Inclusion body myositis-like phenotype induced by transgenic overexpression of beta APP in skeletal muscle.
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Inclusion body myositis (IBM), the most common age-related muscle disease in the elderly population, is an incurable disorder leading to severe disability. Sporadic IBM has an unknown etiology, although affected muscle fibers are characterized by many of the pathobiochemical alterations traditionally associated with neurodegenerative brain disorders such as Alzheimer's disease. Accumulation of the amyloid-beta peptide, which is derived from proteolysis of the larger amyloid-beta precursor protein (betaAPP), seems to be an early pathological event in Alzheimer's disease and also in IBM, where in the latter, it predominantly occurs intracellularly within affected myofibers. To elucidate the possible role of betaAPP mismetabolism in the pathogenesis of IBM, transgenic mice were derived in which we selectively targeted betaAPP overexpression to skeletal muscle by using the muscle creatine kinase promoter. Here we report that older (>10 months) transgenic mice exhibit intracellular immunoreactivity to betaAPP and its proteolytic derivatives in skeletal muscle. In this transgenic model, selective overexpression of betaAPP leads to the development of a subset of other histopathological and clinical features characteristic of IBM, including centric nuclei, inflammation, and deficiencies in motor performance. These results are consistent with a pathogenic role for betaAPP mismetabolism in human IBM. (+info)
Laparoscopic management of abdominopelvic abscesses in tropical pyomyositis.
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Tropical pyomyositis is a suppurative infectious disease of skeletal muscles. The most common causative organism is Staphylococcus aureus. Penicillin-resistant strains are frequently encountered. Abscesses may develop in muscle groups or body cavities remotely located from one another. We report a case of tropical pyomyositis presenting as a suppurative process in the left foreleg. Further workup, including CT scanning, demonstrated large, multi-loculated intraabdominal and pelvic abscesses. The abdominal and pelvic components were managed by laparoscopic exploration and drainage. This is the first known report of laparoscopic management of abdominopelvic abscesses associated with tropical pyomyositis. (+info)
Myositis and swollen knees: disease or treatment complication?
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Interesting and unusual causes of knee pain in three patients with idiopathic inflammmatory myositis seen in the clinic over the past 12 months are reported. Their clinical features are described and treatment discussed emphasising the importance of being able to differentiate between a manifestation of the rheumatic disease and a treatment complication. Publications on this topic are also reviewed. (+info)
Experimental myositis in rats. II. The sensitivity of spleen cells to syngeneic muscle antigen.
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The transformation responses to a syngeneic muscle homogenate of spleen cells, lymph node cells and blood lymphocytes have been studied in rats with allergic myositis. Significantly increased responses to muscle were obtained only for spleen cells from rats which had received two or more immunizing injections of heterologous muscle with Freund's complete adjuvant. Other populations of lymphoid cells which had previously been shown to be capable of transferring the disease did not show significant transformation responses to muscle. Increased responses in spleen cells were obtained using a supernatant ultracentrifugal fraction as well as a whole muscle homogenate. Fractionation of the antigen showed blast stimulating activity to be present in fractions of differing molecular size, suggesting that the antigen(s) responsible may be present in polymeric form or may be bound to molecules of varying molecular size. (+info)
Granulomatous myopathy: its relationship to sarcoidosis and polymyositis.
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In three cases of generalized muscle weakness, muscle biopsy revealed well-defined, non-caseating epithelioid granulomata with giant cells. In one of these patients there was, in addition, a high serum CPK and histological evidence of widespread muscle cell degeneration and regeneration, apparently unrelated to the granulomatous process. In a re-examination of the histopathology of these cases, using biopsy material from a fourth case of proven sarcoidosis as a standard, it was concluded that there are no special features of the granulomatous/giant cell process which permit the separation of the case of presumed polymyositis. However, it appeared that granulomata per se do not exert a significant ill effect on surrounding muscle cells, and that evidence of widespread degeneration of muscle cells is the important point of distinction. (+info)
Differences in idiopathic inflammatory myopathy phenotypes and genotypes between Mesoamerican Mestizos and North American Caucasians: ethnogeographic influences in the genetics and clinical expression of myositis.
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OBJECTIVE: As part of a larger, worldwide study of the ethnogeography of myositis, we evaluated the clinical, serologic, and immunogenetic features of Mestizo (Mexican and Guatemalan) and North American Caucasian patients with idiopathic inflammatory myopathy (IIM). METHODS: Clinical manifestations, autoantibodies, HLA-DRB1 and DQA1 alleles, and immunoglobulin Gm/Km allotypes were compared between 138 Mestizos with IIM and 287 Caucasians with IIM, using the same classification criteria and standardized questionnaires. RESULTS: IIM in Mestizo patients was characterized by a higher proportion of dermatomyositis (69% of adult Mestizos versus 35% of adult Caucasians; P < 0.001) and anti-Mi-2 autoantibodies (30% versus 7% of adults, respectively, and 32% versus 4% of children, respectively; P < 0.01). Genetic risk factors also differed in these populations. Whereas Mestizos had no HLA risk factors for IIM, HLA-DRB1*0301, the linked allele DQA1*0501, and DRB1 alleles sharing the first hypervariable region motif (9)EYSTS(13) were major risk factors in Caucasian patients with IIM. Furthermore, different HLA-DRB1 and DQA1 alleles were associated with anti-Mi-2 autoantibodies (DRB1*04 and DQA1*03 in Mestizos and DRB1*07 and DQA1*02 in Caucasians). Immunoglobulin gamma-chain allotypes Gm(1), Gm(17) (odds ratio for both 11.3, P = 0.008), and Gm(21) (odds ratio 7.3, P = 0.005) and kappa-chain allotype Km(3) (odds ratio 7.3, P = 0.005) were risk factors for IIM in Mestizos; however, no Gm or Km allotypes were risk or protective factors in Caucasians. In addition, Gm and Km phenotypes were unique risk factors (Gm 1,3,17 5,13,21 and Gm 1,17 23 21 and Km 3,3) or protective factors (Km 1,1) for the development of myositis and anti-Mi-2 autoantibodies (Gm 1,2,3,17 23 5,13,21) in adult Mestizos. CONCLUSION: IIM in Mesoamerican Mestizos differs from IIM in North American Caucasians in the frequency of phenotypic features and in the immune-response genes predisposing to and protecting from myositis and anti-Mi-2 autoantibodies at 4 chromosomal loci. These and other data suggest the likelihood that the expression of IIM is modulated by different genes and environmental exposures around the world. (+info)
New insights into the relationship between airway inflammation and asthma.
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Asthma is a condition characterized by variable airflow obstruction, airway hyper-responsiveness (AHR) and airway inflammation which is usually, but not invariably, eosinophilic. Current thoughts on the pathogenesis of asthma are focused on the idea that it is caused by an inappropriate response of the specific immune system to harmless antigens, particularly allergens such as cat dander and house dust mite, that result in Th2-mediated chronic inflammation. However, the relationship between inflammation and asthma is complex, with no good correlation between the severity of inflammation, at least as measured by the number of eosinophils, and the severity of asthma. In addition, there are a number of conditions, such as eosinophilic bronchitis and allergic rhinitis, in which there is a Th2-mediated inflammatory response, but no asthma, as measured by variable airflow obstruction or AHR. Bronchoconstriction can also occur without obvious airway inflammation, and neutrophilic inflammation can in some cases be associated with asthma. When we compared the immunopathology of eosinophilic bronchitis and asthma, the only difference we observed was that, in asthma, the airway smooth muscle (ASM) was infiltrated by mast cells, suggesting that airway obstruction and AHR are due to an ASM mast cell myositis. This observation emphasizes that the features that characterize asthma, as opposed to bronchitis, are due to abnormalities in smooth muscle responsiveness, which could be intrinsic or acquired, and that inflammation is only relevant in that it leads to these abnormalities. It also emphasizes the importance of micro-localization as an organizing principle in physiological responses to airway inflammation. Thus, if inflammation is localized to the epithelium and lamina propria, then the symptoms of bronchitis (cough and mucus hypersecretion) result, and it is only if the ASM is involved -- for reasons that remain to be established -- that asthma occurs. (+info)
Monocytic fasciitis: a newly recognized clinical feature of tumor necrosis factor receptor dysfunction.
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Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is a dominantly inherited autoinflammatory syndrome that results from mutations in TNFRSF1A, the gene that encodes the 55-kd tumor necrosis factor receptor. Clinically, patients present with recurrent episodes of fever in conjunction with localized inflammation at various sites. Myalgia is one of the most characteristic features of this syndrome and is frequently associated with an overlying erythematous, macular rash that, together with the myalgia, displays centrifugal migration. This has previously been believed to occur as a result of myositis. We describe herein the case of a 60-year-old man with TRAPS, in whom magnetic resonance imaging of the left thigh demonstrated edematous changes in the muscle compartments and surrounding soft tissues. A full-thickness wedge biopsy was performed, and hematoxylin and eosin staining and immunohistochemistry analysis of the specimen demonstrated normal myofibrils but a severely destructive monocytic fasciitis. These results suggest that the myalgia experienced by individuals with TRAPS is due to a monocytic fasciitis and not to myositis. (+info)