Gen Sobue

Japan Science and Technology Agency (JST), Edo, Tokyo, Japan

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Publications (811)3090.13 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: There are two distinct phenotypes of multiple sclerosis (MS) in Asians, optic-spinal MS (OSMS) and conventional MS (CMS). In 2004, we performed the fourth nationwide epidemiological survey of MS. The epidemiological features were reported elsewhere; here we report the characteristic features of patients with each MS phenotype, classified according to the clinically estimated sites of involvement and MRI findings. Among 1493 MS patients collated, 57.7% were classified as having CMS and 16.5% were classified as having OSMS. Based on MRI findings, MS patients were further subdivided into those with OSMS with or without longitudinally extensive spinal cord lesions (LESCLs) and those with CMS with or without LESCLs. Although disease duration did not differ significantly among the four groups, EDSS scores were significantly higher in patients with LESCLs than in those without LESCLs, irrespective of OSMS or CMS phenotype. Similar trends were found for the frequencies of bilateral visual loss, transverse myelitis, and marked CSF pleocytosis and neutrophilia. Increased IgG index, brain lesions fulfilling the Barkhof criteria and secondary progression were more commonly found in CMS patients than in OSMS patients, while negative brain MRIs were more commonly encountered in OSMS patients than CMS patients, irrespective of the presence of LESCLs. These findings suggest that demographic features not only vary based on CMS or OSMS phenotype, but also with the presence or absence of LESCLs, and that nonetheless, these four phenotypes constitute a continuum.
    Journal of the neurological sciences 03/2009; 280(1-2):22-8. DOI:10.1016/j.jns.2009.01.008 · 2.47 Impact Factor
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    ABSTRACT: Intravenous glucose administration is the most common cause of hypophosphataemia in hospitalised patients. While most of these cases are asymptomatic, severe hypophosphataemia, when combined with phosphorus depletion, can cause acute neuropathy that mimics Guillain-Barré syndrome. A malnourished patient who received intravenous hyperalimentation (IVH) without intravenous phosphate (IP) developed hypophosphataemia and acute sensorimotor neuropathy. F waves in the peripheral nerve trunk were absent or diminished, while nerve conduction velocities were nearly normal. The sural nerve biopsy revealed the presence of some subperineurial oedema and mild axonal atrophy. Prompt IP administration reversed the patients' neurological symptoms and normalised F waves. Our data suggest that hypophosphataemia plays a role in the pathogenesis of neuropathy that develops in patients following IVH without IP.
    Case Reports 02/2009; 2009. DOI:10.1136/bcr.08.2008.0718
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    ABSTRACT: This study was performed to analyze the locomotion outcome of hemiplegic patients with stroke and to explore the factors influencing it. A total of 247 patients (mean age 65.6 +/- 10.5 years) admitted to our hospital for rehabilitation were included in the study. Their cardinal neurologic sign was hemiplegia caused by infarction in the middle cerebral artery as a result of a first stroke. When rehabilitation programs were completed, the final motor outcome was evaluated and compared between patients with right and left hemispheric infarct. In addition, the following items were analyzed: size, location, and subtype of the infarct; hemispatial neglect and aphasia; cerebral blood flow (CBF); and periventricular lucency on computed tomography scan. (1) There was a negative relationship between the infarct size and the locomotion outcome. The difference in locomotion outcome was not significant between the patients with infarction of the perforating arteries and those of the cortical arteries. No significant difference in the locomotion outcome was found between the patients with an atherothrombotic or cardioembolic infarction. (2) In spite of the existence of hemispatial neglect or aphasia, the patients with a right-sided infarction were significantly inferior to patients with a left-sided one in locomotion outcome, except for those with a large infarction. (3) In patients with infarction in the territory of the perforating arteries, there was a negative relationship between the area of decreased CBF or periventricular lucency and the locomotion outcome. When the area of decreased CBF on the homolateral hemisphere involving the infarction extended to less than or equal to two cerebral lobes, the locomotion outcome was significantly worse in the patients with a right-sided infarction. Overall, for the patients with middle cerebral artery infarction, the locomotion outcome was poorer in patients with a right hemispheric infarction than a left-sided one, except in the case of a large infarction.
    Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 02/2009; 18(1):60-7. DOI:10.1016/j.jstrokecerebrovasdis.2008.09.003 · 1.67 Impact Factor
  • Y Kawai · M Suenaga · H Watanabe · Gen Sobue ·
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    ABSTRACT: It has been reported that patients with spinocerebellar degenerations (SCDs) have cognitive dysfunction as well as limb and truncal ataxia, dysarthria and dysphagia. We review cognitive dysfunction in common types of SCD, including spinocerebellar ataxia types 1, 2, 3, 6, and 17, dentatorubral-pallidoluysian atrophy, Friedreich's ataxia, and multiple system atrophy. There are few studies that address cognitive function in SCD. Although there are few comparison studies among the various SCDs, cognitive dysfunction may be more common and severe in spinocerebellar ataxia type 17 and dentatorubral-pallidoluysian atrophy. While cognitive dysfunction in SCD appears to represent frontal dysfunction, the mechanisms of cognitive dysfunction have not been directly clarified. Nevertheless, various lesions, including those in the cerebrocerebellar circuitry, cortico-striatal-thalamocortical circuitry, and the frontal lobe, may influence cognitive function to various degrees for each disease.
    European Neurology 02/2009; 61(5):257-68. DOI:10.1159/000206850 · 1.36 Impact Factor
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    ABSTRACT: Spinal and bulbar muscular atrophy (SBMA) is a hereditary motor neuron disease caused by the expansion of a polyglutamine tract in the androgen receptor (AR). Animal studies have shown that the pathogenesis of SBMA is dependent on serum testosterone level. This study is aimed at evaluating the efficacy and safety of androgen deprivation by leuprorelin acetate in patients with SBMA. Fifty SBMA patients underwent subcutaneous injections of leuprorelin acetate or placebo in a randomized, placebo-controlled trial for 48 weeks, followed by an open-label trial for an additional 96 weeks, in which 19 patients of the leuprorelin group and 15 of the placebo group received leuprorelin acetate. The patients who did not participate in the open-label trial were also followed up for the 96-week period (UMIN000000474). Leuprorelin acetate significantly extended the duration of cricopharyngeal opening in videofluorography and decreased mutant AR accumulation in scrotal skin biopsy. The patients treated with leuprorelin acetate for 144 weeks exhibited significantly greater functional scores and better swallowing parameters than those who received placebo. Autopsy of one patient who received leuprorelin acetate for 118 weeks suggested that androgen deprivation inhibits the nuclear accumulation or stabilization, or both, of mutant AR in the motor neurons of the spinal cord and brainstem. These observations suggest that administration of leuprorelin acetate suppresses the deterioration of neuromuscular impairment in SBMA by inhibiting the toxic accumulation of mutant AR. The results of this phase 2 trial support the start of large-scale clinical trials of androgen deprivation for SBMA.
    Annals of Neurology 02/2009; 65(2):140-50. DOI:10.1002/ana.21540 · 9.98 Impact Factor
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    ABSTRACT: A clinical diagnosis of Creutzfeldt-Jakob disease (CJD) can be established readily in typical cases but not in atypical cases. To investigate the accuracy of clinical diagnosis of CJD, such diagnoses were evaluated retrospectively in autopsy cases. Sixty cases were clinically diagnosed as cases of CJD, of which seven were excluded on the basis of pathologic analysis. These seven misdiagnosed patients showed progressive dementia or disturbed consciousness. Myoclonus and periodic sharp-wave complexes (PSWCs) similar to those of CJD were noted in five and four of the seven patients, respectively. Fifty-six cases were pathologically confirmed as cases of CJD, and three of these were not diagnosed clinically as cases of CJD. Myoclonus was noted in 53 of the 56 pathologically confirmed cases, and PSWCs were noted in 49 cases. According to the difficulties that occur in atypical CJD cases lacking typical clinical findings, the importance of pathologic examination was emphasized. Further information from clinicopathologically investigated cases, particularly atypical cases, will aid in the definitive clinical diagnosis of CJD.
    Journal of the Neurological Sciences 02/2009; 277(1-2):119-23. DOI:10.1016/j.jns.2008.10.026 · 2.47 Impact Factor
  • H Watanabe · M Hirayama · A Noda · M Ito · N Atsuta · J Senda · T Kaga · A Yamada · M Katsuno · T Niwa · F Tanaka · G Sobue ·
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    ABSTRACT: To elucidate the usefulness of plasma B-type natriuretic peptide (BNP) values for evaluating adverse effects of pergolide or cabergoline on cardiovalvulopathy in patients with Parkinson disease. Twenty-five patients treated with pergolide or cabergoline (ergot group) and 25 patients never treated with ergot derivatives (non-ergot group) were enrolled. Plasma BNP values and detailed echocardiography were evaluated. Thirty age- and gender-matched controls were similarly evaluated. Patients with regurgitation more than grade 3 were more frequent in the ergot group than in the non-ergot group as well as control groups (24%, 0%, 3%, p = 0.001). Both composite regurgitation scores and plasma BNP values were significantly higher in the ergot group than in controls. In the ergot group, the cumulative dose correlated to both tenting area (r = 0.57, p = 0.004) and tenting distance (r = 0.62, p = 0.001). Furthermore, plasma BNP values were higher in patients with severe or multiple regurgitation groups (p < 0.001), and were correlated with composite regurgitation score (r = 0.70, p < 0.001). Multiple regression analyses revealed that BNP values were independently correlated with both composite regurgitation and left ventricular ejection fraction. The combination of comprehensive echocardiography and plasma B-type natriuretic peptide levels elucidates the presence of cardiac damage in patients with Parkinson disease using ergot derivative dopamine agonists.
    Neurology 02/2009; 72(7):621-6. DOI:10.1212/01.wnl.0000342467.47860.f2 · 8.29 Impact Factor
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    ABSTRACT: Patients with painful sensory neuropathy associated with Sjögren's syndrome-associated neuropathy often show severe neuropathic pain which is not relieved by conventional treatments. To evaluate the effect of intravenous immunoglobulin (IVIg) therapy in the treatment of neuropathic pain associated with Sjögren's syndrome. We examined 5 patients affected by painful sensory neuropathy associated with Sjögren's syndrome. All patients were treated with IVIg (0.4 g/kg/day for 5 days) and pain rating was assessed by the Visual Analogue Scale (VAS). All five patients showed a remarkable improvement in neuropathic pain following IVIg therapy. Pain, assessed by the determination of mean VAS score, was reduced by 73.4% from days 2-14 following treatment. The observed clinical improvement persisted for 2 to 6 months. One patient, examined by quantitative sensory testing (QST), showed an improvement of superficial sensory deficit accompanied by pain relief. IVIg might be an effective treatment for pain in Sjögren's syndrome-associated neuropathy. Further studies should be done in a controlled, blind study.
    Journal of the neurological sciences 02/2009; 279(1-2):57-61. DOI:10.1016/j.jns.2008.12.018 · 2.47 Impact Factor
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    ABSTRACT: A 57-year-old man with type 2 diabetes mellitus for 10 years showed progressive loss of muscle strength in both legs, pain and muscle atrophy in the femoral region and significant weight loss. On admission, he could not stand alone and used a wheelchair. He also complained of severe pain in the lower extremities. He was diagnosed with proximal diabetic neuropathy (PDN) by characteristic clinical and electrophysiological features. Intravenous immunoglobulin therapy (IVIg 0.4 g/kg×5 days) markedly reduced the severe pain and muscle weakness in the legs. Eventually, pain assessed by the Visual Analogue Scale was relieved by 80% and muscle strength was also well recovered, thereby enabling the patient to walk with a cane. The present case suggests that IVIg therapy may be effective for the relief of pain in PDN.
    Case Reports 01/2009; 2009. DOI:10.1136/bcr.08.2008.0656
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    ABSTRACT: Our aim was to evaluate the location and extent of white matter involvement in patients with amyotrophic lateral sclerosis (ALS) using diffusion-tensor magnetic resonance imaging (DTI). We obtained fractional anisotropy (FA) values from the internal capsule and various white matter regions of 46 patients with sporadic ALS and 19 control subjects. In ALS patients, FA values in the internal capsule, frontal white matter, genu and splenium of the corpus callosum (p<0.001), parietal and temporal lobe white matter, and posterior cingulum (p<0.05) were significantly lower than in controls. FA values in frontal white matter were lower than in parietal white matter (p<0.001). Decreased FA values in frontal, parietal, and temporal white matter, and the genu of the corpus callosum, correlated significantly with those in the internal capsule (r=0.66 and p<0.001, r=0.47 and p=0.001, r=0.33 and p=0.021, r=0.41 and p=0.005, respectively). No such correlations were found for FA values in other white matter areas or in controls. Patient FA values generally were not correlated with disease duration. DTI demonstrated more widespread involvement of the cerebral white matter in ALS patients than previously believed. The severity of involvement in the frontal, temporal and parietal white matter correlated with severity in the pyramidal tract.
    Amyotrophic Lateral Sclerosis 01/2009; 10(5-6):288-94. DOI:10.3109/17482960802651717 · 2.37 Impact Factor
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    ABSTRACT: Neurodegenerative diseases including amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease, and polyglutamine (polyQ) diseases are thought to be caused by protein misfolding. Heat shock proteins (HSPs), which function mainly as molecular chaperones, play an important role in the folding and quality control of proteins. The histopathological hallmark of neurodegenerative diseases is accumulation and/or inclusions of the disease-causing proteins in residual neurons in targeted regions of the nervous system. The inclusions combine with many components of molecular chaperone pathways and ubiquitin-proteasome, raising the possibility that misfolding and altered degradation of mutant proteins may be involved in the pathogenesis of neurodegenerative diseases. Overexpression of HSPs has been reported to reduce the number and size of inclusions and accumulation of disease-causing proteins, and ameliorate the phenotypes in neuronal cell and mouse models. Hsp90 inhibitors also exert therapeutic effects through selective proteasome degradation of its client proteins. Elucidation of its pathophysiology using animal models has led to the development of disease-modifying drugs, i.e., Hsp90 inhibitor and HSP inducer, which inhibit the pathogenic process of neuronal degeneration. These findings may provide the basis for development of an HSP-related therapy for neurodegenerative diseases.
    International Journal of Hyperthermia 01/2009; 25(8):647-54. DOI:10.3109/02656730903315823 · 2.65 Impact Factor
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    ABSTRACT: There are many reports that obstructive sleep apnea syndrome (OSAS) is a risk factor for ischemic stroke of arterial origin, however, the relationship between OSAS and cerebral venous thrombosis (CVT) remains unknown. We report the case of a 44-year-old man who had episodic headaches, unconsciousness attacks and seizures. Cerebral angiography showed CVT. He was obese and had severe OSAS. Noninvasive continuous positive airway pressure (CPAP) therapy prevented the recurrence of CVT as well as of headache. OSAS may be one of the multiple risk factors of CVT as well as arterial ischemic stroke.
    Internal Medicine 01/2009; 48(20):1837-40. DOI:10.2169/internalmedicine.48.2037 · 0.90 Impact Factor
  • Naoki Hattori · Haruki Koike · Gen Sobue ·
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    ABSTRACT: We assessed whether postgastrectomy polyneuropathy associated with thiamine deficiency is clinicopathologically identical to beriberi neuropathy, including a biochemical determination of thiamine status. The typical presentation for the two etiologies was as a symmetric sensorimotor polyneuropathy predominantly involving the lower limbs. In both groups, the main electrophysiologic findings were those of axonal neuropathy, most prominently in the lower limbs. Sural nerve biopsy specimens also indicated axonal degeneration in both groups. Subperineurial edema was commonly observed. Thiamine-deficiency neuropathies due to gastrectomy and dietary imbalance are identical despite variability in their clinicopathologic features and suggested that thiamine deficiency can be a major cause of postgastrectomy polyneuropathy. Characteristics of alcoholic neuropathy have been obscured by difficulty in isolating them from features of thiamine-deficiency neuropathy. We assessed 64 patients with alcoholic neuropathy including subgroups without and with coexisting thiamine deficiency. Thirty-two patients with nonalcoholic thiamine-deficiency neuropathy also were investigated for comparison. We concluded that pure-form of alcoholic neuropathy was distinct from pure-form of thiamine-deficiency neuropathy, supporting the view that alcoholic neuropathy can be caused by direct toxic effect of ethanol or its metabolites. However, features of alcoholic neuropathy is influenced by concomitant thiamine-deficiency state, having so far caused the obscure clinicopathological entity of alcoholic neuropathy.
    Rinsho shinkeigaku = Clinical neurology 12/2008; 48(11):1026-7. DOI:10.5692/clinicalneurol.48.1026
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    ABSTRACT: There are two distinct phenotypes of multiple sclerosis (MS) in Asians, manifesting as optic-spinal (OSMS) and conventional (CMS) forms. In Japan, four nationwide surveys of MS have been conducted. The first three were in 1972, 1982, and 1989, and we performed the fourth in 2004. The recent survey showed six main findings as follows: (1) a four-fold increase in the estimated number of clinically definite patients with MS in 2003 (9900; crude MS prevalence, 7.7/100,000) compared with 1972; (2) a shift in the peak age at onset from early 30s in 1989 to early 20s in 2003; (3) a successive proportional decrease in optic-spinal involvement in clinically definite patients with MS; (4) a significant north-south gradient for the CMS/OSMS ratio; (5) after subdivision of the mainland (30-45 degrees North) into northern and southern parts at 37 degrees N, northern-born northern residents (northern patients) showed a significantly higher CMS/OSMS ratio and higher frequency of brain lesions fulfilling the Barkhof criteria (Barkhof brain lesions) than southern-born southern residents (southern patients); (6) among northern patients, the absolute numbers of patients with CMS and those with Barkhof brain lesions rapidly increased with advancing birth year. These findings suggest that MS phenotypes are drastically altered by environmental factors, such as latitude and "Westernization."
    Multiple Sclerosis 12/2008; 15(2):159-73. DOI:10.1177/1352458508098372 · 4.82 Impact Factor
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    ABSTRACT: The mechanism underlying the characteristic selective motor neuron degeneration in amyotrophic lateral sclerosis (ALS) has remained elusive. Modest advances in this research field have been achieved by the identification of copper/zinc superoxide dismutase 1 (SOD1) as one of the causative genes for rare familial ALS and by the development and analysis of mutant SOD1 transgenic animal models. However, in sporadic ALS (SALS) with many more patients, causative or critical genes situated upstream of the disease pathway have not yet been elucidated and no available disease models have been established. We have been working on screening these genes employing and combining several new technologies such as cDNA microarray, molecular indexing, and laser capture microdissection. Many of the resultant genes are of intense interest and may provide a powerful tool for determining the molecular mechanisms of SALS. Of these, in this paper, we will focus on Dorfin, a RING finger-type E3 ubiquitin ligase and dynactin1, a major component of dynein/dynactin complex that is important for retrograde axonal transport. We are now challenging creation of the disease models by simulating the gene expression changes specifically observed in SALS patients.
    Rinsho shinkeigaku = Clinical neurology 12/2008; 48(11):970-2. DOI:10.5692/clinicalneurol.48.970
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    ABSTRACT: To profile the detailed clinical features of sporadic amyotrophic lateral sclerosis (ALS) on large-scale samples in Japan. We assessed the clinical features of sporadic ALS patients in Japan, based on the nationwide registration system of the Ministry of Health, Labor and Welfare of Japan. We described 3,428 new cases registered cases between 2003 and 2006 to analyze initial symptoms and related clinical features, 4,202 cases registered in the single year of 2005 to describe the cross-sectional overview of the ALS patients, and a total of 2,128 cases with tracheostomy positive pressure ventilation (TPPV) from all of the registration data from 2003 to 2006 to describe the features of ALS patients with TPPV. The patients with an older age at onset progressed more rapidly to the TPPV stage than those with a younger age at onset. The subpopulation of patients with long-standing TPPV showed ophthalmoplegia, while its appearance rate was less in the patients with an older age at onset than in those with a younger age at onset. Furthermore, age at onset strongly influenced the frequency of initial symptoms: dysarthria, dysphagia, neck weakness and respiratory disturbance were more frequent in patients with an older age at onset, while upper or lower limb weakness was observed more frequently in patients with a younger age at onset. In addition, those initial symptoms were still the most prominent at the follow-up stage, suggesting that the initial symptoms determine the major clinical features even in advanced illness. Our present study demonstrated that symptomatic features of ALS are strongly influenced by the age at onset by the large scale of samples.
    Journal of the Neurological Sciences 11/2008; 276(1-2):163-9. DOI:10.1016/j.jns.2008.09.024 · 2.47 Impact Factor
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    ABSTRACT: Comprehensive resequencing of the causative and disease-related genes of neurodegenerative diseases is expected to enable (1) comprehensive mutational analysis of familial cases, (2) identification of sporadic cases with de novo or low-penetrant mutations, (3) identification of rare variants conferring disease susceptibility, and ultimately (4) better understanding of the molecular basis of these diseases. To develop a microarray-based high-throughput resequencing system for the causative and disease-related genes of amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. Validation of the system was conducted in terms of the signal-to-noise ratio, accuracy, and throughput. Comprehensive gene analysis was applied for patients with ALS. Subjects Ten patients with familial ALS, 35 patients with sporadic ALS, and 238 controls. The system detected point mutations with 100% accuracy and completed the resequencing of 270 kilobase pairs in 3 working days with greater than 99.9% accuracy of base calls, or the determination of base(s) at each position. Analysis of patients with familial ALS revealed 2 SOD1 mutations. Analysis of the 35 patients with sporadic ALS revealed a previously known SOD1 mutation, S134N, a novel putative pathogenic DCTN1 mutation, R997W, and 9 novel variants including 4 nonsynonymous heterozygous variants consisting of 2 in ALS2, 1 in ANG, and 1 in VEGF that were not found in the controls. The DNA microarray-based resequencing system is a powerful tool for high-throughput comprehensive analysis of causative and disease-related genes. It can be used to detect mutations in familial and sporadic cases and to identify numerous novel variants potentially associated with genetic risks.
    Archives of neurology 11/2008; 65(10):1326-32. DOI:10.1001/archneur.65.10.1326 · 7.42 Impact Factor
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    ABSTRACT: Through the development of gene diagnostic techniques, late-onset transthyretin Met30-associated familial amyloid polyneuropathy (FAP TTR Met30) has been shown to be more prevalent than is generally believed. To examine the electrophysiological features of late-onset FAP TTR Met30 unrelated to endemic foci. Nerve conduction findings in 44 cases with an onset of more than 50 years of age in a non-endemic area were assessed and compared with findings from 21 earlier-onset cases related to endemic foci. The extent of the reduction of the compound muscle action potential and, especially, the sensory nerve action potential was more profound in the late-onset group even when the decline of these indices with aging in normal control subjects was taken into account. The feature of predominant lower-limb involvement seemed to be more conspicuous in the late-onset group. Electrophysiological indices tended to be aggravated as the duration of neuropathic symptoms increased in the early-onset group, while most of these indices in the lateonset group did not show this correlation. A slowing of conduction velocity and a prolongation of distal latency, which suggests demyelination, were conspicuous in some patients. Pathologically, a predominant loss of small-fibers was not conspicuous in sural nerve biopsy specimens from late-onset patients. Large myelinated fiber density showed a negative correlation with the disease duration in early-onset cases, but not in late-onset cases. Electrophysiological differences between late- and early-onset cases were present, probably reflecting the different underlying pathogenic mechanisms of neuropathy. The demyelinating feature does not exclude the possibility of this disease.
    Journal of Neurology 10/2008; 255(10):1526-33. DOI:10.1007/s00415-008-0962-z · 3.38 Impact Factor
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    ABSTRACT: Neural stem/progenitor cells (NS/PCs) can generate a wide variety of neural cells. However, their fates are generally restricted, depending on the time and location of NS/PC origin. Here we demonstrate that we can recapitulate the spatiotemporal regulation of central nervous system (CNS) development in vitro by using a neurosphere-based culture system of embryonic stem (ES) cell-derived NS/PCs. This ES cell-derived neurosphere system enables the efficient derivation of highly neurogenic fibroblast growth factor-responsive NS/PCs with early temporal identities and high cell-fate plasticity. Over repeated passages, these NS/PCs exhibit temporal progression, becoming epidermal growth factor-responsive gliogenic NS/PCs with late temporal identities; this change is accompanied by an alteration in the epigenetic status of the glial fibrillary acidic protein promoter, similar to that observed in the developing brain. Moreover, the rostrocaudal and dorsoventral spatial identities of the NS/PCs can be successfully regulated by sequential administration of several morphogens. These NS/PCs can differentiate into early-born projection neurons, including cholinergic, catecholaminergic, serotonergic, and motor neurons, that exhibit action potentials in vitro. Finally, these NS/PCs differentiate into neurons that form synaptic contacts with host neurons after their transplantation into wild-type and disease model animals. Thus, this culture system can be used to obtain specific neurons from ES cells, is a simple and powerful tool for investigating the underlying mechanisms of CNS development, and is applicable to regenerative treatment for neurological disorders.
    Stem Cells 09/2008; 26(12):3086-98. DOI:10.1634/stemcells.2008-0293 · 6.52 Impact Factor
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    ABSTRACT: Pathological studies have shown remarkable pyramidal tract involvement in multiple system atrophy (MSA), while clinical pyramidal signs are relatively rare. We investigated the fractional anisotropy (FA) values to assess the degree of pyramidal tract involvement in MSA, in comparison with amyotrophic lateral sclerosis (ALS) and controls. Furthermore, we compared FA values between MSA patients with or without clinical pyramidal signs and controls, and between MSA patients with or without positive conventional MRI findings and controls. We evaluated FA values in the internal capsule, corona radiate and whole pyramidal tract using visualized tractography of 65 subjects (20 probable MSA patients, 28 age-matched ALS patients, and 17 age-matched healthy controls) using a 3.0T magnetic resonance system. The FA values in the internal capsule, corona radiate, and whole pyramidal tract were significantly lower in MSA patients than in controls and were at a level similar to those of ALS patients. In addition, low FA values were prominent in MSA patients, even in those with short duration of illness, lacking precentral gyrus hyperintensity in FLAIR images, and without pyramidal signs. FA values could identify pyramidal tract degeneration even in patients with early phase MSA and those without clinical pyramidal signs or abnormal MRI findings. More extensive degeneration of the pyramidal tract occurs in MSA than so far believed.
    Journal of the Neurological Sciences 09/2008; 271(1-2):40-6. DOI:10.1016/j.jns.2008.03.013 · 2.47 Impact Factor

Publication Stats

17k Citations
3,090.13 Total Impact Points


  • 2012-2015
    • Japan Science and Technology Agency (JST)
      Edo, Tokyo, Japan
    • Juntendo University
      • Department of Neurology
      Tokyo, Tokyo-to, Japan
  • 1991-2015
    • Nagoya University
      • • Division of Neurology
      • • Division of Pathology
      Nagoya, Aichi, Japan
  • 2013
    • Nagoya Second Red Cross Hospital
      Nagoya, Aichi, Japan
  • 1986-2006
    • Aichi Medical University
      • • Department of Neurology
      • • Division of Internal Medicine
      Koromo, Aichi, Japan
  • 2005
    • Osaka City University
      Ōsaka, Ōsaka, Japan
  • 2000
    • Nara Institute of Science and Technology
      Ikuma, Nara, Japan
  • 1993-1996
    • Kyoto Daini Red Cross Hospital
      Kioto, Kyōto, Japan
  • 1984-1988
    • The Children's Hospital of Philadelphia
      • Department of Neurology
      Philadelphia, Pennsylvania, United States
  • 1985
    • University of Pennsylvania
      • Department of Neurology
      Filadelfia, Pennsylvania, United States