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

In 11 of 11 inclusion-body myositis (IBM) patients, including one hereditary case, vacuolated muscle fibers contained large and multiple small inclusions immunoreactive for beta-amyloid protein (beta AP). All IBM muscle biopsies had characteristic cytoplasmic tubulo-filaments (CTFs) by electron microscopy. None of 14 control muscle biopsies contained the beta AP immunoreactive (IR) inclusions characteristic of IBM. On the light microscopy level, beta AP-IR inclusions colocalized with ubiquitin immunoreactivity. By immunogold electronmicroscopy, beta AP immunoreactivity was localized to a) amorphous, poorly defined structures, b) dense floccular material, c) clusters of loosely packed amyloidlike fibrils 6-8 nm in diameter, and d) poorly defined loose fibrillar structures 6-8 nm in diameter. beta AP immunoreactive structures were often in proximity to CTFs, but CTFs themselves never contained beta AP-IR. Our study provides the first demonstration of beta AP accumulations in abnormal human muscle. This finding suggests that in addition to Alzheimer's disease, Down syndrome, and Dutch-type hereditary cerebrovascular amyloidosis, beta AP may play an important role in the pathogenesis of other diseases, including ones outside the central nervous system, for example, IBM.
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PMID:Light and electron microscopic localization of beta-amyloid protein in muscle biopsies of patients with inclusion-body myositis. 132 64

The nature of the inclusions in the human muscle disease inclusion-body myositis (IBM) has been the subject of debate. Parallels with Alzheimer's disease have been drawn after these inclusions were found to be ubiquitinated, and immunoreactive with antibodies to beta-amyloid (A beta) and certain amyloid-associated proteins. We have used a battery of antibodies against A beta and associated proteins to immunostain muscle biopsies from patients with IBM. Although the inclusions are ubiquitinated, we could not show immunoreactivity for A beta or the associated proteins investigated. We did, however, find that the ubiquitinated inclusions colocalised with the lysosomal marker, cathepsin D.
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PMID:Ubiquitinated inclusions in inclusion-body myositis patients are immunoreactive for cathepsin D but not beta-amyloid. 747 7

The apolipoprotein E genotype was determined for 11 patients with sporadic inclusion-body myositis. Seven cases had the genotype epsilon 3/epsilon 3, the other four cases, epsilon 3/epsilon 4. The frequency of the epsilon 4 allele in this group of patients (0.182) was not significantly increased compared with elderly controls (0.147; n = 58), in contrast to Alzheimer's disease in which there was a significant increase (0.328; n = 67). The epsilon 2 allele was not found in any of the 11 sporadic inclusion-body myositis patients and its frequency was decreased in Alzheimer's disease. Despite certain pathological similarities that exist between inclusion body myositis and Alzheimer's disease, their association with particular apolipoprotein E genotypes is distinct.
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PMID:Apolipoprotein E type epsilon 4 allele frequency is not increased in patients with sporadic inclusion-body myositis. 774 81

In the beta/A4 protein of Alzheimer's disease, on chromosome 21, three mutations at the same locus have been described (Val 717 Ile, Val 171 Phe, and Val 171 Gly). The heterogeneity of the disease was indicated in individuals with mutations involving chromosomes 19 and 14 as well. beta Protein has also been demonstrated in the rimmed vacuoles of inclusion-body myositis. Therapeutic advances include orthotopic liver transplantation to remove the site of synthesis of the mutant transthyretin molecule. Clinical manifestations of the various forms of amyloidosis involve virtually every system in the body; the breadth of the curious series of proteins called amyloid has been extended considerably in the past year.
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PMID:Clinical aspects of amyloidosis, including related proteins and central nervous system amyloid. 791 35

Sporadic inclusion-body myositis is the most common progressive muscle disease of older patients. The muscle biopsy demonstrates mononuclear cell inflammation and vacuolated muscle fibers containing paired helical filaments and 6 to 10-nm fibrils, both resembling those of Alzheimer brain, and Congo-red positivity. Hereditary inclusion-body myopathy designates patients cytopathologically similar but without inflammation. In both muscle diseases, prion, and several proteins characteristic of Alzheimer brain--eg, beta-amyloid protein and hyperphosphorylated tau (which normally are expressed mainly in neurons), and apolipoprotein E--are abnormally accumulated in vacuolated muscle fibers, by unknown mechanisms. We now demonstrate in both muscle diseases that prion mRNA is strongly expressed in the vacuolated muscle fibers, which suggests that their accumulated prion protein results, at least partly, from increased gene expression. This, to our knowledge, is the first demonstration of abnormally increased prion mRNA in human disease. Another novel finding is the increased prion mRNA in human muscle macrophages, and both increased prion protein and prion mRNA in regenerating muscle fibers. The latter indicates that prion may play a role in human muscle development.
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PMID:Abnormal accumulation of prion protein mRNA in muscle fibers of patients with sporadic inclusion-body myositis and hereditary inclusion-body myopathy. 799 30

The major new advances in seeking the pathogenic mechanisms of sporadic inclusion-body myositis and hereditary inclusion-body myopathy are discussed. Hypotheses are presented regarding the possible causes and significance of amyloid deposits in sporadic inclusion-body myositis and the roles of abnormally accumulated ubiquitin, beta-amyloid protein, beta-amyloid precursor protein, alpha 1-antichymotrypsin, hyperphosphorylated tau, and prion protein in the vacuolated muscle fibers in both sporadic inclusion-body myositis and hereditary inclusion-body myopathy. Because hereditary inclusion-body myopathy is virtually free of Congophilic amyloid deposits but, like sporadic inclusion-body myositis, contains large accumulations of beta-amyloid protein, it is possible that the lesions in hereditary inclusion-body myopathy may represent "early" changes. There are striking similarities between the pathology of inclusion-body myositis muscle and brains affected by Alzheimer's disease in regard to accumulation of ubiquitin, beta-amyloid protein and its precursor protein, alpha 1-antichymotrypsin, and hyperphosphorylated tau.
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PMID:New advances in inclusion-body myositis. 811 35

In 10 of 10 inclusion-body myositis (IBM) patients, including 1 hereditary case, vacuolated muscle fibers contained large or small cytoplasmic inclusions immunoreactive for alpha 1-antichymotrypsin (alpha 1-ACT). All IBM muscle biopsies had characteristic cytoplasmic tubulo-filaments by electron microscopy. None of 17 control muscle biopsies contained the alpha 1-ACT immunoreactive inclusions characteristic of IBM. In vacuolated muscle fibers, alpha 1-ACT immunoreactive inclusions colocalized with beta-amyloid protein and ubiquitin immunoreactivities. Our study provides the first demonstration of alpha 1-ACT accumulations in abnormal human muscle, and it suggest that, as in Alzheimer's disease and Down's syndrome, alpha 1-ACT may be involved in the pathogenesis of IBM.
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PMID:Strong immunoreactivity of alpha 1-antichymotrypsin co-localizes with beta-amyloid protein and ubiquitin in vacuolated muscle fibers of inclusion-body myositis. 838 97

As in Alzheimer-disease (AD) brain, vacuolated muscle fibers of inclusion-body myositis (IBM) contain abnormally accumulated beta-amyloid precursor protein (beta APP), including its beta-amyloid protein epitope, and increased beta APP-751 mRNA. Other similarities between IBM muscle and AD brain phenotypes include paired helical filaments, hyperphosphorylated tau protein, apolipoprotein E, and mitochondrial abnormalities, including decreased cytochrome-c oxidase (COX) activity. The pathogenesis of these abnormalities in IBM muscle and AD brain is not known. We now report that direct transfer of the beta APP gene, using adenovirus vector, into cultured normal human muscle fibers causes structural abnormalities of mitochondria and decreased COX activity. In this adenovirus-mediated beta APP gene transfer, we demonstrated that beta APP overproduction can induce mitochondrial abnormalities. The data suggest that excessive beta APP may be responsible for mitochondrial and COX abnormalities in IBM muscle and perhaps AD brain.
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PMID:Transfer of beta-amyloid precursor protein gene using adenovirus vector causes mitochondrial abnormalities in cultured normal human muscle. 857 61

This review emphasizes new advances in seeking the pathogenic mechanisms of sporadic inclusion-body myositis and hereditary inclusion-body myopathy syndromes. Clinical and pathologic similarities and differences between sporadic and hereditary forms are described. Hypotheses are presented regarding the possible causes and consequences of abnormally accumulated intramyofiber beta-amyloid precursor protein (beta APP) (including beta-amyloid protein and C- and N-terminal epitopes), hyperphosphorylated tau, alpha 1-antichymotrypsin, apolipoprotein E, prion protein, ubiquitin, nicotinic acetylcholine receptor and its 43-kD associated protein, fibroblast growth factor, and transforming growth factor-beta. Also increased are beta APP mRNA and prion protein mRNA. Striking similarities between the pathology of muscle specimens from sporadic inclusion-body myositis and samples from the brains of patients with Alzheimer's disease in regard to Congo red positivity and accumulations of several proteins are discussed. Because most of the proteins that pathologically accumulate throughout the abnormal muscle fibers also accumulate focally at normal human neuromuscular junctions, the possible "junctionalization" of nonjunctional nuclei as a pathogenic mechanism in the muscle fiber is discussed.
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PMID:New advances in the understanding of sporadic inclusion-body myositis and hereditary inclusion-body myopathies. 857 68

Sporadic inclusion-body myositis (s-IBM) and the hereditary inclusion-body myopathies (h-IBMs) are severe and progressive muscle diseases, characterized pathologically by vacuolated muscle fibers containing paired-helical filaments (PHFs). An interesting feature of the s- and h-IBM muscle phenotype is its striking similarity to Alzheimer-disease (AD) brain. We immunostained muscle biopsies of 9 s-IBM patients, 9 autosomal-recessive h-IBM patients, 1 autosomal-dominant h-IBM patients, and 18 normal and disease-controls with several antibodies known to react with the hyperphosphorylated tau of AD-PHFs. Those included SMI-31, SMI-310, PHF-1, and AT8. In both s- and h-IBM, virtually all vacuolated muscle fibers had strongly immunoreactive inclusions with SMI-31, and by immuno-electronmicroscopy SMI-31 was exclusively localized to PHFs. Approximately 40 to 50% of both s- and h-IBM vacuolated muscle fibers were also immunoreactive with AT8 antibody. To the contrary, in h-IBM, there was no immunoreactivity with SMI-310 and PHF-1 antibodies, whereas in s-IBM the vacuolated muscle fibers had strong immunoreactivity with those two antibodies. By immunoelectronmicorscopy, SMI-310 and PHF-1 also were localized to PHFs. Within s-IBM muscle fibers, the structures immunoreactive with SMI-310 were congophilic, whereas h-IBM muscle fibers did not have congophilia. Our studies: (a) demonstrate a distinct difference between s-IBM and the h-IBMs in regard to expression of immunoreactive phosphorylated tau and congophilia; (b) demonstrate a new "diagnostic duo" combination of SMI-31 and SMI-310 antibodies for identifying and distinguishing s-IBM and the h-IBMs; and (c) provide another close similarity of pathologic phenotypes between s-IBM muscle and AD brain, suggesting that similar cellular pathogenic mechanisms may be active in both diseases.
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PMID:Difference in expression of phosphorylated tau epitopes between sporadic inclusion-body myositis and hereditary inclusion-body myopathies. 893 1


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