Masashi Mizuguchi

The University of Tokyo, Edo, Tōkyō, Japan

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Publications (260)751.09 Total impact

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    ABSTRACT: We describe two unrelated patients with terminal deletions in the long arm of chromosome 13 showing brain malformation consisting of holoprosencephaly and cerebellar vermis hypoplasia. Array comparative genomic hybridization analysis revealed a pure terminal deletion of 13q31.3q34 in one patient and a mosaic ring chromosome with 13q32.2q34 deletion in the other. Mutations in ZIC2, located within region 13q32, cause holoprosencephaly, whereas the 13q32.2q32.3 region is associated with cerebellar vermis hypoplasia (Dandy–Walker syndrome). The rare concurrence of these major brain malformations in our patients provides further evidence that 13q32.2q32.3 deletion, harboring ZIC2 and ZIC5, leads to cerebellar dysgenesis.
    Brain and Development 11/2014; · 1.67 Impact Factor
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    ABSTRACT: Voltage-gated sodium channels regulate neuronal excitability, as well as survival and the patterning of neuronal connectivity during development. Mutations in SCN2A, which encodes the Na+ channel Nav1.2, cause epilepsy syndromes and predispose children to acute encephalopathy. Here, we report the case of a young male with recurrent acute encephalopathy who carried a novel missense mutation in the SCN2A gene. He was born by normal delivery and developed repetitive apneic episodes at 2 days of age. Diffusion-weighted imaging revealed high-intensity areas in diffuse subcortical white matter, bilateral thalami, and basal nuclei. His symptoms improved gradually without any specific treatment, but he exhibited a motor milestone delay after the episode. At the age of 10 months, he developed acute cerebellopathy associated with a respiratory syncytial viral infection. He received high-dose intravenous gammaglobulin and methylprednisolone pulse therapy and seemed to have no obvious sequelae after the episode. He then developed severe diffuse encephalopathy associated with gastroenteritis at the age of 14 months. He received high-dose intravenous gammaglobulin and methylprednisolone pulse therapy but was left with severe neurological sequelae. PCR-based analysis revealed a novel de novo missense mutation, c.4979T>G (p.Leu1660Trp), in the SCN2A gene. This case suggests that SCN2A mutations might predispose children to repetitive encephalopathy with variable clinical and imaging findings.
    Brain and Development. 10/2014;
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    ABSTRACT: Human cosavirus (HCoSV) is a genus recently identified in the family Picornaviridae, which includes important pathogens in human health. The pathogenicity of HCoSV remains unclear. This study reports that an HCoSV strain, 10928/2012/JPN, was identified and collected from the stool sample of a child with acute gastroenteritis in Japan, with the detection rate of 0.16%. The patient was not co-infected with other common diarrhea-causal viruses, suggesting HCoSV as a causal pathogen in this pediatric patient. Phylogenetic and sequence analyses exhibited that the virus strain was classified as a new genotype in HCoSV A species, and this study is first to detect HCoSV in a clinical specimen collected in Japan. These results showed that surveillance of HCoSV is important for detecting viral agents in children with diarrhea, despite being the low detection rate.
    Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 09/2014; · 3.22 Impact Factor
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    Clinical and Experimental Nephrology 08/2014; · 1.25 Impact Factor
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    ABSTRACT: Background Theophylline has recently been suspected as a risk factor of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), although there has been no systematic study on the relationship between acute encephalopathy in children taking theophylline (AET) and AESD. Methods We recruited 16 Japanese patients (11 male and 5 female, median age of 2 years and 7 months) with AET from 2008 to 2013. We evaluated their clinical features, such as the duration of first seizure, biphasic clinical course and cranial CT/MRI imaging and compared them with those of AESD. We analyzed the polymorphisms or mutations of genes which are associated with AESD. Results Clinically, 12 patients had neurological and/or radiological features of AESD. Only one patient died, whereas all 15 surviving patients were left with motor and/or intellectual deficits. Genetically, 14 patients had at least one of the following polymorphisms or mutations associated with AESD: thermolabile variation of the carnitine palmitoyltransferase 2 (CPT2) gene, polymorphism causing high expression of the adenosine receptor A2A (ADORA2A) gene, and heterozygous missense mutation of the voltage gated sodium channel 1A (SCN1A) and 2A (SCN2A) gene. Conclusions Our results demonstrate that AET overlaps with AESD, and that AET is a multifactorial disorder sharing a genetic background with AESD.
    Brain and Development 08/2014; · 1.67 Impact Factor
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    ABSTRACT: To develop a score that predicts the prognosis of children with acute necrotizing encephalopathy (ANE).
    Brain & development. 06/2014;
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    ABSTRACT: Acute respiratory infections are the major cause of morbidity and mortality globally. Human bocavirus (HBoV), a novel virus, is recognized to increasingly associate with previously unknown etiology respiratory infections in young children. In this study, the epidemiological, clinical, and molecular characteristics of HBoV infections were described in hospitalized Vietnamese pediatric patients. From April 2010 to May 2011, 1,082 nasopharyngeal swab samples were obtained from patients with acute respiratory infections at the Children's Hospital 2, Ho Chi Minh City, Vietnam. Samples were screened for HBoV by PCR and further molecularly characterized by sequencing. HBoV was found in 78 (7.2%) children. Co-infection with other viruses was observed in 66.7% of patients infected with HBoV. Children 12–24 months old were the most affected age group. Infections with HBoV were found year-round, though most cases occurred in the dry season (December–April). HBoV was possible to cause severe diseases as determined by higher rates of hypoxia, pneumonia, and longer hospitalization duration in patients with HBoV infection than in those without (P-value <0.05). Co-infection with HBoV did not affect the disease severity. The phylogenetic analysis of partial VP1 gene showed minor variations and all HBoV sequences belonged to species 1 (HBoV1). In conclusion, HBoV1 was circulating in Vietnam and detected frequently in young children during dry season. Acute respiratory infections caused by HBoV1 were severe enough for hospitalization, which implied that HBoV1 may have an important role in acute respiratory infections among children. J. Med. Virol. 86:988–994, 2014. © 2013 Wiley Periodicals, Inc.
    Journal of Medical Virology 06/2014; 86(6). · 2.37 Impact Factor
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    ABSTRACT: Aichivirus C is the third species in the genus Kobuvirus, family Picornaviridae, and the virus is circulating in pigs worldwide. Aichivirus A in humans and Aichivirus B in cows have been shown to associate with diarrheal diseases, however, the pathogenesis of Aichivirus C has not been demonstrated clearly. In this study, the full genome nucleotide sequence of the Thai strain, CMP06/2007/THA collected from stool sample of a diarrheal piglet was analyzed and identified as a variant type with a 90-nucleotide deletion in the 2B-coding region. In addition, molecular characterization of nucleotide sequences of the 2B-coding region of Aichivirus C strains from six diarrheal and six healthy piglets in Thailand, and four strains from healthy pigs in Japan revealed that all of the strains in this study were variant types. These findings indicate that variant strains of Aichivirus C are circulating in Asian countries such as China, Thailand and Japan, and deletion of tandem repeat of 2B-region is unlikely to associate with the pathogenesis of the virus.
    Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 05/2014; · 3.22 Impact Factor
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    ABSTRACT: Neonatal hypoxic-ischemic encephalopathy (HIE) remains a serious burden in neonatal care. Hypothermia provides a good outcome in some babies with HIE. Here, we investigated the biological mechanisms of its neuroprotective effect and sought for a new therapeutic target. We made neonatal HIE rats and subjected some of them to hypothermia at 28°C for 3 hours. We pathologically confirmed the efficacy of hypothermia against the neonatal HIE brain. To clarify the molecular mechanism of hypothermia's efficacy, we analyzed mRNA expression, immunoassay, and pathology in the brain with or without HIE and/or hypothermia. We selected from these analyses 12 molecules with possible neuroprotective effects. After identification of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) as a therapeutic target candidate, we examined the efficacy of an anti-LOX-1 neutralizing antibody in neonatal HIE rats. Administration of an anti-LOX-1 neutralizing antibody reduced infarction area, brain edema, and apoptotic cell death to a degree comparable with hypothermia. Protection from those pathological conditions was considered part of the therapeutic mechanism of hypothermia. The efficacy of administering anti-LOX-1 neutralizing antibody was similar to that of hypothermia. LOX-1 is a promising therapeutic target in neonatal HIE, and the inhibition of LOX-1 may become a novel treatment for babies who have experienced asphyxia.
    American Journal Of Pathology 04/2014; · 4.60 Impact Factor
  • 04/2014; 34(2):51-2.
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    ABSTRACT: To elucidate the clinical and radiologic features and analyze factors associated with neurologic outcomes of encephalopathy secondary to Shiga toxin-producing Escherichia coli (STEC) O111. We reviewed medical records and neuroimaging in 22 patients with neurologic symptoms among 86 with STEC O111 infection. Twenty-one (6 males and 15 females, 10 children and 11 adults) of the 22 patients were diagnosed with encephalopathy. All patients with encephalopathy also presented with hemolytic-uremic syndrome. Five patients died, from day 1 to 6 months (days 1-5 in 4 patients), due to progressive encephalopathy with severe cerebral edema observed in neuroimaging (4 patients). Fifteen of the 16 surviving patients clinically recovered completely. Statistical analysis revealed differences between patients with poor (n = 6) and good (n = 15) outcomes in the interval from hemolytic-uremic syndrome presentation to encephalopathy, creatinine levels, and the methylprednisolone administration ratio. We note a high incidence of encephalopathy in the Toyama STEC O111 outbreak. All fatal cases resulted from progressive encephalopathy. Methylprednisolone pulse therapy represents a possible therapeutic choice. This study provides Class III evidence that methylprednisolone pulse therapy increases the probability of a good outcome for patients with encephalopathy associated with STEC O111.
    Neurology 01/2014; · 8.30 Impact Factor
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    ABSTRACT: In late 2012, an outbreak of acute gastroenteritis due to norovirus variant Sydney_2012 occurred and have been reported from many counties. In this study, we described surveillance study of the incidence of norovirus infections among Japanese pediatric patients in association with gastroenteritis and investigated the antigenic change of the new variant Sydney_2012 circulated in Japanese populations. A total of 2,381 fecal specimens collected from children with acute gastroenteritis in Hokkaido, Tokyo, Shizuoka, Kyoto, Osaka, and Saga from 2009 to 2013 were examined for norovirus and further analyzed molecularly. A high proportion (39.3%) of norovirus positive samples and several genotypes were detected. Norovirus GII.4 dominated over other genotypes (71.4%). The Den_Haag_2006b (43.2%) was detected as the predominant variant and co-circulated with New_Orleans_2009 (17.8%) until March 2012. Subsequently, they were displaced by Sydney_2012. The Sydney_2012 variant has been responsible for the majority of norovirus infections in 2012-2013 (85.7%). Although Sydney_2012 variant has a common ancestor with New_Orleans_2009 variant, analysis of P2 sub-domain showed a high level of diversity in comparison with other variants in four amino acid changes at the antigenic sites. The change in particular residue 393 of new variant may affect HBGA recognition. Analysis of noroviruses circulating in the past 4 years revealed a change of predominant variant of norovirus GII.4 in each epidemic season. The change of amino acid in putative epitopes may have led the virus escape from the existing herd immunity and explain the increase of new variant outbreaks.
    Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 01/2014; · 3.22 Impact Factor
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    ABSTRACT: Aichivirus C is the third species in the genus Kobuvirus, family Picornaviridae, and the virus is circulating in pigs worldwide. Aichivirus A in humans and Aichivirus B in cows have been shown to associate with diarrheal diseases, however, the pathogenesis of Aichivirus C has not been demonstrated clearly. In this study, the full genome nucleotide sequence of the Thai strain, CMP06/2007/THA collected from stool sample of a diarrheal piglet was analyzed and identified as a variant type with a 90-nucleotide deletion in the 2B-coding region. In addition, molecular characterization of nucleotide sequences of the 2B-coding region of Aichivirus C strains from six diarrheal and six healthy piglets in Thailand, and four strains from healthy pigs in Japan revealed that all of the strains in this study were variant types. These findings indicate that variant strains of Aichivirus C are circulating in Asian countries such as China, Thailand and Japan, and deletion of tandem repeat of 2B-region is unlikely to associate with the pathogenesis of the virus.
    Infection, Genetics and Evolution. 01/2014;
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    ABSTRACT: We detected Campylobacter spp. in 5% (20/380) of diarrheal stool samples collected at an outpatient clinic in Kyoto using a commercial loop-mediated isothermal amplification (LAMP) kit with a fluorescent detection reagent after DNA extraction. The sensitivity and specificity were 100% in comparison with those of semi-nested PCR for the differentiation of Campylobacter jejuni and Campylobacter coli. Fourteen of the 20 samples were already determined as C. jejuni by the culture method. All 20 samples were also positive for C. jejuni by the PCR method. Among the 58 cultured samples, the sensitivity of the culture method against the LAMP method was 93.3% (14/15) and the specificity was 100% (43/43). The detection rate of Campylobacter spp. from the heated supernatants by the LAMP method was lower than that from the supernatant after DNA extraction. In total, 25% (5/20) of the Campylobacter-positive samples by the LAMP method were co-infected with norovirus (3/20), rotavirus (1/20), and human parechovirus (1/20), although no other bacterial co-infection was identified by the culture method. C. jejuni was mostly detected in children aged >5 years throughout the year. Based on these results, we concluded that care should be taken while diagnosing Campylobacter infection in children. Our newly modified LAMP method is a rapid, easy, and useful method for this diagnosis.
    Japanese journal of infectious diseases. 01/2014; 67(5):374-8.
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    Masashi Mizuguchi
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    ABSTRACT: Influenza is occasionally complicated by CNS disorders, in particular impairment of consciousness. Severe disorders encompass multiple, distinct syndromes manifesting acute encephalopathy, whereas mild disorders represent multiple, ill-defined neuropsychiatric syndromes. Acute encephalopathy is manifested with seizures and coma, with or without multi-organ involvement. The outcome varies from death or neurologic sequelae to recovery and differs among syndromes. Transient neuropsychiatric disorders are manifested with delirium and/or abnormal behavior. There also are multiple syndromes. The outcome is usually favorable, although occasional fatal accidents warrant caution.
    Influenza and Other Respiratory Viruses 11/2013; 7 Suppl 3:67-71. · 1.47 Impact Factor
  • Masashi Mizuguchi
    Brain & development 10/2013; · 1.74 Impact Factor
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    ABSTRACT: In this study, a more detailed genetic characterization of the VP1 capsid protein of uncommon norovirus (NoV) GII.14 strains reported previously in Japan and China was performed using sequence analyses and homology modeling technique. The result of genetic comparison with the M7 prototype strain of GII.14 revealed that 10 amino acid mutations were observed at the same positions across the P2 and P1-2 subdomains in both Japanese and Chinese strains. By the homology modeling of the P domain, 7 out of these 10 mutations were predicted to be located on the surface-exposed P2 and P1-2 subdomains. All GII.14 strains had an altered RGD-like motif (RGT → KGT). While the Chinese strains contained 5 random amino acid changes in the S domain and the P2 subdomain, these changes were not detected in the Japanese strains. In addition, the histo-blood group antigen (HBGA)-binding interfaces remain identical to those of the previously determined GII.4 structure (VA387), suggesting the conservation of HBGA binding profile within the GII genogroup. Taken together, this report provides supportive structural data that antigenic drifts that occurred mostly in the P2 and P1-2 subdomains might be sufficient to generate new mutants, thus permitting the GII.14 virus to escape the host pre-existing immunity. These results also suggest the need for comparing the evolutionary profiles and structural models of rare NoV genotypes to an insight into NoV evolution. J. Med. Virol. © 2013 Wiley Periodicals, Inc.
    Journal of Medical Virology 09/2013; · 2.37 Impact Factor
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    ABSTRACT: We studied the altered molecular species of lipids in brain and liver tissues, and fibroblasts from patients with Zellweger syndrome (ZS). ZS cerebellum samples contained a higher amount of sphingomyelin with shorter chain fatty acids compared to that in normal controls. The amount of phosphatidylethanolamine (PE) was less than half of that in controls, with the absence of the PE-type of plasmalogen. Gangliosides were accumulated in the brains and fibroblasts of ZS patients. To investigate whether or not impaired beta-oxidation of very long chain fatty acids and/or plasmalogen synthesis affects glycolipids metabolism, RNAi of peroxisomal acylCo-A oxidase (ACOX1) and glyceronephosphate O-acyltransferase (GNPAT) was performed using cultured neural cells. In neuronal F3-Ngn1 cells, ACOX1 and GNPAT silencing up-regulated ceramide galactosyltransferase (UGT8) mRNA expression, and down-regulated UDP-glucose ceramide glucosyltransferase UGCG. These results suggest that both impaired beta-oxidation of very long chain fatty acids and plasmalogen synthesis affect glycolipid metabolism in neuronal cells.
    Neuroscience Letters 08/2013; · 2.03 Impact Factor
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Publication Stats

3k Citations
751.09 Total Impact Points

Institutions

  • 1993–2014
    • The University of Tokyo
      • • Department of International Health
      • • Faculty & Graduate School of Medicine
      • • Department of Reproductive, Developmental and Aging Sciences
      • • Department of Pediatrics
      Edo, Tōkyō, Japan
  • 2013
    • Tokyo Medical University
      • Division of Pediatrics
      Edo, Tōkyō, Japan
    • Ho Chi Minh City Medicine and Pharmacy University
      Thành phố Hồ Chí Minh, Ho Chi Minh City, Vietnam
  • 2012
    • Chiang Mai University
      • Department of Microbiology
      Chiang Mai, Chiang Mai Province, Thailand
    • Tamkang University
      T’ai-pei, Taipei, Taiwan
    • University of Maryland, College Park
      • Department of Animal and Avian Sciences
      College Park, MD, United States
    • Tokyo Metropolitan Institute of Medical Science
      Edo, Tōkyō, Japan
  • 2011
    • University Hospital Medical Information Network
      Edo, Tōkyō, Japan
  • 2009–2010
    • Aino University
      Takatuki, Ōsaka, Japan
    • Juntendo University
      • Department of Paediatrics
      Edo, Tōkyō, Japan
  • 2007
    • Tokyo Bay Rehabilitation Hospital
      Edo, Tōkyō, Japan
  • 1997–2007
    • Jichi Medical University
      • Department of Pediatrics
      Tochigi, Tochigi-ken, Japan
    • University of Tsukuba
      • Institute of Basic Medical Sciences
      Tsukuba, Ibaraki, Japan
  • 2006
    • Athens State University
      Athens, Alabama, United States
    • Dokkyo Medical University
      Totigi, Tochigi, Japan
  • 2003–2006
    • Tokyo Women's Medical University
      • Department of Pediatrics
      Edo, Tōkyō, Japan
    • Nagoya University
      Nagoya, Aichi, Japan
  • 1995–2001
    • National Center of Neurology and Psychiatry
      • Department of Mental Retardation and Birth Defect Research
      Кодаиры, Tōkyō, Japan
  • 1992–1999
    • Niigata University
      • Department of Pathology
      Niahi-niigata, Niigata, Japan
  • 1995–1996
    • Kyoto Institute of Technology
      Kioto, Kyōto, Japan
  • 1991–1992
    • University of British Columbia - Vancouver
      • Department of Medicine
      Vancouver, British Columbia, Canada