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Kunihiro Yoshida

Publications and source records attributed to Kunihiro Yoshida.

At least 19 recordsLinked to original sources
PubMed2006

A Japanese case of SCA14 with the Gly128Asp mutation.

Spinocerebellar ataxia type 14 (SCA14) is a rare form of autosomal dominant cerebellar ataxias caused by mutations in the protein kinase Cgamma gene (PRKCG). We have identified a Japanese patient with SCA14 who carried the Gly128Asp mutation in PRKCG. She first noticed gait unsteadiness at around age 42, and then her gait ataxia worsened very slowly for more than 20 years. At age 62, she was still ambulatory, although cerebellar ataxia was clinically evident. She is the second patient identified with the G128D mutation. Both patients with this mutation showed pure cerebellar ataxia. With only two families with SCA14 found in Japan prior to this study, the clinical features and disease-causing mutations in PRKCG are heterogeneous in the same ethnic background.

Adult↗
PubMed2006

A -16C>T substitution in the 5' UTR of the puratrophin-1 gene is prevalent in autosomal dominant cerebellar ataxia in Nagano.

The molecular bases of autosomal dominant cerebellar ataxia (ADCA) have been increasingly elucidated, but 17-50% of ADCA families still remain genetically undefined in Japan. In this study we investigated 67 genetically undefined ADCA families from the Nagano prefecture, and found that 63 patients from 51 families possessed the -16C>T change in the puratrophin-1 gene, which was recently found to be pathogenic for 16q22-linked ADCA. Most patients shared a common haplotype around the puratrophin-1 gene. All patients with the -16C>T change had pure cerebellar ataxia with middle-aged or later onset. Only one patient in a large, -16C>T positive family did not have this change, but still shared a narrowed haplotype with, and was clinically indistinguishable from, the other affected family members. In Nagano, 16q22-linked ADCA appears to be much more prevalent than either SCA6 or dentatorubral-pallidoluysian atrophy (DRPLA), and may explain the high frequency of spinocerebellar ataxia.

5' Untranslated Regions↗
PubMed2006

Dystonia, mental deterioration, and dyschromatosis symmetrica hereditaria in a family with ADAR1 mutation.

A family with dystonia associated with dyschromatosis symmetrica hereditaria (DSH), mental deterioration, and tissue calcification is described. The proband possessed an adenosine deaminase acting on the RNA 1 gene (ADAR1) mutation Gly1007Arg. This ADAR1 mutation could disturb RNA editing at Q/R sites of glutamate receptor in the brain and increase Ca(2+) influx into neurons, which is thought to induce dystonia and mental deterioration. The observations in our family raise the possibility that the ADAR1 mutation might be a direct cause or a predisposing factor for heredodegenerative dystonia. Further investigation of ADAR1 mutations will shed light on the genotype-phenotype correlation in DSH.

Adenosine Deaminase↗
PubMed2005

Thalamic stimulation for disabling tremor in a patient with spinocerebellar degeneration.

Thalamic stimulation alleviated coarse action tremor in a patient with spinocerebellar degeneration (SCD) and led to substantial improvement in daily functioning, though disability from ataxia remained. Intraoperative microrecording revealed a significant correlation between neuronal activity of the ventral intermediate nucleus (Vim) and tremor electromyograms. The tremor-correlated activities of Vim neurons and abolition of the tremor by Vim stimulation suggest that Vim may be related to the generation of action tremor in SCD. Thalamic stimulation can be a useful treatment option for SCD patients with disabling tremor.

Aged↗
PubMed2005

Dystonia and parkinsonism in GM1 type 3 gangliosidosis.

GM1 gangliosidosis is due to beta-galactosidase deficiency. Only patients with type 3 disease survive into adulthood and develop movement disorders. Clinical descriptions of this form are rare, particularly in non-Japanese patients. We describe four new patients and systematically analyze all previous reports found by a literature search and contacts with the authors for additional information. Generalized dystonia remained the predominant feature throughout the disease course and was often associated with akinetic-rigid parkinsonism. GM1 gangliosidosis must be considered as a cause of early-onset generalized dystonia, particularly in patients with short stature and skeletal dysplasia.

Adolescent↗
PubMed2005

Mutation analysis of the ADAR1 gene in dyschromatosis symmetrica hereditaria and genetic differentiation from both dyschromatosis universalis hereditaria and acropigmentatio reticularis.

Dyschromatosis symmetrica hereditaria (DSH) (also called "reticulate acropigmentation of Dohi") is a pigmentary genodermatosis of autosomal dominant inheritance. We have clarified for the first time four pathological mutations of the double-stranded RNA-specific adenosine deaminase gene (ADAR1 or DSRAD) in four DSH pedigrees. In this paper, we report 16 novel mutations containing six missense substitutions (p.V906F, p.K1003R, p.G1007R, p.C1036S, p.S1064F, p.R1078C), two splice site mutations (IVS2+2T>G, IVS8+2T>A), six frameshift mutations (p.H216fs, p.K433fs, p.G507fs, p.P727fs, p.V955fs, p.K1201fs), and two nonsense mutations (p.R426X, p.Q600X) found in Japanese patients with DSH. We did not establish any clear correlation between the clinical phenotypes and the genotypes of ADAR1 gene mutations in our examination of 16 cases plus four pedigrees. None of the different mutations identified in our studies of 20 cases suggested any founder effect. Furthermore, we did not identify any mutations in the ADAR1 gene of three patients with dyschromatosis universalis hereditaria or three patients with acropigmentatio reticularis, indicating that the two diseases are completely different from DSH, although they have sometimes been suggested to be phenotypical variations of DSH.

Adenosine Deaminase↗
PubMed2004

Up-regulation of mitogen activated protein kinases in mdx skeletal muscle following chronic treadmill exercise.

Dystrophin, a product of the Duchenne muscular dystrophy gene, is a cytoskeletal protein of skeletal and cardiac muscle fibers. Dystrophin-deficient muscle fibers are abnormally vulnerable to mechanical stress including physical exercise, which is a powerful stimulator of mitogen-activated protein kinases (MAPKs). To examine how treadmill exercise affects MAPK family members in dystrophin-deficient skeletal muscle, we subjected both mdx mice, an animal model for Duchenne muscular dystrophy, and C57BL/10 mice to treadmill exercise and examined the phosphorylated protein levels of extracellular-signal regulated kinase (ERK1/2), p38 MAPK and c-Jun N terminal kinase 1 and 2 (JNK1 and JNK2) in the gastrocnemius muscle. Phosphorylation of ERK1/2, p38 MAPK and JNK2, but not JNK1, increased more in the muscles of exercise trained mdx mice than in muscles of trained C57BL/10 or untrained mdx mice. These results show that physical exercise aberrantly up-regulates the phosphorylated form of ERK1/2, p38 MAPK and JNK2 in dystrophin-deficient skeletal muscle and that their up-regulation might play a role in the degeneration and regeneration process of dystrophic features.

Analysis of Variance↗
PubMed2004

Regional features of autosomal-dominant cerebellar ataxia in Nagano: clinical and molecular genetic analysis of 86 families.

The frequency of autosomal-dominant cerebellar ataxia (ADCA) subtypes was examined in 86 unrelated families originating from Nagano prefecture. In Nagano, the prevalence of spinocerebellar degeneration (SCD) was approximately 22 per 100,000 population. Among ADCA families, SCA6 was the most prevalent subtype (16 families, 19%), followed by DRPLA (nine families, 10%), SCA3/MJD (three families, 3%), SCA1 (two families, 2%), and SCA2 (one family, 1%). No families with SCA7, SCA12, or SCA17 were detected. Compared with other districts in Japan, the prevalence of SCA3/MJD was very low in Nagano. More interestingly, the ratio of genetically undetermined ADCA families was much higher in Nagano (55 families, 65%) than in other districts in Japan. These families tended to accumulate in geographically restricted areas such as Kiso, Saku, and Ina, indicating that the founder effect might be responsible for the high frequency of ADCA in these areas. Most patients clinically showed slowly progressive pure cerebellar ataxia of late-onset (ADCA III). In the case of 36 patients from 36 genetically undetermined ADCA III families, however, no one was completely consistent with the founder allele proposed for 16q-ADCA. These results indicate that there might be genetically distinct ADCA subtypes in Nagano.

Cerebellar Ataxia↗
PubMed2004

Efficacy of tacrolimus in treatment of polymyositis associated with myasthenia gravis.

We report a patient with polymyositis (PM) associated with myasthenia gravis (MG). Both disorders had been controlled for around 15 years by oral prednisolone and a cholinesterase inhibitor following surgical removal of invasive thymoma and radiotherapy, but muscular weakness due to myalgia and an increase in serum levels of myogenic enzymes, mainly ascribable to the recurrence of PM, reappeared immediately after cessation of these drugs, which was done because the patient had multiple bone fractures and severe osteoporosis due to the long-term corticosteroid therapy. Oral tacrolimus was therefore tried, and produced an improvement in muscular symptoms in association with normalization of myogenic enzymes. PM associated with MG as in this patient might be the best indication for tacrolimus, considering its efficacy in MG, but this drug should also be actively considered as a therapeutic option in refractory cases of PM alone, particularly when either corticosteroids or other immunosuppressive agents are not usable.

Adrenal Cortex Hormones↗
PubMed2004

Late-onset autosomal recessive limb-girdle muscular dystrophy with rimmed vacuoles.

We report on two siblings with late-onset, limb-girdle muscular dystrophy (LGMD) inherited in an autosomal recessive manner. The LGMD was characterized by many rimmed vacuoles and reduced expression of the laminin beta1 chain in skeletal muscle. Both patients developed a progressive wasting and weakness of limb-girdle muscles in the late forties or early fifties; their facial, ocular, bulbar, and cardiac muscles were not involved. Histopathology of skeletal muscles biopsies showed typical dystrophic changes with many rimmed vacuoles. The immunoreactivity of the laminin beta1 chain was reduced in the muscle fibers, while dystrophin, sarcoglycans, beta-dystroglycan, dysferlin, and other laminin components were normally expressed. A mutation search revealed that no mutation existed in the coding region of the calpain 3, telethonin and UDP-N-acetylglucosamine 2-epimerase/N-acetylmanosamine kinase (GNE) genes. We conclude that this autosomal recessive LGMD is unknown and characterized by its late onset, rimmed vacuoles and reduction of the laminin beta1 chain in muscle fibers.

Actin Cytoskeleton↗
PubMed2003

Periodic alternating nystagmus and rebound nystagmus in spinocerebellar ataxia type 6.

We report on a family with ataxia type 6 (SCA6) showing peculiar oculomotor symptoms. The proband presented with periodic alternating nystagmus (PAN), and her 2 brothers had rebound nystagmus and gaze-evoked nystagmus. They carried the identical mutation (the number of expanded CAG repeat, 24) in the CACNA1A gene. The intrafamilial variability of oculomotor symptoms may be ascribed to factors other than CAG repeat expansion size in SCA6.

Calcium Channels↗
PubMed2003

Aceruloplasminemia with juvenile-onset diabetes mellitus caused by exon skipping in the ceruloplasmin gene.

We herein report a case of aceruloplasminemia in a 27-year-old man who had a 10-year history of diabetes mellitus. The patient developed a convulsion, most likely as a result of hypoglycemia. Unexpectedly, this episode left him in a prolonged state of unconsciousness, which necessitated neurological testing and imaging. Brain MRI showed bilateral hypo-intensities in the basal ganglia and thalamus. Molecular analysis revealed a novel splicing mutation in the ceruloplasmin (CP) gene that would result in the skipping of exon 3 during transcription. This case suggests that diabetes associated with aceruloplasminemia can become manifest in the teens.

Adult↗
PubMed2003

[Neuropsychiatric systemic lupus erythematosus associated with anti-phospholipid syndrome, showing massive intracranial calcifications].

We report a 46-year-old woman who extensively showed intracranial calcifications possibly due to neuropsychiatric systemic lupus erythematosus (NPSLE) and antiphospholipid syndrome (APS). She had been treated with oral prednisolone for SLE since age 15, and experienced two abortions due to APS at ages 28 and 35 respectively. After a convulsion attack due to NPSLE at age 30, she had been suffering from dysarthria and choreic movement in her extremities. On admission to our hospital brain CT demonstrated extensive and symmetrical calcifications bilaterally in basal ganglia, subcortical white matter of the frontal lobe and dentate nuclei. She was shown to have neither metabolic nor congenital disorders causing these intracranial abnormalities. In this patient both NPSLE and APS, therefore, might have contributed to the remarkable intracranial calcifications in a long clinical course.

Antiphospholipid Syndrome↗
PubMed2002

Quantitative evaluation of expression of iron-metabolism genes in ceruloplasmin-deficient mice.

Aceruloplasminemia is an autosomal recessive disorder caused by mutations in the ceruloplasmin (CP) gene, and is characterized by a unique combination of neurovisceral iron overload and iron deficiency anemia. We generated CP-deficient (CP(-/-)) mice to investigate the functional involvement of CP in iron metabolism. The mice showed a marked iron overload in the liver and mild iron deficiency anemia. We examined the expression of iron-metabolism genes in the duodenum and liver using TaqMan RT-PCR. The divalent metal transporter 1 (DMT1), ferroportin 1 (FPN1), and hephaestin (HEPH) genes were not up-regulated in the duodenum from CP(-/-) mice. These data suggest that the mechanism of hepatic iron overload in aceruloplasminemia is quite different from that in hemochromatoses and atransferrinemia. In the liver, CP(-/-) mice showed no increase of gene expression for DMT1 and transferrin receptors (TFR and TFR2), indicating that none of the known pathways of iron uptake is activated in hepatocytes of CP(-/-) mice. This result supports the hypothesis that CP mainly acts to release iron from cells in the liver.

Anemia, Iron-Deficiency↗
PubMed2002

Progression of dystrophic features and activation of mitogen-activated protein kinases and calcineurin by physical exercise, in hearts of mdx mice.

We have previously demonstrated that calcineurin and p38 mitogen-activated protein kinase (MAPK) are up-regulated in the hearts of mdx mice. However, the degree of up-regulation observed was variable, which may reflect variable levels of daily physical activities among the mice. To investigate whether or not exercise affects dystrophic features and activates intracellular signaling molecules in mdx hearts, we subjected mdx and C57BL/10 mice to treadmill exercise and examined intracellular signaling molecules in cardiac muscles, at the protein level. The heart to body weight ratio was significantly increased in exercised mdx mice. Histopathology in exercised mdx hearts showed extensive infiltration of inflammatory cells, together with increases in interstitial fibrosis and adipose tissues, all of which were not observed either in exercised C57BL/10 or non-exercised mdx hearts. Phosphorylated p38 MAPK, phosphorylated extracellular signal-regulated kinase 1/2 and calcineurin, but not phosphorylated c-Jun N-terminal kinase 1, were up-regulated in exercised mdx hearts compared to exercised C57BL/10 or non-exercised mdx hearts. These data suggest that physical exercise accelerates the dystrophic process through activation of intracellular signaling molecules in dystrophin-deficient hearts.

Animals↗
PubMed2002

Aceruloplasminemia: new clinical, pathophysiological and therapeutic insights.

Aceruloplasminemia is an autosomal recessive disease of iron overload associated with mutation(s) in the ceruloplasmin gene. We report here a new case of aceruloplasminemia in a woman who is a compound heterozygote for two new mutations. Besides this novel genotypic profile, this observation provides new insights on: (i) iron metabolism with normal erythroid repartition, in the absence of serum non-transferrin-bound iron and with an increase of 59Fe plasma clearance; (ii) hepatic abnormalities associated with the presence of iron-free foci; (iii) the therapeutic management of the disease, chronic subcutaneous infusion of deferrioxamine being remarkably effective at reducing hepatic iron overload.

Ceruloplasmin↗
PubMed2002

Glial fibrillary acidic protein is greatly modified by oxidative stress in aceruloplasminemia brain.

Aceruloplasminemia is an autosomal recessive disorder of iron metabolism caused by mutations in the ceruloplasmin (Cp) gene. The neuropathological hallmark of this disease is intracellular iron overload, which is thought to lead to neuronal cell death through increased oxidative stress. We evaluated and characterized protein oxidation in the brain of a patient with this disease. The protein carbonyl content in the cerebral cortex of the patient was elevated compared to controls. Furthermore, peptide mass fingerprinting and partial amino acid sequencing identified glial fibrillary acidic protein (GFAP) as the major carbonylated protein in the cerebral cortex of the patient. In conjunction with the facts that Cp mainly localizes to astrocytes in the central nervous system and that astrocytes are loaded with much more iron than neurons in the cerebral cortex, our findings indicate that Cp deficiency may primarily damage astrocytes. We speculate that the dysfunction of astrocytes may be causatively related to neuronal cell loss in aceruloplasminemia.

Brain↗