Gender differences in muscle inflammation after eccentric exercise.
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Unaccustomed exercise is followed by delayed-onset muscle soreness and morphological changes in skeletal muscle. Animal studies have demonstrated that women have an attenuated response to muscle damage. We studied the effect of eccentric exercise in untrained male (n = 8) and female (n = 8) subjects using a unilateral exercise design [exercise (Ex) and control (Con) legs]. Plasma granulocyte counts [before (Pre) and 48 h after exercise (+48h)] and creatine kinase activity [Pre, 24 h after exercise (+24h), +48h, and 6 days after exercise (+6d)] were determined before (Pre) and after (+24h, +48h, +6d) exercise, with biopsies taken from the vastus lateralis of each leg at +48h for determination of muscle damage and/or inflammation. Plasma granulocyte counts increased for men and decreased for women at +48h (P < 0.05), and creatine kinase activity increased for both genders at +48h and +6d (P < 0.01). There were significantly greater areas of both focal (P < 0.001) and extensive (P < 0.01) damage in the Ex vs. Con leg for both genders, which was assessed by using toluidine blue staining. The number of leukocyte common antigen-positive cells/mm(2) tissue increased with exercise (P < 0.05), and men tended to show more in their Ex vs. Con leg compared with women (P = 0.052). Men had a greater total (Ex and Con legs) number of bcl-2-positive cells/mm(2) tissue vs. women (P < 0.05). Atrophic fibers with homogeneous bcl-2-positive staining were seen only in men (n = 3). We conclude that muscle damage is similar between genders, yet the inflammatory response is attenuated in women vs. men. Finally, exercise may stimulate the expression of proteins involved in apoptosis in skeletal muscle. (+info)
Myositis associated graft-versus-host-disease presenting as respiratory muscle weakness.
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Myositis associated with graft-versus-host-disease (GVHD) typically presents with proximal muscle weakness, myalgias, and a raised creatinine phosphokinase (CPK) level. We report a case of a 51 year old man who developed respiratory muscle weakness five years after an allogeneic bone marrow transplant for multiple myeloma. His symptoms included tachypnoea, abdominal paradox, and orthopnoea. Pulmonary function tests revealed diminished vital capacity and maximal inspiratory and expiratory pressures. Serum CPK levels were raised and a peripheral muscle biopsy specimen was consistent with GVHD. He improved with immunosuppressive therapy. (+info)
Autoantibody profiles in the sera of European patients with myositis.
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OBJECTIVE: To determine the prevalence of myositis specific autoantibodies (MSAs) and several myositis associated autoantibodies (MAAs) in a large group of patients with myositis. METHODS: A total of 417 patients with myositis from 11 European countries (198 patients with polymyositis (PM), 181 with dermatomyositis (DM), and 38 with inclusion body myositis (IBM)) were serologically analysed by immunoblot, enzyme linked immunosorbent assay (ELISA) and/or immunoprecipitation. RESULTS: Autoantibodies were found in 232 sera (56%), including 157 samples (38%) which contained MSAs. The most commonly detected MSA was anti-Jo-1 (18%). Other anti-synthetase, anti-Mi-2, and anti-SRP autoantibodies were found in 3%, 14%, and 5% of the sera, respectively. A relatively high number of anti-Mi-2 positive PM sera were found (9% of PM sera). The most commonly detected MAA was anti-Ro52 (25%). Anti-PM/Scl-100, anti-PM/Scl-75, anti-Mas, anti-Ro60, anti-La, and anti-U1 snRNP autoantibodies were present in 6%, 3%, 2%, 4%, 5%, and 6% of the sera, respectively. Remarkable associations were noticed between anti-Ro52 and anti-Jo-1 autoantibodies and, in a few sera, also between anti-Jo-1 and anti-SRP or anti-Mi-2 autoantibodies. CONCLUSIONS: The incidence of most of the tested autoantibody activities in this large group of European patients is in agreement with similar studies of Japanese and American patients. The relatively high number of PM sera with anti-Mi-2 reactivity may be explained by the use of multiple recombinant fragments spanning the complete antigen. Furthermore, our data show that some sera may contain more than one type of MSA and confirm the strong association of anti-Ro52 with anti-Jo-1 reactivity. (+info)
Expression of specific matrix metalloproteinases in inflammatory myopathies.
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The family of matrix metalloproteinases (MMPs) comprises endopeptidases that are capable of degrading all extracellular matrix components. Given these actions, it is conceivable that MMPs may play a pathogenic role in inflammatory myopathies. These immune-mediated disorders are characterized by the invasion of mononuclear phagocytes and T lymphocytes and the loss of muscle fibres. We examined whether specific MMPs and their natural inhibitors (tissue inhibitors of metalloproteinases; TIMPs) are expressed in muscle during acute inflammatory attacks by studying muscle biopsies obtained from patients diagnosed as having polymyositis, dermatomyositis, sporadic inclusion body myositis and, for comparison, from cases of various muscular dystrophies. Quantitative polymerase chain reaction analysis revealed significantly elevated mRNA expression of interstitial collagenase (MMP-1) and gelatinase B (MMP-9) in polymyositis and dermatomyositis and to a lesser extent in inclusion body myositis, whereas the level of expression of TIMPs remained unchanged in comparison with controls. Increased mRNA levels were associated with enhanced enzyme expression, as determined by immunoblotting, gelatin zymography and in situ zymography. Immunohistochemically, MMP-1 could be localized around the sarcolemma of diseased muscle fibres and to cells resembling fibroblasts, whereas MMP-9 seemed to be expressed primarily by invading T lymphocytes. Raised levels of MMPs could not be detected in the sera of affected patients, emphasizing the crucial action of MMPs in the inflamed muscle. Our results imply a pathogenic role for specific MMPs in the genesis of inflammatory myopathies, and open new strategies for therapeutic intervention. (+info)
Selectin-independent leukocyte rolling and adhesion in mice deficient in E-, P-, and L-selectin and ICAM-1.
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To study selectin-independent leukocyte recruitment and the role of intercellular adhesion molecule-1 (ICAM-1), we generated mice lacking all three selectins and ICAM-1 (E/P/L/I-/-) by bone marrow transplantation. These mice were viable and appeared healthy under vivarium conditions, although they showed a 97% reduction in leukocyte rolling, a 63% reduction in leukocyte firm adhesion, and a 99% reduction of neutrophil recruitment in a thioglycollate-induced model of peritonitis at 4 and 24 h. Mononuclear cell recruitment was almost unaffected. All residual leukocyte rolling and most leukocyte adhesion in these mice depended on alpha(4)-integrins, but a small number of leukocytes (6% of wild-type control) still became adherent in the absence of all known rolling mechanisms (E-, P-, L-selectin and alpha(4)-integrins). A striking similarity of leukocyte adhesion efficiency in E/P/L-/- and E/P/I-/- mice suggests a pathway in which leukocyte rolling through L-selectin requires ICAM-1 for adhesion and recruitment. Comparison of our data with mice lacking individual or other combinations of adhesion molecules reveal that elimination of more adhesion molecules further reduces leukocyte recruitment but the effect is less than additive. (+info)
Hypothyroidism presenting as hypercholesterolaemia and simvastatin-induced myositis.
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We report on a 50-year-old woman who presented with hypertension. She was given simvastatin for hypercholesterolaemia. The creatine kinase level was 3180 U/L at the 3-month follow-up visit, which was thought to be due to simvastatin treatment. Although treatment was discontinued, the creatine kinase level 4 months later remained higher than 3000 U/L. Echocardiography revealed mild pericardial effusion and normal left ventricular function; the electromyogram was also normal. The patient subsequently showed signs and symptoms suggestive of hypothyroidism, which was confirmed by measurements of the concentration of thyroid-stimulating hormone (>100 mU/L) and free thyroxine (<2 pmol/L). Thyroxine replacement therapy normalised the creatine kinase and cholesterol levels. This case illustrates the importance of excluding underlying causes of hypercholesterolaemia before contemplating lipid-lowering therapy. (+info)
The DNA mismatch repair enzyme PMS1 is a myositis-specific autoantigen.
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OBJECTIVE: The specificity of the autoantibody response in different autoimmune diseases makes autoantibodies useful for diagnostic purposes. It also focuses attention on tissue- and event-specific circumstances that may select unique molecules for an autoimmune response in specific diseases. Defining additional phenotype-specific autoantibodies may identify such circumstances. This study was undertaken to investigate the disease specificity of PMS1, an autoantigen previously identified in some sera from patients with myositis. METHODS: We used immunoprecipitation analysis to determine the frequency of autoantibodies to PMS1 in sera from patients with myositis, systemic lupus erythematosus, or scleroderma and from healthy controls. Additional antigens recognized by PMS1-positive sera were further characterized in terms of their susceptibility to cleavage by apoptotic proteases. RESULTS: PMS1, a DNA mismatch repair enzyme, was identified as a myositis-specific autoantigen. Autoantibodies to PMS1 were found in 4 of 53 patients with autoimmune myositis (7.5%), but in no sera from 94 patients with other systemic autoimmune diseases (P = 0.016). Additional mismatch repair enzymes (PMS2, MLH1) were targeted, apparently independently. Sera recognizing PMS1 also recognized several other proteins involved in DNA repair and remodeling, including poly(ADP-ribose) polymerase, DNA-dependent protein kinase, and Mi-2. All of these autoantigens were efficiently cleaved by granzyme B, generating unique fragments not observed during other forms of cell death. CONCLUSION: PMS1 autoantibodies are myositis specific. The striking correlation between an immune response to a group of granzyme B substrates (functioning in DNA repair and remodeling) and the myositis phenotype strongly implies that tissue- and event-specific biochemical events play a role in selecting these molecules for an autoimmune response. Understanding the role of granzyme B cleavage in this response is an important priority. (+info)
Pyomyositis of the iliacus muscle in a child.
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Pyomyositis is rarely seen in temperate climates. Typically, it presents with the formation of an abscess requiring surgical drainage and it has been reported as a differential diagnosis for septic arthritis of the hip. We describe the occurrence of pyomyositis of the iliacus muscle in a ten-year-old girl which was diagnosed by MRI and blood culture. Formation of an abscess did not occur despite marked focal inflammation and swelling of the muscle. Conservative treatment with antibiotics alone led to complete clinical and radiological resolution of the infection. We could find no previous description of pyomyositis in a child in the British orthopaedic literature. Orthopaedic surgeons, particularly those with a paediatric interest, should be aware of this condition and its presentation, diagnosis and treatment. (+info)