Mamoru Satoh

Kitasato University, Edo, Tōkyō, Japan

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Publications (57)155.72 Total impact

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    ABSTRACT: To identify serum cytokine networks specific to chronic inflammatory demyelinating polyneuropathy (CIDP), serum samples of two subgroups (18 patients with typical CIDP and 12 patients with multifocal acquired demyelinating sensory and motor neuropathy [MADSAM]) were analyzed with multiplex magnetic bead-based cytokine assay. TNF-α, HGF, MIP-1β and IL-1β levels were significantly higher in total CIDP patients than in normal controls. Of these, HGF levels were elevated in typical CIDP patients, but not in MADSAM patients. Patients with high HGF levels showed good responses to steroid treatment. Different cytokine profiles among the CIDP subtypes presumably reflect differences in pathophysiology.
    Journal of Neuroimmunology. 12/2014;
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    ABSTRACT: Erbium-doped yttrium aluminum garnet (Er:YAG) laser treatment has demonstrated favorable wound healing effect after periodontal therapy. One of the reasons may be the positive biological effect of the low-level laser on the irradiated tissues, although the mechanism remains unclear. The aim of this study was to investigate the effect of low-level Er:YAG laser irradiation on cell proliferation and laser-induced differential expression of proteins in human gingival fibroblasts (HGFs) by proteomic analysis. In the first experiment, HGFs were exposed to low-level Er:YAG laser irradiation and the laser-induced cell proliferation and damage were evaluated on day 3. In the second experiment, proteomic analysis was performed on day 1 after irradiation. The peptides prepared from HGFs were analyzed by a hybrid ion trap-Fourier transform mass spectrometer, Mascot search engine, and UniProtKB database. A significant increase in cell proliferation without cell damage after irradiation was observed. Among the total identified 377 proteins, 59 proteins, including galectin-7, which was associated with the process of wound healing, were upregulated and 15 proteins were downregulated in laser-treated HGFs. In the third experiment, the increase in messenger RNA (mRNA) and protein expression of galectin-7 in the irradiated HGFs was validated by various analytical techniques. In addition, the effect of recombinant human galectin-7 on the modulation of HGFs proliferation was confirmed. The results indicate that low-level Er:YAG laser irradiation can promote HGF proliferation and induce a significant change in protein expression and the upregulation of galectin-7 expression may partly contribute to the increase in cell proliferation.
    Lasers in Medical Science 11/2014; · 2.40 Impact Factor
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    ABSTRACT: Most human cancers show chromosomal instability (CIN), but the precise mechanisms remain uncertain. Annexin A2 is frequently overexpressed in human cancers, and its relationship to tumorigenesis is poorly understood. We found that annexin A2 is overexpressed in the nuclei of CIN cells compared with cells with microsatellite instability (MIN). Ectopic annexin A2 expression in MIN cells results in a high level of aneuploidy and induces lagging chromosomes; suppression of annexin A2 in CIN cells reduces such CIN signatures with apoptosis of highly aneuploid cells. Ectopic expression of annexin A2 in MIN cells reduces the expression of centromere proteins. Conversely, annexin A2-knockdown in CIN cells increases the expression of centromere proteins. Moreover, the endogenous expression levels of centromere proteins in CIN cells were greatly reduced compared with MIN cell lines. The reduced expression of centromere proteins likely occurred due to aberrant centromere localization of coilin, a major component of the Cajal bodies. These results suggest that nuclear accumulation of annexin A2 has a crucial role in CIN by disrupting centromere function.
    Oncogene 10/2014; · 8.56 Impact Factor
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    ABSTRACT: The isolation of Brassica napus leaf protoplasts induces reactive oxygen species generation and accumulation in the chloroplasts. An activated isoform of NADPH oxidase-like protein was detected in the protoplasts and the protoplast chloroplasts. The purpose of this study is to define the NADH oxidase-like activities in the H2O2-accumulating protoplast chloroplasts. Proteomic analysis of this protein revealed an isoform of ferredoxin:NADPH oxidoreductase (FNR1). While leaves highly expressed the LFNR1 transcript, protoplasts decreased the expression significantly. The protoplast chloroplasts predominantly expressed soluble FNR1 proteins. While the albino leaves of white kale (Brassica oleracea var. acephala f. tricolor cv. white pigeon) expressed FNR1 protein at the same level as B. napus leaves, the protoplasts of albino leaves displayed reduced FNR1 expression. The albino leaf protoplasts of white kale generated and accumulated H2O2 in the cytoplasm and on the plasma membrane. Intracellular pH showed that the chloroplasts were acidic, which suggest that excess H+ was generated in chloroplast stroma. NADPH content of the protoplast chloroplasts increased by over sixfold during the isolation of protoplasts. This study reports a possibility of mediating electrons to oxygen by an overproduced soluble FNR, and suggests that the FNR has a function in utilizing any excess reducing power of NADPH.
    Plant Molecular Biology 09/2014; · 3.52 Impact Factor
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    ABSTRACT: Humans have three major apolipoprotein E(ApoE) alleles (APOE;ε2,ε3,and ε4) that produce three ApoE protein isoforms. The ε2 allele encodes the ApoE2 isoform (Cys112,Cys158), whereas ε3 encodes the wild-type ApoE3 isoform (Cys112,Arg158), and ε4 encodes the ApoE4 isoform (Arg112,Arg158). Because the type of ApoE expressed is related to sporadic Alzheimer’s disease risk and familial hyperlipidemia, many clinical studies have utilized ApoE typing in recent years. ApoE serotyping is based on the correlation between ApoE genotype and isoform; it is therefore possible to determine the genotype from the blood ApoE isoform combination. Serotyping ApoE using Mass Spectrometry (MS) promises highly accurate results while requiring minimal amounts of blood and reagents, resulting in lower costs, which suggest that proteomic-based ApoE serotyping may eventually become a routine clinical laboratory test. Not limited to ApoE, proteomic analysis of human samples could be used to intentionally determine — and perhaps unintentionally reveal — personal genetic information.
    Expert Review of Proteomics 06/2014; · 3.90 Impact Factor
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    ABSTRACT: Bacterial meningitis is a neurological emergency. Early diagnosis and rapid initiation of antimicrobial therapy are vital. Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) is increasingly used as a rapid and accurate microbial diagnostic method for species identification of pathogens. Although this technology requires a growth step to obtain bacterial colonies for the acquisition of substantial spectra in most cases, it can also be used to analyze clinical specimens such as urine and cerebrospinal fluid for direct bacterial identification. There are very few reports describing the use of MALDI-TOF MS for the direct detection of microorganisms causing bacterial meningitis. We describe a case of bacterial meningitis caused by Klebsiella pneumoniae in which MALDI-TOF MS provided a rapid bacteriological diagnosis, thus enabling early and appropriate treatment. Identification of microbes based on MALDI-TOF MS is now an important technology in clinical microbiology laboratories that are required to provide a rapid diagnosis of bacterial meningitis.
    Clinica chimica acta; international journal of clinical chemistry 05/2014; · 2.54 Impact Factor
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    ABSTRACT: Objective: Previous histochemical studies in demyelinating form of Guillain-Barré syndrome (GBS), acute inflammatory demyelinating polyneuropathy (AIDP), have shown complement deposition on the surface of the Schwann cells, and therefore unknown epitopes would be present on the outer surface of the Schwann cells. Methods: We used proteomic-based approach to search for the target molecules of AIDP in the extracted proteins from schwannoma cells. Sera were obtained from 40 GBS patients, 31 inflammatory disease controls, and 46 normal controls. Results: We found that patients with AIDP after cytomegalovirus (CMV) infection have serum autoantibodies against membrane-organizing extension spike protein (moesin), which is expressed in the Schwann cell processes at the nodes of Ranvier and is crucial for myelination. Of the 40 GBS patients, six had recent CMV infection and five of them (83%) had high levels of serum IgG antibodies against moesin. The anti-moesin antibodies were found in none of disease controls including five with CMV infection but no neuropathy, and only two (4%) of the 46 normal control subjects. Immunocytochemistry showed that moesin was stained at the distal tips of schwannoma cells by sera from the CMV-related AIDP patients but not by sera from controls. Conclusion: Moesin is a possible immunological target molecule of pathogenic autoantibodies in patients with CMV-related AIDP. Classification of Evidence: This study provides Class II evidence that levels of serum anti-moesin antibodies accurately distinguishes CMV-related AIDP from non-CMV related AIDP (sensitivity 83%, specificity 93%).
    Neurology 02/2014; · 8.30 Impact Factor
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    ABSTRACT: Apolipoprotein E (ApoE) typing is considered important because of the association between ApoE and Alzheimer's disease and familial dyslipidemia and is currently performed by genetic testing (APOE genotyping). ApoE levels in plasma and serum are clinically determined by immunoassay. Combining an ApoE immunoassay reagent with proteomic analysis using an Orbitrap mass spectrometer, we attempted to resequence ApoE from trace amounts of serum for typing (serotyping). Most (24 of 33) ApoE mutant proteins registered to date with Online Mendelian Inheritance in Man, such as ApoE2 and ApoE4, involve lysine and arginine mutations. Digestion of mutant ApoE with trypsin will thus result in fragments that differ substantially from wild-type ApoE3 in terms of mass, making serotyping ideally suited to mass spectrometry analysis. The mean coverage of the amino acid sequence of full-length ApoE was 91.6% in the protein resequence. Residues 112 and 158 (which are mutated in ApoE2 and ApoE4) were covered in all samples, and the protein sequences were used for serotyping. Serotypes including all heterozygous combinations (ApoE2/E3, E2/E4, E3/E4) corresponded exactly to the APOE genotyping results in each of the subjects. Our novel ApoE serotyping method with protein resequencing requires no synthesis of stable isotope-labeled peptides or genome analysis. The method can use residual blood from samples collected for routine clinical tests, thus enabling retrospective studies with preserved body fluids. The test could be applied to samples from subjects whose DNA is unavailable. In future studies, we hope to demonstrate the capability of our method to detect rare ApoE mutations.
    PLoS ONE 01/2014; 9(1):e85356. · 3.53 Impact Factor
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    ABSTRACT: Periodontal disease is a bacterial infection that destroys the gingiva and surrounding tissues of the oral cavity. In recent years, studies have shown a definite association between periodontal disease and other inflammatory conditions of the body. High-throughput analysis of proteins has become possible with the development of mass spectrometry technology. This breakthrough in proteome technology enables comparative studies of comprehensive protein expression and identification of protein. In case of periodontal disease, proteome analysis using two-dimensional electrophoresis (2-DE), as well as gel-free methods, has been reported. As a fluid lying in close proximity to periodontal tissue, the gingival crevicular fluid (GCF) is the principal target in the search for biomarkers of periodontal disease, because its protein composition may reflect the disease pathophysiology. Biochemical marker analysis of GCF is effective for objective diagnosis in the early and advanced stages of periodontal disease. Increasing numbers of recent reports have provided evidence that the proteomic approach is a promising tool for the discovery and identification of biochemical markers of periodontal disease. This search is of continuing interest in the field of experimental and clinical periodontal disease research. In this article, we summarize recent comprehensive proteomic studies aimed at discovering and identifying biomarkers of periodontal disease in GCF.
    PROTEOMICS 01/2014; · 4.13 Impact Factor
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    ABSTRACT: Background Bacterial meningitis is a neurological emergency. Early diagnosis and rapid initiation of antimicrobial therapy are vital. Methods Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) is increasingly used as a rapid and accurate microbial diagnostic method for species identification of pathogens. Although this technology requires a growth step to obtain bacterial colonies for the acquisition of substantial spectra in most cases, it can also be used to analyze clinical specimens such as urine and cerebrospinal fluid for direct bacterial identification. There are very few reports describing the use of MALDI-TOF MS for the direct detection of microorganisms causing bacterial meningitis. Results We describe a case of bacterial meningitis caused by Klebsiella pneumoniae in which MALDI-TOF MS provided a rapid bacteriological diagnosis, thus enabling early and appropriate treatment. Conclusions Identification of microbes based on MALDI-TOF MS is now an important technology in clinical microbiology laboratories that are required to provide a rapid diagnosis of bacterial meningitis.
    Clinica Chimica Acta. 01/2014; 435:59–61.
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    ABSTRACT: The majority of human cancer shows chromosomal instability (CIN). Although the precise mechanism remains largely uncertain, proper progression of mitosis is crucial. B-type lamins were suggested to be components of the spindle matrix of mitotic cells and to be involved in mitotic spindle assembly; thus, B-type lamins may contribute to the maintenance of chromosome integrity. Here, using a proteomic approach, we identified lamin B2 as a novel protein involved in CIN. Lamin B2 expression decreased in colorectal cancer cell lines exhibiting CIN, as compared with colorectal cancer cell lines exhibiting microsatellite instability (MIN), which is mutually exclusive to CIN. Importantly, lamin B2 knockdown in MIN-type colorectal cancer cells induced CIN phenotypes such as aneuploidy, chromosome mis-segregation and aberrant spindle assembly, whereas ectopic expression of lamin B2 in CIN-type colorectal cancer cells prevented their CIN phenotypes. Additionally, immunohistochemical analysis showed a lower expression of lamin B2 in cancer tissues extracted from patients with sporadic colorectal cancer (CIN-type) than that from patients with hereditary non-polyposis colorectal cancer (HNPCC; MIN type). Intriguingly, mitotic lamin B2 in MIN cancer cells was localized outside the spindle poles and mitotic lamin B2 localization was diminished in CIN cancer cells, suggesting an important role of lamin B2 in proper mitotic spindle formation. The obtained results suggest that lamin B2 maintains chromosome integrity by ensuring proper spindle assembly and that its downregulation causes CIN in colorectal cancer.
    Oncogenesis. 01/2014; 3:e94.
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    ABSTRACT: Objectives: Recent advances in sophisticated technologies in proteomics should provide promising ways to discover novel markers for hepatocellular carcinoma (HCC) in the early diagnosis. Methods: Serum peptide and protein profiling was conducted by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Profiling was carried out in a training set of 16 patients with HCC and a testing set of 15 patients with cirrhosis without HCC. All the patients were hepatitis C virus positive. Candidate peaks were processed to partial purification, followed by protein identification by amino acid sequence analysis. Immunoprecipitation was conducted to confirm the protein identity. Results: Partial purification and protein identification revealed that one peak that was up-regulated in HCC sera both in the training and the testing sets was a fragment of apolipoprotein A-I (apo A-I). Immunoprecipitation confirmed this result. Conclusions: MALDI-TOF MS analysis revealed that apo A-I is a potential novel serum marker of HCC. Combination of these pretreatments and the current magnet bead-assisted MALDI-TOF MS will further enhance the efficiency of biomarker discovery for HCC.
    American Journal of Clinical Pathology 01/2014; 141(1):52-61. · 2.88 Impact Factor
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    ABSTRACT: Schizophyllum commune is one of the causative agents of basidiomycosis including disorders such as allergic bronchopulmonary mycosis, allergic fungal sinusitis, and mucoid impaction of bronchi, the incidence of those of which has been increasing. These mycoses are difficult to diagnose because only a limited number of diagnostic tools are currently available. The biggest problem is that no specific antigens of S. commune have been identified to enable serodiagnosis of the disease. In this study, we attempted to identify a major antigen of S. commune to establish a reliable serodiagnostic method. We used mass spectrometry to identify an antigen that reacted with the serum of a patient with allergic bronchopulmonary mycosis caused by S. commune. The protein was expressed in Escherichia coli, highly purified, and the patient sera IgG and IgE titers against the protein were determined by enzyme-linked immunosorbent assay. The protein identified as a major antigen of S. commune was named Sch c 1; it was a homolog of glucoamylase. The IgG and IgE titers against Sch c 1 in patient sera were significantly higher than those in healthy volunteer sera (p < 0.01). Sch c 1 is recognized by the host immune system of patients as an antigen/allergen. The purified glucoamylase Sch c 1 is a promising candidate antigen for the serodiagnosis of S. commune-induced mycosis. This article is protected by copyright. All rights reserved.
    Clinical & Experimental Allergy 12/2013; · 4.79 Impact Factor
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    ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of diseases, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), which carries a significant risk of progression to cirrhosis and hepatocellular carcinoma. Since NASH is a progressive but reversible condition, it is desirable to distinguish NASH from simple steatosis, and to treat NASH patients at an early stage. To establish appropriate diagnosis and therapy, the pathological mechanisms of the disease should be elucidated; however, these have not been fully clarified for both NASH and simple steatosis. This study aims to reveal the differences between simple steatosis and NASH. This study used fatty liver Shionogi (FLS) mice as a NASH model, for comparison with dd Shionogi (DS) mice as a model of simple steatosis. Genome-wide gene expression analysis was performed using Affymetrix GeneChip Mouse Genome 430 2.0 Array, which contains 45101 probe sets for known and predicted genes. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry were used to investigate gene expression changes and protein localizations. DNA microarray analysis of the liver transcriptomes and qRT-PCR of both types of mice revealed that LCN2, CXCL1 and CXCL9 mRNAs were overexpressed in FLS mouse livers. Immunohistochemistry showed that CXCL1 protein was mainly localized to steatotic hepatocytes. CXCL9 protein-expressing hepatocytes and sinusoidal endothelium were localized in some areas of inflammatory cell infiltration. Most interestingly, hepatocytes expressing LCN2, a kind of adipokine, were localized around almost all inflammatory cell clusters. Furthermore, there was a positive correlation between the number of LCN2-positive hepatocytes in the specimen and the number of inflammatory foci. Overexpression and distinct localization of LCN2, CXCL1 and CXCL9 in the liver of fatty liver Shionogi mice suggest significant roles of these proteins in the pathogenesis of NASH.
    BMC Gastroenterology 07/2013; 13(1):120. · 2.11 Impact Factor
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    ABSTRACT: Periodontal disease is a bacterial infection that destroys the gingiva and surrounding tissues of the oral cavity. Gingival crevicular fluid (GCF) is extracted from the gingival sulcus and pocket. Analysis of biochemical markers in GCF, which predict the progression of periodontal disease, may facilitate disease diagnosis. However, no useful GCF biochemical markers with high sensitivity for detecting periodontal disease have been identified. Thus, the search for biochemical markers of periodontal disease is of continued interest in experimental and clinical periodontal disease research. Using tandem mass tag (TMT) labeling, we analyzed GCF samples from healthy subjects and patients with periodontal disease, and identified a total of 619 GCF proteins based on proteomic analysis. Of these, we focused on two proteins, MMP-9 and LCN2, which are involved in the progression of periodontal disease. Western blot analysis revealed that the levels of MMP-9 and LCN2 were significantly higher in patients with periodontal disease than in healthy subjects. In addition, ELISA also detected significantly higher levels of LCN2 in patients with periodontal disease than in healthy subjects. Thus, LC-MS/MS analyses of GCF using TMT labeling led to the identification of LCN2, which may be a promising GCF biomarker for the detection of periodontal disease.
    PROTEOMICS 05/2013; · 4.13 Impact Factor

Publication Stats

275 Citations
155.72 Total Impact Points

Institutions

  • 2013–2014
    • Kitasato University
      • School of Science
      Edo, Tōkyō, Japan
  • 2007–2014
    • Chiba University
      • • Department of Molecular Diagnosis
      • • Clinical Proteomics Research Center
      • • Graduate School of Medicine
      Tiba, Chiba, Japan
  • 2009–2013
    • Chiba University Hospital
      Tiba, Chiba, Japan