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Biomedical subjects

I Higuchi

Publications and source records attributed to I Higuchi.

At least 109 records · Page 6Linked to original sources
PubMed1995

In situ polymerase chain reaction detection of HTLV-I provirus and expression of the p53 tumor suppressor gene in infiltrating cells in skeletal muscle from a patient with adult T cell leukemia.

We report the pathological changes in skeletal muscle from a patient with acute adult T cell leukemia (ATL). HTLV-I provirus was detected in infiltrating cells using in situ polymerase chain reaction in frozen sections. Furthermore, aberrant expression of the p53 protein was observed in the infiltrating cells. As p53 protein was not observed in mononuclear inflammatory cells in patients with polymyositis, expression of the p53 protein was considered to be one of the characteristic findings in ATL cells. This is the first direct detection of ATL cells in skeletal muscle.

Gene Expression↗
PubMed1995

Cardiac dystrophin abnormalities in Becker muscular dystrophy assessed by endomyocardial biopsy.

Duchenne and Becker muscular dystrophy (DMD/BMD) are allelic variants caused by mutations in gene-encoding dystrophin. Abnormal expression of dystrophin in skeletal muscle has been shown to correlate with severity of disease. However, in BMD the severity of skeletal and cardiac involvement are not well correlated. We studied the immunostaining pattern of cardiac dystrophin in endomyocardial biopsy specimens from 83 patients with heart disease. Immunohistochemical assessment of dystrophin in four patients with BMD and cardiomyopathy showed a variable distributions of myocytes with continuous, discontinuous, or absent membrane immunostaining patterns. These patterns were obviously different from patterns of other heart diseases. We conclude that the discontinuous immunostaining pattern of cardiac dystrophin is characteristic of BMD and that an absent pattern may be associated with more severe cardiac dysfunction. Because genetic analysis cannot determine the correct diagnosis in 35% of DMD/BMD cases, we recommend routine examination of immunostaining patterns of dystrophin in endomyocardial biopsy specimens in patients with cardiomyopathy suspected to be the result of BMD.

Adult↗
PubMed1995

Type II muscle fibers are stained by anti-Fas antibody.

To examine whether apoptosis related proteins are present in skeletal muscles we studied biopsied muscles immunohistochemically and by Western blot analysis. Biopsied muscles from patients with several disorders were studied with anti-Fas antibody and anti-BCL2 antibody. Type II muscle fibers identified by ATPase staining were positively stained by anti-Fas antibody in both normal control and diseased muscles. Anti-BCL2 antibody did not stain any muscle fibers. Western blot analysis using anti-Fas antibody showed a single band at 45 kDa in both skeletal muscle and lymphocytes. Anti-Fas antibody has been reported to induce apoptosis in the cells. The presence of anti-Fas antibody reactive materials in type II muscle fibers might be related to type II fiber atrophy in muscular disorders.

Antibodies, Monoclonal↗
PubMed1995

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.

Adolescent↗
PubMed1995

Familial mitochondrial encephalomyopathy with deaf-mutism, ophthalmoplegia and leukodystrophy.

We report two sisters (32 and 36 years old) with familial deaf-mutism, progressive external ophthalmoplegia, leukodystrophy and mitochondrial myopathy. T2-weighted brain MRI demonstrated diffuse symmetrical high intensity areas in the white matter. Their muscle biopsies showed ragged-red fibers and cytochrome c oxidase (CCO)-negative fibers. CCO activity in biopsied muscle decreased to about 20% of normal control. They had no deletions of the mitochondrial DNA and no point mutations in mitochondrial tRNA. Their brother was diagnosed as having Kugelberg-Welander disease, grand mal seizures and urinary dysfunction. Their parents and grandparents had consanguinity. Three relatives were found to have deaf-mutism without accompanying ophthalmoplegia. This rare combination of mitochondrial encephalomyopathy and familial deaf-mutism might be caused by a nuclear DNA mutation in these sisters.

Adult↗
PubMed1995

[Paroxysmal dystonic choreoathetosis with chronic hemolytic anemia and morphologically abnormal erythrocytes].

A 38-year-old man was admitted to our hospital because of paroxysmal involuntary movement. He had a normal birth and normal development. No other members of his family had similar symptoms. He had attacks of choreoathetoic involuntary movement without loss of consciousness since about 11 years of age. Paroxysmal choreic movement occurred once or twice a month and lasted for 30 minutes to 4 hours. The attacks were intractable with phenytoin, phenobarbital, valproic acid, etc. He had slight disturbance of visual acuity due to toxoplasmosis and low intelligence (IQ 59, WAIS-R test). There were no other abnormal findings on general and neurological examinations. He was diagnosed as paroxysmal dystonic choreoathetosis (PDC) because of the typical attacks of paroxysmal choreic movement. He had macrocytic anemia with elliptocytes (13%) and stomatocytes (12%) but no acanthocytosis. There were increased reticulocytosis and low level of haptoglobin. Bone marrow aspiration showed increased erythroblasts. However, other hemolytic findings including bilirubin levels, Coombs test, osmolality tolerance test were normal. Biochemical analyses of erythrocyte membrane proteins and lipids, glycolytic enzymes activities and intermetabolites contents showed no abnormality. EEG revealed slow waves without abnormal paroxysmal discharges, and CT revealed no abnormal calcification. T2 weighted MRI showed bilateral multiple high intensity spots in the subcortical area, but no atrophy of the caudate nucleus. The pathogenesis of PDC is still unknown. In the present case, we suspect that a biochemical defect which had not been disclosed might result in abnormal erythrocyte membrane and PDC.

Adult↗
PubMed1995

Laminin abnormality in severe childhood autosomal recessive muscular dystrophy.

BACKGROUND: In skeletal muscle, dystrophin exists in a large oligomeric complex tightly associated with several novel sarcolemmal proteins, including the 50-kDa transmembrane glycoprotein called adhalin. The dystrophin-glycoprotein complex links the subsarcolemmal actin cytoskeleton to the basal lamina component laminin, thus providing stability to the sarcolemma. Disturbance of this linkage due to the absence of dystrophin plays a crucial role in the molecular pathogenesis of muscle fiber necrosis in Duchenne muscular dystrophy. Severe childhood autosomal recessive muscular dystrophy (SCARMD) is similar to Duchenne muscular dystrophy in phenotype but is characterized by the deficiency of adhalin. At present, the status of the link between the dystrophin-glycoprotein complex and laminin is unclear in SCARMD. EXPERIMENTAL DESIGN: We investigated, by immunohistochemistry using confocal laser scanning microscopy, the status of the expression of laminin subunits, A, M, B1, B2, and S chains, in skeletal muscle biopsy specimens of eight SCARMD patients from various human populations. In addition, we correlated the severity of laminin abnormality with the severity of both clinical symptoms and histopathologic changes in these patients. RESULTS: The reduction of laminin B1 chain and the overexpression of the S chain, a homologue of B1, in the extrajunctional basal lamina were observed in the five patients who had advanced clinical symptoms and histopathologic changes. Abnormalities in the expression of laminin were not observed in the three less affected patients. CONCLUSIONS: The expression of laminin is greatly disturbed in severely diseased SCARMD muscle deficient in adhalin. Disturbance of sarcolemma-basal lamina interaction may play an important role in the molecular pathogenesis of muscle fiber necrosis in SCARMD.

Adolescent↗
PubMed1995

[Changes of type IV collagen 7S and fibronectine in a patient with isolated ACTH deficiency].

A 60-year-old man presented with waste, muscle weakness and pain of knees and shoulders. Endocrinological investigations revealed low plasma cortisol and ACTH levels, delayed response of plasma cortisol to ACTH, no response of plasma ACTH to CRF and normal response to other pituitary hormone to corresponding stimulate test. He was diagnosed as isolated ACTH deficiency. Then we examined plasma type IV collagen 7S and fibronectin, because experimentally, corticosteroid regulates the extracellular matrix structure composed of type IV collagen, fibronectin and so on. These parameters were elevated and rapidly decreased to the normal range with the replacement of hydrocortisone, simultaneously his arthralgia was improved. These parameters can reflect the biochemistric change in cortisol deficiency state.

Adrenocorticotropic Hormone↗
PubMed1994

Morphologic findings in biopsied skeletal muscle and cultured fibroblasts from a female patient with Danon's disease (lysosomal glycogen storage disease without acid maltase deficiency).

A family is reported in which three members were affected by cardiomyopathy. Two members died unexpectedly in their second decade. Only a 23-year-old male suffered from the triad of clinical manifestations (cardiomyopathy, mental retardation and vacuolar myopathy). Morphologic findings and biochemical studies of his biopsied skeletal muscle and cultured fibroblasts confirmed lysosomal glycogen storage disease with normal acid maltase that was first described by Danon et al. In this study we demonstrated early morphologic changes, storage of glycogen and abnormal membranous structures in disorganized myofibers in biopsied skeletal muscle from the elder sister, who only showed cardiomyopathy clinically. The aggregation of autophagosomes was prominent in cultured fibroblasts, with an increased glycogen content. The activity of acid alpha-glucosidase was higher than normal. This is a systemic storage disease with different expression in males and females.

Adolescent↗
PubMed1994

Characteristics of dynamic mutation in Japanese myotonic dystrophy.

To study the characteristics, if any, of unstable CTG repeat sequence in Japanese myotonic dystrophy (DM), we analyzed DNA from 351 at risk individuals (including affected and non-affected carriers and their descendants) from 105 families in Japan. A total of 93 DM families (196 affected and 116 unaffected individuals), including 84 DM parent-child pairs (44 father-child and 40 mother-child pairs), were examined, many of which had been previously tested by linkage analysis. We detected unstable CTG repeat mutations between 0.15 kb and 8.7 kb in size. The size of the mutation correlated with the age of onset of symptoms. There was a significant difference in DM allele size among the four groups (congenital, juvenile onset, classical, and minimal). Congenital DM had on average the largest repeat sizes. Comparison of parent-child pairs showed that most offspring had a larger repeat size than their parents, with only 2 of 84 showing a definite decrease in repeat size. The correlation coefficients for maternal and paternal transmission were 0.41 and 0.15, respectively. The parental age (maternal and paternal) did not correlate with intergenerational change of repeat. These observations are similar to those reported in Caucasians.

Adolescent↗
PubMed1994

A case of paternally inherited congenital myotonic dystrophy.

We report two sisters with congenital myotonic dystrophy (CDM) born to a normal mother and an affected father. The congenitally affected daughters had symptoms from birth. The age of onset of DM in the father was 39 years. Analysis of the CTG trinucleotide expansion in this family showed increase in the repeat length with increasing severity, with the smallest expansion in the grandfather and the largest expansion in the younger of the two CDM sisters. This family shows that exceptionally it is possible for CDM to be inherited paternally and refutes the hypothesis that CDM is exclusively of maternal origin. This contradicts several of the previous hypotheses concerning the mechanisms by which the CDM phenotype arises.

Adolescent↗
PubMed1994

Abnormal expression of laminin suggests disturbance of sarcolemma-extracellular matrix interaction in Japanese patients with autosomal recessive muscular dystrophy deficient in adhalin.

Dystrophin is associated with several novel sarcolemmal proteins, including a laminin-binding extracellular glycoprotein of 156 kD (alpha-dystroglycan) and a transmembrane glycoprotein of 50 kD (adhalin). Deficiency of adhalin characterizes a severe autosomal recessive muscular dystrophy prevalent in Arabs. Here we report for the first time two mongoloid (Japanese) patients with autosomal recessive muscular dystrophy deficient in adhalin. Interestingly, adhalin was not completely absent and was faintly detectable in a patchy distribution along the sarcolemma in our patients. Although the M and B2 subunits of laminin were preserved, the B1 subunit was greatly reduced in the basal lamina surrounding muscle fibers. Our results raise a possibility that the deficiency of adhalin may be associated with the disturbance of sarcolemma-extracellular matrix interaction leading to sarcolemmal instability.

Adult↗
PubMed1994

Dystrophin-related protein in Becker muscular dystrophy.

A benign Becker muscular dystrophy (BMD) patient with a marked decrease in dystrophin exhibited remarkable expression of dystrophin-related protein (DRP) on most of the muscle cell membrane. A phenotypic Duchenne muscular dystrophy patient with a truncated form of dystrophin exhibited no DRP expression on the muscle cell membrane except for the neuromuscular junction. Increased DRP expression might compensate for a lack of dystrophin in some BMD patients.

Adolescent↗
PubMed1994

[A family case of HAM and HTLV-I carrier including two sisters presenting with myositis].

We reported a family case of HAM and HTLV-I carrier including two sisters presenting with myositis. Both the 65-year-old elder sister and her 53-year-old younger sister initially noted lumbago and developed difficulty in walking several years later. Neurologic examination revealed muscle weakness of the proximal parts of the upper and lower limbs (especially the latter). Mild hyperreflexia in all extremities, urinary disturbance and constipation were detected in the elder sister, while only urinary disturbance and constipation were seen in the younger. Anti-HTLV-I antibody in both serum and CSF was positive in both sisters. Muscle biopsy specimens showed features of myositis with perivascular, perimysial and endomysial lymphocyte infiltration. Although an association between HTLV-I and polymyositis had not yet been established, we think that our cases support such an association.

Aged↗
PubMed1993

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.

Antigens, CD↗
PubMed1993

Histochemical and ultrastructural pathology of skeletal muscle in a patient with abetalipoproteinemia.

Pathological examination was carried out of the skeletal muscle of an 8-year-old boy with abetalipoproteinemia. The patient complained of diarrhea, and showed a deficiency of betalipoprotein, decreased fat-soluble vitamins, acanthocytosis and a mild increase in serum creatine kinase. The prominent histochemical finding was punctate deposits of acid phosphatase activity in most fibers. Ultrastructural lesions revealed a number of giant lysosomes. Although these pathological findings seemed to be related to vitamin E deficiency, other pathological findings such as concentric laminated bodies or filamentous bodies were also observed. The clinical course and the changes in the pathological findings in our patient after long-term vitamin E therapy need to be observed.

Abetalipoproteinemia↗
PubMed1993

Experimental germanium dioxide-induced neuropathy in rats.

We report an experimental model of germanium dioxide (GeO2)-induced neuropathy in rats. More than 6 months administration of GeO2 to young rats produced neuropathy characterized by segmental demyelination/remyelination and nerve edema. Electron microscopic studies demonstrated that changes in Schwann cells, such as an increased cytoplasmic volume or disintegration of the cytoplasm, were the earliest pathological findings. Schwann cell mitochondria contained high electron-dense materials. Subsequent removal of necrotic Schwann cell debris and myelin by invading macrophages was evident. These findings suggested that the Schwann cells themselves are the primary target of the toxin. The deposition of electron-dense granules in the intra-axonal vesicles, which was suggestive of glycogen granules in mitochondria, was observed in the advanced stage of the neuropathy. The findings of endoneurial edema with splitting of myelin lamellae were noted at the early stage of demyelination. Nerve edema may be the result of GeO2-induced endothelial cell injury.

Animals↗