RETRACTED: Changes in the supporting muscles of the fractured hip in elderly women.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. The Journal has been made aware of concerns regarding the ethical approval for this study, and the study protocol and data were disputed. Since Dr Sato passed away, the co-authors were contacted about the complaint. Dr Izumi Kondo confirmed that the T score for sufficient 25OHD group in Table 2 was out of range and this was overlooked at the time of writing. He was unable to confirm whether the proper ethical approval was obtained or comment on the study protocol as his role was to advise on the statistical methodology of the revised paper. The other two co-authors did not respond, and one could not be located. This constitutes a violation of our publishing policies and publishing ethics standards.

Microvascular endothelial abnormality in skeletal muscle from a patient with gastric cancer without dermatomyositis.

We found a microvascular endothelial abnormality in a biopsy specimen from the gastrocnemius muscle of a patient with gastric cancer, who had severe myalgia and angialgia in the calf region with the symptoms of thrombophlebitis. There were no definite findings of inflammatory myopathy in histochemical and immunohistochemical studies. Electron microscopic examination revealed the accumulation of abnormal mitochondria in the subsarcolemmal area, and a fair number of degenerating capillaries. Immunohistochemical analysis of procoagulant or anticoagulant factors revealed marked reduction of thrombomodulin (TM) expression on small vessels and capillaries. Although a reduction of TM on small vessels has been observed around perifascicular atrophic fibers in patients with dermatomyositis, histochemical findings of the present patient showed no perifascicular atrophy or severely degenerating fibers. These pathological findings in the patient may be related to a malignant neoplasm and may be one of the causes of disseminated intravascular coagulation (DIC), which is the main complication of malignant neoplasms. Further studies are necessary to determine whether the reduction of TM on the small vessels and capillaries in skeletal muscle is a predictor of some severe condition such as DIC or a rare pathological finding in some special condition such as scirrhous carcinoma with thrombophlebitis.

Characteristic expression of thrombomodulin in the muscle sarcoplasm in patients with the acute phase of rhabdomyolysis.

The expression of thrombomodulin and neural cell adhesion molecule (NCAM) was studied immunocytochemically in biopsied muscle specimens from 10 patients with rhabdomyolysis with different etiologic factors, including 5 with malignant hyperthermia. We have already reported that thrombomodulin was expressed on regenerating muscle cell membranes as well as on vessel walls in patients with various neuromuscular diseases, including Duchenne muscular dystrophy, Becker muscular dystrophy and inflammatory myopathy. We found increased expression of thrombomodulin not only on the sarcolemma, but also in the sarcoplasm of a fair number of muscle fibers in the acute phase of rhabdomyolysis. The granular pattern of thrombomodulin expression in the sarcoplasm seems to be a characteristic finding in the acute phase of rhabdomyolysis. Most muscle fibers which expressed NCAM on the sarcolemma also expressed thrombomodulin. However, the muscle fibers which expressed thrombomodulin in the sarcoplasm did not express NCAM, and showed a degenerative appearance on electron microscopic examination. These results suggest that thrombomodulin is expressed in the sarcoplasm during the acute degeneration phase of rhabdomyolysis in addition to the expression on the sarcolemma during the muscle fiber regeneration as shown in our previous study, and the former process, which is characterized by the granular expression of thrombomodulin in the sarcoplasm, may be a characteristic finding in rhabdomyolysis.

An overexpression of fibroblast growth factor (FGF) and FGF receptor 4 in a severe clinical phenotype of facioscapulohumeral muscular dystrophy.

We evaluated the expression of a select panel of growth factors and their receptors, including fibroblast growth factor 1 (FGF-1), fibroblast growth factor 2 (FGF-2), platelet-derived growth factor (PDGF), FGF receptor 1 (FGF-R1), FGF receptor 3 (FGF-R3), FGF receptor 4 (FGF-R4), PDGF receptor alpha (PDGF-Ralpha), PDGF receptor beta (PDGF-Rbeta), and heparan sulfate proteoglycan (HSPG), in muscle biopsy specimens from nine facioscapulohumeral muscular dystrophy (FSHD) patients using immunohistochemistry. Two cases of Duchenne-type muscular dystrophy (DMD), two of Becker-type muscular dystrophy (BMD), and one of limb-girdle-type muscular dystrophy (LGMD) were also investigated. Widespread immunostaining for FGF-1 and FGF-2 on the sarcolemma and overexpression of FGF-R4 in endomysial and perimysial connective tissue were seen in one patient with a severe clinical phenotype of FSHD who had respiratory failure. Standard histochemistry in this patient revealed marked interstitial fibrosis and lobulated fibers. The overexpression of FGF and FGF-R4 in this severe FSHD case may be associated with the muscle fibrosis and disease severity.

[A study of clinical symptoms, muscle pathology, therapeutic response, and prognosis of myositis in patients with HTLV-1 associated myelopathy (HAM)].

Myositis is one of well-known complications of HTLV-1 associated myelopathy (HAM). On twelve HAM patients, 10 women and 2 men complicated with myositis, we examined their clinical symptoms, muscle pathology, and therapeutic response. Clinical examination revealed gait disturbance in 10, weakness of upper limbs in 6, muscle atrophy in 4, and myalgia in 3 patients. Blood test disclosed elevated serum CK level in 6 patients. Muscle biopsy showed marked inflammatory changes with many necrotic and degenerating fibers in 7 patients, and the rest showed only focal invasion of inflammatory cells. Eight patients received corticosteroid or immunosuppressant therapy. The neurological symptoms were improved in 5 of 8 patients 3 months after the treatment. And only one out of 5 patients whom we followed up 3 years after the treatment showed improvement.

Multiple episodes of thrombosis in a patient with Becker muscular dystrophy with marked expression of utrophin on the muscle cell membrane.

We previously reported a patient with Becker muscular dystrophy (BMD) who exhibited a benign clinical phenotype and marked expression of utrophin on the muscle cell membrane. The patient developed multiple episodes of thrombosis (middle cerebral and femoral arteries) in the course of the disease. We re-examined the biopsy muscle specimen from the patient immunohistochemically as to the expression of procoagulant or anticoagulant factors. We found a lower expression of thrombomodulin on the muscle cell membrane in the BMD patient compared with other BMD or Duchenne muscular dystrophy (DMD) patients. Although utrophin up-regulation in muscle is thought to prevent the muscle wasting in dystrophin-deficient DMD or BMD, the data obtained in the present study indicate that up-regulated utrophin may have an unexpected influence on the function of the vascular or coagulation system.

Caveolin-3 and sarcoglycans in the vacuolar myopathies and centronuclear myopathy.

Expression of dystrophin, beta-spectrin, merosin, and alpha- and beta-sarcoglycans on the vacuolar membranes in some types of vacuolar myopathies has previously been reported. We studied expression of caveolin-3; alpha-, beta-, gamma-, and delta-sarcoglycans; dystrophin; and merosin on the vacuolar membranes in various vacuolar myopathies. Caveolin-3 and dystrophin were expressed on the vacuolar membranes in lysosomal glycogen storage disease with normal acid maltase, hypokalemic myopathy, and centronuclear myopathy. Sarcoglycans and merosin were expressed only on the vacuolar membrane in lysosomal glycogen storage disease with normal acid maltase. Immunostain of caveolin-3 and sarcoglycans is therefore useful for differential diagnosis of vacuolar myopathies.

Effects of cytogenin, a novel microbial product, on embryonic and tumor cell-induced angiogenic responses in vivo.

Cytogenin (8-hydroxy-3-hydroxymethyl-6-methoxyisocoumarin) is a new microbial product with antitumor and antirheumatoid arthritis effects in vivo when administered orally, although its mechanism(s) of action is not known well. Both neoplasia and rheumatoid arthritis are referred to as angiogenesis-dependent diseases. The aim of the present study was to investigate the effects of cytogenin on both physiological and pathological angiogenesis, using the growing chick embryo chorioallantoic membrane and mouse dorsal air sac assay systems, respectively. The microbial product at doses up to 100 micrograms/egg did not significantly affect embryonic angiogenesis when topically placed on the surface of the chorioallantoic membrane, suggesting that it has no effect on the physiological (or normal) angiogenic response. By contrast, systemic administration of cytogenin (100 mg/kg p.o., for 5 consecutive days) significantly suppressed angiogenesis induced by malignant tumor cells (S-180), one of pathological neovascularization, in a mouse dorsal air sac assay system. Pharmacokinetic studies in mice revealed that the maximal concentration of cytogenin in plasma after a single 100 mg/kg oral dose of the compound was 32 microM. In vitro experiments involving cultured vascular endothelial cells showed that cytogenin at concentrations determined by pharmacokinetic study, had little effect on plasminogen activator secretion, tube formation and the proliferation of endothelial cells. These results suggest that cytogenin is a novel oral antiangiogenic agent, that the mechanism of its antiangiogenic action contributes to its suppressive effects on both tumor growth and rheumatoid arthritis that we previously found, and that it could be developed as a potential therapeutic agent for cancer, rheumatoid arthritis and other angiogenesis-dependent disorders such as diabetic retinopathy.

Characteristic expression of cell adhesion molecules in adhalin deficiency.

We have reported the reduction of the B1 subunit of laminin and that of heparan sulfate proteoglycan (HSPG) in two Japanese patients with adhalin deficiency. We here investigated immunohistochemically the expression of cell adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1), neural cell adhesion molecule (NCAM), and CD44 (HCAM), in four Japanese patients with adhalin deficiency, compared to other types of muscular dystrophy. We found that NCAM was upregulated in a fair number of muscle fibers, regardless of the type of muscular dystrophy. ICAM-1 was detected on the rare muscle cell membrane in all patients. CD44 was barely detected on the muscle cell membrane in adhalin deficiency, in contrast to the strong expression of CD44 which was observed in other types of muscular dystrophy. These findings suggest that a different degenerative or regenerative process is involved in adhalin deficiency compared to other types of muscular dystrophy.

Abnormal expression of heparin sulfate proteoglycan on basal lamina of muscle fibers in two Japanese patients with adhalin deficiency.

We recently reported the selective reduction of the B1 subunit of laminin in two Japanese patients with adhalin deficiency. We here investigated immunohistochemically the expression of other components of the extracellular matrix (ECM), including collagen type IV, heparan sulfate proteoglycan can (HSPG), chondroitin-4-sulfate proteoglycan, decorin, and fibronectin in adhalin deficiency, compared with other types of muscular dystrophy. We found a reduction of HSPG on the basal lamina surrounding each muscle fiber in adhalin deficiency compared with HSPG in other diseases. This finding may be characteristic evidence of the disturbance of the sarcolemma-ECM interaction and the sarcolemmal instability in adhalin deficiency. Recently, a direct role of HSPG in fibroblast growth factor (FGF) signal transduction was demonstrated. Further investigation is required to determine if the dysfunction of FGF is relevant to the pathogenesis of adhalin deficiency.

Depudecin, a microbial metabolite containing two epoxide groups, exhibits anti-angiogenic activity in vivo.

Depudecin, a microbial metabolite containing two epoxide groups, was tested for its anti-angiogenic activity in an in vivo assay system involving the chorioallantoic membrane of growing chick embryo. The microbial metabolite inhibited embryonic angiogenesis in a dose-dependent manner with an ID50 of 320 ng (1.5 nmol) per egg. It also affected the growth of vascular endothelial cells, a key event in the process of angiogenesis in vivo. These results suggest that depudecin could be promising as an anti-angiogenic agent and that its anti-angiogenic action involves an inhibitory effect on vascular endothelial cell growth.

Detection of HTLV-I provirus by in situ polymerase chain reaction in mononuclear inflammatory cells in skeletal muscle of viral carriers with polymyositis.

We tested for HTLV-I proviral DNA in skeletal muscle from patients with polymyositis infected with HTLV-I using the in situ polymerase chain reaction. We found the HTLV-I provirus in some of the CD4-positive cells in HTLV-I-positive polymyositis cases but not in HTLV-I-negative polymyositis ones. We could not detect HTLV-I within the muscle fibers. We suggest that HTLV-I-associated polymyositis is not due to direct, persistent infection of the muscle fiber by the virus, but to a T-cell-mediated immunological process triggered by the HTLV-I-infected cells.

Three cases of juvenile onset HTLV-I-associated myelopathy with pseudohypoparathyroidism.

Among 201 patients diagnosed with HAM/TSP at Kagoshima University, 21 juvenile onset patients had manifested clinical signs and symptoms at less than 15 years of age. They appeared to have common characteristics such as short stature and slight mental retardation. These signs prompted us to investigate five of them endocrinologically; and three patients with pseudohypoparathyroidism (PHP) were confirmed. Serum calcium levels were low, and human parathyroid hormone (PTH) infusion (Ellsworth-Howard test) caused low response in urinary cyclic AMP and phosphorus excretion. The first case had IgA nephropathy, which is generally associated with infectious diseases, while the second case had muscular lymphocytic infiltration. The mothers of cases 1 and 2, who were both seropositive for HTLV-I, were suspected to have abnormal calcium metabolism based on Ellsworth-Howard test. A brother of case 1 and two sisters of case 3 had also HAM/TSP and short stature. The early clinical onset of HAM/TSP may be due to PTH receptor anomaly and a low level of 1,25-dihydroxyvitamin D, which is deficient in PHP and is involved in the regulation of the immune response. The association with IgA nephropathy or myositis may result from progressive HTLV-I infection.

Immunohistochemical characteristics of polymyositis in patients with HTLV-I-associated myelopathy and HTLV-I carriers.

The immunohistochemical characteristics of polymyositis in patients with HTLV-I-associated myelopathy (HAM) and HTLV-I carriers were studied. Infiltrating cells were predominantly T cells and were not different from in the control group. All specimens contained positively staining muscle fibers for MHC class I antigens, but class II antigens were also expressed in some muscle fibers in 1 patient with HTLV-I-negative polymyositis, 3 patients with HTLV-I-positive polymyositis, and all 5 HAM patients with polymyositis. Expression of the neural cell adhesion molecule was lowest in the HAM patients. These findings may suggest a different immune environment in polymyositis with HAM.

Steroid-responsive myalgia in a patient with Becker muscular dystrophy.

We report a male patient with exercise-induced focal myalgia in the leg muscles. Dystrophin immunostaining of a biopsied muscle specimen from the patient showed the absence of or only faint immunoreactivity in 20% of the muscle fibers. The patient was diagnosed as having Becker muscular dystrophy. The myalgia was intractable and did not respond to non-steroidal anti-inflammatory drugs. The patient was placed on prednisone and found to be sensitive to it. Although he had recurrences of the symptom during tapering of the steroid, slower tapering over one year was tolerated. Steroid treatment may be useful for other Becker muscular dystrophy patients with myalgia.

Chronic demyelinating neuropathy and intra-axonal polyglucosan bodies.

In this study we evaluated the relationship between polyglucosan bodies and peripheral nerve lesions. The biopsied sural nerve from a patient with late-onset chronic sensori-motor neuropathy showed many intra-axonal polyglucosan bodies and segmental demyelination/remyelination. The formation of Schwann cell hyperplasia around the demyelinated axons was found at the sites of polyglucosan bodies. These findings suggest that demyelinating neuropathy is a part of the spectrum of the diseases characterized by the accumulation of polyglucosan bodies within cellular compartments.

Pathological changes in skeletal muscle in HTLV-I-associated myelopathy.

The main lesion site of HTLV-I-associated myelopathy or tropical spastic paraparesis (HAM/TSP) is the pyramidal tract. In some HAM patients, clinical symptoms and findings indicate neuromuscular involvement, such as muscular atrophy, fasciculation, elevated serum creatine kinase (CK) or significant electrophysiological data. Cases of HAM/TSP complicated with polymyositis or motor neuron disease have been reported. But no investigation has been directed to muscular pathology in many patients of HAM/TSP. We conducted muscle biopsies on 13 HAM patients. Four patients showed neurogenic changes. Six patients showed histological findings indicative of inflammatory myopathy. We investigated surface marker of invading cells in these 6 patients. In all patients, T lymphocytes were more predominant than B lymphocytes and in three of them T helper/inducer cells were more predominant than T suppressor cells. In 2 patients, only slight myopathic change could be seen, such as variation in fiber diameter and increase in the number of internal nuclei. In 1 patient, type 2 fiber atrophy was seen, and was possibly the result of disuse. Disturbance of secondary motor neurons or inflammatory myopathy is thus shown to be possibly associated with HAM/TSP.