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Homocysteine-induced endoplasmic reticulum protein (Herp) is up-regulated in sporadic inclusion-body myositis and in endoplasmic reticulum stress-induced cultured human muscle fibers.

Herp is a stress-response protein localized in the endoplasmic reticulum (ER) membrane. Herp was proposed to improve ER-folding, decrease ER protein load, and participate in ER-associated degradation (ERAD). Intra-muscle-fiber ubiquitinated multiprotein-aggregates containing, among other proteins, either amyloid-beta (Abeta) or phosphorylated tau are characteristic of sporadic inclusion-body myositis (s-IBM). ER stress and proteasome inhibition appear to play a role in s-IBM pathogenesis. We have now studied Herp in s-IBM muscle fibers and in ER-stress-induced or proteasome-inhibited cultured human muscle fibers. In s-IBM muscle fibers: (i) Herp was strongly immunoreactive in the form of aggregates, which co-localized with Abeta, GRP78, and beta2 proteasome subunit; (ii) Herp mRNA and protein were increased. In ER-stress-induced cultured human muscle fibers: (i) Herp immunoreactivity was diffusely increased; (ii) Herp mRNA and protein were increased. In proteasome-inhibited cultured human muscle fibers: (i) Herp immunoreactivity was in the form of aggregates; (ii) Herp protein was increased, but its mRNA was not. Accordingly, in s-IBM muscle fibers: (i) increase of Herp might be due to both ER-stress and proteasome inhibition; (ii) co-localization of Herp with Abeta, proteasome, and ER-chaperone GRP78 could reflect its possible role in processing and degradation of cytotoxic proteins in ER.

Amyloid beta-Peptides↗

Brachiola vesicularum, n. g., n. sp., a new microsporidium associated with AIDS and myositis.

Brachiola vesicularum, n. g., n. sp., is a new microsporidum associated with AIDS and myositis. Biopsied muscle tissue, examined by light and electron microscopy, revealed the presence of organisms developing in direct contact with muscle cell cytoplasm and fibers. No other tissue types were infected. All parasite stages contain diplokaryotic nuclei and all cell division is by binary fission. Sporogony is disporoblastic, producing 2.9 x 2 microns diplokaryotic spores containing 8-10 coils of the polar filament arranged in one to three rows, usually two. Additionally, this microsporidium produces electron-dense extracellular secretions and vesiculotubular appendages similar to Nosema algerae. However, the production of protoplasmic extensions which may branch and terminate in extensive vesiculotubular structures is unique to this parasite. Additionally, unlike Nosema algerae, its development occurred at warm blooded host temperature (37-38 degrees C) and unlike Nosema connori, which disseminates to all tissue types, B. vesicularum infected only muscle cells. Thus, a new genus and species is proposed. Because of the similarities with the genus Nosema, this new genus is placed in the family Nosematidae. Successful clearing of this infection (both clinically and histologically) resulted from treatment with albendazole and itraconozole.

AIDS-Related Opportunistic Infections↗

Focal myositis of the thigh: report of two cases.

Focal myositis is a benign inflammatory pseudotumor of skeletal muscle, presenting as a localized painful swelling within the soft tissue of an extremity. Histological examination reveals lymphocytic infiltration, scattered muscle fiber necrosis and regeneration, and interstitial fibrosis. Complete recovery follows surgical removal of the lesion. Two cases are presented of young active males with a localized painful swelling of the thigh. Clinical examination, standard laboratory tests, electromyography (EMG), magnetic resonance imaging (MRI) and surgical biopsies were performed. Surgical biopsies were formalin-fixed, paraffin-embedded and sections were stained with hematoxylin and eosin, van Gieson, modified Gomori trichrome and Mallory's method for iron. Clinical examination in both cases revealed an indolent lump in the quadriceps femoris muscle. Standard laboratory tests and electromyography were normal. MRI prior to surgery visualized the focal nature of the lesions. Histological examination of repeated surgical biopsies showed scattered muscle fiber necrosis, regeneration, and interstitial fibrosis but few lymphocytes. Both patients recovered after surgical removal of the lesion. Two years after surgery there was no recurrence of the lesions and repeated EMGs were normal.

Adolescent↗

Inclusion body myositis: clinical, morphological, physiological and laboratory findings in 18 cases.

Eighteen consecutive patients with inclusion body myositis (IBM) were studied. The mean age of onset of symptoms was 60 years. A typical clinical pattern with insidious onset of muscle weakness in knee extensors and finger flexors combined with dysphagia was observed. Serial measurements of the maximal voluntary muscle strength revealed a mean loss of muscle strength of 1.4% per month. Two of the cases had common variable immunodeficiency, and three cases had reduced levels of the IgG3 subclass. Treatment with prednisone resulted in a temporary improvement of muscle function in three patients. No positive effect of azathioprine or cyclosporine A could be documented. The results show that IBM may be associated with immunodeficiency, and that prednisone treatment may temporarily improve the clinical signs. The results from our studies on the progression of the muscle weakness may provide basis for future studies on treatment of IBM.

Adrenal Cortex Hormones↗

Myositis ossificans progressiva: a 10-year follow-up on a patient treated with etidronate disodium.

We describe a child who was treated for 10 years with etidronate disodium for myositis ossificans. There were no typical bouts of swelling, reddening or hardening of areas over the skeletal muscles with this treatment and there were no side effects. Nevertheless, a constant gradual progression of the disease led to severe limitation of joint movement. This is the first report on long-term treatment with etidronate disodium.

Adolescent↗

Immuno-histochemical and ultrastructural characteristics of a cyst-forming sporozoon associated with encephalomyelitis and myositis in dogs.

Light-microscopy, including immuno-histochemical staining, and transmission and scanning electron microscopy were applied for the characterization of a Toxoplasma-like parasite associated with encephalomyelitis and myositis in dogs of the boxer breed. Most parasites were tachyzoites, occurring in clusters, up to 60 micron in diameter, in parasitophorous vacuoles of host cells. Cyst stages with a definite cyst wall were few, but could be demonstrated in all cases. Immunostaining with antiserum against Toxoplasma gondii was negative, while both tachyzoites and bradyzoites were stained with serum from affected dogs. Ultrastructurally, the parasite was characterized by a great number of rhoptries, few amylopectin granules, lack of micropores in the tachyzoites, and the occurrence of numerous dense bodies in the bradyzoites. Numerous intravacuolar tubules were present in the space of the parasitophorous vacuole. The cyst wall resembled that of T. gondii. Until a definite host is found, the parasite may be regarded as an "orphan", cyst-forming sporozoon that is ultrastructurally different from other known protozoan parasites. It has a light-microscopical similarity to T. gondii but is antigenically different.

Animals↗

Management of a femoral fracture complicated by clostridial myositis.

A clinical case of clostridial myositis secondary to a comminuted femoral fracture is described. This case is unusual because, despite the severe degree of obvious muscle necrosis and gas production, the dog had minimal signs of systemic toxicity. Union of the fracture was achieved but six months postoperatively muscular contracture had resulted in permanent stifle extension.

Animals↗

Increased expression of the normal cellular isoform of prion protein in inclusion-body myositis, inflammatory myopathies and denervation atrophy.

The cellular isoform of the prion protein (PrPc) is a glycosylphosphatidylinositol-anchored glycoprotein, normally expressed in neural and non-neural tissues, including skeletal muscle. In transmissible spongiform encephalopathies, or prion diseases, PrPc, which is soluble in nondenaturing detergent and sensitive to proteinase K (PK)-treatment, represents the molecular substrate for the production of a detergent-insoluble and PK-resistant isoform, termed PrP(Sc). In human prion diseases, PrP(Sc) accumulation occurs only in brain tissues, with the exception of new variant Creutzfeldt-Jakob disease, where PrP(Sc) is also detected in lymphoid tissues. Increased amounts of prion protein expression and deposition have been described in pathological muscle fibers of two human muscle disorders, called sporadic inclusion-body myositis (s-IBM) and hereditary inclusion-body myopathy, but it is unknown whether accumulated prion protein reflects normal PrPc or PrP(Sc). We investigated the biochemical characteristics of prion protein in normal human muscle, s-IBM, other inflammatory myopathies and denervation atrophy. We report that 1) both the glycoform profile and size of the normal muscle PrPc are different from those of human brain PrPc; 2) in addition to s-IBM, increased PrPc expression is seen in polymyositis, dermatomyositis and neurogenic muscle atrophy, but PrPc glycoforms are unchanged; 3) only the normal PrPc isoform, and not PrP(Sc), is detected in s-IBM. The present results exclude that s-IBM is a prion disease.

Adult↗

Involvement of clusterin and the aggresome in abnormal protein deposits in myofibrillar myopathies and inclusion body myositis.

Myofibrillar myopathies (MM) are characterized morphologically by the presence of non-hyaline structures corresponding to foci of dissolution of myofibrils, and hyaline lesions composed of aggregates of compacted and degraded myofibrillar elements. Inclusion body myositis (IBM) is characterized by the presence of rimmed vacuoles, eosinophilic inclusions in the cytoplasm, rare intranuclear inclusions, and by the accumulation of several abnormal proteins. Recent studies have demonstrated impaired proteasomal expression and activity in MM and IBM, thus accounting, in part, for the abnormal protein accumulation in these diseases. The present study examines other factors involved in protein aggregation in MM and IBM. Clusterin is a multiple-function protein which participates in Abeta-amyloid, PrP(res) and a-synuclein aggregation in Alzheimer disease, prionopathies and a-synucleinopathies, respectively. gamma-Tubulin is present in the centrosome and is an intracellular marker of the aggresome. Moderate or strong clusterin immunoreactivity has been found in association with abnormal protein deposits, as revealed by immunohistochemistry, single and double-labeling immunofluorescence and confocal microscopy, in MM and IBM, and in target structures in denervation atrophy. Gamma-Tubulin has also been observed in association with abnormal protein deposits in MM, IBM, and in target fibers in denervation atrophy. These morphological findings are accompanied by increased expression of clusterin and gamma-tubulin in muscle homogenates of MM and IBM cases, as revealed by gel electrophoresis and Western blots. Together, these observations demonstrate involvement of clusterin in protein aggregates, and increased expression of aggresome markers in association with abnormal protein inclusions in MM and IBM and in targets, as crucial events related to the pathogenesis of abnormal protein accumulation and degradation in these muscular diseases.

Adult↗

The use of intraosseous anesthesia in a patient with myositis ossificans progressiva.

The case of a pediatric patient with myositis ossificans progressiva in whom it became increasingly difficult to obtain local anesthesia is presented. Intraosseous anesthesia was successful in allowing pain-free dental treatment to be completed. This approach should be considered in other patients who have limited mouth-opening ability due to injury or disease.

Adolescent↗

[Four cases of acute myositis associated with influenza A infection in the elderly].

In nursing home belonging to our hospital, influenza like syndromes were recognized in 40 of 250 cases (16%) in 1994, and 5 cases were admitted to our hospital. On admission, three patients were unable to walk, and creatine phosphokinase levels were elevated in all patients, ranging from 337 IU/l to 20,672 IU/l. There were normal test findings for electrocardiography, ultrasonic cardiography. Three patients showed a significant antibody titer fall (Hemagglutinin Inhibition) in six months. The other patient did not show it, but his symptom was compatible with influenza. All patients recovered rapidly without sequelae. We reported four cases in the elderly of acute myositis associated with influenza A (H3N2) infection.

Acute Disease↗

[Imported trichinellosis with severe myositis--report of a case].

A 38-year-old Japanese male who had traveled in China from September 13 to October 5, 1997, developed fever and severe conjunctivitis from October 20. After he was hospitalized in Kyoto City Hospital for persistent high fever on October 29, he developed muscular weakness and dysphagia which continued for two weeks. An electromyogram showed a myogenic pattern, and laboratory findings showed significant elevation of serum enzyme levels of muscle origin: CPK, 3,095 IU/l; aldorase, 195 IU/l; myoglobin, 7,570 ng/ml, and myoglobinuria, 94,700 ng/ml. The WBC was 10,800/microliter with 45% eosinophils. Muscular biopsy showed degeneration of muscle fibers with infiltration of macrophages and lymphocytes. On further inquiry, it was revealed that the patient had eaten smoked bear meat in China on September 30, three weeks prior to the onset of symptoms. A dot-ELISA serologic test for parasites was positive for Trichinella. Further, a coiled 1.2 mm long Trichinella larve was recovered from approximately 100 mg of frozen biopsied muscle by an enzyme digestion method. Mebendazole was given to the patient at a dosage of 200 mg/day for seven days. CPK levels were normalized within 3 days of the beginning of the treatment, and he was discharged without any symptoms. Physicians must be aware of trichinellosis and should include it in their differential diagnosis when examining patients with myositis and eosinophilia of unknown origin.

Adult↗

[A successful treatment of progressive necrotizing myositis caused by Aeromonas veronii biotype sobria].

We report a 52 year-old patient with malignant lymphoma who developed necrotizing soft tissue infection in the left lower extremity by Aeromonas veronii biotype sobria during a neutropenic period after intensive chemotherapy. We decided to amputate the involved leg when signs and symptoms of necrotizing myositis were progressing despite administration of sensitive antibiotics. He survived with subsequent intensive supportive care. It is to note that even though the patient's neutrophil count is zero, he or she should be treated aggressively by drainaging the lesion or even amputation of the involved extremities in combination with proper antibiotics.

Aeromonas↗

Local and regional applications of hydrogen peroxide in the control of clostridial myositis in rabbits.

The intra-arterial infusion of hydrogen peroxide has been used as a method for producing a hyperoxic environment in experimental animals for the treatment of experimentally induced clostridial myositis. Eighty-five rabbits were employed in this study; 43 were controls and 42 were experimental animals. In the experimental study, 21 animals were treated with hydrogen peroxide by each route of administration. In this group, 52.4% of the animals receiving the intra-arterial infusion and 66.6% receiving intramuscular clysis survived. There were no survivors past 72 hr in the control group.

Animals↗

Characterization of Ross River virus tropism and virus-induced inflammation in a mouse model of viral arthritis and myositis.

Mosquito-borne alphaviruses are a significant cause of both encephalitic and arthritic disease in humans worldwide. In contrast to the encephalitic alphaviruses, the pathogenesis of alphavirus-induced arthritic disease is not well understood. Utilizing a mouse model of Ross River virus (RRV) disease, we found that the primary targets of RRV infection are bone, joint, and skeletal muscle tissues of the hind limbs in both outbred CD-1 mice and adult C57BL/6J mice. Moreover, histological analyses demonstrated that RRV infection resulted in severe inflammation of these tissues. Characterization of the inflammatory infiltrate within the skeletal muscle tissue identified inflammatory macrophages, NK cells, and CD4+ and CD8+ T lymphocytes. To determine the contribution of the adaptive immune system, the outcome of RRV-induced disease was examined in C57BL/6J RAG-1(-/-) mice, which lack functional T and B lymphocytes. RAG-1(-/-) and wild-type mice developed similar disease signs, infiltration of inflammatory macrophages and NK cells, and muscle pathology, suggesting that the adaptive immune response does not play a critical role in the development of disease. These results establish the mouse model of RRV disease as a useful system for the identification of viral and host factors that contribute to alphavirus-induced arthritis and myositis.

Alphavirus Infections↗

Acute transient myositis due to Toxocara.

Two children presented with spontaneous, isolated swelling of the lower half of the left leg; this was diagnosed as acute myositis of unknown aetiology. Further investigations showed antibodies to Toxocara. The symptoms resolved within 72 hours and the children were discharged on no treatment.

Animals↗

Familial inflammatory inclusion body myositis.

OBJECTIVE: To compare familial inflammatory inclusion body myositis (IBM) with hereditary inclusion body myopathies and sporadic IBM. PATIENTS AND METHODS: Clinical, biological, MRI, and histological data were analysed in two siblings with inflammatory IBM and compared with those of patients with sporadic and hereditary IBM. RESULTS: Both patients had a clinical phenotype of sporadic IBM, which differs from hereditary myopathies because of late age of onset--respectively 65 and 66 years, and different pattern of muscular involvement--asymmetric, mainly distal but also involving quadriceps. MRI showed selective fatty infiltration and oedema in the extensor compartment of thigh muscles. The diagnosis of IBM was confirmed by muscle biopsy, showing muscle fibres containing numerous rimmed vacuoles, a characteristic shared by all types of IBM. In contrast with hereditary IBM, histological analysis also showed inflammatory mononuclear infiltrate invading non-necrotic fibres, ragged red and oxidase c negative fibres, and positive Congo red staining. Moreover, HLA class II typing disclosed DR beta 1 0301 haplotype, which is significantly related to sporadic but not to hereditary IBM. With steroid treatment and monthly intravenous immunoglobulins, the disease was stabilised in both patients at protracted follow up. CONCLUSION: Sporadic and familial inflammatory IBM share the same clinical, biological, MRI, and histological features.

Aged↗

Malignant myositis ossificans: occult gastric carcinoma presenting as an acute rheumatic disorder.

A patient developed ossifying skeletal muscle metastases from a primary gastric mucin-producing adenocarcinoma. The unusual nature of skeletal muscle metastases and the inflammatory-like syndrome associated with heterotopic ossification is reviewed. It is suggested that this case of 'neoplasm-induced post-traumatic myositis ossificans' may be caused by the interaction of local haemorrhage and thrombosis, mucin-producing tumour implants, and the presence of large quantities of gamma-carboxyglutamic acid, an amino acid associated with the calcification of bone matrix formation.

1-Carboxyglutamic Acid↗