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Query: UMLS:C0027121 (myositis)
 4,538 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate whether abnormally accumulated betaAPP may be responsible for denervation of muscle fibers that are present in hereditary inclusion-body myopathy (h-IBM) and sporadic inclusion-body myositis (s-IBM), we cultured five h-IBM and eight normal muscle biopsies. In eight other experiments, a 3 kb human 751-betaAPP-cDNA was transferred, using adenovirus vector, into cultured normal myotubes immediately after myoblast fusion. In all experiments, cultured muscle fibers were co-cultured with fetal rat spinal cord. Controls had no detectable betaAPP epitopes, whereas betaAPP epitopes were greatly increased in cultured h-IBM muscle and in cultured normal muscle after betaAPP-gene transfer. Innervated normal cultured muscle fibers were continuously contracting and fully cross-striated, and they had acetylcholine receptors (AChRs) and acetylcholinesterase (AChE) accumulated only at the neuromuscular junctions (NMJs). By contrast, both groups of betaAPP-overexpressing cultured muscle fibers were not contracting and not cross-striated; and did not have NJMs containing AChRs and AChE. Our results suggest that over-expression of betaAPP in cultured muscle fibers inhibits their innervation, and that the accumulation of betaAPP in muscle fibers of both h- and s-IBM patients may be responsible for their not becoming or remaining properly innervated or reinnervated, i.e. a 'myogenous-dysinnervation' mechanism.
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PMID:Impaired innervation of cultured human muscle overexpressing betaAPP experimentally and genetically: relevance to inclusion-body myopathies. 983 51

Inflammatory myopathy with cytochrome oxidase negative muscle fibers (IM/COX-) is characterized by slowly progressive weakness, most prominent in the quadriceps, muscle fibers with reduced COX staining and mitochondrial DNA mutations, and a poor response to corticosteroid treatment. We reviewed records of quantitative measurements of muscle strength in 7 IM/COX- patients to evaluate the outcomes after treatment with oral, once weekly, methotrexate for an average of 15 months. We compared the results to 6 patients with IM/COX- who received no long-term immunosuppression, and to 4 with inclusion body myositis (IBM) who received methotrexate during the same period. Methotrexate treatment of IM/ COX- was followed by improved muscle strength in 5 of 7 patients, averaging 17+/-5%. In contrast, there was no improvement in the strength of 6 untreated IM/COX- patients (-6+/-4%; P=0.003), or 4 methotrexate-treated IBM patients (1+/-2%; P=0.03). We conclude that, despite clinical similarities to inclusion body myositis, which is usually refractory to immunosuppressive therapy, strength in IM/COX- appears to improve with methotrexate treatment. Biopsy studies of inflammatory myopathies with evaluation of muscle for mitochondrial changes and vacuoles can help to direct the choice of appropriate immunomodulating treatments.
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PMID:Inflammatory myopathy with cytochrome oxidase negative muscle fibers: methotrexate treatment. 984 75

Sporadic inclusion-body myositis (s-IBM) is the most common, debilitating and progressive muscle disease beginning at the age 50 or later. The most characteristic pathologic feature is vacuolar degeneration of muscle fibers accompanied by intrafiber congophilia and clusters ("tangles") of paired-helical filaments, containing phosphorylated tau. An unusual feature of sporadic inclusion-body myositis is accumulation within its abnormal muscle fibers of several proteins that are characteristic of Alzheimer disease brain, including epitopes of beta-amyloid precursor protein (betaAPP), phosphorylated tau, alpha-1-antichymotrypsin, apolipoprotein E, and presenilin-1. Indicators of oxidative stress are also present within abnormal s-IBM muscle fibers. In this review, we describe new advances seeking the pathogenic mechanism of sporadic inclusion-body myositis. We hypothesize on the possible pathogenic role of abnormally accumulated proteins, and we propose that important contributory factors leading to inclusion-body myositis are the milieu of muscle-fiber aging and oxidative stress. In addition, we present evidence that overexpression of adenovirus-transferred betaAPP gene in cultured human muscle fibers induces aspects of the inclusion-body myositis phenotype, and suggest that betaAPP-overexpression is an early event in the pathogenic cascade causing inclusion-body myositis.
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PMID:Sporadic inclusion-body myositis and its similarities to Alzheimer disease brain. Recent approaches to diagnosis and pathogenesis, and relation to aging. 985 8

Polymyositis, dermatomyositis, and inclusion body myositis, although immunopathologically distinct, share 3 dominant histological features: inflammation, fibrosis, and loss of muscle fibers. Progress in molecular immunology and immunogenetics has enhanced our understanding of these cellular processes. Based on the T-cell receptor gene rearrangement, the autoinvasive CD8+ T cells in polymyositis and inclusion body myositis, but not dermatomyositis, are specifically selected and clonally expanded in situ by heretofore unknown muscle-specific autoantigens. The messenger RNA of cytokines is variably expressed, except for a persistent up-regulation of interleukin 1beta in inclusion body myositis and transforming growth factor beta in dermatomyositis. In inclusion body myositis, the interleukin 1, secreted by the chronically activated endomysial inflammatory cells, may participate in the formation of amyloid because it up-regulates beta-amyloid precursor protein (beta-APP) gene expression and beta-APP promoter and colocalizes with beta-APP within the vacuolated muscle fibers. In dermatomyositis, transforming growth factor beta is overexpressed in the perimysial connective tissue but is down-regulated after successful immunotherapy and reduction of inflammation and fibrosis. The degenerating muscle fibers express several antiapoptotic molecules, such as Bcl-2, and resist apoptosis-mediated cell death. In myositis, several of the identified molecules and adhesion receptors play a role in the process of inflammation, fibrosis, and muscle fiber loss, and could be targets for the design of semispecific therapeutic interventions.
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PMID:Molecular immunology and genetics of inflammatory muscle diseases. 986 93

The inflammatory myopathies are a heterogeneous group of diseases due to autoimmunitary or infective causes. They are diagnosed by clinical electrophysiological features, and muscle biopsy. The autoimmunity group is subdivided in dermatomyositis, polimyositis and inclusion body myositis. The second group caused by viral genesis are called generally "myositis". The two groups have a different prognosis and therapy. The infective group denominated myositis have usually a viral etiology. We have evaluated 6 patients with viral myositis that are studied by physical examination, blood test (CK included), electromyographic pattern and muscle biopsy. The Authors emphasized the role of muscle biopsy for the diagnosis of this pathology and in particular for the myositis.
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PMID:[Post-influenza viral myositis: report of a case]. 1057 Jul 86

Sporadic inclusion-body myositis (s-IBM) is the most common progressive muscle disease of older persons. Pathologically, the muscle biopsy manifests various degrees of inflammation and specific vacuolar degeneration of muscle fibers characterized by paired helical filaments (PHFs) composed of phosphorylated tau. IBM vacuolated fibers also contain accumulations of several other Alzheimer-characteristic proteins. Molecular mechanisms leading to formation of the PHFs and accumulations of proteins in IBM muscle are not known. We report that the abnormal muscle fibers of IBM contained (i) acridine-orange-positive RNA inclusions that colocalized with the immunoreactivity of phosphorylated tau and (ii) survival motor neuron protein immunoreactive inclusions, which by immuno-electron microscopy were confined to paired helical filaments. This study demonstrates two novel components of the IBM paired helical filaments, which may lead to better understanding of their pathogenesis.
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PMID:Paired helical filaments of inclusion-body myositis muscle contain RNA and survival motor neuron protein. 1075 38

The mechanism of injury and death of muscle cells in the inflammatory myopathies (dermatomyositis, polymyositis, and inclusion body myositis) remains obscure. We and others have not detected apoptosis in the muscle biopsies from patients with myositis despite clear evidence of cell damage and loss. We provide evidence in this study that Fas ligand (FasL) as well as Fas is present on muscle cells and inflammatory cells in myositis biopsies: Fas is present on most muscle cells and lymphocytes, and FasL is present on degenerating muscle cells and many infiltrating mononuclear cells. The expression of both Fas and FasL in the inflamed tissue makes the absence of apoptosis more striking. To address the mechanisms of this resistance to classical apoptosis in muscle cells, we have investigated the expression of the antiapoptotic molecule FLICE (Fas-associated death domain-like IL-1-converting enzyme)-inhibitory protein (FLIP) in muscle biopsies of myositis patients and in cultured human skeletal muscle cells. Using laser capture microscopy, we have shown that FLIP is expressed in the muscle fibers and on infiltrating lymphocytes of myositis biopsies. Furthermore, we have shown that FLIP, but not Bcl-2, is expressed in cultured human skeletal muscle cells stimulated with proinflammatory cytokines, and inhibition of FLIP with antisense oligonucleotides promotes significant cleavage of poly(ADP-ribose) polymerase autoantigen, a sensitive indicator of apoptosis. These studies strongly suggest that the resistance of muscle to Fas-mediated apoptosis is due to the expression of FLIP in muscle cells in the inflammatory environment in myositis.
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PMID:The inhibition of apoptosis in myositis and in normal muscle cells. 1079 13

Hereditary inclusion-body myopathy (h-IBM) is a heterogeneous group of disorders characterized by progressive weakness of some skeletal muscles and pathological feature, intercellular rimmed vacuoles in the muscular filaments. h-IBM is not associated with inflammatory infiltrations and term myopathy is used as opposite to spontaneous inclusion-body myositis. h-IBM is classified into autosomal recessive and autosomal dominant subgroups.
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PMID:[Hereditary inclusion-body myopathy]. 1080 May 87

It is becoming evident that clinical phenotypes associated with partial laminin alpha2 chain deficiency are variable. We recently observed a 29-year-old man with leukoencephalopathy and vacuolar myopathy resembling inclusion body myositis. Laminin alpha2 immunohistochemical analysis showed reduction of the protein on muscle fiber surfaces. Molecular analysis revealed two novel compound heterozygous mutations in the LAMA2 gene. This is the first report linking a mutation in the LaMA2 gene with leukoencephalopathy and inclusion body-like myositis.
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PMID:Partial laminin alpha2 chain deficiency in a patient with myopathy resembling inclusion body myositis. 1085 49

Alpha-synuclein (alpha-syn) is an important component of neuronal and glial inclusions in brains of patients with several neurodegenerative disorders. Sporadic inclusion-body myositis (s-IBM) is the most common progressive muscle disease of older patients. Its muscle phenotype shows several similarities with Alzheimer disease brain. A distinct feature of s-IBM pathology is specific vacuolar degeneration of muscle fibers characterized by intracellular amyloid inclusions formed by both amyloid-beta (Abeta) and paired-helical filaments composed of phosphorylated tau. We immunostained alpha-syn in muscle biopsies of s-IBM, disease-control, and normal patients. Approximately 60% of Abeta-positive vacuolated muscle fibers (VMF) contained well-defined inclusions immunoreactive with antibodies against alpha-syn. In those fibers. alpha-syn co-localized with Abeta, both by light microscopy, and ultrastructurally. Paired-helical filaments did not contain alpha-syn immunoreactivity. In all muscle biopsies, alpha-syn was strongly immunoreactive at the postsynaptic region of the neuromuscular junctions. alpha-syn immunoreactivity also occurred diffusely in regenerating and necrotic muscle fibers. In cultured human muscle fibers, alpha-syn and its mRNA were expressed by immunocytochemistry, immunoblots, and Northern blots. Our study provides the first demonstration that alpha-syn participates in normal and pathologic processes of human muscle. Therefore. its function is not exclusive to the brain and neurodegenerative diseases.
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PMID:Novel immunolocalization of alpha-synuclein in human muscle of inclusion-body myositis, regenerating and necrotic muscle fibers, and at neuromuscular junctions. 1090 Dec 30


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