept dual to that of the time domain stability. It is also shown that vibration confinement can be produced if the rod density and/or stiffness are varied with respect to the space variable while the cross-section area is kept constant. Several case studies, supporting the developed conditions imposed on the spatially dependent functions for vibration confinement in vibrating rods, are discussed. Because variation in the geometric and material properties might decrease the critical buckling loads, we also discuss the buckling problem.

  5. Wetting of a partially immersed compliant rod

    Science.gov (United States)

    Hui, Chung-Yuen; Jagota, Anand

    2016-11-01

    The force on a solid rod partially immersed in a liquid is commonly used to determine the liquid-vapor surface tension by equating the measured force required to remove the rod from the liquid to the vertical component of the liquid-vapor surface tension. Here, we study how this process is affected when the rod is compliant. For equilibrium, we enforce force and configurational energy balance, including contributions from elastic energy. We show that, in general, the contact angle does not equal that given by Young's equation. If surface stresses are tensile, the strain in the immersed part of the rod is found to be compressive and to depend only on the solid-liquid surface stress. The strain in the dry part of the rod can be either tensile or compressive, depending on a combination of parameters that we identify. We also provide results for compliant plates partially immersed in a liquid under plane strain and plane stress. Our results can be used to extract solid surface stresses from such experiments.

  6. Single Rod Vibration in Axial Flow

    Science.gov (United States)

    Weichselbaum, Noah; Wang, Shengfu; Bardet, Philippe

    2013-11-01

    Fluid structure interaction of a single rod in axial flow is a coupled dynamical system present in many application including nuclear reactors, steam generators, and towed antenna arrays. Fluid-structure response can be quantified thanks to detailed experimental data where both structure and fluid responses are recorded. Such datum deepen understanding of the physics inherent to the system and provide high-dimensionality quantitative measurements to validate coupled structural and CFD codes with various level of complexity. In this work, single rods fixed on both ends in a concentric pipe, are subjected to an axial flow with Reynolds number based on hydraulic diameter of Re =4000. Rods of varying material stiffness and diameter are utilized in the experiment resulting in a range of dimensionless U between 0.5 and 1, where U = (ρA/EI)1/2uL. Experimental measurements of the velocity field around the rod are taken with PIV from time-resolved Nd:YLF laser and a high speed CMOS camera. Three-dimensional and temporal vibration and deflection of the rod is recorded with shadowgraphy utilizing two sets of pulsed high power LED and dedicated CMOS camera. Through integration of these two diagnostics, it is possible to reconstruct the full FSI domain providing unique validation data.

  7. Dielectric rod feed for compact range reflector

    CERN Document Server

    Balabukha, Nikolay P; Shapkina, Natalia E

    2014-01-01

    A dielectric rod feed with a special radiation pattern of a tabletop form used for the compact range reflector is developed and analyzed. Application of this feed increases the size of the compact range quiet zone generated by the reflector. The feed consists of the dielectric rod made of polystyren, the rod is inserted into the circular waveguide with a corrugated flange. The waveguide is excited by the H11-mode. The rod is covered by the textolite biconical bushing and has a fluoroplastic insert in the vicinity of the bushing. Mathematical modeling was used to obtain the parameters of the feed for the optimal tabletop form of the radiation pattern. The problem of the electromagnetic radiation was solved for metal-dielectric bodies of rotation by method of integral equations with further solving of the problem of the synthesis for feed parameters. The dielectric rod feed was fabricated for the X-frequency range. Feed amplitude and phase patterns were measured in the frequency range 8.2-12.5 GHz. Presented re...

  8. Sporadic late-onset nemaline myopathy with MGUS: Long-term follow-up after melphalan and SCT

    NARCIS (Netherlands)

    Voermans, N.C.; Benveniste, O.; Minnema, M.C.; Lokhorst, H.; Lammens, M.; Meersseman, W.; Delforge, M.; Kuntzer, T.; Novy, J.; Pabst, T.; Bouhour, F.; Romero, N.; Leblond, V.; Bergh, P.; Vekemans, M.C.; Engelen, B.G.M. van; Eymard, B.

    2014-01-01

    OBJECTIVE: Sporadic late-onset nemaline myopathy (SLONM) is a rare, late-onset myopathy that progresses subacutely. If associated with a monoclonal gammopathy of unknown significance (MGUS), the outcome is unfavorable: the majority of these patients die within 1 to 5 years of respiratory failure.

  9. Canine inflammatory myopathy associated with Leishmania Infantum infection.

    Science.gov (United States)

    Paciello, Orlando; Oliva, Gaetano; Gradoni, Luigi; Manna, Laura; Foglia Manzillo, Valentina; Wojcik, Slawomir; Trapani, Francesca; Papparella, Serenella

    2009-02-01

    Inflammatory myopathy associated with several infectious diseases occurs in dogs including those caused by Toxoplasma gondii, Neospora caninum, Ehrlichia canis and Hepatozoon canis. However, muscle disease due to Leishmania infection has been poorly documented. The aim of this study was to examine the distribution and types of cellular infiltrates and expression of MHC class I and II in muscle biopsies obtained from 15 male beagle dogs from a breeder group with an established diagnosis of leishmaniasis. Myopathic features were characterized by necrosis, regeneration, fibrosis and infiltration of mononuclear inflammatory cells consisting of lymphocytes, plasma cells and histiocytes. The predominant leukocyte populations were CD3+, CD8+ and CD45RA+ with lesser numbers of CD4+ cells. Many muscle fibers had MHC class I and II positivity on the sarcolemma. There was a direct correlation between the severity of pathological changes, clinical signs, and the numbers of Leishmania amastigotes. Our studies provided evidence that: 1) Leishmania should be considered as a cause of IM in dogs; 2) Leishmania is not present within muscle fibers but in macrophages, and that 3) the muscle damage might be related to immunological alterations associated with Leishmania infection. Leishmania spp. should also be considered as a possible cause in the pathogenesis of human myositis.

  10. Muscle sonography in six patients with hereditary inclusion body myopathy

    Energy Technology Data Exchange (ETDEWEB)

    Adler, Ronald S. [Weill Medical College of Cornell University, Division of Ultrasound and Body Imaging, Hospital for Special Surgery, New York, NY (United States); Garolfalo, Giovanna [Ospedale Residenza Sanitaria Riabilitativa, Fermo, AP (Italy); Paget, Stephen; Kagen, Lawrence [Weill Medical College of Cornell University, Rheumatology Division, Hospital for Special Surgery, New York, NY (United States)

    2008-01-15

    To evaluate the morphological changes of muscle with sonography in six patients affected by hereditary inclusion body myopathy (HIBM). We studied a group of six Persian Jews diagnosed with HIBM. All were homozygous for the GNE mutation M712T. Ultrasonographic examinations of the quadriceps femoris and hamstring muscle groups were performed. A follow-up ultrasound examination was performed, after an interval of 3 years, in four of these patients. Muscles were assessed subjectively as to echogenicity, determined by gray-scale assessment, and loss of normal muscle morphology. Power Doppler sonography (PDS) was used to assess vascularity. A sonographic finding of central atrophy and peripheral sparing resulting in a target-like appearance was noted in the hamstring compartment of all six patients. The quadriceps compartment also showed involvement of the rectus femoris of all patients, which, in some cases, was the only muscle involved in the quadriceps. Vascularity was markedly reduced in the affected areas, with blood flow demonstrated in the peripherally spared areas. The severity of atrophy increased with disease duration. In this case series, we describe a new sonographic finding as well as document progression of HIBM disease, which has generally been described as quadriceps sparing. The myopathic target lesion, as well as isolated rectus femoris atrophy, may provide a useful adjunct to disease diagnosis. (orig.)

  11. Typhoid myopathy or typhoid hepatitis: A matter of debate

    Directory of Open Access Journals (Sweden)

    Mirsadraee M

    2007-01-01

    Full Text Available Purpose: The aim of the present study was to evaluate the major source of increased serum enzyme level in typhoid fever and to determine the most relevant clinical entity, hepatitis or myopathy, during typhoid fever. Methods: A total of 118 subjects proved to have typhoid fever were evaluated for serum enzymes such as transaminases, alkaline phosphatase, lactate dehydrogenase (LDH and creatinine kinase (CK; and their relation with each other, clinical symptoms and serum bilirubin were evaluated by regression methods. Results: Hepatomegaly was revealed in 14% of the cases and was correlated with elevated serum biliribin (5.05 ± 13.03 mg/dL in hepatomegalic subjects. Alanine aminotransferase (ALT and CK were elevated in 22 and 60% of the cases, respectively. Correlation coefficient of CK with aspartate aminotransferase (AST and LDH was R 2 = 0.68 and 0.75, respectively, which were higher than that of ALT with that two enzymes. Conclusions: In conclusion, elevation of serum enzymes in typhoid is mostly of muscular origin.

  12. Mechanical signaling in the pathophysiology of critical illness myopathy

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    Rebeca Corpeño Kalamgi

    2016-02-01

    Full Text Available The complete loss of mechanical stimuli of skeletal muscles, i.e., the loss of external strain, related to weight bearing, and internal strain, related to the contraction of muscle cells, is uniquely observed in pharmacologically paralyzed or deeply sedated mechanically ventilated intensive care unit (ICU patients. The preferential loss of myosin and myosin associated proteins in limb and trunk muscles is a significant characteristic of critical illness myopathy (CIM which separates CIM from other types of acquired muscle weaknesses in ICU patients. Mechanical silencing is an important factor triggering CIM. Microgravity or ground based microgravity models form the basis of research on the effect of muscle unloading-reloading, but the mechanisms and effects may differ from the ICU conditions. In order to understand how mechanical tension regulates muscle mass, it is critical to know how muscles sense mechanical information and convert stimulus to intracellular biochemical actions and changes in gene expression, a process called cellular mechanotransduction. In adult skeletal muscles and muscle fibers, this process may differ, the same stimulus can cause divergent response and the same fiber type may undergo opposite changes in different muscles. Skeletal muscle contains multiple types of mechano-sensors and numerous structures that can be affected differently and hence respond differently in distinct muscles

  13. Incidence of malignancies in biopsy-proven inflammatory myopathy

    Directory of Open Access Journals (Sweden)

    Meena A Kannan

    2013-01-01

    Full Text Available Background: Inflammatory myopathy (IM as a manifestation of paraneoplastic syndrome has been well-documented. However, the prevalence of malignancies reported varies across the studies. There are very few studies reported from Asia, only one from India. Aim: The aim of this analysis was to study the prevalence of malignancy in biopsy-proven cases of IM in India and to study the difference between malignant and non-malignant groups. Materials and Methods: The study was a retrospective review of case records of patients with a biopsy-proven IM attending Tertiary Care University Hospital. Results: Of the total 86 patients with biopsy-proven IM, 22 patients were polymyositis, 63 patients had dermatomyositis (DM and one was with an inclusion body myositis, not included for further analysis. Associated malignancy was diagnosed in 6 (7% patients, and five of them were females. Diagnosis of associated malignancy was identified at the time of diagnosis of IM in four (66.7% patients. All the six patients with an associated malignancy had DM. Only one patient died within 1 year of diagnosis. Creatinine kinase was much lower in patients with malignancy associated IM than in patients with no malignancy (P < 0.0001. Conclusion: The prevalence of malignancy was very low in our cohort as compared to the studies from other countries. Breast cancer was the most common malignancy associated with DM. The type of associated malignancy was quite variable.

  14. Pathogenesis and therapies of immune-mediated myopathies.

    Science.gov (United States)

    Dalakas, Marinos C

    2012-01-01

    The most common autoimmune muscle disorders include dermatomyositis (DM), polymyositis (PM), necrotizing autoimmune myositis (NAM) and sporadic inclusion body myositis (sIBM). DM is a complement-mediated microangiopathy leading to destruction of capillaries, hypoperfusion and inflammatory cell stress on the perifascicular regions. NAM is an increasingly recognized subacute myopathy triggered by statins, viral infections, cancer or autoimmunity with macrophages as the final effector cells causing fiber injury. PM and IBM are T cell-mediated disorders where cytotoxic CD8(+) T cells clonally expand in situ and invade major histocompatibility complex class I expressing muscle fibers. In sIBM, in addition to autoreactive T cells, there are degenerative features characterized by vacuolization and accumulation of stressor or amyloid-related misfolded proteins; an interrelationship between inflammatory and degeneration-associated molecules is prominent and enhances the cascade of pathogenic factors. These disorders are treatable, hence the need to make the correct diagnosis from the outset. The applied therapeutic strategies are outlined and the promising new agents are reviewed.

  15. How to diagnose and treat the inflammatory myopathies.

    Science.gov (United States)

    Dalakas, M C

    1994-06-01

    The inflammatory myopathies include 3 distinct entities, PM, DM, and IBM. These diseases differ clinically, immunopathologically, and in their response to therapies. Although DM and IBM are easy to diagnose on the basis of characteristic clinicopathologic findings, PM still remains a diagnosis of exclusion. A T cell-mediated cytotoxic process in PM and IBM and a complement-mediated microangiopathy in DM, along with the various serologic markers of autoimmunity, are the hallmarks of the underlying autoimmune processes in these groups. Although in uncontrolled studies PM and DM appear to respond to prednisone and immunosuppressive drugs to some degree and for some period of time, IBM is resistant to all therapies. Currently, high-dose intravenous immunoglobulin (IVIG) appears to be an encouraging and safe new modality of treatment for some of these conditions when other therapies have failed. In a controlled study, IVIG has been shown to be effective in DM and, in uncontrolled studies, in some patients with PM or IBM.

  16. [Statin associated myopathy in clinical practice. Results of DAMA study].

    Science.gov (United States)

    Millán, Jesús; Pedro-Botet, Juan; Climent, Elisenda; Millán, Joaquín; Rius, Joan

    Muscle symptoms, with or without elevation of creatin kinase are one of the main adverse effects of statin therapy, a fact that sometimes limits their use. The aim of this study was to evaluate the clinical characteristics of patients treated with statins who have complained muscle symptoms and to identify possible predictive factors. A cross-sectional one-visit, non-interventional, national multicenter study including patients of both sexes over 18 years of age referred for past or present muscle symptoms associated with statin therapy was conducted. 3,845 patients were recruited from a one-day record from 2,001 physicians. Myalgia was present in 78.2% of patients included in the study, myositis in 19.3%, and rhabdomyolysis in 2.5%. Patients reported muscle pain in 77.5% of statin-treated individuals, general weakness 42.7%, and cramps 28.1%. Kidney failure, intense physical exercise, alcohol consumption (>30g/d in men and 20g/d in women) and abdominal obesity were the clinical situations associated with statin myopathy. Myalgia followed by myositis are the most frequent statin-related side effects. It should be recommended control environmental factors such as intense exercise and alcohol intake as well as abdominal obesity and renal function of the patient treated with statins. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Repository Corticotropin Injection for Treatment of Idiopathic Inflammatory Myopathies

    Directory of Open Access Journals (Sweden)

    Aarat Patel

    2016-01-01

    Full Text Available Idiopathic inflammatory myopathies are a group of systemic autoimmune diseases that involve inflammation of skeletal muscle. The two most common forms are dermatomyositis and polymyositis, the former of which entails a skin component. There are few approved therapeutics available for treatment of this group of diseases and the first-line therapy is usually corticosteroid treatment. Considering that a large proportion of patients do not respond to or cannot tolerate corticosteroids, additional treatments are required. There are second-line therapies available, but many patients are also refractory to those options. H.P. Acthar® Gel (repository corticotropin injection [RCI] is a melanocortin peptide that can induce steroid-dependent effects and steroid-independent effects. Herein, we present a series of cases that involved the use of RCI in the management of dermatomyositis and polymyositis. RCI treatments resulted in improvement in three of four patients, despite failure with previous therapies. The use of RCI did not exacerbate any comorbidity and no significant changes in blood pressure, weight, or glycemic control were observed. Overall, these results are encouraging and suggest that randomized, controlled clinical trials applying RCI to dermatomyositis and polymyositis are warranted.

  18. Long term functional outcome of idiopathic inflammatory myopathies

    Directory of Open Access Journals (Sweden)

    G. Pasero

    2011-09-01

    Full Text Available The idiopathic inflammatory myopathies (IIM comprise a group of diseases characterized by chronic inflammation of the skeletal muscles. The definition of the long-term outcome of IIM, has been limited by the difficulty in objectively evaluating the rate of muscle function impairment. Aim of our study, was to define the long term outcome in a group of 37 IIM patients, followed at our centres between 1979 and 1999. A protocol, evaluating CK levels, muscle function, and disability in daily life activity was prospectively designed. The disease outcome was defined on the basis the patient’s functional evaluation. Disease activity was defined as the presence of an increase in serum CK levels associated with an increase of therapy. At the end of follow up, 27% of the patients had an active disease and 35% had a poor functional outcome. On the basis of our results we could distinguish three different outcomes of IIM: (i good functional outcome (65%; (ii poor functional outcome with inactive disease (13.5%; (iii poor functional outcome and active disease (21,5%. In conclusion, although IIM seem to have a good evolution in terms of disease activity, in about 46% of patients they are associated with an elevated incidence of functional impairement, probably attributable both to the disease’s damage and to the side effects of therapy.

  19. Episodic weakness and vacuolar myopathy in hypokalemic periodic paralysis.

    Science.gov (United States)

    Basali, Diana; Prayson, Richard A

    2015-11-01

    We report a 50-year-old woman who presented with a 20 year history of gradually progressive lower extremity weakness, characterized by knee buckling with occasional falls and foot dragging. She also experienced difficulty in lifting her arms above her shoulders. The primary periodic paralyses are rare disorders caused by dysfunctional ion channels in skeletal muscle. The hypokalemic type is generally an autosomal dominant condition, due to missense mutations in the alpha subunits of the skeletal muscle L-type calcium channel genes, CACN1AS, or the skeletal muscle sodium channel gene, SCN4A. The affected patients typically present with episodic weakness. For our patient, the consumption of foods high in carbohydrates seemed to precipitate the episodes of weakness. Her family history was significant for six blood relatives, including three sons and three relatives on the paternal side, who had experienced similar symptoms. A biopsy of the left rectus femoralis muscle showed vacuolar myopathic changes in the scattered muscle fibers, accompanied by occasional degenerating and regenerating muscle fibers. There was no evidence of inflammation on the biopsy. The vacuoles were often associated with increased acid phosphatase staining. An electron microscopic examination showed that the vacuolar changes were due to T-tubule dilation, a characteristic of hypokalemic periodic paralysis. Other metabolic etiologies of vacuolar myopathy, such as acid phosphatase (lysosomal) associated acid maltase deficiency (a glycogen storage disease), need to be considered in the differential diagnosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Steroid myopathy in patients with chronic respiratory diseases.

    Science.gov (United States)

    Levin, Oleg S; Polunina, Anna G; Demyanova, Marina A; Isaev, Fedor V

    2014-03-15

    Corticosteroid-induced myopathy is a well known clinical entity, and experimental studies showed decreased rate of protein synthesis and increased rate of protein breakdown in muscles of chronically treated animals. The present observational study was aimed to evaluate skeletal muscle functions in asthmatics and patients with other chronic respiratory diseases treated by inhaled or oral corticosteroids. Thirty six patients with respiratory diseases were included into the study. The physician-rated peripheral motor deficits scale, stepper test and ankle/wrist index were used for assessment of muscle functions. The effects of length of glucocorticoids intake on muscle functions were evaluated. Sixty five per cent of patients using corticosteroids daily during 1 year and longer reported weakness in legs, and 20% of these patients demonstrated objective signs of the muscle weakness. The performance on the stepper test was significantly worse in patients chronically using corticosteroids in comparison with the control group (10.9 ± 3.4 steps vs 16.1 ± 2.4 steps per 10s, respectively; F=21.6, pmuscle hypotrophy at a dominant leg. Chronic intake of inhaled corticosteroids induces clinically significant decrease of muscle functions at least after 1-year of daily treatment. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Rod consolidation at the West Valley Demonstration Project

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, W.J.

    1986-12-01

    A rod consolidation demonstration with irradiated pressurized water reactor fuel was recently conducted by personnel from Nuclear Assurance Corporation and West Valley Nuclear Services Company at the West Valley Demonstration Project in West Valley, New York. The rod consolidation demonstration involved pulling all of the fuel rods from six fuel Assemblies. In general, the rod pulling proceeded smoothly. The highest compaction ratio attained was 1:8:1. Among the total of 1074 fuel rods were some known degraded rods (they had collapsed cladding, a result of in-reactor fuel densification), but no rods were broken or dropped during the demonstration. One aim was to gather information on the effect of rod consolidation operations on the integrity of the fuel rods during subsequent handling and storage. Another goal was to collect information on the condition and handling of intact, damaged, and failed fuel that has been in storage for an extended period. 9 refs., 8 figs., 1 tab.

  2. Magnetic switch for reactor control rod. [LMFBR

    Science.gov (United States)

    Germer, J.H.

    1982-09-30

    A magnetic reed switch assembly is described for activating an electromagnetic grapple utilized to hold a control rod in position above a reactor core. In normal operation the magnetic field of a permanent magnet is short-circuited by a magnetic shunt, diverting the magnetic field away from the reed switch. The magnetic shunt is made of a material having a Curie-point at the desired release temperature. Above that temperature the material loses its ferromagnetic properties, and the magnetic path is diverted to the reed switch which closes and short-circuits the control circuit for the control rod electro-magnetic grapple which allows the control rod to drop into the reactor core for controlling the reactivity of the core.

  3. On a case of respiratory failure due to diaphragmatic paralysis and dilated cardiomyopathy in a patient with nemaline myopathy.

    Science.gov (United States)

    Taglia, Antonella; D'Ambrosio, Paola; Palladino, Alberto; Politano, Luisa

    2012-12-01

    Nemaline myopathy is a rare congenital disease that generally occurs in childhood. We report a case of a 50-year-old man who presented with severe heart failure as the initial manifestation of nemaline myopathy. Soon after he developed acute restrictive respiratory failure due to the diaphragmatic paralysis. The diagnosis of "nemaline myopathy" was obtained on muscle biopsy performed one year later. After starting appropriate cardiological treatment and non-invasive ventilation, his cardiac and pulmonary functions improved substantially, remaining stable for over the 10 years since diagnosis. In the last two years the patient had a progressive deterioration of respiratory function, enabling him to attend daily activities. Few cases of respiratory failure in patients with adult-onset nemaline myopathy are reported, but the insidious onset in this case is even more unusual. This case highlights the wide spectrum of presenting features of adult-onset nemaline myopathy and the temporary efficacy of non invasive ventilation on respiratory function.

  4. EVALUATION OF PLASMA LACTATE CONCENTRATION IN UNEXPLAINED MYOPATHIES WITH MULTI-ORGAN INVOLVEMENT

    Directory of Open Access Journals (Sweden)

    Papia

    2013-02-01

    Full Text Available ABSTRACT: Myopathies are disorders of muscle with structural c hanges or functional impairment. Mitochondrial myopathies are caused by g enetic mutations that directly influence the functioning of the electron transport chain. The ubiquitous distribution of the mitochondria in the human body explains the multiple organ involv ement. Diagnosis often requires a multifaceted approach with measurements of serum lact ate, magnetic resonance spectroscopy, muscle histology and ultrastructure, enzymology, ge netic analysis, and exercise testing. The present study was conducted to find out the reason b ehind unexplained myopathies with multi- organ involvement by measuring plasma lactate concen tration in patients who were suspected to be suffering from mitochondrial disorders. Muscl e biopsy samples of those patients were also subjected for histopathological assessment. Out of t wenty suspected patients, nine patients showed high lactate concentration and their muscle biopsy sample also revealed some changes suggestive of mitochondrial disorders.

  5. Lipid storage myopathy with clinical markers of Marfan syndrome: A rare association

    Directory of Open Access Journals (Sweden)

    Subasree Ramakrishnan

    2012-01-01

    Full Text Available Disorders of lipid metabolism can cause variable clinical presentations, often involving skeletal muscle, alone or together with other tissues. A 19-year-old boy presented with a 2-year history of muscle pain, cramps, exercise intolerance and progressive weakness of proximal lower limbs. Examination revealed skeletal markers of Marfan syndrome in the form of increased arm span compared with height, Kyphoscoliois, moderate pectus excavatum, high arched palate and wrist sign. He also had mild neck flexor weakness and proximal lower limb weakness with areflexia. Pathologic findings revealed lipid-laden fine vacuoles in the muscle fibers. Possibility of carnitine deficiency myopathy was considered and the patient was started on carnitine and Co Q. The patient made remarkable clinical improvement over the next 2 months. This case is reported for rarity of the association of clinical markers of Marfan syndrome and lipid storage myopathy and sparse literature on lipid storage myopathy in the Indian context.

  6. Statin-Induced Myopathy Is Associated with Mitochondrial Complex III Inhibition.

    Science.gov (United States)

    Schirris, Tom J J; Renkema, G Herma; Ritschel, Tina; Voermans, Nicol C; Bilos, Albert; van Engelen, Baziel G M; Brandt, Ulrich; Koopman, Werner J H; Beyrath, Julien D; Rodenburg, Richard J; Willems, Peter H G M; Smeitink, Jan A M; Russel, Frans G M

    2015-09-01

    Cholesterol-lowering statins effectively reduce the risk of major cardiovascular events. Myopathy is the most important adverse effect, but its underlying mechanism remains enigmatic. In C2C12 myoblasts, several statin lactones reduced respiratory capacity and appeared to be strong inhibitors of mitochondrial complex III (CIII) activity, up to 84% inhibition. The lactones were in general three times more potent inducers of cytotoxicity than their corresponding acid forms. The Qo binding site of CIII was identified as off-target of the statin lactones. These findings could be confirmed in muscle tissue of patients suffering from statin-induced myopathies, in which CIII enzyme activity was reduced by 18%. Respiratory inhibition in C2C12 myoblasts could be attenuated by convergent electron flow into CIII, restoring respiration up to 89% of control. In conclusion, CIII inhibition was identified as a potential off-target mechanism associated with statin-induced myopathies.

  7. Ultrastructural changes in muscle cells of patients with collagen VI-related myopathies.

    Science.gov (United States)

    Tagliavini, Francesca; Sardone, Francesca; Squarzoni, Stefano; Maraldi, Nadir Mario; Merlini, Luciano; Faldini, Cesare; Sabatelli, Patrizia

    2013-10-01

    Collagen VI is an extracellular matrix protein expressed in several tissues including skeletal muscle. Mutations in COL6A genes cause Bethlem Myopathy (BM), Ullrich Congenital Muscular Dystrophy (UCMD) and Myosclerosis Myopathy (MM). Collagen VI deficiency causes increased opening of the mitochondrial permeability transition pore (mPTP), leading to ultrastructural and functional alterations of mitochondria, amplified by impairment of autophagy. Here we report for the first time ultrastructural studies on muscle biopsies from BM and UCMD patients, showing swollen mitochondria with hypodense matrix, disorganized cristae and paracrystalline inclusions, associated with dilated sarcoplasmic reticulum and apoptotic changes. These data were supported by scanning electron microscopy analysis on BM and UCMD cultured cells, showing alterations of the mitochondrial network. Morphometric analysis also revealed a reduced short axis and depicted swelling in about 3% of mitochondria. These data demonstrate that mitochondrial defects underlie the pathogenetic mechanism in muscle tissue of patients affected by collagen VI myopathies.

  8. THE PATHOGENESIS OF EXPERIMENTAL MODEL OF MITOCHONDRIAL MYOPATHY INDUCED BY GERMANIUM DIOXIDE

    Institute of Scientific and Technical Information of China (English)

    李晓东; 高枫; 陈清棠

    2001-01-01

    Objective. The purpose of the study was to build up an animal model of mitochondrial myopathy in order to analyse the pathogenesis of the disease.Methods. The skeletal muscles from Wistar rats treated with germanium dioxide for 24 weeks were analysed by histopathologic and electron-microscopic studies. A quantitative analysis was carried out in mitochondrial DNAs of these samples. The biological function of the model was determined.``Results. An animal model of mitochondrial myopathy was built up, in which oxygen free radicals were increased and mitochondrial DNA copies were decreased contrasted with controls.``Conclusion. It suggested that environmental toxin may play a role in the pathogenesis of mitochondrial myopathy. The increase of oxygen free radicals is an important link causing the disease.

  9. THE PATHOGENESIS OF EXPERIMENTAL MODEL OF MITOCHONDRIAL MYOPATHY INDUCED BY GERMANIUM DIOXIDE

    Institute of Scientific and Technical Information of China (English)

    李晓东; 高枫; 陈清棠

    2001-01-01

    Objective. The purpose of the study was to build up an animal model of mitochondrial myopathy in order to analyse the pathogenesis of the disease. Methods. The skeletal muscles from Wistar rats treated with germanium dioxide for 24 weeks were analysed by histopathologic and electron-microscopic studies. A quantitative analysis was carried out in mitochondrial DNAs of these samples. The biological function of the model was determined. Results. An animal model of mitochondrial myopathy was built up, in which oxygen free radicals were increased and mitochondrial DNA copies were decreased contrasted with controls. Conclusion. It suggested that environmental toxin may play a role in the pathogenesis of mitochondrial myopathy. The increase of oxygen free radicals is an important link causing the disease.

  10. Exons 16 and 17 of the amyloid precursor protein gene in familial inclusion body myopathy.

    Science.gov (United States)

    Sivakumar, K; Cervenáková, L; Dalakas, M C; Leon-Monzon, M; Isaacson, S H; Nagle, J W; Vasconcelos, O; Goldfarb, L G

    1995-08-01

    Accumulation of beta-amyloid protein (A beta) occurs in some muscle fibers of patients with inclusion body myopathy and resembles the type of amyloid deposits seen in the affected tissues of patients with Alzheimer's disease and cerebrovascular amyloidosis. Because mutations in exons 16 and 17 of the beta-amyloid precursor protein (beta APP) gene on chromosome 21 have been identified in patients with early-onset familial Alzheimer's disease and Dutch-type cerebrovascular amyloidosis, we searched for mutations of the same region in patients with familial inclusion body myopathy. Sequencing of both alleles in 8 patients from four unrelated families did not reveal any mutations in these exons. The amyloid deposition in familial forms of inclusion body myopathy may be either due to errors in other gene loci, or it is secondary reflecting altered beta APP metabolism or myocyte degeneration and cell membrane degradation.

  11. Molecular and cellular insights into a distinct myopathy of Great Dane dogs.

    Science.gov (United States)

    Chang, Kin-Chow; McCulloch, Maj-Lis C; Anderson, Thomas James

    2010-03-01

    A myopathy in the Great Dane dog with characteristic pathological and molecular features is reported. Young adults present with progressive weakness and generalised muscle atrophy. To better define this condition, an investigation using histopathology, confocal microscopy, biochemistry and microarray analysis was undertaken. The skeletal muscles of affected dogs exhibited increased oxidative fibre phenotype and core fibre lesions characterised by the disruption of the sarcomeric architecture and the accumulation of mitochondrial organelles. Affected muscles displayed co-ordinated expression of genes consistent with a slow-oxidative phenotype, which was possibly a compensatory response to chronic muscle damage. There was disruption of Z-lines in affected muscles which, at the molecular level, manifested as transcriptional dysregulation of several Z-line associated genes, including alpha-actinin, myotilin, desmin, vimentin and telethonin. The pathology of this canine myopathy is distinct from that of human central core myopathies that are characterised by cores devoid of mitochondria and by the presence of myofibrillar breakdown products.

  12. Adult-onset Nemaline Myopathy Coexisting With Myasthenia Gravis: A Case Report.

    Science.gov (United States)

    Cao, Lingling; Wang, Yanling; Liu, Xiaofeng; Hu, Yanxia; Li, Nianchun; Qiu, Guoping; Luo, Yun; Li, Weidong

    2016-01-01

    Myasthenia gravis (MG) is an autoimmune neuromuscular junction disorder which is characterized by fluctuating muscle fatigue. However, the association of MG with nemaline myopathy is rarely reported. Here we report a case of MG coexisting with adult-onset nemaline myopathy. A 55-year-old man endured fluctuating muscle weakness with positive acetylcholine receptor and titin antibodies. After the patient was administrated cholinergic drugs and immunosuppression, the muscle weakness of the patient had mildly been alleviated. Electromyography showed a progressive decrement in the amplitude of muscle action potential at low frequency. Muscle biopsy showed numerous nemalines in the muscle fibers. This is the first reported case of nemalines present in the muscle fibers of adult patient with MG. The pathogenesis of nemaline may be related to titin antibody in adult-onset nemaline myopathy with MG.

  13. Centronuclear myopathy and type-1 hypotrophy without central nuclei. Distinct nosologic entities?

    Science.gov (United States)

    Lo, W D; Barohn, R J; Bobulski, R J; Kean, J; Mendell, J R

    1990-03-01

    Four infants presented with severe hypotonia, weakness, and hypoventilation or apnea at birth. Their clinical presentations and courses resembled those of the x-linked recessive form of centronuclear myopathy. Histologic examination of their muscle biopsy specimens showed patterns ranging between centronuclear myopathy and type-1 hypotrophy without central nuclei. Regardless of their gender or the appearance of their biopsy specimens, the children all had a poor outcome. The clinical and biopsy findings in these infants suggest that centronuclear myopathy and type-1 hypotrophy without central nuclei do not represent distinct nosologic entities. It seems more likely that the histologic changes represent abnormalities in fiber size distribution and development, which are nonspecific and which reflect a primary defect at one or more sites in the neuraxis.

  14. Myopathy in hyperthyroidism as a consequence of rapid reduction of thyroid hormone: A case report.

    Science.gov (United States)

    Li, Qianrui; Liu, Yuping; Zhang, Qianying; Tian, Haoming; Li, Jianwei; Li, Sheyu

    2017-07-01

    Myalgia and elevated creatine kinase (CK) are occasionally observed during the treatment of hyperthyroid patients. Relative hypothyroidism resulted from rapid thyroid hormone reduction had been promoted as a plausible cause of these myopathic changes, however rarely reported. We hereby presented a 20-year-old female with Grave's disease, who developed myopathy and elevated CK during rapid correction of thyroid hormone. Relative hypothyroidism-induced myopathy. Antithyroid drug (ATD) dosage was reduced without levothyroxine replacement. The muscular symptoms were recovered with CK level returned to normal after adoption of the euthyroid status. Differentiation of relative hypothyroidism from other causes of myopathy, especially with the effect of ATD, is important for clinical practice, although difficult in many cases.

  15. HIGH STRENGTH CONTROL RODS FOR NEUTRONIC REACTORS

    Science.gov (United States)

    Lustman, B.; Losco, E.F.; Cohen, I.

    1961-07-11

    Nuclear reactor control rods comprised of highly compressed and sintered finely divided metal alloy panticles and fine metal oxide panticles substantially uniformly distributed theretbrough are described. The metal alloy consists essentially of silver, indium, cadmium, tin, and aluminum, the amount of each being present in centain percentages by weight. The oxide particles are metal oxides of the metal alloy composition, the amount of oxygen being present in certain percentages by weight and all the oxygen present being substantially in the form of metal oxide. This control rod is characterized by its high strength and resistance to creep at elevated temperatures.

  16. Sensitivity study of control rod depletion coefficients

    OpenAIRE

    Blomberg, Joel

    2015-01-01

    This report investigates the sensitivity of the control rod depletion coefficients, Sg, to different input parameters and how this affects the accumulated 10B depletion, β. Currently the coefficients are generated with PHOENIX4, but the geometries can be more accurately simulated in McScram. McScram is used to calculate Control Rod Worth, which in turn is used to calculate Nuclear End Of Life, and Sg cannot be generated in the current version of McScram. Therefore, it is also analyzed whether...

  17. Quivers For Special Fuel Rods-Disposal Of Special Fuel Rods In CASTOR V Casks

    Energy Technology Data Exchange (ETDEWEB)

    Bannani, Amin; Cebula, Wojciech; Buchmuller, Olga; Huggenberg, Roland [GNS, Essen (Germany); Helmut Kuhl [WTI, Julich (Germany)

    2015-05-15

    While GNS casks of the CASTOR family are a suitable means to transfer fuel assemblies (FA) from the NPP to an interim dry storage site, Germanys phase-out of nuclear energy has triggered the demand for an additional solution to dispose of special fuel rods (SFR), normally remaining in the fuel pond until the final shutdown of the NPP. SFR are fuel rods that had to be removed from fuel assemblies mainly due to their special condition, e. g. damages in the cladding of the fuel rods which may have occurred during reactor operations. SFR are usually stored in the spent fuel pond after they are removed from the FA. The quiver for special fuel rods features a robust yet simple design, with a high mechanical stability, a reliable leak-tightness and large safety margins for future requirements on safety analysis. The quiver for special fuel rods can be easily adapted to a large variety of different damaged fuel rods and tailored to the specific need of the customer. The quiver for special fuel rods is adaptable e.g. in length and diameter for use in other types of transport and storage casks and is applicable in other countries as well. The overall concept presented here is a first of its kind solution for the disposal of SFRs via Castor V-casks. This provides an important precondition in achieving the status 'free from nuclear fuel' of the shut down German NPPs.

  18. Adult-onset autosomal dominant centronuclear myopathy due to BIN1 mutations.

    Science.gov (United States)

    Böhm, Johann; Biancalana, Valérie; Malfatti, Edoardo; Dondaine, Nicolas; Koch, Catherine; Vasli, Nasim; Kress, Wolfram; Strittmatter, Matthias; Taratuto, Ana Lia; Gonorazky, Hernan; Laforêt, Pascal; Maisonobe, Thierry; Olivé, Montse; Gonzalez-Mera, Laura; Fardeau, Michel; Carrière, Nathalie; Clavelou, Pierre; Eymard, Bruno; Bitoun, Marc; Rendu, John; Fauré, Julien; Weis, Joachim; Mandel, Jean-Louis; Romero, Norma B; Laporte, Jocelyn

    2014-12-01

    Centronuclear myopathies are congenital muscle disorders characterized by type I myofibre predominance and an increased number of muscle fibres with nuclear centralization. The severe neonatal X-linked form is due to mutations in MTM1, autosomal recessive centronuclear myopathy with neonatal or childhood onset results from mutations in BIN1 (amphiphysin 2), and dominant cases were previously associated to mutations in DNM2 (dynamin 2). Our aim was to determine the genetic basis and physiopathology of patients with mild dominant centronuclear myopathy without mutations in DNM2. We hence established and characterized a homogeneous cohort of nine patients from five families with a progressive adult-onset centronuclear myopathy without facial weakness, including three sporadic cases and two families with dominant disease inheritance. All patients had similar histological and ultrastructural features involving type I fibre predominance and hypotrophy, as well as prominent nuclear centralization and clustering. We identified heterozygous BIN1 mutations in all patients and the molecular diagnosis was complemented by functional analyses. Two mutations in the N-terminal amphipathic helix strongly decreased the membrane-deforming properties of amphiphysin 2 and three stop-loss mutations resulted in a stable protein containing 52 supernumerary amino acids. Immunolabelling experiments revealed abnormal central accumulation of dynamin 2, caveolin-3, and the autophagic marker p62, and general membrane alterations of the triad, the sarcolemma, and the basal lamina as potential pathological mechanisms. In conclusion, we identified BIN1 as the second gene for dominant centronuclear myopathy. Our data provide the evidence that specific BIN1 mutations can cause either recessive or dominant centronuclear myopathy and that both disorders involve different pathomechanisms. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights

  19. Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes unveiled by valproate

    Directory of Open Access Journals (Sweden)

    Neera Chaudhry

    2013-01-01

    Full Text Available Valproic acid (VPA is widely used as an anti-epileptic drug. The primary mechanism of VPA toxicity is interference with mitochondrial beta-oxidation, and it can exacerbate an underlying mitochondrial cytopathy. We report a case of Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes unmasked by use of Sodium Valproate in a 12-year-old boy who presented with headache and seizures. There was precipitation of encephalopathy, myopathy, lactic acidosis, and hepatic damage within two days of valproate use, after withdrawing of which there was a remarkable clinical and biochemical recovery.

  20. Abnormal desmin protein in myofibrillar myopathies caused by desmin gene mutations.

    Science.gov (United States)

    Li, M; Dalakas, M C

    2001-04-01

    Muscle proteins were extracted in various sodium dodecyl sulfate buffers from 6 patients with myofibrillar myopathy (MFM) and previously identified with mutations in the desmin gene (desmin myopathy; DesM), 6 with MFM without mutations, and 14 disease controls to search for alterations in biochemistry and solubility of mutated desmin filaments. In the 1% posthigh-speed pellet fraction, desmin was detected with immunoblots only in DesM and not the other MFM. We conclude that mutant desmin forms insoluble aggregates that are specific for the DesM and can be detected with Western blots.

  1. Absence of persistent infection with enteroviruses in muscles of patients with inflammatory myopathies.

    Science.gov (United States)

    Leon-Monzon, M; Dalakas, M C

    1992-08-01

    We searched for enteroviral nucleic acid sequences using the polymerase chain reaction and slot-blot hybridization in coded muscle biopsy specimens from 39 patients with active inflammatory myopathies (polymyositis, dermatomyositis, and inclusion-body myositis) and from 16 patients with other neuromuscular diseases, including patients with postpolio syndrome. For primers, we used sequences of the noncoding region at the 5' end of the viral RNA. We failed to detect specific enteroviral nucleic acid sequences in the muscle biopsy specimens. Because this sensitive technique can amplify even low copy numbers of the viral genome, it appears unlikely that a persistent enteroviral infection is the cause of inflammatory myopathies.

  2. Modeling and simulation performance of sucker rod beam pump

    Science.gov (United States)

    Aditsania, Annisa; Rahmawati, Silvy Dewi; Sukarno, Pudjo; Soewono, Edy

    2015-09-01

    Artificial lift is a mechanism to lift hydrocarbon, generally petroleum, from a well to surface. This is used in the case that the natural pressure from the reservoir has significantly decreased. Sucker rod beam pumping is a method of artificial lift. Sucker rod beam pump is modeled in this research as a function of geometry of the surface part, the size of sucker rod string, and fluid properties. Besides its length, sucker rod string also classified into tapered and un-tapered. At the beginning of this research, for easy modeling, the sucker rod string was assumed as un-tapered. The assumption proved non-realistic to use. Therefore, the tapered sucker rod string modeling needs building. The numerical solution of this sucker rod beam pump model is computed using finite difference method. The numerical result shows that the peak of polished rod load for sucker rod beam pump unit C-456-D-256-120, for non-tapered sucker rod string is 38504.2 lb, while for tapered rod string is 25723.3 lb. For that reason, to avoid the sucker rod string breaks due to the overload, the use of tapered sucker rod beam string is suggested in this research.

  3. Modeling and simulation performance of sucker rod beam pump

    Energy Technology Data Exchange (ETDEWEB)

    Aditsania, Annisa, E-mail: annisaaditsania@gmail.com [Department of Computational Sciences, Institut Teknologi Bandung (Indonesia); Rahmawati, Silvy Dewi, E-mail: silvyarahmawati@gmail.com; Sukarno, Pudjo, E-mail: psukarno@gmail.com [Department of Petroleum Engineering, Institut Teknologi Bandung (Indonesia); Soewono, Edy, E-mail: esoewono@math.itb.ac.id [Department of Mathematics, Institut Teknologi Bandung (Indonesia)

    2015-09-30

    Artificial lift is a mechanism to lift hydrocarbon, generally petroleum, from a well to surface. This is used in the case that the natural pressure from the reservoir has significantly decreased. Sucker rod beam pumping is a method of artificial lift. Sucker rod beam pump is modeled in this research as a function of geometry of the surface part, the size of sucker rod string, and fluid properties. Besides its length, sucker rod string also classified into tapered and un-tapered. At the beginning of this research, for easy modeling, the sucker rod string was assumed as un-tapered. The assumption proved non-realistic to use. Therefore, the tapered sucker rod string modeling needs building. The numerical solution of this sucker rod beam pump model is computed using finite difference method. The numerical result shows that the peak of polished rod load for sucker rod beam pump unit C-456-D-256-120, for non-tapered sucker rod string is 38504.2 lb, while for tapered rod string is 25723.3 lb. For that reason, to avoid the sucker rod string breaks due to the overload, the use of tapered sucker rod beam string is suggested in this research.

  4. Spent nuclear fuel rods encapsulated in copper

    Energy Technology Data Exchange (ETDEWEB)

    Hanes, H.D.

    1984-04-01

    Using hot isostatic pressing, spent nuclear fuel rods and other radioactive wastes can be encapsulated in solid copper. The copper capsule which is formed is free of pores and cracks, and is highly resistant to attack by reducing ground waters. Such capsules should contain radioactive materials safely for hundreds of thousands of years in underground storage.

  5. Solitary waves on nonlinear elastic rods. I

    DEFF Research Database (Denmark)

    Sørensen, Mads Peter; Christiansen, Peter Leth; Lomdahl, P. S.

    1984-01-01

    Acoustic waves on elastic rods with circular cross section are governed by improved Boussinesq equations when transverse motion and nonlinearity in the elastic medium are taken into account. Solitary wave solutions to these equations have been found. The present paper treats the interaction between...

  6. ELECTRIC FIELD MEASUREMENT IN ROD-DISCONTINUED ...

    African Journals Online (AJOL)

    2014-06-30

    Jun 30, 2014 ... The used arrangement with homogeneous system is made up of a square metallic sheet ... This distance is considered positive when the rod is located ... in the case of the discontinuous earth which were defined according to ...

  7. Fabrication of preliminary fuel rods for SFR

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sun Ki; Oh, Seok Jin; Ko, Young Mo; Woo, Youn Myung; Kim, Ki Hwan [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2012-05-15

    Metal fuels was selected for fueling many of the first reactors in the US, including the Experimental Breeder Reactor-I (EBR-I) and the Experimental Breeder Reactor-II (EBR-II) in Idaho, the FERMI-I reactor, and the Dounreay Fast Reactor (DFR) in the UK. Metallic U.Pu.Zr alloys were the reference fuel for the US Integral Fast Reactor (IFR) program. Metallic fuel has advantages such as simple fabrication procedures, good neutron economy, high thermal conductivity, excellent compatibility with a Na coolant and inherent passive safety. U-Zr-Pu alloy fuels have been used for SFR (sodium-cooled fast reactor) related to the closed fuel cycle for managing minor actinides and reducing a high radioactivity levels since the 1980s. Fabrication technology of metallic fuel for SFR has been in development in Korea as a national nuclear R and D program since 2007. For the final goal of SFR fuel rod fabrication with good performance, recently, three preliminary fuel rods were fabricated. In this paper, the preliminary fuel rods were fabricated, and then the inspection for QC(quality control) of the fuel rods was performed

  8. Brownian rod scheme in microenvironment sensing

    Directory of Open Access Journals (Sweden)

    Ian Gralinski

    2012-03-01

    Full Text Available Fluctuations of freely translating spherical particles via Brownian motion should provide inexhaustible information about the micro-environment, but is beset by the problem of particles drifting away from the venue of measurement as well as colliding with other particles. We propose a scheme here to circumvent this in which a Brownian rod that lies in proximity to a cylindrical pillar is drawn in by a tuneable attractive force from the pillar. The force is assumed to act through the centre of each body and the motion exclusive to the x-y plane. Simulation studies show two distinct states, one in which the rod is moving freely (state I and the other in which the rod contacts the cylinder surface (state II. Information about the micro-environment could be obtained by tracking the rotational diffusion coefficient Dθ populating in either of these two states. However, the magnitude of the normalized charge product in excess of 6.3x104 was found necessary for a rod of 6.81 × 0.93 μm2 (length × diameter and 10μm diameter cylindrical pillar to minimize deviation errors. It was also found that the extent of spatial sensing coverage could be controlled by varying the charge level. The conditions needed to ascertain the rotational sampling for angle determination through the Hough transform were also discussed.

  9. Piston rod seal for a Stirling engine

    Science.gov (United States)

    Shapiro, Wilbur

    1984-01-01

    In a piston rod seal for a Stirling engine, a hydrostatic bearing and differential pressure regulating valve are utilized to provide for a low pressure differential across a rubbing seal between the hydrogen and oil so as to reduce wear on the seal.

  10. Adjustable solitary waves in electroactive rods

    Science.gov (United States)

    Wang, Y. Z.; Zhang, C. L.; Dai, H.-H.; Chen, W. Q.

    2015-10-01

    This paper presents an asymptotic analysis of solitary waves propagating in an incompressible isotropic electroactive circular rod subjected to a biasing longitudinal electric displacement. Several asymptotic expansions are introduced to simplify the rod governing equations. The boundary conditions on the lateral surface of the rod are satisfied from the asymptotic point of view. In the limit of finite-small amplitude and long wavelength, a set of ten simplified one-dimensional nonlinear governing equations is established. To validate our approach and the derivation, we compare the linear dispersion relation with the one directly derived from the three-dimensional linear theory in the limit of long wavelength. Then, by the reductive perturbation method, we deduce the far-field equation (i.e. the KdV equation). Finally, the leading order of the electroelastic solitary wave solution is presented. Numerical examples are provided to show the influences of the biasing electric displacement and material constants on the solitary waves. It is found that the biasing electric displacement can modulate the velocity of solitary waves with a prescribed amplitude in the electroactive rod, a very interesting result which may promote the particular application of solitary waves in solids with multi-field coupling.

  11. On contact numbers in random rod packings

    NARCIS (Netherlands)

    Wouterse, A.; Luding, Stefan; Philipse, A.P.

    2009-01-01

    Random packings of non-spherical granular particles are simulated by combining mechanical contraction and molecular dynamics, to determine contact numbers as a function of density. Particle shapes are varied from spheres to thin rods. The observed contact numbers (and packing densities) agree well

  12. Autophagy, inflammation and innate immunity in inflammatory myopathies.

    Directory of Open Access Journals (Sweden)

    Cristina Cappelletti

    Full Text Available Autophagy has a large range of physiological functions and its dysregulation contributes to several human disorders, including autoinflammatory/autoimmune diseases such as inflammatory myopathies (IIMs. In order to better understand the pathogenetic mechanisms of these muscular disorders, we sought to define the role of autophagic processes and their relation with the innate immune system in the three main subtypes of IIM, specifically sporadic inclusion body myositis (sIBM, polymyositis (PM, dermatomyositis (DM and juvenile dermatomyositis (JDM. We found that although the mRNA transcript levels of the autophagy-related genes BECN1, ATG5 and FBXO32 were similar in IIM and controls, autophagy activation in all IIM subgroups was suggested by immunoblotting results and confirmed by immunofluorescence. TLR4 and TLR3, two potent inducers of autophagy, were highly increased in IIM, with TLR4 transcripts significantly more expressed in PM and DM than in JDM, sIBM and controls, and TLR3 transcripts highly up-regulated in all IIM subgroups compared to controls. Co-localization between autophagic marker, LC3, and TLR4 and TLR3 was observed not only in sIBM but also in PM, DM and JDM muscle tissues. Furthermore, a highly association with the autophagic processes was observed in all IIM subgroups also for some TLR4 ligands, endogenous and bacterial HSP60, other than the high-mobility group box 1 (HMGB1. These findings indicate that autophagic processes are active not only in sIBM but also in PM, DM and JDM, probably in response to an exogenous or endogenous 'danger signal'. However, autophagic activation and regulation, and also interaction with the innate immune system, differ in each type of IIM. Better understanding of these differences may lead to new therapies for the different IIM types.

  13. The spectrum of renal involvement in patients with inflammatory myopathies.

    Science.gov (United States)

    Couvrat-Desvergnes, Grégoire; Masseau, Agathe; Benveniste, Olivier; Bruel, Alexandra; Hervier, Baptiste; Mussini, Jean-Marie; Buob, David; Hachulla, Eric; Rémy, Philippe; Azar, Raymond; Mac Namara, Evelyne; MacGregor, Brigitte; Daniel, Laurent; Lacraz, Adeline; De Broucker, Thomas; Rouvier, Philippe; Carli, Philippe; Laville, Maurice; Dantan, Etienne; Hamidou, Mohamed; Moreau, Anne; Fakhouri, Fadi

    2014-01-01

    Data regarding the incidence and outcome of renal involvement in patients with inflammatory myopathies (IM) remain scarce. We assessed the incidence and causes of acute kidney injury (AKI) and chronic kidney disease (CKD) in 150 patients with dermatomyositis, polymyositis, and antisynthetase syndrome followed in 3 French referral centers. Renal involvement occurred in 35 (23.3%) patients: AKI in 16 (10.7%), and CKD in 31 (20.7%) patients. The main cause of AKI was drug or myoglobinuria-induced acute tubular necrosis. Male sex, cardiovascular risk factors, cardiac involvement, and initial proteinuria >0.3 g/d were associated with the occurrence of AKI. The outcome of patients with AKI was poor: 13 (81%) progressed to CKD and 2 (12.5%) reached end-stage renal disease. In multivariate survival analysis, age at IM onset, male sex, a history of cardiovascular events, and a previous episode of AKI were associated with the risk of CKD. We also identified 14 IM patients who underwent a kidney biopsy in 10 nephrology centers. Renal pathology disclosed a wide range of renal disorders, mainly immune-complex glomerulonephritis. We identified in 5 patients a peculiar pattern of severe acute renal vascular damage consisting mainly of edematous thickening of the intima of arterioles. We found that AKI and CKD are frequent in patients with IM. Prevention of AKI is crucial in these patients, as AKI is a major contributor to their relatively high risk of CKD. A peculiar pattern of acute vascular damage is part of the spectrum of renal diseases associated with IM.

  14. Comparison of two pretransplant predictive models and a flexible HCT-CI using different cut off points to determine low-, intermediate-, and high-risk groups: the flexible HCT-CI Is the best predictor of NRM and OS in a population of patients undergoing allo-RIC.

    Science.gov (United States)

    Barba, Pere; Piñana, Jose Luis; Martino, Rodrigo; Valcárcel, David; Amorós, Alex; Sureda, Anna; Briones, Javier; Delgado, Julio; Brunet, Salut; Sierra, Jorge

    2010-03-01

    Patient comorbidities are being increasingly analyzed as predictors for outcome after hematopoietic stem cell transplantation (HSCT), especially in allogeneic HSCT (Allo-HSCT). Researchers from Seattle have recently developed several pretransplant scoring systems (hematopoietic cell transplantation comorbidity index [HCT-CI] and the Pretransplantation Assessment of Mortality (PAM) model) from large sets of HSCT recipients with the aim of improving non-transplant models, mainly the Charlson Comorbidity Index (CCI). The validation of these comorbidity indexes in other institutions and in different disease and conditioning-related settings is of interest to determine whether these models are potentially applicable in clinical practice and in research settings. We performed a retrospective study in our institution including 194 consecutive reduced-intensity conditioning (RIC) AlloHSCT (allo-RIC) recipients to compare the predictive value of the PAM score, CCI, the original HCT-CI, and the flexible HCT-CI using a different risk group stratification. The median patient pretransplant scores for the HCT-CI, PAM, and CCI were 3.5, 22, and 0, respectively. The flexible HCT-CI risk-scoring system (restratified as: low risk [LR] 0-3 points, intermediate risk [IR] 4-5 points, and high risk [HR] >5 points) was the best predictor for non-relapse mortality (NRM). The 100-day and 2-year NRM incidence in these risk categories was 4% (95% confidence interval C.I. 2%-11%), 16% (95% C.I. 9%-31%), and 29% (95% C.I. 19%-45%), respectively (P HR. In conclusion, our single-center study suggests that the flexible HCT-CI is a good predictor of 2-year NRM and survival after an allo-RIC. Copyright (c) 2010 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  15. Stimulus-evoked outer segment changes in rod photoreceptors

    Science.gov (United States)

    Zhao, Xiaohui; Thapa, Damber; Wang, Benquan; Lu, Yiming; Gai, Shaoyan; Yao, Xincheng

    2016-06-01

    Rod-dominated transient retinal phototropism (TRP) has been recently observed in freshly isolated mouse and frog retinas. Comparative confocal microscopy and optical coherence tomography revealed that the TRP was predominantly elicited from the rod outer segment (OS). However, the biophysical mechanism of rod OS dynamics is still unknown. Mouse and frog retinal slices, which displayed a cross-section of retinal photoreceptors and other functional layers, were used to test the effect of light stimulation on rod OSs. Time-lapse microscopy revealed stimulus-evoked conformational changes of rod OSs. In the center of the stimulated region, the length of the rod OS shrunk, while in the peripheral region, the rod OS swung toward the center region. Our experimental observation and theoretical analysis suggest that the TRP may reflect unbalanced rod disc-shape changes due to localized visible light stimulation.

  16. Validation Test of CARR Safety Rod Driving Mechanism

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    <正>CARR safety Rods are driven by hydraulic force. The safety rod driving mechanism is designed by Tsinghua University and manufactured by Shenyang LIMING factory. Two sets of the mechanism are used for the validation test.

  17. Longitudinal Vibrations of Rheological Rod With Variable Cross Section

    Institute of Scientific and Technical Information of China (English)

    Katica(Stevanovic)HEDRIH; AleksandarFILIPOVSKI

    1999-01-01

    Longitudinal vibrations of rheological rod with variable cross section are examined.Particular solutions and eigenfunction are accomplished for natural vibrations of the rod with hereditary material of standard hereditary body.Some examples are given.

  18. Computer simulation of rod-sphere mixtures

    Energy Technology Data Exchange (ETDEWEB)

    Antypov, Dmytro

    2003-07-01

    Results are presented from a series of simulations undertaken to investigate the effect of adding small spherical particles to a fluid of rods which would otherwise represent a liquid crystalline (LC) substance. Firstly, a bulk mixture of Hard Gaussian Overlap particles with an aspect ratio of 3:1 and hard spheres with diameters equal to the breadth of the rods is simulated at various sphere concentrations. Both mixing-demixing and isotropic-nematic transition are studied using Monte Carlo techniques. Secondly, the effect of adding Lennard-Jones particles to an LC system modelled using the well established Gay-Berne potential is investigated. These rod-sphere mixtures are simulated using both the original set of interaction parameters and a modified version of the rod-sphere potential proposed in this work. The subject of interest is the internal structure of the binary mixture and its dependence on density, temperature, concentration and various parameters characterising the intermolecular interactions. Both the mixing-demixing behaviour and the transitions between the isotropic and any LC phases have been studied for four systems which differ in the interaction potential between unlike particles. A range of contrasting microphase separated structures including bicontinuous, cubic, and micelle-like arrangement have been observed in bulk. Thirdly, the four types of mixtures previously studied in bulk are subjected to a static magnetic field. A variety of novel phases are observed for the cases of positive and negative anisotropy in the magnetic susceptibility. These include a lamellar structure, in which layers of rods are separated by layers of spheres, and a configuration with a self-assembling hexagonal array of spheres. Finally, two new models are presented to study liquid crystal mixtures in the presence of curved substrates. These are implemented for the cases of convex and concave spherical surfaces. The simulation results obtained in these geometries

  19. Control rod reactivity measurement by rod-drop method at a fast critical assembly

    Energy Technology Data Exchange (ETDEWEB)

    Song, L.; Yin, Y.; Lian, X.; Zheng, C. [Inst. of Nuclear Physics and Chemistry in CAEP, P. O. Box 919 210, Mianyang, Sichuan, 621900 (China)

    2012-07-01

    Rod-drop experiments were carried out to estimate the reactivity of the control rod of a fast critical assembly operated by CAEP. Two power monitor systems were used to obtain the power level and integration method was used to process the data. Three experiments were performed. The experimental results of the reactivity from the two power monitor systems were consistent and showed a reasonable range of reactivity compared to results from positive period method. (authors)

  20. Dependence of control rod worth on fuel burnup

    Energy Technology Data Exchange (ETDEWEB)

    Savva, P., E-mail: savvapan@ipta.demokritos.g [NCSR ' DEMOKRITOS' , PoB 60228, 15310 Aghia Paraskevi (Greece); Varvayanni, M., E-mail: melina@ipta.demokritos.g [NCSR ' DEMOKRITOS' , PoB 60228, 15310 Aghia Paraskevi (Greece); Catsaros, N., E-mail: nicos@ipta.demokritos.g [NCSR ' DEMOKRITOS' , PoB 60228, 15310 Aghia Paraskevi (Greece)

    2011-02-15

    Research highlights: Diffusion and MC calculations for rod worth dependence on burnup and Xe in reactors. One-step rod withdrawal/insertion are used for rod worth estimation. The study showed that when Xe is present the rods worth is significantly reduced. Rod worth variation with burnup depends on rod position in core. Rod worth obtained with MC code is higher than that obtained from deterministic. - Abstract: One important parameter in the design and the analysis of a nuclear reactor core is the reactivity worth of the control rods, i.e. their efficiency to absorb excess reactivity. The control rod worth is affected by parameters such as the fuel burnup in the rod vicinity, the Xe concentration in the core, the operational time of the rod and its position in the core. In the present work, two different computational approaches, a deterministic and a stochastic one, were used for the determination of the rods worth dependence on the fuel burnup level and the Xe concentration level in a conceptual, symmetric reactor core, based on the MTR fuel assemblies used in the Greek Research Reactor (GRR-1). For the deterministic approach the neutronics code system composed by the SCALE modules NITAWL and XSDRN and the diffusion code CITATION was used, while for the stochastic one the Monte Carlo code TRIPOLI was applied. The study showed that when Xe is present in the core, the rods worth is significantly reduced, while the rod worth variation with increasing burnup depends on the rods position in the core grid. The rod worth obtained with the use of the Monte Carlo code is higher than the one obtained from the deterministic code.

  1. Sucker rod string design of the pumping systems

    Directory of Open Access Journals (Sweden)

    Chun Hua Liu

    2015-08-01

    Full Text Available The existing design of sucker rod string mainly focuses on the simplifying assumptions that rod string was exposed to simple tension loading. And its goal was to have equal modified stress at the top of each taper. The improved rod design was to have the same degree of safety at each section, and it used a dynamic force distribution that was proportional along the whole string. However, the available procedures did not provide the desired accuracy of its pertinent analysis, and the operators could not identify the specific phenomena that occur in CBM wells. In this paper, the mathematical models of rod loads and string length were developed based on the cyclic nature of rod string loading; the fatigue endurance method is used to design the single rod string; and the tapered rod string is designed to have an equal equivalent stress at the top of each section. Its application characteristics are demonstrated by the example of CBM wells in Ordos Basin. The interpretations of results show that the previous design gave the single rods a larger diameter and the top rods in the string a greater percent than the proposed method. The calculation should concern about inertial, vibration and friction forces to illustrate the elastic force waves travelling in the rod material with the speed of sound. The single string should be designed using fatigue endurance ratings due to asymmetric pulsating tension of rod loading; and the tapered string should involve a balanced design by setting the fatigue endurance at each section equal. A shorter stroke length gives a greater rod taper percentage and an increased load capacity results to an enhanced rod diameter. The rod diameter increases with the pump size and load capacity for the single string, and the rod taper percentage of the top rod strings increases with plunger diameter for the tapered string. The proposed research improves efficiency of the pumping system, assures good operating conditions, and reduces

  2. Absence of anti-HMG-CoA reductase autoantibodies in severe self-limited statin-related myopathy.

    Science.gov (United States)

    Floyd, James S; Brody, Jennifer A; Tiniakou, Eleni; Psaty, Bruce M; Mammen, Andrew

    2016-06-01

    Patients with self-limited statin-related myopathy improve spontaneously when statins are stopped. In contrast, patients with statin-associated autoimmune myopathy have autoantibodies recognizing 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) and usually require immunosuppressive therapy to control their disease. On initial presentation, it can sometimes be difficult to distinguish between these 2 diseases, as both present with muscle pain, weakness, and elevated serum creatine kinase (CK) levels. The goal of this study was to determine whether patients with severe self-limited statin-related myopathy also make anti-HMGCR autoantibodies. We screened 101 subjects with severe self-limited cerivastatin-related myopathy for anti-HMGCR autoantibodies. No patient with severe self-limited cerivastatin-related myopathy had anti-HMGCR autoantibodies. Anti-HMGCR autoantibody testing can be used to help differentiate whether a patient has self-limited myopathy due to cerivastatin or autoimmune statin-associated myopathy; these findings may apply to other statins as well. Muscle Nerve 54: 142-144, 2016. © 2016 Wiley Periodicals, Inc.

  3. Treatment with ActRIIB-mFc Produces Myofiber Growth and Improves Lifespan in the Acta1 H40Y Murine Model of Nemaline Myopathy.

    Science.gov (United States)

    Tinklenberg, Jennifer; Meng, Hui; Yang, Lin; Liu, Fujun; Hoffmann, Raymond G; Dasgupta, Mahua; Allen, Kenneth P; Beggs, Alan H; Hardeman, Edna C; Pearsall, R Scott; Fitts, Robert H; Lawlor, Michael W

    2016-06-01

    Nemaline myopathies (NMs) are a group of congenital muscle diseases caused by mutations in at least 10 genes and associated with a range of clinical symptoms. NM is defined on muscle biopsy by the presence of cytoplasmic rod-like structures (nemaline rods) composed of cytoskeletal material. Myofiber smallness is also found in many cases of NM and may represent a cause of weakness that can be counteracted by treatment. We have used i.p. injection of activin type IIB receptor (ActRIIB)-mFc (an inhibitor of myostatin signaling) to promote hypertrophy and increase strength in our prior murine work; we therefore tested whether ActRIIB-mFc could improve weakness in NM mice through myofiber hypertrophy. We report a study of ActRIIB-mFc treatment in the Acta1 H40Y mouse model of NM. Treatment of Acta1 H40Y mice produced significant increases in body mass, muscle mass, quadriceps myofiber size, and survival, but other measurements of strength (forelimb grip strength, ex vivo measurements of contractile function) did not improve. Our studies also identified that the complications of urethral obstruction are associated with mortality in male hemizygote Acta1 H40Y mice. The incidence of urethral obstruction and histologic evidence of chronic obstruction (inflammation) were significantly lower in Acta1 H40Y mice that had been treated with ActRIIB-mFc. ActRIIB-mFc treatment produces a mild benefit to the disease phenotype in Acta1 H40Y mice. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  4. Investigation of control rod worth and nuclear end of life of BWR control rods

    Energy Technology Data Exchange (ETDEWEB)

    Magnusson, Per

    2008-01-15

    This work has investigated the Control Rod Worth (CRW) and Nuclear End of Life (NEOL) values for BWR control rods. A study of how different parameters affect NEOL was performed with the transport code PHOENIX4. It was found that NEOL, expressed in terms of {sup 10}B depletion, can be generalized beyond the conditions for which the rod is depleted, such as different power densities and void fractions, the corresponding variation in the NEOL will be about 0.2-0.4% {sup 10}B. It was also found that NEOL results for different fuel types and different fuel enrichments have a variation of about 2-3% in {sup 10}B depletion. A comparative study on NHOL and CRW was made between PHOENIX4 and the stochastic Monte Carlo code MCNP. It was found that there is a significant difference, both due to differences in the codes and to limitations in the geometrical modeling in PHOENIX4. Since MCNP is considered more physically correct, a methodology was developed to calculate the nuclear end of life of BWR control rods with MCNP. The advantages of the methodology are that it does not require other codes to perform the depletion of the absorber material, it can describe control rods of any design and it can deplete the control rod absorber material without burning the fuel. The disadvantage of the method is that is it time-consuming.

  5. Rod Has High Tensile Strength And Low Thermal Expansion

    Science.gov (United States)

    Smith, D. E.; Everton, R. L.; Howe, E.; O'Malley, M.

    1996-01-01

    Thoriated tungsten extension rod fabricated to replace stainless-steel extension rod attached to linear variable-differential transformer in gap-measuring gauge. Threads formed on end of rod by machining with special fixtures and carefully chosen combination of speeds and feeds.

  6. 77 FR 1504 - Stainless Steel Wire Rod From India

    Science.gov (United States)

    2012-01-10

    ... COMMISSION Stainless Steel Wire Rod From India Determination On the basis of the record \\1\\ developed in the... antidumping duty order on stainless steel wire rod From India would be likely to lead to continuation or... contained in USITC Publication 4300 (January 2012), entitled Stainless Steel Wire Rod From...

  7. Carbon Inverse Opal Rods for Nonenzymatic Cholesterol Detection.

    Science.gov (United States)

    Zhong, Qifeng; Xie, Zhuoying; Ding, Haibo; Zhu, Cun; Yang, Zixue; Gu, Zhongze

    2015-11-18

    Carbon inverse opal rods made from silica photonic crystal rods are used for nonenzymatic cholesterol sensing. The characteristic reflection peak originating from the physical periodic structure works as sensing signals for quantitatively estimating cholesterol concentrations. Carbon inverse opal rods work both in cholesterol standard solutions and human serum. They are suitable for practical use in clinical diagnose.

  8. Management of cases suffering from atypical myopathy: interpretations of descriptive, epidemiological and pathophysiological findings

    DEFF Research Database (Denmark)

    van Galen Verwilghen, Gaby; Votion, D.-M.

    2013-01-01

    Atypical myopathy is highly fatal, but about a quarter of affected horses survive. This highlights the need for provision of supportive treatment for these patients. This review is a practical guideline for equine practitioners and includes suggestions for close monitoring of involved organ syste...

  9. The Cutaneous Assessment Tool : development and reliability in juvenile idiopathic inflammatory myopathy

    NARCIS (Netherlands)

    Huber, A. M.; Dugan, E. M.; Lachenbruch, P. A.; Feldman, B. M.; Perez, M. D.; Zemel, L. S.; Lindsley, C. B.; Rennebohm, R. M.; Wallace, C. A.; Passo, M. H.; Reed, A. M.; Bowyer, S. L.; Ballinger, S. H.; Miller, F. W.; Rider, L. G.

    2007-01-01

    Objectives. Clinical care and therapeutic trials in idiopathic inflammatory myopathies (IIM) require accurate and consistent assessment of cutaneous involvement. The Cutaneous Assessment Tool (CAT) was designed to measure skin activity and damage in IIM. We describe the development and inter-rater r

  10. Management of cases suffering from atypical myopathy: interpretations of descriptive, epidemiological and pathophysiological findings

    DEFF Research Database (Denmark)

    van Galen Verwilghen, Gaby; Votion, D.-M.

    2013-01-01

    Atypical myopathy is highly fatal, but about a quarter of affected horses survive. This highlights the need for provision of supportive treatment for these cases. This review is a practical guideline for equine practitioners and includes suggestions for close monitoring of involved organ systems...

  11. Cardiac abnormalities assessed by non-invasive techniques in patients with newly diagnosed idiopathic inflammatory myopathies

    DEFF Research Database (Denmark)

    Diederichsen, Louise Pyndt; Simonsen, Jane Angel; Diederichsen, Axel Cosmus Pyndt

    2015-01-01

    inflammatory myopathies (IIM) by means of non-invasive techniques. METHODS: Fourteen patients with IIM (8 polymyositis, 4 dermatomyositis, 2 cancer-associated dermatomyositis) and 14 gender- and age- matched healthy control subjects were investigated. Participant assessments included a cardiac questionnaire...

  12. Rehabilitation of Critical Illness Polyneuropathy and Myopathy Patients: An Observational Study

    Science.gov (United States)

    Novak, Primoz; Vidmar, Gaj; Kuret, Zala; Bizovicar, Natasa

    2011-01-01

    Critical illness polyneuropathy and myopathy (CIPNM) frequently develops in patients hospitalized in intensive care units. The number of patients with CIPNM admitted to inpatient rehabilitation is increasing. The aim of this study was to comprehensively evaluate the outcome of their rehabilitation. Twenty-seven patients with CIPNM were included in…

  13. Cyclophilin D, a target for counteracting skeletal muscle dysfunction in mitochondrial myopathy.

    Science.gov (United States)

    Gineste, Charlotte; Hernandez, Andres; Ivarsson, Niklas; Cheng, Arthur J; Naess, Karin; Wibom, Rolf; Lesko, Nicole; Bruhn, Helene; Wedell, Anna; Freyer, Christoph; Zhang, Shi-Jin; Carlström, Mattias; Lanner, Johanna T; Andersson, Daniel C; Bruton, Joseph D; Wredenberg, Anna; Westerblad, Håkan

    2015-12-01

    Muscle weakness and exercise intolerance are hallmark symptoms in mitochondrial disorders. Little is known about the mechanisms leading to impaired skeletal muscle function and ultimately muscle weakness in these patients. In a mouse model of lethal mitochondrial myopathy, the muscle-specific Tfam knock-out (KO) mouse, we previously demonstrated an excessive mitochondrial Ca(2+) uptake in isolated muscle fibers that could be inhibited by the cyclophilin D (CypD) inhibitor, cyclosporine A (CsA). Here we show that the Tfam KO mice have increased CypD levels, and we demonstrate that this increase is a common feature in patients with mitochondrial myopathy. We tested the effect of CsA treatment on Tfam KO mice during the transition from a mild to terminal myopathy. CsA treatment counteracted the development of muscle weakness and improved muscle fiber Ca(2+) handling. Importantly, CsA treatment prolonged the lifespan of these muscle-specific Tfam KO mice. These results demonstrate that CsA treatment is an efficient therapeutic strategy to slow the development of severe mitochondrial myopathy.

  14. Whole-body MRI in adult inflammatory myopathies: Do we need imaging of the trunk?

    Energy Technology Data Exchange (ETDEWEB)

    Filli, Lukas; Manoliu, Andrei; Andreisek, Gustav; Guggenberger, Roman [University Hospital Zurich, University of Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland); Maurer, Britta [University Hospital Zurich, University of Zurich, Division of Rheumatology, Zurich (Switzerland)

    2015-12-15

    To evaluate whether imaging of the trunk could be omitted in patients with inflammatory myopathies without losing diagnostic accuracy using a restricted whole-body magnetic resonance imaging (rWB-MRI) protocol. After approval by the institutional review board, this study was performed in 63 patients (male/female, 13/50; median age, 52 years; range, 20-81 years) with new-onset myopathic symptoms (group 1, n = 41) or previously diagnosed inflammatory myopathy (group 2, n = 22). After performing whole-body MRI (WB-MRI) at 3.0 Tesla, myositis and fatty atrophy were evaluated in different muscles by two independent radiologists. The intra-class correlation coefficient (ICC) was calculated to evaluate inter-observer reliability. Acquisition time was 56:01 minutes for WB-MRI and 37:37 minutes (32.8 % shorter) for rWB-MRI. In group 1, 14 patients were diagnosed with inflammatory myopathy based on muscle biopsy. rWB-MRI and WB-MRI showed equal sensitivity (42.9 %) and specificity (100 %) for myositis, and showed equal sensitivity (71.4 %) and similar specificity (63.0 % and 48.1 %, respectively) for fatty atrophy. No myositis was found in the body trunk in any patient. Inter-observer reliability was between substantial and perfect (ICC, 0.77-1.00). rWB-MRI showed diagnostic accuracy similar to WB-MRI for inflammatory myopathy at markedly reduced overall acquisition time. (orig.)

  15. Joint hypermobility as a distinctive feature in the differential diagnosis of myopathies.

    NARCIS (Netherlands)

    Voermans, N.C.; Bonnemann, C.G.; Hamel, B.C.J.; Jungbluth, H.; Engelen, B.G.M. van

    2009-01-01

    Congenital and adult-onset inherited myopathies represent a wide spectrum of syndromes. Classification is based upon clinical features and biochemical and genetic defects. Joint hypermobility is one of the distinctive clinical features that has often been underrecognized so far. We therefore present

  16. Clinical Manifestation and a New "ISCU" Mutation in Iron-Sulphur Cluster Deficiency Myopathy

    Science.gov (United States)

    Kollberg, Gittan; Tulinius, Mar; Melberg, Atle; Darin, Niklas; Andersen, Oluf; Holmgren, Daniel; Oldfors, Anders; Holme, Elisabeth

    2009-01-01

    Myopathy with deficiency of succinate dehydrogenase and aconitase is a recessively inherited disorder characterized by childhood-onset early fatigue, dyspnoea and palpitations on trivial exercise. The disease is non-progressive, but life-threatening episodes of widespread weakness, severe metabolic acidosis and rhabdomyolysis may occur. The…

  17. Development of autoantibodies against muscle-specific FHL1 in severe inflammatory myopathies.

    Science.gov (United States)

    Albrecht, Inka; Wick, Cecilia; Hallgren, Åsa; Tjärnlund, Anna; Nagaraju, Kanneboyina; Andrade, Felipe; Thompson, Kathryn; Coley, William; Phadke, Aditi; Diaz-Gallo, Lina-Marcela; Bottai, Matteo; Nennesmo, Inger; Chemin, Karine; Herrath, Jessica; Johansson, Karin; Wikberg, Anders; Ytterberg, A Jimmy; Zubarev, Roman A; Danielsson, Olof; Krystufkova, Olga; Vencovsky, Jiri; Landegren, Nils; Wahren-Herlenius, Marie; Padyukov, Leonid; Kämpe, Olle; Lundberg, Ingrid E

    2015-12-01

    Mutations of the gene encoding four-and-a-half LIM domain 1 (FHL1) are the causative factor of several X-linked hereditary myopathies that are collectively termed FHL1-related myopathies. These disorders are characterized by severe muscle dysfunction and damage. Here, we have shown that patients with idiopathic inflammatory myopathies (IIMs) develop autoimmunity to FHL1, which is a muscle-specific protein. Anti-FHL1 autoantibodies were detected in 25% of IIM patients, while patients with other autoimmune diseases or muscular dystrophies were largely anti-FHL1 negative. Anti-FHL1 reactivity was predictive for muscle atrophy, dysphagia, pronounced muscle fiber damage, and vasculitis. FHL1 showed an altered expression pattern, with focal accumulation in the muscle fibers of autoantibody-positive patients compared with a homogeneous expression in anti-FHL1-negative patients and healthy controls. We determined that FHL1 is a target of the cytotoxic protease granzyme B, indicating that the generation of FHL1 fragments may initiate FHL1 autoimmunity. Moreover, immunization of myositis-prone mice with FHL1 aggravated muscle weakness and increased mortality, suggesting a direct link between anti-FHL1 responses and muscle damage. Together, our findings provide evidence that FHL1 may be involved in the pathogenesis not only of genetic FHL1-related myopathies but also of autoimmune IIM. Importantly, these results indicate that anti-FHL1 autoantibodies in peripheral blood have promising potential as a biomarker to identify a subset of severe IIM.

  18. A case of anti-nuclear matrix protein 2 antibody positive myopathy associated with lung cancer.

    Science.gov (United States)

    Ohta, Shin; Unoda, Ki-Ichi; Nakajima, Hideto; Ikeda, Soichiro; Hamaguchi, Yasuhito; Kimura, Fumiharu

    2016-08-31

    Myositis-specific autoantibodies (MSAs) are associated with myositis. Anti-nuclear matrix protein 2 (NXP-2) antibody was recently identified as a major MSA and was observed mostly in juvenile dermatomyositis. We report the case of a 44-year-old man who presented with myopathy with anti-NXP-2 antibody and large cell carcinoma of the lung. He was hospitalized because of myalgia and edema of limbs. Neurological examination revealed mild proximal-dominant weakness in all four extremities, and laboratory studies showed elevated creatine kinase level (6,432 IU/l). Needle electromyography showed myogenic patterns. MRI of the lower limbs demonstrated inflammatory lesions in the thighs. Biopsied specimen from the left quadriceps femoris muscle showed mild mononuclear inflammatory infiltrate surrounding muscle fibres but no fiber necrosis. He was diagnosed with myopathy based on neurological examinations and clinical symptoms. His chest X-ray and CT showed tumor shadow on the right upper lung field, but CT didn't indicate the findings of interstitial lung disease. This was surgically removed, and a histological diagnosis of non-small cell lung cancer was suspected. He was also treated with definitive chemoradiotherapy before and after operation. His symptoms of myopathy promptly remitted with the preoperative chemotherapy. His serum analysis was positive for the anti-NXP-2. Further investigation and experience of MSAs are necessary to evaluate the therapeutic strategy against cancer-associated myopathy/myositis.

  19. Sporadic cardiac and skeletal myopathy caused by a de novo desmin mutation.

    Science.gov (United States)

    Park, K Y; Dalakas, M C; Semino-Mora, C; Lee, H S; Litvak, S; Takeda, K; Ferrans, V J; Goldfarb, L G

    2000-06-01

    Desmin myopathy is a familial or sporadic disorder characterized by intracytoplasmic accumulation of desmin in the muscle cells. We and others have previously identified desmin gene mutations in patients with familial myopathy, but close to 45% of the patients do not report previous family history of the disease. The present study was conducted to determine the cause of desmin myopathy in a sporadic patient presenting with symmetrical muscle weakness and atrophy combined with atrioventricular conduction block requiring a permanent pacemaker. A novel heterozygous R406W mutation in the desmin gene was identified by sequencing cDNA and genomic DNA. Expression of a construct containing the patient's mutant desmin cDNA in SW13 (vim-) cells demonstrated a high pathogenic potential of the R406W mutation. This mutation was not found in the patient's father, mother or sister by sequencing and restriction analysis. Testing with five microsatellite markers and four intragenic single nucleotide polymorphisms excluded alternative paternity. Haplotype analysis indicates that the patient's father was germ-line mosaic for the desmin mutation. We conclude that de novo mutations in the desmin gene may be the cause of sporadic forms of desmin-related cardiac and skeletal myopathy.

  20. Aerobic Exercise and Pharmacological Therapies for Skeletal Myopathy in Heart Failure: Similarities and Differences

    Directory of Open Access Journals (Sweden)

    Aline V. Bacurau

    2016-01-01

    Full Text Available Skeletal myopathy has been identified as a major comorbidity of heart failure (HF affecting up to 20% of ambulatory patients leading to shortness of breath, early fatigue, and exercise intolerance. Neurohumoral blockade, through the inhibition of renin angiotensin aldosterone system (RAS and β-adrenergic receptor blockade (β-blockers, is a mandatory pharmacological therapy of HF since it reduces symptoms, mortality, and sudden death. However, the effect of these drugs on skeletal myopathy needs to be clarified, since exercise intolerance remains in HF patients optimized with β-blockers and inhibitors of RAS. Aerobic exercise training (AET is efficient in counteracting skeletal myopathy and in improving functional capacity and quality of life. Indeed, AET has beneficial effects on failing heart itself despite being of less magnitude compared with neurohumoral blockade. In this way, AET should be implemented in the care standards, together with pharmacological therapies. Since both neurohumoral inhibition and AET have a direct and/or indirect impact on skeletal muscle, this review aims to provide an overview of the isolated effects of these therapeutic approaches in counteracting skeletal myopathy in HF. The similarities and dissimilarities of neurohumoral inhibition and AET therapies are also discussed to identify potential advantageous effects of these combined therapies for treating HF.

  1. Triacylglycerol infusion improves exercise endurance in patients with mitochondrial myopathy due to complex I deficiency

    NARCIS (Netherlands)

    Roef, MJ; de Meer, K; Reijngoud, DJ; Straver, HWHC; de Barse, M; Kalhan, SC; Berger, R

    2002-01-01

    Background: A high-fat diet has been recommended for the treatment of patients with mitochondrial myopathy due to complex I (NADH dehydrogenase) deficiency (CID). Objective: This study evaluated the effects of intravenous infusion of isoenergetic amounts of triacylglycerol or glucose on substrate ox

  2. Statin-Induced Myopathy Is Associated with Mitochondrial Complex III Inhibition

    NARCIS (Netherlands)

    Schirris, T.J.J.; Renkema, G.H.; Ritschel, T.; Voermans, N.C.; Bilos, A.; Engelen, B.G. van; Brandt, U.; Koopman, W.J.; Beyrath, J.D.; Rodenburg, R.J.; Willems, P.H.; Smeitink, J.A.; Russel, F.G.

    2015-01-01

    Cholesterol-lowering statins effectively reduce the risk of major cardiovascular events. Myopathy is the most important adverse effect, but its underlying mechanism remains enigmatic. In C2C12 myoblasts, several statin lactones reduced respiratory capacity and appeared to be strong inhibitors of

  3. Effects of ubiquinone (coenzyme Q10) on myopathy in statin users.

    NARCIS (Netherlands)

    Schaars, C.F.; Stalenhoef, A.F.H.

    2008-01-01

    PURPOSE OF REVIEW: Statins are associated with muscle complaints, including myositis. The mechanism through which statin use causes muscle toxicity is unknown. One of the theories is that statin therapy reduces coenzyme Q10 levels in muscle mitochondria, which leads to muscle injury and myopathy. Th

  4. Ileocolonic transfer of solid chyme in small intestinal neuropathies and myopathies

    Energy Technology Data Exchange (ETDEWEB)

    Greydanus, M.P.; Camilleri, M.; Colemont, L.J.; Phillips, S.F.; Brown, M.L.; Thomforde, G.M. (Mayo Clinic and Foundation, Rochester, MN (USA))

    1990-07-01

    The aims of this study were to assess gastric emptying, small bowel transit and colonic filling in patients with motility disorders, with particular attention to the patterns of colonic filling. Gastrointestinal transit was assessed using a previously validated radiolabeled mixed meal. Fourteen patients with clinical and manometric features of chronic intestinal pseudoobstruction classified as intestinal neuropathy and 6 as intestinal myopathy, were studied. The results were compared with those from 10 healthy controls studied similarly. Gastric emptying and small bowel transit of solids were significantly slower in both groups of patients than in healthy controls (P less than 0.05). In health, the ileocolonic transit of solid chyme was characterized by intermittent bolus transfers. The mean size of boluses transferred to the colon (expressed as a percentage of ingested radiolabel) was significantly less (P less than 0.05) in patients with intestinal myopathy (10% +/- 4% (SEM)) than in healthy controls (25% +/- 4%) or in patients with intestinal neuropathy (25% +/- 4%). The intervals between bolus transfer of solids (plateaus in the colonic filling curve) were longer (P less than 0.05) in myopathies (212 +/- 89 minutes) than in health (45 +/- 7 minutes) or neuropathies (53 +/- 11 minutes). Thus, gastric emptying and small bowel transit were delayed in small bowel neuropathies and myopathies. Bolus filling of the colon was less frequent and less effective in patients with myopathic intestinal pseudoobstruction, whereas bolus transfer was preserved in patients with neuropathic intestinal pseudoobstruction.

  5. Severe myopathy in mice lacking the MEF2/SRF-dependent gene leiomodin-3

    Science.gov (United States)

    Cenik, Bercin K.; Garg, Ankit; McAnally, John R.; Shelton, John M.; Richardson, James A.; Bassel-Duby, Rhonda; Olson, Eric N.; Liu, Ning

    2015-01-01

    Maintenance of skeletal muscle structure and function requires a precise stoichiometry of sarcomeric proteins for proper assembly of the contractile apparatus. Absence of components of the sarcomeric thin filaments causes nemaline myopathy, a lethal congenital muscle disorder associated with aberrant myofiber structure and contractility. Previously, we reported that deficiency of the kelch-like family member 40 (KLHL40) in mice results in nemaline myopathy and destabilization of leiomodin-3 (LMOD3). LMOD3 belongs to a family of tropomodulin-related proteins that promote actin nucleation. Here, we show that deficiency of LMOD3 in mice causes nemaline myopathy. In skeletal muscle, transcription of Lmod3 was controlled by the transcription factors SRF and MEF2. Myocardin-related transcription factors (MRTFs), which function as SRF coactivators, serve as sensors of actin polymerization and are sequestered in the cytoplasm by actin monomers. Conversely, conditions that favor actin polymerization de-repress MRTFs and activate SRF-dependent genes. We demonstrated that the actin nucleator LMOD3, together with its stabilizing partner KLHL40, enhances MRTF-SRF activity. In turn, SRF cooperated with MEF2 to sustain the expression of LMOD3 and other components of the contractile apparatus, thereby establishing a regulatory circuit to maintain skeletal muscle function. These findings provide insight into the molecular basis of the sarcomere assembly and muscle dysfunction associated with nemaline myopathy. PMID:25774500

  6. A gene for autosomal recessive nemaline myopathy assigned to chromosome 2q by linkage analysis

    NARCIS (Netherlands)

    Wallgren-Pettersson, C.; Avela, K.; Marchand, S.; Kolehmainen, J.; Tahvanainen, E.; Hansen, F.J.; Muntoni, F.; Dubowitz, V.; de Visser, Marianne; Van Langen, I.M.; Laing, N.G.; Faure, S.; De la Chapelle, A.

    1995-01-01

    Clinical genetic evidence suggests the existence of an autosomal recessive form of congenital nemaline myopathy in addition to the autosomal dominant one(s). One mutation in an Australian kindred has been identified as causing an autosomal dominant form of the disease. This mutation in the

  7. Leiomodin-3-deficient mice display nemaline myopathy with fast-myofiber atrophy.

    Science.gov (United States)

    Tian, Lei; Ding, Sheng; You, Yun; Li, Tong-ruei; Liu, Yan; Wu, Xiaohui; Sun, Ling; Xu, Tian

    2015-06-01

    Nemaline myopathy (NM) is one of the most common forms of congenital myopathy, and affects either fast myofibers, slow myofibers, or both. However, an animal model for congenital myopathy with fast-myofiber-specific atrophy is not available. Furthermore, mutations in the leiomodin-3 (LMOD3) gene have recently been identified in a group of individuals with NM. However, it is not clear how loss of LMOD3 leads to NM. Here, we report a mouse mutant in which the piggyBac (PB) transposon is inserted into the Lmod3 gene and disrupts its expression. Lmod3(PB/PB) mice show severe muscle weakness and postnatal growth retardation. Electron microscopy and immunofluorescence studies of the mutant skeletal muscles revealed the presence of nemaline bodies, a hallmark of NM, and disorganized sarcomeric structures. Interestingly, Lmod3 deficiency caused muscle atrophy specific to the fast fibers. Together, our results show that Lmod3 is required in the fast fibers for sarcomere integrity, and this study offers the first NM mouse model with muscle atrophy that is specific to fast fibers. This model could be a valuable resource for interrogating myopathy pathogenesis and developing therapeutics for NM as well as other pathophysiological conditions with preferential atrophy of fast fibers, including cancer cachexia and sarcopenia. © 2015. Published by The Company of Biologists Ltd.

  8. Distinct underlying mechanisms of limb and respiratory muscle fiber weaknesses in nemaline myopathy.

    Science.gov (United States)

    Lindqvist, Johan; Cheng, Arthur J; Renaud, Guillaume; Hardeman, Edna C; Ochala, Julien

    2013-06-01

    Nemaline myopathy is the most common congenital myopathy and is caused by mutations in various genes such as ACTA1 (encoding skeletal α-actin). It is associated with limb and respiratory muscle weakness. Despite increasing clinical and scientific interest, the molecular and cellular events leading to such weakness remain unknown, which prevents the development of specific therapeutic interventions. To unravel the potential mechanisms involved, we dissected lower limb and diaphragm muscles from a knock-in mouse model of severe nemaline myopathy expressing the ACTA1 His40Tyr actin mutation found in human patients. We then studied a broad range of structural and functional characteristics assessing single-myofiber contraction, protein expression, and electron microscopy. One of the major findings in the diaphragm was the presence of numerous noncontractile areas (including disrupted sarcomeric structures and nemaline bodies). This greatly reduced the number of functional sarcomeres, decreased the force generation capacity at the muscle fiber level, and likely would contribute to respiratory weakness. In limb muscle, by contrast, there were fewer noncontractile areas and they did not seem to have a major role in the pathogenesis of weakness. These divergent muscle-specific results provide new important insights into the pathophysiology of severe nemaline myopathy and crucial information for future development of therapeutic strategies.

  9. Treatment of critical illness polyneuropathy and/or myopathy - a systematic review

    DEFF Research Database (Denmark)

    Ydemann, Mogens; Eddelien, Heidi Shil; Lauritsen, Anne Øberg

    2012-01-01

    The objective was to search the literature with a view to providing a general description of critical illness myopathy/polyneuropathy (CIM/CIP), including its genesis and prevention. Furthermore, it was our aim to determine whether new treatments have occurred in the past five years....

  10. Leiomodin-3-deficient mice display nemaline myopathy with fast-myofiber atrophy

    Directory of Open Access Journals (Sweden)

    Lei Tian

    2015-06-01

    Full Text Available Nemaline myopathy (NM is one of the most common forms of congenital myopathy, and affects either fast myofibers, slow myofibers, or both. However, an animal model for congenital myopathy with fast-myofiber-specific atrophy is not available. Furthermore, mutations in the leiomodin-3 (LMOD3 gene have recently been identified in a group of individuals with NM. However, it is not clear how loss of LMOD3 leads to NM. Here, we report a mouse mutant in which the piggyBac (PB transposon is inserted into the Lmod3 gene and disrupts its expression. Lmod3PB/PB mice show severe muscle weakness and postnatal growth retardation. Electron microscopy and immunofluorescence studies of the mutant skeletal muscles revealed the presence of nemaline bodies, a hallmark of NM, and disorganized sarcomeric structures. Interestingly, Lmod3 deficiency caused muscle atrophy specific to the fast fibers. Together, our results show that Lmod3 is required in the fast fibers for sarcomere integrity, and this study offers the first NM mouse model with muscle atrophy that is specific to fast fibers. This model could be a valuable resource for interrogating myopathy pathogenesis and developing therapeutics for NM as well as other pathophysiological conditions with preferential atrophy of fast fibers, including cancer cachexia and sarcopenia.

  11. Nebulin deficiency in adult muscle causes sarcomere defects and muscle-type-dependent changes in trophicity: novel insights in nemaline myopathy.

    Science.gov (United States)

    Li, Frank; Buck, Danielle; De Winter, Josine; Kolb, Justin; Meng, Hui; Birch, Camille; Slater, Rebecca; Escobar, Yael Natelie; Smith, John E; Yang, Lin; Konhilas, John; Lawlor, Michael W; Ottenheijm, Coen; Granzier, Henk L

    2015-09-15

    Nebulin is a giant filamentous protein that is coextensive with the actin filaments of the skeletal muscle sarcomere. Nebulin mutations are the main cause of nemaline myopathy (NEM), with typical adult patients having low expression of nebulin, yet the roles of nebulin in adult muscle remain poorly understood. To establish nebulin's functional roles in adult muscle, we studied a novel conditional nebulin KO (Neb cKO) mouse model in which nebulin deletion was driven by the muscle creatine kinase (MCK) promotor. Neb cKO mice are born with high nebulin levels in their skeletal muscles, but within weeks after birth nebulin expression rapidly falls to barely detectable levels Surprisingly, a large fraction of the mice survive to adulthood with low nebulin levels (Muscles rich in glycolytic fibers upregulate proteolysis pathways (MuRF-1, Fbxo30/MUSA1, Gadd45a) and undergo hypotrophy with smaller cross-sectional areas (CSAs), worsening their force deficit. Muscles rich in oxidative fibers do not have smaller weights and can even have hypertrophy, offsetting their specific-force deficit. These studies reveal nebulin as critically important for force development and trophicity in adult muscle. The Neb cKO phenocopies important aspects of NEM (muscle weakness, oxidative fiber-type predominance, variable trophicity effects, nemaline rods) and will be highly useful to test therapeutic approaches to ameliorate muscle weakness. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Evaluation of ubiquinone concentration and mitochondrial function relative to cerivastatin-induced skeletal myopathy in rats.

    Science.gov (United States)

    Schaefer, William H; Lawrence, Jeffery W; Loughlin, Amy F; Stoffregen, Dana A; Mixson, Lori A; Dean, Dennis C; Raab, Conrad E; Yu, Nathan X; Lankas, George R; Frederick, Clay B

    2004-01-01

    As a class, hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors can potentially cause skeletal myopathy. One statin, cerivastatin, has recently been withdrawn from the market due to an unacceptably high incidence of rhabdomyolysis. The mechanism underlying statin-induced myopathy is unknown. This paper sought to investigate the relationship among statin-induced myopathy, mitochondrial function, and muscle ubiquinone levels. Rats were administered cerivastatin at 0.1, 0.5, and 1.0 (mg/kg)/day or dose vehicle (controls) by oral gavage for 15 days. Samples of type I-predominant skeletal muscle (soleus) and type II-predominant skeletal muscle [quadriceps and extensor digitorum longus (EDL)], and blood were collected on study days 5, 10, and 15 for morphological evaluation, clinical chemistry, mitochondrial function tests, and analysis of ubiquinone levels. No histological changes were observed in any of the animals on study days 5 or 10, but on study day 15, mid- and high-dose animals had necrosis and inflammation in type II skeletal muscle. Elevated creatine kinase (CK) levels in blood (a clinical marker of myopathy) correlated with the histopathological diagnosis of myopathy. Ultrastructural characterization of skeletal muscle revealed disruption of the sarcomere and altered mitochondria only in myofibers with degeneration, while adjacent myofibers were unaffected and had normal mitochondria. Thus, mitochondrial effects appeared not to precede myofiber degeneration. Mean coenzyme Q9 (CoQ9) levels in all dose groups were slightly decreased relative to controls in type II skeletal muscle, although the difference was not significantly different in most cases. Mitochondrial function in skeletal muscle was not affected by the changes in ubiquinone levels. The ubiquinone levels in high-dose-treated animals exhibiting myopathy were not significantly different from low-dose animals with no observable toxic effects. Furthermore, ubiquinone levels did not correlate

  13. Muscular myopathies other than myotonic dystrophy also associated with (CTG n expansion at the DMPK locus

    Directory of Open Access Journals (Sweden)

    Vasavi Mohan

    2012-01-01

    Full Text Available Objective: Assess triplet repeat expansion (CTG n at the ′dystrophia-myotonica protein kinase′ (DMPK locus in muscular myopathies to elucidate its role in myopathic symptoms and enable genetic counseling and prenatal diagnosis in families. Methods and Results: Individuals with symptoms of myopathy, hypotonia and controls selected randomly from the population were evaluated for triplet repeat expansion of (CTG n repeats in the 3′untranslated region (UTR of DMPK gene, the causative mutation in myotonic dystrophy (DM. DNA was isolated from peripheral blood of 40 individuals; they presented symptoms of muscle myopathy ( n = 11, muscle hypotonia ( n = 4, members of their families ( n = 5 and control individuals from random population ( n = 20. Molecular analysis of genomic DNA by polymerase chain reaction (PCR using primers specific for the DMPK gene encompassing the triplet repeat expansion, showed that all controls ( n = 20 gave a 2.1 kb band indicating normal triplet repeat number. Three out of 11 cases (two clinically diagnosed DM and one muscular dystrophy had an expansion of the (CTG n repeat in the range of 1000-2100 repeats corresponding to the repeat number in cases of severe DM. Other two of these 11 cases, showed a mild expansion of ~ 66 repeats. Three samples, which included two cases of hypotonia and the father of a subject with muscular dystrophy, also gave a similar repeat expansion (~66 repeats. Conclusion: Results suggest a role of (CTG n expansion at the DMPK locus in unexplained hypotonias and muscular myopathies other than DM. This calls for screening of the triplet repeat expansion at the DMPK locus in cases of idiopathic myopathies and hypotonia.

  14. Dysphagia in inflammatory myopathy: clinical characteristics, treatment strategies, and outcome in 62 patients.

    Science.gov (United States)

    Oh, Terry H; Brumfield, Kathlyn A; Hoskin, Tanya L; Stolp, Kathryn A; Murray, Joseph A; Bassford, Jeffrey R

    2007-04-01

    To assess the clinical characteristics, treatment, and outcome of patients with inflammatory myopathy-associated dysphagia. We retrospectively reviewed the medical records of all patients with inflammatory myopathy-associated dysphagia seen at the Mayo Clinic in Rochester, Minn, between January 1, 1997, and December 31, 2001. A total of 783 patients were diagnosed as having inflammatory myopathy during the 5-year study period. Of these, 62 patients (41 women and 21 men; mean age, 68.6 years) had inflammatory myopathy-associated dysphagia: 26 with inclusion body myositis (IBM), 18 with dermatomyositis, 9 with polymyositis, and 9 with overlap syndrome. Dysphagia was a presenting symptom in 13 patients (21%), with the highest incidence in the IBM group. Videofluoroscopic examinations revealed pharyngeal pooling and impaired oropharyngeal and cricopharyngeal function. The benefits of swallowing compensation techniques and exercises were difficult to establish. Interventional procedures were performed in 24 patients (39%) and most frequently (62%) in patients with IBM, with cricopharyngeal myotomy being most beneficial. Patients with IBM had the least symptomatic improvement. Overall, 11 patients died during the median follow-up of 38 months, with respiratory failure due to aspiration pneumonia as the most common cause. Mortality was high in patients who required percutaneous endoscopic gastrostomy (7/11, 64%), and 1- year mortality was highest (31%) in those with dermatomyositis. Dysphagia is a serious and at times presenting problem in patients with inflammatory myopathy. It occurs most frequently and appears to be most refractory in patients with IBM. The mortality rate was high in patients who required percutaneous endoscopic gastrostomy, and the 1-year mortality rate was the highest in patients with dermatomyositis.

  15. ColVI myopathies: where do we stand, where do we go?

    Directory of Open Access Journals (Sweden)

    Allamand Valérie

    2011-09-01

    Full Text Available Abstract Collagen VI myopathies, caused by mutations in the genes encoding collagen type VI (ColVI, represent a clinical continuum with Ullrich congenital muscular dystrophy (UCMD and Bethlem myopathy (BM at each end of the spectrum, and less well-defined intermediate phenotypes in between. ColVI myopathies also share common features with other disorders associated with prominent muscle contractures, making differential diagnosis difficult. This group of disorders, under-recognized for a long time, has aroused much interest over the past decade, with important advances made in understanding its molecular pathogenesis. Indeed, numerous mutations have now been reported in the COL6A1, COL6A2 and COL6A3 genes, a large proportion of which are de novo and exert dominant-negative effects. Genotype-phenotype correlations have also started to emerge, which reflect the various pathogenic mechanisms at play in these disorders: dominant de novo exon splicing that enables the synthesis and secretion of mutant tetramers and homozygous nonsense mutations that lead to premature termination of translation and complete loss of function are associated with early-onset, severe phenotypes. In this review, we present the current state of diagnosis and research in the field of ColVI myopathies. The past decade has provided significant advances, with the identification of altered cellular functions in animal models of ColVI myopathies and in patient samples. In particular, mitochondrial dysfunction and a defect in the autophagic clearance system of skeletal muscle have recently been reported, thereby opening potential therapeutic avenues.

  16. Statins' effect on plasma levels of Coenzyme Q10 and improvement in myopathy with supplementation.

    Science.gov (United States)

    Littlefield, Nate; Beckstrand, Renea L; Luthy, Karlen E

    2014-02-01

    Heart disease is the leading cause of death in the United States. HMG-CoA reductase inhibitors, or statins, are medications at the forefront of the battle against cardiovascular disease. Despite their effectiveness, patient compliance with statins has lagged because of medication cost and adverse effects, namely myopathy. Myopathy is the most common side effect of statin use. The purpose of this review is to report plasma levels of CoQ10 in patients taking statins and then to determine the benefit of Coenzyme Q10 (CoQ10) supplementation on statin-related myopathy as evidenced by symptomatic improvement and increase in serum levels of CoQ10. CINAHL, Medline, Health Source: Nursing/Academic Edition, and Cochrane Library. Evidence from this review suggests that studies showed a significant relationship between statin intake and decreased serum levels of CoQ10. A few studies showed a benefit in symptoms of myalgia or improvement of serum levels of CoQ10 with supplementation. One study showed no benefit of CoQ10 supplementation when taken with statins. There were no risks of supplementation reported in any of the studies. CoQ10 supplementation might benefit those patients suffering from statin-induced myopathy as evidenced by the results of these studies. Supplementation of CoQ10 at a dose of between 30 and 200 mg daily has shown to have beneficial effects on statin myopathy with no noted side effects. Further research is necessary. ©2013 The Author(s) ©2013 American Association of Nurse Practitioners.

  17. Axial mitochondrial myopathy in a patient with rapidly progressive adult-onset scoliosis.

    Science.gov (United States)

    Hiniker, Annie; Wong, Lee-Jun; Berven, Sigurd; Truong, Cavatina K; Adesina, Adekunle M; Margeta, Marta

    2014-01-01

    Axial myopathy can be the underlying cause of rapidly progressive adult-onset scoliosis; however, the pathogenesis of this disorder remains poorly understood. Here we present a case of a 69-year old woman with a family history of scoliosis affecting both her mother and her son, who over 4 years developed rapidly progressive scoliosis. The patient had a history of stable scoliosis since adolescence that worsened significantly at age 65, leading to low back pain and radiculopathy. Paraspinal muscle biopsy showed morphologic evidence of a mitochondrial myopathy. Diagnostic deficiencies of electron transport chain enzymes were not detected using standard bioassays, but mitochondrial immunofluorescence demonstrated many muscle fibers totally or partially deficient for complexes I, III, IV-I, and IV-IV. Massively parallel sequencing of paraspinal muscle mtDNA detected multiple deletions as well as a 40.9% heteroplasmic novel m.12293G > A (MT-TL2) variant, which changes a G:C pairing to an A:C mispairing in the anticodon stem of tRNA Leu(CUN). Interestingly, these mitochondrial abnormalities were not detected in the blood of either the patient or her son, suggesting that the patient's rapidly progressive late onset scoliosis was due to the acquired paraspinal mitochondrial myopathy; the cause of non-progressive scoliosis in the other two family members currently remains unexplained. Notably, this case illustrates that isolated mitochondrial myopathy can underlie rapidly-progressive adult-onset scoliosis and should be considered in the differential diagnosis of the primary axial myopathy.

  18. [Sibling cases of severe infantile form of nemaline myopathy with ACTA1-gene mutation].

    Science.gov (United States)

    Sudo, Akira; Hayashi, Yukiko; Sano, Hitomi; Kawamura, Nobuaki; Nishino, Ichizo; Nonaka, Ikuya

    2013-11-01

    Severe infantile form of nemaline myopathy is clinically characterized by marked muscle hypotonia and weakness with respiratory and feeding difficulties since infancy. Recently, mutations in the skeletal muscle alpha-actine gene (ACTA1) have been identified in many patients with the nemaline myopathy. We experienced two cases of severe infantile form of nemaline myopathy with ACTA1 mutation (missence heterozygous mutation;c.553C>T, p.R185C) in siblings presenting with different clinical symptoms and courses. The elder brother was a typical "floppy infant" at birth. Because he could not suck and swallow at all, he was fed completely through a nasogastric tube. At 2 months of age, he developed respiratory insufficiency and was placed on a respirator all day. He was diagnosed with having nemaline myopathy from his muscle biopsy, which revealed marked variation in muscle fiber size with large numbers of nemaline bodies on Gomori-trichrome stain. In contrast, the younger brother presented with mild muscular hypotonia and feeding difficulty during the neonatal stage;therefore, he was partly fed through a nasogastric tube. At 2 months of age, he was admitted to our hospital because of respiratory distress, and he required nasal continuous positive airway pressure with oxygen followed by noninvasive positive pressure ventilation intermittently, mainly at night. He was followed at his home by parents with no serious problems;however he unexpectedly died at the age of 15 months. Although most cases of severe infantile form of nemaline myopathy caused by ACTA1 mutations are sporadic and have no family history, we emphasize that clinical symptoms are variable in siblings with the same mutation.

  19. Ryanodine myopathies without central cores--clinical, histopathologic, and genetic description of three cases.

    Science.gov (United States)

    Rocha, João; Taipa, Ricardo; Melo Pires, Manuel; Oliveira, Jorge; Santos, Rosário; Santos, Manuela

    2014-08-01

    Mutations in ryanodine receptor 1 gene (RYR1) are frequent causes of myopathies. They classically present with central core disease; however, clinical variability and histopathologic overlap are being increasingly recognized. Patient 1 is a 15-year-old girl with mild proximal, four-limb weakness from age 5, presenting with a progressive scoliosis starting at age 10. Patient 2 is an 18-year-old girl with progressively worsening muscle hypotrophy and mild proximal, four-limb weakness. She developed a rapidly progressive scoliosis from age 11 and needed surgical treatment at age 14 years. Patient 3 is an 11-year-old boy with moderate proximal limb weakness and progressive neck flexor weakness, first noticed at age 2. Muscle biopsies revealed type 1 fiber predominance (Patients 1 and 2) or abnormal type 1 fiber uniformity (Patient 3). Different RYR1 variants were identified in all patients. In Patients 1 and 3, these changes were validated as being pathogenic. These patients illustrate early-onset, progressive myopathies with predominant axial involvement. Histopathologic findings were abnormal but not specific for a diagnosis, particularly central core myopathy. Genetic testing helped broaden the range of phenotypes included in the RYR1-related myopathies. Our patients reinforce the need to recognize the broad histopathologic variability of RYR1-related myopathies and sometimes lack of pathognomonic findings that may reduce the diagnostic threshold of this disease. We suggest that the predominance of type 1 fibers and involvement of axial muscles may be an important element to consider the RYR1 gene as candidate. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. STUDY ON A HYDROPHOBIC-HYDROPHILIC GRADIENT ROD

    Institute of Scientific and Technical Information of China (English)

    Jun Ma; Bai-yu Li; Hai-yun Liu; Zhi-min Zheng; Jian Xu

    2004-01-01

    A hydrophobic-hydrophilic gradient rod with a length of 40 mm and a diameter of 3 mm was prepared by heating a polymethylsilsesquioxane rod in a cylindrical stove with temperature gradient. The rod was thus pyrolyzed under a temperature gradient condition. The organic end of the gradient rod appears hydrophobic with a contact angle of 109.9° while the other end is hydrophilic with a contact angle of 62.4°. The gradient chemical structure and the gradient microstructure along the rod were characterized by FTIR and SEM, respectively.

  1. Test Research on Special Sucker Rod for Screw Pump

    Institute of Scientific and Technical Information of China (English)

    Zhang Mingyi; Chen Mingzhan; Li Zhi

    2006-01-01

    @@ According to the statistics of straight thread sucker rods' application in screw pump in Daqing Oilfield before2000, the proportion of sucker rods' yearly breakaway reached to 41.6%, taking up 70% of the total wells that were checked. Thus it can be seen that the rods breakaway problem was becoming the main barrier restricting screw pump large-scale population and application. Since then,the development work on the special sucker rods for screw pump had been carried on. Through the analysis on the failure position and failure form of the sucker rods',the following conclusions arepresented:

  2. Photonic mesophases from cut rod rotators

    Energy Technology Data Exchange (ETDEWEB)

    Stelson, Angela C.; Liddell Watson, Chekesha M., E-mail: cml66@cornell.edu [Materials Science and Engineering, Cornell University, Ithaca, New York 14853 (United States); Avendano, Carlos [Chemical Engineering and Analytical Science, The University of Manchester, Manchester M13 9PL (United Kingdom)

    2016-01-14

    The photonic band properties of random rotator mesophases are calculated using supercell methods applied to cut rods on a hexagonal lattice. Inspired by the thermodynamic mesophase for anisotropic building blocks, we vary the shape factor of cut fraction for the randomly oriented basis. We find large, stable bandgaps with high gap isotropy in the inverted and direct structures as a function of cut fraction, dielectric contrast, and filling fraction. Bandgap sizes up to 34.5% are maximized at high dielectric contrast for rods separated in a matrix. The bandgaps open at dielectric contrasts as low as 2.0 for the transverse magnetic polarization and 2.25 for the transverse electric polarization. Additionally, the type of scattering that promotes the bandgap is correlated with the effect of disorder on bandgap size. Slow light properties are investigated in waveguide geometry and slowdown factors up to 5 × 10{sup 4} are found.

  3. Oligo(naphthylene–ethynylene) Molecular Rods

    DEFF Research Database (Denmark)

    Cramer, Jacob Roland; Ning, Yanxiao; Shen, Cai;

    2013-01-01

    Molecular rods designed for surface chirality studies have been synthesized in high yields. The molecules are composed of oligo(naphthylene–ethynylene) skeletons and functionalized at their two termini with carboxylic acids and hydrophobic groups. The molecular skeletons were constructed by means...... of palladium-catalyzed Sonogashira reactions between naphthyl halides and acetylenes. The triazene functionality was used as a protected iodine precursor to allow linear extension of the molecular rods during the synthe-ses. The carboxylic acid groups in the target molecules were protected as esters during...... the synthesis to keep the large aromatic molecules soluble during their syntheses. These rigid oligomers were designed to form lamella-like structures when adsorbed on a surface, through which multiple distinguishable surface conformations should be obtainable. Preliminary scanning tunneling microscopy imaging...

  4. [Rod of Asclepius. Symbol of medicine].

    Science.gov (United States)

    Young, Pablo; Finn, Bárbara C; Bruetman, Julio E; Cesaro Gelos, Jorge; Trimarchi, Hernán

    2013-09-01

    Symbolism is one of the most archaic forms of human thoughts. Symbol derives from the Latin word symbolum, and the latter from the Greek symbolon or symballo, which means "I coincide, I make matches". The Medicine symbol represents a whole series of historical and ethical values. Asclepius Rod with one serpent entwined, has traditionally been the symbol of scientific medicine. In a misconception that has lasted 500 years, the Caduceus of Hermes, entwined by two serpents and with two wings, has been considered the symbol of Medicine. However, the Caduceus is the current symbol of Commerce. Asclepius Rod and the Caduceus of Hermes represent two professions, Medicine and Commerce that, in ethical practice, should not be mixed. Physicians should be aware of their real emblem, its historical origin and meaning.

  5. Composites reinforcement by rods: a SAS study

    Energy Technology Data Exchange (ETDEWEB)

    Urban, V. [ESRF, BP220, 38043 Grenoble Cedex (France); Botti, A.; Pyckhout-Hintzen, W.; Richter, D. [IFF-Forschungszentrum Juelich, 52425 Juelich (Germany); Straube, E. [University of Halle, FB Physik, 06099 Halle (Germany)

    2002-07-01

    The mechanical properties of composites are governed by size, shape and dispersion degree of so-called reinforcing particles. Polymeric fillers based on thermodynamically driven microphase separation of block copolymers offer the opportunity to study a model system of controlled rod-like filler particles. We chose a triblock copolymer (PBPSPB) and carried out SAS measurements with both X-rays and neutrons, in order to characterize separately the hard phase and the cross-linked PB matrix. The properties of the material depend strongly on the way that stress is carried and transferred between the soft matrix and the hard fibers. The failure of the strain-amplification concept and the change of topological contributions to the free energy and scattering factor have to be addressed. In this respect the composite shows a similarity to a two-network system, i.e. interpenetrating rubber and rod-like filler networks. (orig.)

  6. Composites reinforcement by rods a SAS study

    CERN Document Server

    Urban, V; Pyckhout-Hintzen, W; Richter, D; Straube, E

    2002-01-01

    The mechanical properties of composites are governed by size, shape and dispersion degree of so-called reinforcing particles. Polymeric fillers based on thermodynamically driven microphase separation of block copolymers offer the opportunity to study a model system of controlled rod-like filler particles. We chose a triblock copolymer (PBPSPB) and carried out SAS measurements with both X-rays and neutrons, in order to characterize separately the hard phase and the cross-linked PB matrix. The properties of the material depend strongly on the way that stress is carried and transferred between the soft matrix and the hard fibers. The failure of the strain-amplification concept and the change of topological contributions to the free energy and scattering factor have to be addressed. In this respect the composite shows a similarity to a two-network system, i.e. interpenetrating rubber and rod-like filler networks. (orig.)

  7. Instabilities of a rotating helical rod

    Science.gov (United States)

    Park, Yunyoung; Ko, William; Kim, Yongsam; Lim, Sookkyung

    2016-11-01

    Bacteria such as Escherichia coli and Vibrio alginolyticus have helical flagellar filament. By rotating a motor, which is located at the bottom end of the flagellar filament embedded in the cell body, CCW or CW, they swim forward or backward. We model a left-handed helix by the Kirchhoff rod theory and use regularized Stokes formulation to study an interaction between the surrounding fluid and the flagellar filament. We perform numerical studies focusing on relations between physical parameters and critical angular frequency of the motor, which separates overwhiring from twirling. We are also interested in the buckling instability of the hook, which is very flexible elastic rod. By measuring buckling angle, which is an angle between rotational axis and helical axis, we observe the effects of physical parameters on buckling of the hook.

  8. Hollow Sucker Rod Applied in Production Engineering

    Institute of Scientific and Technical Information of China (English)

    Wang Tongbin; Liu Liandong; Hu Daoming; Jia Yanshan

    1997-01-01

    @@ Working Principle A positive cycle system or a working channel can be formed by means of hollow sucker rod and its mating parts in the oil tube ofa well, through which heat carriers (such as hot water,hot oil and steam), chemicals and heating cable can be pumped or put into the well so as to lower the viscosity of crude, dissolve the paraffin building-up and open the conduit, thus leading to the smooth oil flow out of well.

  9. Rod Driven Frequency Entrainment and Resonance Phenomena

    Directory of Open Access Journals (Sweden)

    Christina Salchow

    2016-08-01

    Full Text Available A controversy exists on photic driving in the human visual cortex evoked by intermittent photic stimulation. Frequency entrainment and resonance phenomena are reported for frequencies higher than 12 Hz in some studies while missing in others. We hypothesized that this might be due to different experimental conditions, since both high and low intensity light stimulation were used. However, most studies do not report radiometric measurements, which makes it impossible to categorize the stimulation according to photopic, mesopic, and scotopic vision. Low intensity light stimulation might lead to scotopic vision, where rod perception dominates. In this study, we investigated photic driving for rod-dominated visual input under scotopic conditions. Twelve healthy volunteers were stimulated with low intensity light flashes at 20 stimulation frequencies, leading to rod activation only. The frequencies were multiples of the individual alpha frequency (α of each volunteer in the range from 0.40–2.30*α. 306-channel whole head magnetoencephalography recordings were analyzed in time, frequency, and spatiotemporal domains with the Topographic Matching Pursuit algorithm. We found resonance phenomena and frequency entrainment for stimulations at or close to the individual alpha frequency (0.90–1.10*α and half of the alpha frequency (0.40–0.55*α. No signs of resonance and frequency entrainment phenomena were revealed around 2.00*α. Instead, on-responses at the beginning and off-responses at the end of each stimulation train were observed for the first time in a photic driving experiment at frequencies of 1.30–2.30*α, indicating that the flicker fusion threshold was reached. All results, the resonance and entrainment as well as the fusion effects, provide evidence for rod-dominated photic driving in the visual cortex.

  10. Rod Driven Frequency Entrainment and Resonance Phenomena

    Science.gov (United States)

    Salchow, Christina; Strohmeier, Daniel; Klee, Sascha; Jannek, Dunja; Schiecke, Karin; Witte, Herbert; Nehorai, Arye; Haueisen, Jens

    2016-01-01

    A controversy exists on photic driving in the human visual cortex evoked by intermittent photic stimulation. Frequency entrainment and resonance phenomena are reported for frequencies higher than 12 Hz in some studies while missing in others. We hypothesized that this might be due to different experimental conditions, since both high and low intensity light stimulation were used. However, most studies do not report radiometric measurements, which makes it impossible to categorize the stimulation according to photopic, mesopic, and scotopic vision. Low intensity light stimulation might lead to scotopic vision, where rod perception dominates. In this study, we investigated photic driving for rod-dominated visual input under scotopic conditions. Twelve healthy volunteers were stimulated with low intensity light flashes at 20 stimulation frequencies, leading to rod activation only. The frequencies were multiples of the individual alpha frequency (α) of each volunteer in the range from 0.40 to 2.30∗α. Three hundred and six-channel whole head magnetoencephalography recordings were analyzed in time, frequency, and spatiotemporal domains with the Topographic Matching Pursuit algorithm. We found resonance phenomena and frequency entrainment for stimulations at or close to the individual alpha frequency (0.90–1.10∗α) and half of the alpha frequency (0.40–0.55∗α). No signs of resonance and frequency entrainment phenomena were revealed around 2.00∗α. Instead, on-responses at the beginning and off-responses at the end of each stimulation train were observed for the first time in a photic driving experiment at frequencies of 1.30–2.30∗α, indicating that the flicker fusion threshold was reached. All results, the resonance and entrainment as well as the fusion effects, provide evidence for rod-dominated photic driving in the visual cortex. PMID:27588002

  11. ELECTROMAGNETIC APPARATUS FOR MOVING A ROD

    Science.gov (United States)

    Young, J.N.

    1957-08-20

    An electromagnetic device for moving an object in a linear path by increments is described. The device is specifically adapted for moving a neutron absorbing control rod into and out of the core of a reactor and consists essentially of an extension member made of magnetic material connected to one end of the control rod and mechanically flexible to grip the walls of a sleeve member when flexed, a magnetic sleeve member coaxial with and slidable between limit stops along the flexible extension, electromagnetic coils substantially centrally located with respect to the flexible extension to flex the extension member into gripping engagement with the sleeve member when ener gized, moving electromagnets at each end of the sleeve to attract the sleeve when energized, and a second gripping electromagnet positioned along the flexible extension at a distance from the previously mentioned electromagnets for gripping the extension member when energized. In use, the second gripping electromagnet is deenergized, the first gripping electromagnet is energized to fix the extension member in the sleeve, and one of the moving electromagnets is energized to attract the sleeve member toward it, thereby moving the control rod.

  12. Description and characterization of HBWR Series H-1 test rods

    Energy Technology Data Exchange (ETDEWEB)

    Wagoner, S.R.; Barner, J.O.; Welty, R.K.

    1979-06-01

    The as-built characterization results are presented for the HBWR Series H-1 test rods to be irradiated as part of the Fuel Performance Improvement Program (FPIP). The irradiation of these rods is to be conducted in the Halden Boiling Water Reactor (HBWR). Series H-1 consists of twelve rods for irradiation and six spares. Rod design types include (1) a reference dished pellet design, (2) an annular pellet design, (3) an annular pellet design combined with graphite-coated cladding, and (4) a packed-particle (vipac) design. The report, which describes the fabrication and detailed characterization results for the rods, is divided into four major sections: (1) experiment description, (2) process development required to fabricate the test rods, (3) methods and procedures used to fabricate and characterize the rods, and (4) a summary of the characterization results.

  13. Nuclear thermionic converter. [tungsten-thorium oxide rods

    Science.gov (United States)

    Phillips, W. M.; Mondt, J. F. (Inventor)

    1977-01-01

    Efficient nuclear reactor thermionic converter units are described which can be constructed at low cost and assembled in a reactor which requires a minimum of fuel. Each converter unit utilizes an emitter rod with a fluted exterior, several fuel passages located in the bulges that are formed in the rod between the flutes, and a collector receiving passage formed through the center of the rod. An array of rods is closely packed in an interfitting arrangement, with the bulges of the rods received in the recesses formed between the bulges of other rods, thereby closely packing the nuclear fuel. The rods are constructed of a mixture of tungsten and thorium oxide to provide high power output, high efficiency, high strength, and good machinability.

  14. Rod and Rod-driven Function in Achromatopsia and Blue Cone Monochromatism

    Science.gov (United States)

    Moskowitz, Anne; Hansen, Ronald M.; Akula, James D.; Eklund, Susan E.; Fulton, Anne B.

    2008-01-01

    Purpose To evaluate rod photoreceptor and postreceptor retinal function in pediatric patients with achromatopsia (ACHR) and blue cone monochromatism (BCM) using contemporary electroretinographic (ERG) procedures. Methods Fifteen patients (age 1 to 20 years) with ACHR and six patients (age 4 to 22 years) with BCM were studied. ERG responses to full-field stimuli were obtained in scotopic and photopic conditions. Rod photoreceptor (Srod, Rrod) and rod-driven postreceptor (log σ, Vmax) response parameters were calculated from the a-wave and b-wave. The ERG records were digitally filtered to demonstrate the oscillatory potentials (OPs); a sensitivity parameter, log SOPA1/2, and an amplitude parameter, SOPAmax, were used to characterize the OP response. Response parameters were compared to those of 12 normal control subjects. Results As expected, photopic responses were non-detectable in patients with ACHR and BCM. In addition, mean scotopic photoreceptor (Rrod) and postreceptor (Vmax and SOPAmax) amplitude parameters were significantly reduced compared to those in normal controls. The flash intensity required to evoke a half maximum b-wave amplitude (log σ) was significantly increased. Conclusions The results of this study provide evidence that deficits in rod and rod mediated function occur in the primary cone dysfunction syndromes, achromatopsia and blue cone monochromatism. PMID:18824728

  15. Between a Map and a Data Rod

    Science.gov (United States)

    Teng, W. L.; Rui, H.; Strub, R. F.; Vollmer, B.

    2015-12-01

    A "Digital Divide" has long stood between how NASA and other satellite-derived data are typically archived (time-step arrays or "maps") and how hydrology and other point-time series oriented communities prefer to access those data. In essence, the desired method of data access is orthogonal to the way the data are archived. Our approach to bridging the Divide is part of a larger NASA-supported "data rods" project to enhance access to and use of NASA and other data by the Consortium of Universities for the Advancement of Hydrologic Science, Inc. (CUAHSI) Hydrologic Information System (HIS) and the larger hydrology community. Our main objective was to determine a way to reorganize data that is optimal for these communities. Two related objectives were to optimally reorganize data in a way that (1) is operational and fits in and leverages the existing Goddard Earth Sciences Data and Information Services Center (GES DISC) operational environment and (2) addresses the scaling up of data sets available as time series from those archived at the GES DISC to potentially include those from other Earth Observing System Data and Information System (EOSDIS) data archives. Through several prototype efforts and lessons learned, we arrived at a non-database solution that satisfied our objectives/constraints. We describe, in this presentation, how we implemented the operational production of pre-generated data rods and, considering the tradeoffs between length of time series (or number of time steps), resources needed, and performance, how we implemented the operational production of on-the-fly ("virtual") data rods. For the virtual data rods, we leveraged a number of existing resources, including the NASA Giovanni Cache and NetCDF Operators (NCO) and used data cubes processed in parallel. Our current benchmark performance for virtual generation of data rods is about a year's worth of time series for hourly data (~9,000 time steps) in ~90 seconds. Our approach is a specific

  16. Between a Map and a Data Rod

    Science.gov (United States)

    Teng, William; Rui, Hualan; Strub, Richard; Vollmer, Bruce

    2015-01-01

    A Digital Divide has long stood between how NASA and other satellite-derived data are typically archived (time-step arrays or maps) and how hydrology and other point-time series oriented communities prefer to access those data. In essence, the desired method of data access is orthogonal to the way the data are archived. Our approach to bridging the Divide is part of a larger NASA-supported data rods project to enhance access to and use of NASA and other data by the Consortium of Universities for the Advancement of Hydrologic Science, Inc. (CUAHSI) Hydrologic Information System (HIS) and the larger hydrology community. Our main objective was to determine a way to reorganize data that is optimal for these communities. Two related objectives were to optimally reorganize data in a way that (1) is operational and fits in and leverages the existing Goddard Earth Sciences Data and Information Services Center (GES DISC) operational environment and (2) addresses the scaling up of data sets available as time series from those archived at the GES DISC to potentially include those from other Earth Observing System Data and Information System (EOSDIS) data archives. Through several prototype efforts and lessons learned, we arrived at a non-database solution that satisfied our objectivesconstraints. We describe, in this presentation, how we implemented the operational production of pre-generated data rods and, considering the tradeoffs between length of time series (or number of time steps), resources needed, and performance, how we implemented the operational production of on-the-fly (virtual) data rods. For the virtual data rods, we leveraged a number of existing resources, including the NASA Giovanni Cache and NetCDF Operators (NCO) and used data cubes processed in parallel. Our current benchmark performance for virtual generation of data rods is about a years worth of time series for hourly data (9,000 time steps) in 90 seconds. Our approach is a specific implementation of

  17. Proposal for a Candidate Core Set of Fitness and Strength Tests for Patients with Childhood or Adult Idiopathic Inflammatory Myopathies

    NARCIS (Netherlands)

    van der Stap, Djamilla K D; Rider, Lisa G; Alexanderson, Helene; Huber, Adam M; Gualano, Bruno; Gordon, Patrick; van der Net, Janjaap|info:eu-repo/dai/nl/14327161X; Mathiesen, Pernille; Johnson, Liam G; Ernste, Floranne C; Feldman, Brian M; Houghton, Kristin M; Singh-Grewal, Davinder; Kutzbach, Abraham Garcia; Munters, Li Alemo; Takken, Tim|info:eu-repo/dai/nl/184586674

    OBJECTIVE: Currently there are no evidence-based recommendations regarding fitness and strength tests for patients with childhood or adult idiopathic inflammatory myopathies (IIM). This hinders clinicians and researchers in choosing the appropriate fitness- or muscle strength-related outcome

  18. Deleting exon 55 from the nebulin gene induces severe muscle weakness in a mouse model for nemaline myopathy

    OpenAIRE

    Ottenheijm, Coen A. C.; Buck, Danielle; de Winter, Josine M; Ferrara, Claudia; Piroddi, Nicoletta; Tesi, Chiara; Jasper, Jeffrey R.; Malik, Fady I.; Meng, Hui; Stienen, Ger J. M.; Beggs, Alan H.; Labeit, Siegfried; Poggesi, Corrado; Lawlor, Michael W.; Granzier, Henk

    2013-01-01

    Nebulin—a giant sarcomeric protein—plays a pivotal role in skeletal muscle contractility by specifying thin filament length and function. Although mutations in the gene encoding nebulin (NEB) are a frequent cause of nemaline myopathy, the most common non-dystrophic congenital myopathy, the mechanisms by which mutations in NEB cause muscle weakness remain largely unknown. To better understand these mechanisms, we have generated a mouse model in which Neb exon 55 is deleted (NebΔExon55) to repl...

  19. Opposed-phase MR imaging of lipid storage myopathy in a case of Chanarin-Dorfman disease

    Energy Technology Data Exchange (ETDEWEB)

    Gaeta, Michele; Celona, Antonio; Racchiusa, Sergio; Mazziotti, Silvio [University of Messina, Department of Radiological Sciences, Messina (Italy); Minutoli, Fabio [University of Messina, Department of Radiological Sciences, Messina (Italy); A.O.U. ' ' Policlinico G. Martino' ' , Dipartimento di Scienze Radiologiche, Messina (Italy); Toscano, Antonio; Musumeci, Olimpia [University of Messina, Department of Neurosciences, Psychiatry and Anaesthesiology, Messina (Italy)

    2008-11-15

    Chanarin-Dorfman disease (CDD) is a rare genetic disorder characterized by ichthyosis, myopathy, central nervous system disturbances, and intracellular lipid storage in muscle fibers, hepatocytes, and granulocytes. We describe skeletal muscle magnetic resonance imaging findings in a case of CDD, outlining the potential role of GE T1-weighted opposed-phase sequence (chemical shift imaging) in the evaluation of lipid storage myopathies. (orig.)

  20. Sporadic late-onset nemaline myopathy with MGUS: long-term follow-up after melphalan and SCT.

    OpenAIRE

    Voermans, Nicol C.; Benveniste, Olivier; Minnema, Monique C.; Lokhorst, Henk; Lammens, Martin; Meersseman, Wouter; Delforge, Michel; Kuntzer, Thierry; Novy, Jan; Pabst, Thomas; Bouhour, Françoise; Romero, Norma; Leblond, Veronique; Bergh, Peter van den; Vekemans, Marie-Christiane

    2014-01-01

    OBJECTIVE Sporadic late-onset nemaline myopathy (SLONM) is a rare, late-onset myopathy that progresses subacutely. If associated with a monoclonal gammopathy of unknown significance (MGUS), the outcome is unfavorable: the majority of these patients die within 1 to 5 years of respiratory failure. This study aims to qualitatively assess the long-term treatment effect of high-dose melphalan (HDM) followed by autologous stem cell transplantation (SCT) in a series of 8 patients with SLONM-MGUS...

  1. Distinct muscle apoptotic pathways are activated in muscles with different fiber types a rat model of critical illness myopathy

    OpenAIRE

    Barnes, Benjamin T.; Confides, Amy L.; Rich, Mark M.; Dupont-Versteegden, Esther E.

    2015-01-01

    Critical illness myopathy (CIM) is associated with severe muscle atrophy and fatigue in affected patients. Apoptotic signaling is involved in atrophy and is elevated in muscles from patients with CIM. In this study we investigated underlying mechanisms of apoptosis-related pathways in muscles with different fiber type composition in a rat model of CIM using denervation and glucocorticoid administration (denervation and steroid-induced myopathy, DSIM). Soleus and tibialis anterior (TA) muscles...

  2. Determination of the rod-wire transition length in colloidal indium phosphide quantum rods.

    Science.gov (United States)

    Wang, Fudong; Buhro, William E

    2007-11-21

    Colloidal InP quantum rods (QRs) having controlled diameters and lengths are grown by the solution-liquid-solid method, from Bi nanoparticles in the presence of hexadecylamine and other conventional quantum dot surfactants. These quantum rods show band-edge photoluminescence after HF photochemical etching. Photoluminescence efficiency is further enhanced after the Bi tips are selectively removed from the QRs by oleic acid etching. The QRs are anisotropically 3D confined, the nature of which is compared to the corresponding isotropic 3D confinement in quantum dots and 2D confinement in quantum wires. The 3D-2D rod-wire transition length is experimentally determined to be 25 nm, which is about 2 times the bulk InP exciton Bohr radius (of approximately 11 nm).

  3. Delayed diagnosis of late-onset Pompe disease in patients with myopathies of unknown origin and/or hyperCKemia.

    Science.gov (United States)

    Pérez-López, Jordi; Selva-O'Callaghan, Albert; Grau-Junyent, Josep M; Gallego-Galindo, Luis; Coll, M Josep; García-Morillo, Salvador; Torralba-Cabeza, Miguel A; Vilardell-Tarrés, Miquel

    2015-04-01

    Pompe disease is a rare metabolic myopathy whose diagnosis is sometimes delayed despite being essential for improving clinical outcomes. We aimed to investigate the prevalence of late-onset Pompe disease among patients with a myopathy of unknown etiology, including polymyositis, or with idiopathic rise of creatine kinase (CK) levels, in a department of internal medicine. A cohort study was conducted in 241 subjects: 140 patients with myopathies of unknown origin or increased CK levels, 30 with polymyositis and 71 who constituted the control group of other myopathies. Acid α-glucosidase (GAA) activity was tested in dried blood spots. If a positive result was obtained, GAA activity in isolated lymphocytes and/or genetic testing was performed as a confirmatory diagnosis. Out of the 140 investigated patients, 2 patients with myopathies of unknown origin were confirmed to be positive for Pompe disease. Thus, late-onset Pompe disease should be considered among adult patients with myopathy of unknown origin.

  4. Establishing baseline rod electroretinogram values in achromatopsia and cone dystrophy.

    Science.gov (United States)

    Wang, Isaac; Khan, Naheed W; Branham, Kari; Wissinger, B; Kohl, Susanne; Heckenlively, J R

    2012-12-01

    To establish the normal range of values for rod-isolated b-wave amplitudes in achromatopsia and cone dystrophies. We reviewed charts of 112 patients with various types of cone dystrophy, and compared their standardized electroretinographic rod b-wave amplitudes with age-matched normal controls. Twenty-six patients had known mutations in achromatopsia and cone dystrophy genes, while 53 were characterized by their inheritance pattern since they had yet to have their gene identified. Visual acuity information and scotomata were documented. We found that patients with achromatopsia and cone dystrophy had rod b-wave amplitudes that were significantly lower than age-matched controls, but found no evidence of rod amplitude progression nor loss of peripheral visual fields in the study group. We found that cone dystrophy patients of all types had depressed rod-isolated ERGs across the board. If typical diagnostic criteria are used, these patients might be considered to have "abnormal" rod-isolated electroretinographic values, and might be called "cone-rod dystrophy", even though the waveforms are stable for years. Patients with cone-rod dysfunction patterns on ERG can be better understood by also performing kinetic (Goldmann) visual fields, which will help to distinguish cone dystrophies from progressive cone-rod dystrophies by central scotomata size and progression over time in many forms of cone-rod dystrophy.

  5. Clinical, histological and genetic characterization of reducing body myopathy caused by mutations in FHL1

    Science.gov (United States)

    Schessl, Joachim; Taratuto, Ana L.; Sewry, Caroline; Battini, Roberta; Chin, Steven S.; Maiti, Baijayanta; Dubrovsky, Alberto L.; Erro, Marcela G.; Espada, Graciela; Robertella, Monica; Saccoliti, Maria; Olmos, Patricia; Bridges, Leslie R.; Standring, Peter; Hu, Ying; Zou, Yaqun; Swoboda, Kathryn J.; Scavina, Mena; Goebel, Hans-Hilmar; Mitchell, Christina A.; Flanigan, Kevin M.; Muntoni, Francesco

    2009-01-01

    We recently identified the X-chromosomal four and a half LIM domain gene FHL1 as the causative gene for reducing body myopathy, a disorder characterized by progressive weakness and intracytoplasmic aggregates in muscle that exert reducing activity on menadione nitro-blue-tetrazolium (NBT). The mutations detected in FHL1 affected highly conserved zinc coordinating residues within the second LIM domain and lead to the formation of aggregates when transfected into cells. Our aim was to define the clinical and morphological phenotype of this myopathy and to assess the mutational spectrum of FHL1 mutations in reducing body myopathy in a larger cohort of patients. Patients were ascertained via the detection of reducing bodies in muscle biopsy sections stained with menadione-NBT followed by clinical, histological, ultrastructural and molecular genetic analysis. A total of 11 patients from nine families were included in this study, including seven sporadic patients with early childhood onset disease and four familial cases with later onset. Weakness in all patients was progressive, sometimes rapidly so. Respiratory failure was common and scoliosis and spinal rigidity were significant in some of the patients. Analysis of muscle biopsies confirmed the presence of aggregates of FHL1 positive material in all biopsies. In two patients in whom sequential biopsies were available the aggregate load in muscle sections appeared to increase over time. Ultrastructural analysis revealed that cytoplasmic bodies were regularly seen in conjunction with the reducing bodies. The mutations detected were exclusive to the second LIM domain of FHL1 and were found in both sporadic as well as familial cases of reducing body myopathy. Six of the nine mutations affected the crucial zinc coordinating residue histidine 123. All mutations in this residue were de novo and were associated with a severe clinical course, in particular in one male patient (H123Q). Mutations in the zinc coordinating residue

  6. Sucker-rod pumping handbook production engineering fundamentals and long-stroke rod pumping

    CERN Document Server

    Takacs, Gabor

    2015-01-01

    Sucker-Rod Pumping Handbook presents the latest information on the most common form of production enhancement in today's oil industry, making up roughly two-thirds of the producing oilwell operations in the world. The book begins with an introduction to the main features of sucker rod pumping and an explanation and comparison of lift methods. It goes on to provide the technical and practical knowledge needed to introduce the new and practicing production engineer and operator to the equipment, technology, and applications required to maintain optimum operating conditions.

  7. [Anesthesia and intensive therapy for a patient with mitochondrial myopathy].

    Science.gov (United States)

    Breucking, E; Mortier, W; Lampert, R; Brandt, L

    1993-10-01

    Since 1983 we have been involved in the diagnostic work-up and emergency treatment of a female patient now 48 years old who has a mitochondrial myopathy resembling Luft's disease. The syndrome was first described in 1959, and in more detail in 1962, by Luft and et al., who reported a picture of hypermetabolism with high temperature, extreme sweating, tachycardia, dyspnoea at rest, polydipsia, polyphagia and irritability but normal thyroid function. In 1971 and 1976 Haydar and Di Mauro presented a second case and proposed treatment with chloramphenicol. Our patient has the third case of the syndrome reported so far: her case was initially published in 1987. CASE REPORT. Since her 17th year of life the patient had suffered from episodes of fever, tachycardia and sweating. At the age of 32 these attacks worsened, leading to unconsciousness and apnoea. The patient then had to be intubated, ventilated and sometimes resuscitated. The diagnosis of MH susceptibility and Luft's disease was made on biochemical grounds after the first muscle biopsy in 1983. Therapy with chloramphenicol failed. Therapy with beta blockers, vitamin C and K or E, coenzyme Q10 and a high-caloric diet was started in 1985. The patient was registered with an emergency service, which flew her to our ICU whenever she had a severe crisis. For milder episodes she was supplied with an oxygen breathing mask at home. Myalgia increased with the episodes starting in 1988, and the patient needed dantrolene infusions and analgesics at home. To facilitate venepuncture a Port-A-Cath system was implanted in 1987, which had to be removed four times due to infection and sepsis. A muscle biopsy was taken in Rotterdam, which revealed differences in mitochondrial function from the biochemical findings recorded in 1983 and not in keeping with Luft's disease. Unfortunately, the patient was not able to undergo further metabolic investigations or therapeutic trials. ANAESTHESIA. The patient received three local and six

  8. A novel PtdIns3P and PtdIns(3,5)P-2 phosphatase with an inactivating variant in centronuclear myopathy

    OpenAIRE

    Tosch, Valerie; Rohde, Holger M.; Tronchere, Helene; Zanoteli, Edmar; Monroy, Nancy; Kretz, Christine; Dondaine, Nicolas; Payrastre, Bernard; Mandel, Jean-Louis; Laporte, Jocelyn

    2006-01-01

    In eukaryotic cells, phosphoinositides are lipid second messengers important for many cellular processes and have been found dysregulated in several human diseases. X-linked myotubular (centronuclear) myopathy is a severe congenital myopathy caused by mutations in a phosphatidylinositol 3-phosphate (PtdIns3P) phosphatase called myotubularin, and mutations in dominant centronuclear myopathy (CNM) cases were identified in the dynamin 2 gene. the genes mutated in autosomal recessive cases of CNM...

  9. Visual transduction in human rod photoreceptors.

    Science.gov (United States)

    Kraft, T W; Schneeweis, D M; Schnapf, J L

    1993-05-01

    1. Photocurrents were recorded with suction electrodes from rod photoreceptors of seven humans. 2. Brief flashes of light evoked transient outward currents of up to 20 pA. With increasing light intensity the peak response amplitude increased along an exponential saturation function. A half-saturating peak response was evoked by approximately sixty-five photoisomerizations. 3. Responses to brief dim flashes rose to a peak in about 200 ms. The waveform was roughly like the impulse response of a series of four to five low-pass filters. 4. The rising phases of the responses to flashes of increasing strength were found to fit with a biochemical model of phototransduction with an 'effective delay time' and 'characteristic time' of about 2 and 800 ms, respectively. 5. Spectral sensitivities were obtained over a wavelength range from 380 to 760 nm. The action spectrum, which peaked at 495 nm, followed the template described for photoreceptors in the macaque retina. Variation between rods in the position of the spectrum on the wavelength axis was small. 6. The scotopic luminosity function derived from human psychophysical experiments was found to agree well with the measured rod action spectrum after adjustments were made for lens absorption and photopigment self-screening in the intact eye. 7. Responses to steps of light rose monotonically to a maintained level, showing little or no relaxation. Nevertheless, the relationship between light intensity and steady-state response amplitude was shallower than that expected from simple response saturation. This is consistent with an adaptation mechanism acting on a rapid time scale. 8. Flash sensitivity fell with increasing intensities of background light according to Weber's law. Sensitivity was reduced twofold by lights evoking about 120 photoisomerizations per second. Background lights decreased the time to peak and the integration time of the flash response by up to 20%.

  10. Transient waves in finite viscoelastic rods

    Energy Technology Data Exchange (ETDEWEB)

    Mainardi, F. (Bologna Univ. (Italy). Ist. di Fisica); Nervosi, R. (Bologna Univ. (Italy))

    1980-11-29

    A method based on the Laplace transform is presented to compute wave-front expansions for transient waves in finite viscoelastic rods using the creep or the relaxation representation. The response is related to the basic solution of the semi-infinite problem, for which a series expansion is obtained by a recursive procedure. The convergence is guaranteed in any space-time domain if the material functions are entirely of exponential type. However, for numerical computation an acceleration of convergence is required and the Pade approximants turn out to be successful as shown by some examples.

  11. Rod-like nano-light harvester.

    Science.gov (United States)

    Ling, Jun; Zheng, Zhicheng; Köhler, Anna; Müller, Axel H E

    2014-01-01

    Imitating the natural "energy cascade" architecture, we present a single-molecular rod-like nano-light harvester (NLH) based on a cylindrical polymer brush. Block copolymer side chains carrying (9,9-diethylfluoren-2-yl)methyl methacrylate units as light absorbing antennae (energy donors) are tethered to a linear polymer backbone containing 9-anthracenemethyl methacrylate units as emitting groups (energy acceptors). These NLHs exhibit very efficient energy absorption and transfer. Moreover, we manipulate the energy transfer by tuning the donor-acceptor distance.

  12. Locally periodic Timoshenko rod: experiment and theory.

    Science.gov (United States)

    Díaz-de-Anda, A; Pimentel, A; Flores, J; Morales, A; Gutiérrez, L; Méndez-Sánchez, R A

    2005-05-01

    The flexural vibrations of a locally periodic rod, which consists of N unit cells, are discussed both from the experimental and theoretical points of view. Timoshenko's beam theory and the transfer matrix method are used to calculate the normal-mode frequencies and amplitudes. The theoretical values are then compared with the experimental ones, which are obtained using an electromagnetic acoustic transducer (EMAT). Good agreement between the numerical results and the experimental measurements is obtained. It is shown that as N grows, a band spectrum emerges.

  13. 4-rod RFQ linac for ion implantation

    Energy Technology Data Exchange (ETDEWEB)

    Fujisawa, Hiroshi; Hamamoto, Nariaki; Inouchi, Yutaka [Nisshin Electric Co. Ltd., Kyoto (Japan)

    1997-03-01

    A 34 MHz 4-rod RFQ linac system has been upgraded in both its rf power efficiency and beam intensity. The linac is able to accelerate in cw operation 0.83 mA of a B{sup +} ion beam from 0.03 to 0.91 MeV with transmission of 61 %. The rf power fed to the RFQ is 29 kW. The unloaded Q-value of the RFQ has been improved approximately 61 % to 5400 by copper-plating stainless steel cooling pipes in the RFQ cavity. (author)

  14. High-yield production of hydrophobins RodA and RodB from Aspergillus fumigatus in Pichia pastoris.

    Science.gov (United States)

    Pedersen, Mona Højgaard; Borodina, Irina; Moresco, Jacob Lange; Svendsen, Winnie Edith; Frisvad, Jens Christian; Søndergaard, Ib

    2011-06-01

    Hydrophobins are small fungal proteins with amphipatic properties and the ability to self-assemble on a hydrophobic/hydrophilic interface; thus, many technical applications for hydrophobins have been suggested. The pathogenic fungus Aspergillus fumigatus expresses the hydrophobins RodA and RodB on the surface of its conidia. RodA is known to be of importance to the pathogenesis of the fungus, while the biological role of RodB is currently unknown. Here, we report the successful expression of both hydrophobins in Pichia pastoris and present fed-batch fermentation yields of 200-300 mg/l fermentation broth. Protein bands of expected sizes were detected by SDS-PAGE and western blotting, and the identity was further confirmed by tandem mass spectrometry. Both proteins were purified using his-affinity chromatography, and the high level of purity was verified by silver-stained SDS-PAGE. Recombinant RodA as well as rRodB were able to convert a glass surface from hydrophilic to hydrophobic similar to native RodA, but only rRodB was able to decrease the hydrophobicity of a Teflon-like surface to the same extent as native RodA, while rRodA showed this ability to a lesser extent. Recombinant RodA and native RodA showed a similar ability to emulsify air in water, while recombinant RodB could also emulsify oil in water better than the control protein bovine serum albumin (BSA). This is to our knowledge the first successful expression of hydrophobins from A. fumigatus in a eukaryote host, which makes it possible to further characterize both hydrophobins. Furthermore, the expression strategy and fed-batch production using P. pastoris may be transferred to hydrophobins from other species.

  15. The titin A-band rod domain is dispensable for initial thick filament assembly in zebrafish.

    Science.gov (United States)

    Myhre, J Layne; Hills, Jordan A; Prill, Kendal; Wohlgemuth, Serene L; Pilgrim, David B

    2014-03-01

    The sarcomeres of skeletal and cardiac muscle are highly structured protein arrays, consisting of thick and thin filaments aligned precisely to one another and to their surrounding matrix. The contractile mechanisms of sarcomeres are generally well understood, but how the patterning of sarcomeres is initiated during early skeletal muscle and cardiac development remains uncertain. Two of the most widely accepted hypotheses for this process include the "molecular ruler" model, in which the massive protein titin defines the length of the sarcomere and provides a scaffold along which the myosin thick filament is assembled, and the "premyofibril" model, which proposes that thick filament formation does not require titin, but that a "premyofibril" consisting of non-muscle myosin, α-actinin and cytoskeletal actin is used as a template. Each model posits a different order of necessity of the various components, but these have been difficult to test in vivo. Zebrafish motility mutants with developmental defects in sarcomere patterning are useful for the elucidation of such mechanisms, and here we report the analysis of the herzschlag mutant, which shows deficits in both cardiac and skeletal muscle. The herzschlag mutant produces a truncated titin protein, lacking the C-terminal rod domain that is proposed to act as a thick filament scaffold, yet muscle patterning is still initiated, with grossly normal thick and thin filament assembly. Only after embryonic muscle contraction begins is breakdown of sarcomeric myosin patterning observed, consistent with the previously noted role of titin in maintaining the contractile integrity of mature sarcomeres. This conflicts with the "molecular ruler" model of early sarcomere patterning and supports a titin-independent model of thick filament organization during sarcomerogenesis. These findings are also consistent with the symptoms of human titin myopathies that exhibit a late onset, such as tibial muscular dystrophy.

  16. Stirring with ghost rods in a lid-driven cavity

    Science.gov (United States)

    Kumar, Pankaj; Chen, Jie; Stremler, Mark

    2009-11-01

    It has shown that passive fluid particles moving on periodic orbits can be used to `stir' a viscous fluid in a two-dimensional lid-driven cavity that exhibits a figure-eight flow pattern (Stremler & Chen 2007). Fluid motion in the vicinity of these particles produces ``ghost rod'' structures that behave like semi-permeable rods in the flow. Since these ghost rods are present due to the system dynamics, perturbations in the boundary conditions lead to variations in the existence and structure of the ghost rods. We discuss these variations and assess the role of ghost rods in mixing over a range of operating conditions for this system. The results suggest that ghost rods can play an important role in mixing for other counter-rotating flows.

  17. Vibration of the Package of Rods Linked by Spacer Grids

    Science.gov (United States)

    Zeman, V.; Hlaváč, Z.

    This paper deals with modelling and vibration analysis of the large package of identical parallel rods which are linked by transverse springs (spacer grids) placed on several level spacings. The vibration of rods is caused by the support plate motion. The rod discretization by FEM is based on Rayleigh beam theory. With respect to cyclic and central package rod symmetry, the system is decomposed to identical revolved rod segments. The modal synthesis method with condensation of the rod segments is used for modelling and determination of steady forced vibration of the whole system. The presented method is the first step to modelling of the nuclear fuel assembly vibration caused by kinematical excitation determined by motion of the support plates which are part of the reactor core.

  18. EMG STUDY IN THE DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS OF LIPID STORAGE MYOPATHY

    Institute of Scientific and Technical Information of China (English)

    崔丽英; 汤晓芙; 张秋滨; 李本红; 杜华; 郭玉璞

    1998-01-01

    Clinical, electromyographic and pathological features were studied in 18 patients with lipid storage myopathy (group I ) and 18 patients with polymyositis and dermatomyositis (group Ⅱ ). The results showed a remarhable lower stxmtaneous activity(SA) incidence (14%) in group I than that (55%) in group Ⅱ ;46% and 34% short-duration motor unit potentials(MUAPs) with polyphasic potentials and 74% and 71% short-duration MUAPs without polyphasie potsntials respectively; the percentages of increased polyphasic MUAPs wre same in the Vwo groupa. The reduced or pathologic interfereuce palms accmmted for 61% in the group I and 50% in group Ⅱ. Increased CPK, LDH and HBD were also found in both of them. It is suggested that the lipid storage myopathy may be diagnosed when patients have muscle weakness and myalgia with short-duration and low-amplitude and polyphasic MUAPs without or with occasional spoataneous activitie*, and increased CPK, LDH and HBD.

  19. Role of Exercise Therapy in Prevention of Decline in Aging Muscle Function: Glucocorticoid Myopathy and Unloading

    Directory of Open Access Journals (Sweden)

    Teet Seene

    2012-01-01

    Full Text Available Changes in skeletal muscle quantity and quality lead to disability in the aging population. Physiological changes in aging skeletal muscle are associated with a decline in mass, strength, and inability to maintain balance. Glucocorticoids, which are in wide exploitation in various clinical scenarios, lead to the loss of the myofibrillar apparatus, changes in the extracellular matrix, and a decrease in muscle strength and motor activity, particularly in the elderly. Exercise therapy has shown to be a useful tool for the prevention of different diseases, including glucocorticoid myopathy and muscle unloading in the elderly. The purpose of the paper is to discuss the possibilities of using exercise therapy in the prevention of glucocorticoid caused myopathy and unloading in the elderly and to describe relationships between the muscle contractile apparatus and the extracellular matrix in different types of aging muscles.

  20. Relationship of Skeletal Muscle Development and Growth to Breast Muscle Myopathies: A Review.

    Science.gov (United States)

    Velleman, Sandra G

    2015-12-01

    Selection in meat-type birds has focused on growth rate, muscling, and feed conversion. These strategies have made substantial improvements but have affected muscle structure, repair mechanisms, and meat quality, especially in the breast muscle. The increase in muscle fiber diameters has reduced available connective tissue spacing, reduced blood supply, and altered muscle metabolism in the breast muscle. These changes have increased muscle fiber degeneration and necrosis but have limited muscle repair mechanisms mediated by the adult myoblast (satellite cell) population of cells, likely resulting in the onset of myopathies. This review focuses on muscle growth mechanisms and how changes in the cellular development of the breast muscle may be associated with breast muscle myopathies occurring in meat-type birds.