Biomedical subjects

I Higuchi

Publications and source records attributed to I Higuchi.

At least 73 records · Page 4Linked to original sources

PubMed2000

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.

Biopsy↗

PubMed2000

Myoadenylate deaminase deficiency with progressive muscle weakness and atrophy caused by new missense mutations in AMPD1 gene: case report in a Japanese patient.

A 46-year-old woman with exertional myalgia developed slowly progressive weakness in her lower extremities. She had slight muscle weakness in her facial and upper extremities, and severe muscle weakness and atrophy in lower extremities more marked in the proximal portions. Serum creatine kinase was slightly elevated. After ischemic forearm exercise test, blood ammonia had no elevation although lactate level increased normally. The computed tomography revealed that a characteristic distribution of skeletal muscle involvement with proximal and flexor muscles more severely affected than distal and extensor in the lower extremities. In addition, the left sternocleidomastoid muscle showed marked atrophy with an asymptomatic weakness of over 20 years duration suggesting abnormal development. Needle EMG examination showed a large number of easily recruited, short-duration, low-amplitude motor unit potentials in all extremities. Muscle biopsy showed absence of adenosine monophosphate deaminase activity with normal cytochrome c oxidase and phosphorylase activity. With the muscle enzyme activity assay, adenosine monophosphate deaminase activity was found to be lower than 0.2% of the controls. The DNA analysis revealed that she was compound heterozygote involving two missense mutations (R388W and R425H) in exon 9 and exon 10 of AMPD1 gene. This is the first report of primary myoadenylate deaminase deficiency with progressive weakness and atrophy caused by novel compound heterozygous mutations of AMPD1 gene, and suggests that adenosine monophosphate deaminase is closely related not only to energy metabolism but also to the development of skeletal muscle.

AMP Deaminase↗

PubMed2000

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.

Adolescent↗

PubMed2000

HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) with amyotrophic lateral sclerosis-like manifestations.

To clarify the existence of HAM/TSP presenting amyotrophic lateral sclerosis (ALS)-like manifestations, we assayed HTLV-I proviral load in peripheral blood mononuclear cells (PBMC) in 15 patients with anti-HTLV-I antibody in serum and ALS-like manifestations (upper motor neuron involvement in at least one region and lower motor neuron involvement in at least two limbs) by quantitative PCR, and compared the proviral load with that of 233 HAM/TSP patients and of 213 HTLV-I carriers. Five of 15 patients with ALS-like manifestations had proviral loads as high as those in the 233 patients with HAM/TSP. Anti-HTLV-I antibody in cerebrospinal fluid (CSF) was present in all of five patients. The proviral load in the remaining 10 patients was similar to that in HTLV-I carriers. Four of five patients with a high proviral load met the diagnostic criterion of HAM/TSP except for lower motor neuron involvement. These four patients showed high neopterin levels in CSF. On the basis of HTLV-I proviral load in PBMC and the clinical symptoms, our tentative conclusion is that these four patients are HAM/TSP presenting ALS-like manifestations.

Adult↗

PubMed2000

[Genetically confirmed spinal muscular atrophy type III with epilepsy, cerebral hypoperfusion, and parahippocampal gyrus atrophy].

We report a 37-year-old female with spinal muscular atrophy (SMA) type III and central nervous system (CNS) involvement. She showed gait disturbance at the age of 12 years, and difficulty of squatting at the age of 19. On examination at the age of 22, she had proximal muscle weakness and atrophy, fasciculation, normal sensory system and elevated creatine kinase in the serum. She was diagnosed as having SMA type III based on clinical, electrophysiological, and muscle biopsy findings. She suffered from subacute necrotizing lymphadenitis at the age of 23 and from epilepsy at the age of 33. Magnetic resonance imaging showed atrophy of parahippocampal gyrus with right side predominance. Single photon emission computed tomography (SPECT) using I123-IMP showed decreased accumulations of I123-IMP in the temporal lobes with left side predominance. Electroencephalogram showed theta wave without epileptic burst. SMA gene analysis revealed deletion of exon 7 and 8 in survival motor neuron (SMN) gene. A few patients with SMA and CNS involvement have been reported without genetic diagnosis. This is the first report of genetically confirmed SMA patient with CNS involvement. SMN gene is distributed not only in spinal cord but also in brain. The CNS involvement detected in this patient may be related to the loss of SMN gene function, although coincidental association of SMA and the CNS abnormalities is still considered in this atypical case.

Adult↗

PubMed1999

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.

Aged↗

PubMed1999

Expression of thrombomodulin, caveolin-3, and desmin on muscle fibers in neuromuscular diseases.

The expression of thrombomodulin (TM) and caveolin-3 on biopsied muscle fibers from 17 patients with various neuromuscular diseases was studied immunocytochemically. We also compared the expression of TM and caveolin-3 with that of desmin, which is a marker for muscle fiber regeneration. Most TM-positive muscle fibers strongly expressed caveolin-3 and desmin. Our results suggest that TM is expressed and caveolin-3 is upregulated during the process of muscle fiber regeneration.

Biomarkers↗

PubMed1999

A rat model of human T lymphocyte virus type I (HTLV-I) infection: in situ detection of HTLV-I provirus DNA in microglia/macrophages in affected spinal cords of rats with HTLV-I-induced chronic progressive myeloneuropathy.

To investigate the pathogenetic role of human T lymphocyte virus type I (HTLV-I) in central nervous system disease, a rat model for HTLV-I-associated myelopathy/tropical spastic paraparesis, designated as HAM rat disease, has been established. Wistar-King-Aptekman-Hokudai strain rats with induced HTLV-I infection develop a chronic progressive myeloneuropathy with paraparesis of hind limbs after an incubation period of 15 months. In the affected spinal cord in these rats, white matter degeneration, demyelination and vacuolar change with microglia/macrophage infiltration are present as are the provirus DNA and the virus mRNA. To identify infected cells in the affected lesions, we carried out in situ hybridization of amplified fragments of the provirus DNA by polymerase chain reaction on thin sections, plus immunohistochemistry on the same sections. The provirus DNA was localized in some microglia/macrophages in the spinal cord lesion. In addition, the HTLV-I provirus was clearly evident not only in ED-1-negative lymphoid cells but also in ED-1-positive macrophages from lymph nodes. These observations suggest that cells of microglia/macrophage lineage may be one of dominant viral reservoirs in the spinal cords and lymph nodes in HAM rat disease. These infected microglia/macrophages may relate to cause the myeloneuropathy through neurotoxic cytokine synthesis.

Animals↗

PubMed1999

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.

Adolescent↗

PubMed1999

Adult onset limb-girdle type mitochondrial myopathy with a mitochondrial DNA np8291 A-to-G substitution.

We analyzed mitochondrial DNA (mtDNA) from 7 patients in four families with adult onset limb-girdle type mitochondrial myopathy to clarify their genetic background. The patients, 2 men and 5 women, showed common clinical features, characterized by isolated skeletal myopathy, high serum creatine kinase level, ragged-red fibers and cytochrome c oxidase-defective fibers. Analysis of muscle biopsy specimens indicated that cytochrome c oxidase activity was decreased relative to that of citrate synthase in 5 of the 7 patients. Southern blotting and direct sequence analyses showed an A-to-G homoplasmic transition at np8291 and intergenic COII/tRNA (Lys) 9bp deletion in all patients. This substitution was detected in only 2 of 600 control individuals including healthy subjects and patients with other neuromuscular disorders; these 2 individuals had diabetes mellitus and myotonic dystrophy, respectively. Consequently, the mtDNA transition at np8291 was a rare polymorphism. However, the 7 patients we studied had identical clinical, pathological, biochemical, and genetic features. Therefore, limb-girdle type mitochondrial myopathy with this rare polymorphism may form a subgroup of adult onset mitochondrial myopathy.

Adult↗

PubMed1999

Nemaline rod and degeneration of Z band of muscle cell in weightlessness at spaceflight.

There are some studies demonstrating the skeletal muscle degeneration associated with the degeneration of Z band and appearance of nemaline rods in experimental animals of the simulation model for spaceflight but not in human heart tissues. In the present study, therefore, we investigated the pathological changes or degeneration in left auricular heart muscles obtained during operations of mitral valves replacement using both electron and light microscopies. The degeneration of Z band even in the myofibrils of comparatively little damaged cell was found. Furthermore, nemaline rods were detected in most of the heart muscle cells. These results suggest that the existence of nemaline rods is involved in the cell injury in the heart muscle of patients with heart disease without nemaline myopathy. Further study is necessary to know whether the similar pathological findings are observed not only in the skeletal muscle but also in the cardiac muscle in experimental animals of the simulation model for spaceflight or in a prolonged spaceflight.

Animals↗

PubMed1999

Statistically significant differences in the number of CD24 positive muscle fibers and satellite cells between sarcoglycanopathy and age-matched Becker muscular dystrophy patients.

OBJECT: The aim of this study was to reveal variations in the patterns of expression of the cell surface proteins in regenerating fibers and those in the number of satellite cells to gain an understanding of the pathological processes involved in sarcoglycanopathy. METHODS: We have reported that there is a reduction of the beta-1 subunit of laminin, heparan sulfate proteoglycan (HSPG), and HCAM (CD44) in Japanese patients with sarcoglycanopathy. Here, we investigated immunohistochemically the expression of the neural cell adhesion molecule (NCAM), which is a marker for human regenerating muscle and satellite cell, and CD24, which appears to be expressed in the early stages of the regeneration process. PATIENTS: We investigated six Japanese patients with sarcoglycanopathy, and compared to age-matched Becker muscular dystrophy. RESULTS: We found that the incidences of muscle fibers with increased NCAM were not statistically different between the two groups. However, the incidences of muscle fibers with increased CD24 and those of NCAM positive satellite cells were very low in sarcoglycanopathy and were statistically different between sarcoglycanopathy and age-matched Becker muscular dystrophies. CONCLUSION: The poor expression of CD24 and the fewer satellite cells in sarcoglycanopathy without significant difference in the number of total regenerating fibers suggest that a different regeneration process is involved in sarcoglycanopathy compared to that in other types of muscular dystrophy.

Adolescent↗

PubMed1999

Familial skeletal myopathy with atrioventricular block.

OBJECTIVE: We studied familial cases of skeletal myopathy with atrial fibrillation (Af) and atrioventricular (AV) block to compare the clinical features to other myopathies associated with cardiac abnormalities. METHODS: Neurologic, cardiologic, electrophysiologic, muscle pathology, and genetic studies were performed on the patients showing muscle weakness. PATIENTS: Four patients (a 63-year-old mother, 30 and 32-year-old sisters, and their maternal grandmother) and three healthy family members from three generations were studied. The mode of inheritance was suspected as autosomal dominant. RESULTS: Two sisters with congenital myopathy without rigid spine developed Af and AV block at the age of 28 and 18, respectively. The mother showed AV block, and underwent pacemaker implantation at the age of 63. The maternal grandmother had dilated cardiomyopathy, Af and severe lordosis. She died of stroke attacks and congestive heart failure at the age of 78. Muscle biopsy obtained from the mother and sisters showed myopathic changes without characteristic abnormalities. No mitochondrial DNA mutations were found. Other inherited myopathies with cardiac complications were not suspected in this family. CONCLUSION: This Japanese family appears to belong to a new genetically heterogeneous group of autosomal dominant skeletal myopathy with severe AV block and Af.

Adult↗

PubMed1999

[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.

Adult↗

PubMed1998

The Influence Function of Principal Component Analysis by Self-Organizing Rule.

This article is concerned with a neural network approach to principal component analysis (PCA). An algorithm for PCA by the self-organizing rule has been proposed and its robustness observed through the simulation study by Xu and Yuille (1995). In this article, the robustness of the algorithm against outliers is investigated by using the theory of influence function. The influence function of the principal component vector is given in an explicit form. Through this expression, the method is shown to be robust against any directions orthogonal to the principal component vector. In addition, a statistic generated by the self-organizing rule is proposed to assess the influence of data in PCA.

Journal Article↗

PubMed1998

Quantitative in situ PCR assay of HTLV-1 infected cells in peripheral blood lymphocytes of patients with ATL, HAM/TSP and asymptomatic carriers.

We established an in situ PCR (IS-PCR) method that amplified the pX region of human T cell lymphotropic virus type 1 (HTLV-1) proviral DNA. The procedure was highly sensitive in accurately detecting the number of cells infected with HTLV-1. We estimated the number of HTLV-1 infected cells in peripheral blood lymphocytes (PBL) from patients with HAM/TSP, ATL and asymptomatic carriers. ATL patients (n = 5) had 8-93% IS-PCR positive cells for HTLV-1 and these percentages correlated with the clinical stages. Asymptomatic carriers (n = 3) had 0.8-3.8% (mean 1.1%, S.D. 1.7) positive cells. HAM/TSP patients (n = 10) had 3.1-8.5% (5.8% (5.8%, 2.7) positive cells. Patients with shorter duration of illness showed larger percentages compared with patients with longer duration. In one HAM/TSP patient, the number of IS-PCR positive cells decreased from 5.1% to 1.5% coincident with the times of lymphocytapheresis treatment. Our studies may suggest that an increased viral load initiates the pathogenic process of HAM/TSP and the estimation of HTLV-1 proviral load by IS-PCR method is useful to understand the clinical state of HAM/TSP.

Adult↗

PubMed1998

Myopathy induced by HMG-CoA reductase inhibitors in rabbits: a pathological, electrophysiological, and biochemical study.

A combination of electrophysiological, pathological, and biochemical studies were performed in myopathy induced by 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors. Simvastatin (a lipophilic inhibitor) or pravastatin (a hydrophilic inhibitor) were administered by gavage to rabbits. In Group I (simvastatin-treated group, 50 mg/kg/day for 4 weeks), four rabbits showed muscle necrosis and high serum creatine kinase (CK) levels, and all six rabbits showed electrical myotonia. In Group II (pravastatin-treated group, 100 mg/kg/day for 4 weeks), no rabbit showed either condition. In Group III (pravastatin-treated group, 200 mg/kg/day for 3 weeks plus 300 mg/kg/day for 3 weeks), one rabbit showed muscle necrosis and high serum CK level and two rabbits showed electrical myotonia. The pathological findings were muscle fiber necrosis and degeneration with increased acid phosphatase activity by light microscopy, autophagic vacuoles and mitochondrial swelling, and disruption and hypercontraction of myofibrils by electron microscopy. Ubiquinone content decreased in skeletal muscle by 22 to 36% in Group I, by 18 to 52% in Group II, and by 49 to 72% in Group III. However, mitochondrial enzyme activities of respiratory chain were normal in all groups. These results indicate that myopathy was not induced by a secondary dysfunction of mitochondrial respiration due to low ubiquinone levels.

Animals↗

PubMed1998

Different manners of sarcoglycan expression in genetically proven alpha-sarcoglycan deficiency and gamma-sarcoglycan deficiency.

We investigated the expression of alpha-sarcoglycan, beta-sarcoglycan, gamma-sarcoglycan, and delta-sarcoglycan immunohistochemically in three patients with mutations of the alpha-sarcoglycan gene and a patient with a mutation of the gamma-sarcoglycan gene. Although each of the four sarcoglycans were decreased on the muscle membranes of all the patients, different expression patterns for each were seen among the patients. In patients with mutations of the alpha-sarcoglycan gene, beta-, gamma- and delta-sarcoglycans were relatively preserved as compared to greatly reduced alpha-sarcoglycan. However, the patient with a mutation of the gamma-sarcoglycan gene showed marked reduction of gamma-sarcoglycan as compared to partially preserved alpha- and beta-sarcoglycans, and well-preserved delta-sarcoglycan. These results suggest that each sarcoglycan component in sarcoglycanopathy does not decrease in the same manner, and that mutations of the sarcoglycan gene can be predicted, at least in part, by means of sensitive immunohistochemistry for each sarcoglycan.

Child↗