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Biomedical subjects

I Higuchi

Publications and source records attributed to I Higuchi.

At least 91 records · Page 5Linked to original sources
PubMed1997

Facioscapulohumeral muscular dystrophy: clinical diversity and genetic abnormalities in Japanese patients.

We studied 71 Japanese individuals, 42 patients (30 familial and 12 sporadic) suspected to have facioscapulohumeral muscular dystrophy (FSHD) and 29 family members, clinically and genetically using the chromosome 4qter DNA marker p13E-11. Early onset FSHD was detected in 7 patients, tortuosity of retinal arterioles and hearing impairment in 3 patients, progressive respiratory failure in 3 patients and limb-girdle type muscular weakness in 6 patients. Thirty-six (85.7%) FSHD patients, 3 asymptomatic family members and 1 of 35 healthy volunteers showed EcoRI digestion fragments shorter than 28kb. New mutations were detected in 25% of the patients with shorter EcoRI fragment. The age of disease onset appeared younger with successive generations in 6 parent-child pairs in FSHD families. We confirmed the existence of phenotypic and genetic diversities in Japanese patients with FSHD. It is still difficult to explain the phenotypic diversity merely by the size of the abnormal EcoRI fragment detected with the p13E-11 probe.

Arterioles↗
PubMed1997

[Recent progress of molecular immunology on inflammatory myopathy].

The pathogenesis of polymyositis(PM), T-cell-mediated disease, and dermatomyositis(DM), humoral immunity-mediated disease, has not been clearly understood. Retroviruses(HIV, HTLV-I) may play a important role in some PM/DM patients. HTLV-I provirus was detected in infiltrating CD4+ lymphocytes, but not within the muscle fibers by PCR in situ hybridization. It is suggested that HTLV-I-associated PM 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. Inclusion body myositis(IBM) is characterized pathologically by vacuolated muscle fibers containing paired-helical filaments(PHFs) similar to Alzheimer-disease brain. Furthermore, prion protein and mRNA are abnormally accumulated in IBM muscle.

Autoimmunity↗
PubMed1996

The main HTLV-I-harboring cells in the muscles of viral carriers with polymyositis are not macrophages but CD4+ lymphocytes.

We have analyzed muscle biopsy specimens from polymyositis patients who are also positive for human T cell lymphotropic virus type I (HTLV-I) using both immunohistochemistry for surface antigens of lymphocytes and macrophages and in situ polymerase chain reaction for HTLV-I proviral DNA on the same sections. We found HTLV-I in CD4+ cells but not in macrophages. This finding suggests that most of the HTLV-I-containing CD4+ cells are not macrophages but lymphocytes.

CD4-Positive T-Lymphocytes↗
PubMed1996

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.

Adult↗
PubMed1996

HAM/TSP: recent perspectives in Japan.

Neurologic diseases associated with human T-cell lymphotropic virus type I (HTLV-I) infection have a clinical spectrum that includes myelopathy (HTLV-I-associated myelopathy/tropical spastic paraparesis, HAM/TSP) as the central manifestation. Many clinical signs of involvement outside the central nervous system (CNS) have been described in some patients with HAM/TSP and have triggered and advanced the discovery of some HTLV-I-associated concepts in HTLV-I-infected individuals without signs of CNS involvement. Most of these HTLV-I-associated diseases exhibit common viroimmunologic characteristics that include a distributional bias of HTLV-I activation between the blood flow and the affected lesions and accumulated cellular immune responses in the lesions. These facts suggest that the vulnerable tissue(s) in some HTLV-I-infected individuals may not be defined by an exclusive tissue specificity, but that common steps of HTLV-I-versus-host interactions may have an important role in the pathologic process(es) in these diseases. This review summarizes the recent perspectives of the clinical spectrum and the pathogenesis of HAM/TSP in Japan. Furthermore, the feasible pathogenic involvement of cellular interactions between infected cells and responding immunocompetent cells in the affected tissues is emphasized.

Adult↗
PubMed1996

Morphological and histochemical study of nonhemiplegic muscle in acute stroke patients manifesting respiratory failure.

There is little information on skeletal muscle changes in patients with acute stroke. We performed morphological and histochemical examinations of nonhemiplegic sternothyroid muscles biopsied at the time of tracheostomy from 13 patients with acute stroke manifesting acute respiratory failure. Degenerating and regenerating fibers were observed in all 13 specimens. Following characteristic myopathic changes suggestive of mitochondrial abnormalities were also demonstrated in a majority of patients. Namely, ragged-red fibers, focal increase in NADH-TR activity in subsarcolemmal areas and increases in acid phosphate activity were found. The changes were similar but extremely slight in control patients with acute respiratory failure due to causes other than stroke and were absent in the other control patients with adenomatous thyroid tumor. The severity and extent of the histopathological changes in the muscle fibers in patients with acute stroke were closely correlated with the duration of hypoxemia but not with such items as type of stroke, site of cerebral lesion, consciousness level, days of biopsy after the stroke, clinical outcome, levels of serum creatine kinase, myoglobin and PaO2. This acute nonhemiplegic muscle involvement was considered to be a very common complication in severe stroke patients.

Acute Disease↗
PubMed1996

Lack of immunoreactivity for myoglobin in skeletal muscle of acute stroke patients.

Sternothyroid muscle biopsy specimens, obtained during tracheostomies from 15 patients with acute stroke and respiratory failure, were examined immunohistochemically to immunoreactivity to myoglobin (Mb). A marked decrease or lack of Mb immunoreactivity in association with hyaline degeneration was observed in 0.8 to 44.4% of the muscle fibers on both the paretic and non-paretic sides of all patients. The percentages of negative staining for Mb were less than 3.1% in 5 patients with acute respiratory failure due to causes other than stroke. The pattern and incidence of attenuated Mb immunoreactivity in the muscle fibers was found to be distinctively different in the two patients groups. In one group of 5 patients, a large number of muscle fibers (24.8 +/- 15.6%) had no Mb staining and were clearly bordered and grouped. In another 10-patient group, only a limited number of muscle fibers (3.3 +/- 2.5%) had no staining for Mb and these fibers were scattered. Four patients in the former group had catastrophic outcomes, while all the patients in the latter group survived. Ischemia, produced by an increase in catecholamines, and the consequent vasoconstriction, rather than hypoxemia seemed to be the cause of the negative immunoreactivity for Mb in the group pattern. In contrast, hypoxemia may have caused the scattered pattern of negative Mb immunoreactivity. It was concluded that negative immunostaining for Mb in muscle fibers represents a common and characteristic complication in acute stroke patients.

Acute Disease↗
PubMed1996

Therapeutic trials in 200 patients with HTLV-I-associated myelopathy/ tropical spastic paraparesis.

We report here the results of therapeutic trials in 200 patients with HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) conducted in our department between 1986 and 1993. Motor disability grades were improved by more than one grade in 69.5% (91/131) of patients by oral administration of prednisolone, 50% (3/6) by eperisone hydrochloride only, 43.8% (7/16) by blood purification (lymphocytapheresis and plasmapheresis), 40.0% (2/5) by intrathecal injection of hydrocortisone, 30.0% (3/10) by intravenous injection of high-dose methylprednisolone, 23.3% (10/43) by interferon-alpha (intramuscular injection and inhalation), 22.2% (2/9) by azathioprine, 20.0% (4/20) by high-dose vitamin C, 16.0% (4/25) by erythromycin, 12.5% (3/24) by salazosulfapyridine, 11.8% (2/17) by mizoribine, 7.1% (1/14) by fosfomycin, and 6.3% (1/16) by thyrotropin releasing hormone. No critical side effects of these therapies were seen with the exceptions of one patient with adult respiratory distress syndrome due to cytomegalovirus infection and one patient with drug-induced hepatitis/hepatic failure. Selection of these treatments for patients with HAM/ TSP must be considered on the basis of age, sex, disease severity and complications to reduce adverse events and to improve quality of life. Although the results were a synopsis of different treatments given to 200 patients with HAM/ TSP as an open trial, we consider this the first report of a large-scale therapeutic trial in patients with HAM/TSP. The results of this study indicate that immunomodulatory therapies have some beneficial effects in HAM/TSP, and the functions of these agents are related to the pathophysiology of this disease.

Administration, Oral↗
PubMed1995

Cardiac involvement in mitochondrial diseases. A study on 17 patients with documented mitochondrial DNA defects.

BACKGROUND: Mutations of mitochondrial DNA have been demonstrated as causes of human mitochondrial diseases. While these disorders typically involve multiple organs, the effect of mitochondrial mutations on the heart has not been systematically studied. METHODS AND RESULTS: We studied mitochondrial mutations and cardiac changes in 17 patients with Kearns-Sayre syndrome; ocular myopathy; myoclonus epilepsy with ragged red fibers (MERRF); and mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). Cardiac involvement was evaluated by chest radiograph, ECG, His-bundle electrogram, and echocardiogram. All 3 patients with Kearns-Sayre syndrome had large deletions of mitochondrial DNA and disturbances in cardiac conduction. ECG abnormalities were found in 2 of 6 patients with ocular myopathy who showed large deletions of mitochondrial DNA. All 3 patients with MERRF had an A-to-G mutation at nucleotide position 8344; 2 had cardiomegaly, asymmetrical septal hypertrophy, and diffuse hypokinesis of the left ventricle. One patient with asymmetrical septal hypertrophy developed dilated cardiomyopathy 2 years later. All 5 patients with MELAS had an A-to-G mutation at nucleotide position 3243, and 2 had symmetrical left ventricular hypertrophy with or without abnormal wall motion. CONCLUSIONS: The clinical features of cardiac involvement in mitochondrial diseases vary in the different subgroups of these disorders. Particular mitochondrial mutations can cause characteristic cardiac abnormalities.

Adult↗
PubMed1995

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.

Adult↗
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↗