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Biomedical subjects

M Suehara

Publications and source records attributed to M Suehara.

At least 19 recordsLinked to original sources
PubMed2003

Gap junction protein beta 1 (GJB1) mutations and central nervous system symptoms in X-linked Charcot-Marie-Tooth disease.

OBJECTIVES: To clarify the clinical variability, including central nervous system (CNS) involvement, in X-linked Charcot-Marie-Tooth disease (CMTX) patients. MATERIAL AND METHODS: We clinically, pathologically and genetically studied six CMTX patients with distinct symptoms and four different GJB1 mutations. RESULTS: One patient with Val63Ile had deafness, low intelligence, saccadic eye movement, upper extremity distal dominant muscle weakness and normal sensation. Another patient with Glu186Lys had severe sensorineural deafness at the age of 6 years, but did not develop muscle weakness until the age of 20 years. Two patients with Arg22Gln had typical CMT1A-like clinical features, no CNS symptoms and obvious onion bulb formations. Two siblings with deletion of the entire GJB1 gene had mild to moderate lower extremity muscle weakness and sensory disturbance without CNS involvement. CONCLUSION: These findings suggest that some gain of function mutations of GJB1 may be related to CNS symptoms because the patients with GJB1 deletion only had peripheral neuropathy, although other unknown associated factors may contribute to their clinical phenotypes.

Adult↗
PubMed2001

Phenotypic variation in a large Japanese family with Miyoshi myopathy with nonsense mutation in exon 19 of dysferlin gene.

Miyoshi myopathy, an autosomal recessive muscular dystrophy involving distal muscles, is caused by dysferlin mutations. We present clinical and genetic studies of two men and six women, aged 25-83 years, from a Japanese family with consanguineous marriages. Onset was between ages 17 and 59 years. Six of the patients had muscle involvement typical of Miyoshi myopathy, one initially had severe proximal muscle involvement, and one had scapuloperoneal-type muscle involvement. Three patients showed steppage gait. Genetic linkage analysis identified a maximum lod score of 3.34 (θ=0.00) at marker D2S292 in 2p13. Analysis of dysferlin revealed the mutation G2090T (Glu573Stop) in exon 19 in all affected patients. This is the largest Japanese family with Miyoshi myopathy showing intrafamilial phenotypic variation and sharing a common mutation in dysferlin.

Adult↗
PubMed2001

Frameshift mutation in the collagen VI gene causes Ullrich's disease.

Patients with Ullrich's disease have generalized muscle weakness, multiple contractures of the proximal joints, and hyperextensibility of the distal joints. Recently, we found a deficiency of collagen VI protein in two patients with Ullrich's disease. In this study, we detected a homozygous 26 bp deletion in exon 14 of the collagen VI alpha 2 gene (COL6A2) in one patient. This mutation causes a frameshift and a premature termination codon, and results in a truncated collagen VI alpha 2 chain. Our data suggest that at least some cases of Ullrich's disease result from recessive mutations in COL6A2.

Adult↗
PubMed2001

Phenotypes of X-linked Charcot-Marie-Tooth disease and altered trafficking of mutant connexin 32 (GJB1).

To clarify the pathomechanism in three patients with X-linked Charcot-Marie-Tooth disease (CMTX) and unique clinical features, we studied three connexin (Cx) 32 (GJB1) mutants with respect to cellular localization in cultured cells. Wild-type Cx32 and three Cx32 mutants (Va163Ile and Glu186Lys, obtained from CMTX patients with hearing impairment; and Arg22Gln, obtained from a CMTX patient with a fair number of onion-bulb formations) were transfected to rat pheochromocytoma cells (PC12). We investigated the expression of Cx32 protein in each clone by immunoblotting and immunohistochemical staining. While Cx32 protein with the Arg22Gln mutation was detectable immunohistochemically only in the cytoplasm, Cx32 protein with the Va163Ile or Glu186Lys mutation was detected in both the plasma membrane and the cytoplasm. Cx32 protein with the wild-type sequence was detected mostly in the plasma membrane, with plaques indicating the existence of active gap junction formation. These three Cx32 mutations associated with CMTX patients with unique clinical and pathological findings caused altered trafficking of the Cx32 protein. These altered expressions indicated loss of active gap junction formation with different expression abnormalities in these CMTX patients.

Animals↗
PubMed2000

Histopathological analysis of four autopsy cases of HTLV-I-associated myelopathy/tropical spastic paraparesis: inflammatory changes occur simultaneously in the entire central nervous system.

Although brain lesions have been described in some cases with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), little is known about the nature of brain lesion and its relation to the spinal cord lesion. In the present study, we performed histopathological analysis of the brain and the spinal cord of four autopsied cases with HAM/TSP to clarify the relationship between the brain and the spinal cord lesions. In two cases with active-chronic inflammation in the spinal cord, perivascular inflammatory infiltration was also seen in the brain, and the composition of cell subsets was similar both in the spinal cord and in the brain. No active inflammatory change was seen in the brain in two cases with inactive-chronic spinal cord lesions. Inflamed vessels were distributed mainly in the deep white matter and in the area between cerebral cortex and white matter of the brain. In the spinal cord inflamed vessels were mainly seen in the bilateral lateral and the ventral posterior columns. Parenchymal infiltration was diffused in the spinal cord but very sparse in the brain, suggesting the importance of parenchymal infiltration in the destruction of tissues. These results suggest that inflammatory changes occurred simultaneously in the spinal cord and in the brain, and that distribution of inflamed vessels closely correlated with the characteristics of vascular architecture of the brain and the spinal cord, which lead to a slow blood flow. This study may help promote a better understanding of the pathogenesis of HAM/TSP.

Aged↗
PubMed2000

[Tracheopulmonary-subcutaneous fistula associated with anaerobic subcutaneous abscess on mechanical ventilator support in a patient with Duchenne muscular dystrophy].

A 29-year-old Japanese man with Duchenne muscular dystrophy was placed on a mechanical ventilator support at 23 years of age and admitted to our hospital at 25 years of age. He had severe neck contracture deviated to the left side which resulted in dysphagia and microaspiration. At 29 years of age, he developed left lobar pneumonia accompanied by slight fever, back pain and a foul odor from the patient's sputum. Although the patient received broad spectrum antibiotics, pneumonia disseminated to the right lung. A week later, chest computed tomography was conducted which revealed tracheopulmonary-subcutaneous fistula, and a massive subcutaneous abscess with free air production. Drainage from the subcutaneous abscess was done through a chest tube; however, respiratory hypercapnia was not corrected and the patient died. From the culture of drained fluid, anaerobic bacteria including peptostreptococcus sp. were detected. This tracheopulmonary-subcutaneous fistula was thought to be caused by chronic microaspiration of mouth anaerobes, mechanical injury of the trachea under long term ventilator support, and decreased deep back muscle bulk with substitution of adipose tissue around the chest.

Abscess↗
PubMed1999

A novel MPZ gene mutation in dominantly inherited neuropathy with focally folded myelin sheaths.

We found the association of a heterozygous novel MPZ gene point mutation, Ile62Phe in exon 2, with autosomal dominant motor and sensory neuropathy with focally folded myelin sheaths. Family study revealed that de novo Ile62Phe mutation on the MPZ gene occurred in the proband and was inherited by her children with early onset slowly progressive neuropathy. Our study suggests that the characteristic pathologic findings of the sural nerve in these patients are closely related to the site and nature of amino acid substitutions of the MPZ gene.

Child↗
PubMed1999

Localized scleroderma associated with progressing ischemic stroke.

We present a 73 year-old Japanese woman with localized scleroderma involving the right side of the scalp accompanied by continuous tingling pain, who developed insidiously progressive left hemiparesis. In magnetic resonance imaging of the brain, an infarct first appeared in the watershed region of the right middle cerebral artery territory and subsequently extended to deep white matter accompanied by scattered hemorrhages. Focal stenosis in the M2 portion of the right middle cerebral artery was revealed on magnetic resonance angiography, and the distal vessels were only shown faintly. A biopsy specimen from the sclerotic scalp lesion showed obvious thickening of vessel walls and mild mononuclear cell infiltration. We believe that the progressing ischemic stroke was caused by hemodynamic disturbances from localized sclerotic obstruction of the middle cerebral artery, with an autoimmune pathogenesis.

Aged↗
PubMed1999

Lambert-Eaton myasthenic syndrome with ophthalmoparesis and pseudoblepharospasm.

We report a patient initially diagnosed as having ocular myasthenia gravis who showed progressive ophthalmoparesis and pseudoblepharospasm together with positive acetylcholine receptor antibodies. Repeated evaluation with high-frequency repetitive stimulation revealed an incremental response and elevated titers of antibodies against presynaptic calcium channels, confirming Lambert-Eaton myasthenic syndrome. Systemic evaluation revealed no malignant neoplasm but revealed euthyroid Hashimoto's disease. Immunomodulative therapy including plasma exchange and administration of an immunosuppressent (azathioprine) combined with a potassium-channel blocker (3,4-diaminopyridine) reduced the ocular abnormalities. We conclude that the ocular manifestations in this patient were probably caused by Lambert-Eaton myasthenic syndrome.

Autoantibodies↗
PubMed1999

Germline mosaicism of MPZ gene in Dejerine-Sottas syndrome (HMSN III) associated with hereditary stomatocytosis.

We report on two sisters with Dejerine-Sottas syndrome (DSS) who had a heterozygous Gly 167 Arg mutation in the myelin protein zero (MPZ) gene and hereditary stomatocytosis (HSt). Genetic haplotype analysis suggested that the allele with the MPZ gene mutation originated from maternal lineage. However, the parents, who were normal clinically and electrophysiologically, had no mutation in the MPZ gene. Therefore, the MPZ gene mutation in these sisters was due to germline mosaicism of the MPZ gene in their mother. Stomatocytosis was detected in their mother and a sister who had no neurological symptoms, and therefore autosomal dominant HSt was suspected in this family. As stomatocytosis is very severe in our patients with DDS, we speculate that the association of DSS with stomatocytosis is coincidental but may have additively affected erythrocyte morphology. To our knowledge, these are the first familial cases of DSS with a mutation due to germline mosaicism of the MPZ gene to be reported.

Adult↗
PubMed1999

Gene for hereditary motor and sensory neuropathy (proximal dominant form) mapped to 3q13.1.

Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) has been reported as a new type of HMSN with the disease gene locus in the 3p14.1-q13 region. To further narrow down the gene locus, we performed fine linkage mapping using the linkage disequilibrium method. Analysis of DNA marker haplotypes and genetic cross-over sites showed the disease gene locus to be in the 3.1 cM interval bracketed by D3S1591 and D3S1281. Linkage disequilibrium analysis with DISMULT using 9 marker loci jointly in this region showed a lod score of 4.93 (P < 0.00000095). Consequently, the HMSN-P gene almost certainly lies on chromosome 3q13.1 and shows evidence of linkage disequilibrium.

Chromosome Mapping↗
PubMed1999

[A patient with intractable myasthenia gravis successfully treated with total lymphoid irradiation].

We report a 20-year-old man with intractable myasthenia gravis successfully treated with total lymphoid irradiation (TLI). An encapsulated thymoma in the anterior mediastinum was resected as extended thymectomy by video-assisted thoracoscopic surgery at 2 months after the onset of ptosis and muscle weakness. Following treatments, such as ambenonium hydrochloride, an immunosuppression therapy (prednisolone and azatioprine), 5 courses of immunoadsorption therapy, and a high dose of cyclophosphamide and methylprednisolone, did not make persistent improvement of myasthenic symptoms. Ageusia occurred twice prior to myasthenic crises and subsided with other myasthenic symptoms after treatments. Steroid psychosis and secondary Cushing's syndrome made us to reduce the dose of prednisolone. Post-operative residual, recurrent, or metastatic thymus was not unveiled, then we added the low dose fractionated irradiation (1.5 Gy x 12 = 18 Gy) to the mediastinum. Three months after the irradiation, however, a crisis occurred and the titer of anti-acetylcholine receptor antibody increased up to 100 nmol/l. Therefore, we performed TLI (Mantle; 1.5 Gy x 9 = 13.5 Gy, paraaortic and inverted-Y; 1.5 Gy x 14 = 21 Gy), which brought about persistent improvement of myasthenic symptoms with decrease in the titer of anti-acetylcholine receptor antibody.

Adult↗
PubMed1998

HLA class I and class II of the Nivkhi, an indigenous population carrying HTLV-I in Sakhalin, Far Eastern Russia.

The Nivkhi are a native people isolated in the Nogliki region of Sakhalin, Far East Russia, where our group recently recognized human T-cell lymphoma virus type I (HTLV-I) infection. In order to trace the Nivkhi's ethnic background and the HTLV-I carriers, we investigated HLA class I and II allele types of 53 Nivkhi (including four HTLV-I carriers). Major HLA class I alleles of the Nivkhi were A*24, A*02, B*40, B*48, B*27, B*35 with allele frequencies similar to the Orochon, a native people isolated in Northeast China. Major Nivkhi class II alleles were DRB1*0901, DRB1*1401, DRB1*1201, DRB1*1106 with allele frequencies similar to the Ainu in Hokkaido, Japan, but dissimilar to other Asian Mongoloids, including the general Japanese population. The same HLA class I and II allele frequencies are found in both Nivkhi HTLV-I carriers and the background population. A dendrogram of HLA class I alleles showed that the Nivkhi were closely related to the Orochon and Yakut, and remotely related to the Japanese, Ainu and other Asian Mongoloids. Interestingly, the Nivkhi were intermediately related to the Amerindians (Inuit, Tlingit and Andeans), a relationship closer than to the Japanese and Asian Mongoloids. These results suggested the Nivkhi might be related to some genetic group of Northeast Asian Mongoloids like the Orochon and Yakut, being infected with HTLV-I in the distant past before diverging into the current major Mongoloid ethnic groups.

Adult↗
PubMed1998

Afterdischarges following F waves observed in a patient with tetanus.

We report a case of non-fluminent and mildly affected tetanus patient who showed afterdischarges following F waves in the affected extremity. The afterdischarges occurred following F waves and showed different configuration respond to each stimuli. Diazepam was also effective for spasms of our patient. This finding disappeared after treatment and showed a good correlation to clinical symptoms. These observations suggest that afterdischarges following F waves are induced by tetanus toxin which puts most of the motor neuron pool in a hyperactive state through its own action to the motor nerve including the spinal motor neuron.

Action Potentials↗
PubMed1997

Antibodies to potassium channels of PC12 in serum of Isaacs' syndrome: Western blot and immunohistochemical studies.

We investigated the pathophysiology of nerve hyperexcitability in a patient with Isaacs' syndrome, who had typical clinical and electromyographic features and responded to plasma exchange. Immunoblotting and immunohistochemistry studies showed that antibodies from this patient reacted with the lysate of a neuronal cell line (PC12). In Western blots, constituents of the patient's serum, particularly immunoglobulin M, reacted with proteins of approximately 50 and 18 kDa, whereas the control serum did not. A cross-linking study with alpha-dendrotoxin (7 kDa) showed a 57 kDa protein-peptide complex. Immunohistochemistry showed that the patient's serum reacted with PC12 cells and human intramuscular nerve axons. Our findings indicate that in Isaac's syndrome nerve hyperexcitability is the result of the immunological involvement of the voltage-dependent potassium channels located along the distal motor nerve or at the nerve terminal.

Aged↗