Masashi Mizuguchi

The University of Tokyo, Edo, Tōkyō, Japan

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Publications (256)743.04 Total impact

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    Clinical and Experimental Nephrology 08/2014; · 1.25 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; · 8.25 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: 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. 01/2014;
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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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    ABSTRACT: Group A rotavirus (RVA) is the most common cause of severe acute viral gastroenteritis in humans and animals worldwide. This study characterized the whole genome sequences of porcine RVAs, 2 G3P[23] strains (CMP40/08 and CMP48/08), 1 G9P[23] strain (CMP45/08), and 1 G3P[13] strain (CMP29/08). These strains were collected from diarrheic piglets less than 7 weeks of age in 4 pig farms in Chiang Mai, Thailand, in 2008. The VP7-VP4-VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5 genes of CMP40/08 and CMP48/08 strains were assigned as G3-P[23]-I5-R1-C1-M1-A8-N1-T1-E1-H1 genotypes based on their nucleotide sequences and phylogenetic analyses. The CMP29/08 strain was different from the CMP40/08 and CMP48/08 strains only in the VP4 gene, since it was assigned as P[13] genotype. Furthermore, the VP7 gene of the CMP45/08 strain was classified as genotype G9, and the NSP3 gene as T7 genotype. The finding of this study supports the porcine-origin of T7 genotype, although the NSP3 gene of this strain was similar to the bovine UK strain at the highest nucleotide sequence identity of 92.6%. Whole genome sequence analysis of the porcine RVAs indicated that multiple inter-genotypic and intra-genotypic reassortment events had occurred among the porcine RVAs circulating in this studied area. Interestingly, the VP7 gene of the CMP45/08 strain, and the VP1, NSP2, and NSP4 genes of all 4 porcine RVAs strains described in this study revealed much similarity to those of 2 porcine-like human RVA strains (RVA/Human-tc/THA/Mc323/1989/G9P[19] and RVA/Human-tc/THA/Mc345/1989/G9P[19]) detected in Thailand in 1989. The present study provided important information on the evolution of porcine RVA.
    Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 05/2013; · 3.22 Impact Factor
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    ABSTRACT: Abstract Context: Pathological upregulation of the RAS/MAPK pathway causes Costello, Noonan and cardio-facio-cutaneous (CFC) syndrome; however, little is known about PI3K/AKT signal transduction in these syndromes. Previously, we found a novel mutation of the SOS1 gene (T158A) in a patient with Costello/CFC overlapping phenotype. Objective: The aim of this study was to investigate how this mutation affects RAS/MAPK as well as PI3K/AKT pathway signal transduction. Materials and methods: Wild-type and mutant (T158A) Son of Sevenless 1 (SOS1) were transfected into 293T cells. The levels of phospho- and total ERK1/2, AKT, p70S6K and pS6 were examined under epidermal growth factor (EGF) stimulation. Results: After EGF stimulation, the ratio of phospho-ERK1/2 to total ERK1/2 was highest at 5 min in mutant (T158A) SOS1 cells, and at 15 min in wild-type SOS1 cells. Phospho-AKT was less abundant at 60 min in mutant than in wild-type SOS1 cells. Phosphorylation at various sites in p70S6K differed between wild-type and mutant cells. Eighteen hours after activation by EGF, the ratio of phospho-ERK1/2 to total ERK1/2 remained significantly higher in mutant than in wild-type SOS1 cells, but that of phospho-AKT to total AKT was unchanged. Discussion: T158A is located in the histone-like domain, which may have a role in auto-inhibition of RAS exchanger activity of SOS1. T158A may disrupt auto-inhibition and enhance RAS signaling. T158A also affects PI3K/AKT signaling, probably via negative feedback via phospho-p70S6K. Conclusion: The SOS1 T158A mutation altered the phosphorylation of gene products involved in both RAS/MAPK and PI3K/AKT pathways.
    Journal of Receptor and Signal Transduction Research 04/2013; 33(2):124-8. · 1.63 Impact Factor
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    ABSTRACT: OBJECTIVE: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a childhood encephalopathy following severe febrile seizures, leaving neurologic sequelae in many patients. However, its pathogenesis remains unclear. In this study, we clarified that genetic variation in the adenosine A2A receptor (ADORA2A), whose activation is involved in excitotoxicity, may be a predisposing factor of AESD. METHODS: We analyzed 4 ADORA2A single nucleotide polymorphisms in 85 patients with AESD. The mRNA expression in brain samples, mRNA and protein expression in lymphoblasts, as well as the production of cyclic adenosine monophosphate (cAMP) by lymphoblasts in response to adenosine were compared among ADORA2A diplotypes. RESULTS: Four single nucleotide polymorphisms were completely linked, which resulted in 2 haplotypes, A and B. Haplotype A (C at rs2298383, T at rs5751876, deletion at rs35320474, and C at rs4822492) frequency in patients was significantly higher than in controls (p = 0.005). Homozygous haplotype A (AA diplotype) had a higher risk of developing AESD (odds ratio 2.32, 95% confidence interval 1.32-4.08; p = 0.003) via a recessive model. mRNA expression was significantly higher in AA than AB and BB diplotypes, both in the brain (p = 0.003 and 0.002, respectively) and lymphoblasts (p = 0.035 and 0.003, respectively). In lymphoblasts, ADORA2A protein expression (p = 0.024), as well as cellular cAMP production (p = 0.0006), was significantly higher in AA than BB diplotype. CONCLUSIONS: AA diplotype of ADORA2A is associated with AESD and may alter the intracellular adenosine/cAMP cascade, thereby promoting seizures and excitotoxic brain damage in patients.
    Neurology 03/2013; · 8.25 Impact Factor
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    ABSTRACT: Background: Norovirus (NoV) is recognized as a significant cause of acute gastroenteritis in infants and young children worldwide. This study investigated the prevalence of NoV infection in hospitalized children with gastro-enteritis in Chiang Mai, Thailand in 2006. Methods: A total of 156 fecal specimens were collected from children with diarrhea admitted to McCormick Hos-pital in 2006. All fecal specimens were examined for NoV by RT-PCR and the genotypes were identified by sequence analysis. Results: A high prevalence of NoV infection was detected (20.5%, 32/156). NoV GII/4 was the most predominant genotype with a prevalence of 87.5% (28/32), while GII/3, GII/6, GII/12, and GII/15 were less common (3.1% each). Among GII/4 strains, 2006b variant (75%, 21/28) emerged as the leading strain and dominated over the Hunter’04-like variant, which was the most common strain in the previous season of 2005. In addition, the 2003, 2004, and 2006a variants were also detected. NoV infections were most commonly observed in the rainy season in Thailand. Conclusions: This study demonstrated the emergence of GII/4 2006b variants as the major pathogen causing acute gastroenteritis among infants and children at the age of less than 5 years old who admitted to hospital in Chiang Mai, Thailand in 2006. Additionally, other GII/4 variants of 2003, 2004, and 2006a were also reported.
    Clinical laboratory 03/2013; 59:271-276. · 0.92 Impact Factor

Publication Stats

3k Citations
743.04 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
  • 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
  • 1992–2000
    • Niigata University
      • Department of Pathology
      Niahi-niigata, Niigata, Japan
  • 1995–1997
    • Kyoto Institute of Technology
      Kioto, Kyōto, Japan
  • 1991–1992
    • University of British Columbia - Vancouver
      • Department of Medicine
      Vancouver, British Columbia, Canada