Details of a Researcher - YOKOTA Shinichi

Papers - YOKOTA Shinichi

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Cerebrospinal fluids containing anti-HSP70 autoantibodies from multiple sclerosis patients augment HSP70-induced proinflammatory cytokine production in monocytic cells

Shin-ichi Yokota, Susumu Chiba, Hiroyasu Furuyama, Nobuhiro Fujii

JOURNAL OF NEUROIMMUNOLOGY ( ELSEVIER SCIENCE BV ) 218 ( 1-2 ) 129 - 133 2010.01 [Refereed]

Anti-heat shock protein 70 (HSP70) autoantibodies are found in cerebrospinal fluids (CSF) from patients with multiple sclerosis. These autoantibodies cross-reacted not only with HSP70 and heat shock cognate protein 70 (HSC70). but also with a bacterial homologue, DnaK. CSF with a high anti-HSP70 autoantibody titer enhanced HSP70-induced proinflammatory cytokine and chemokine production in the human monocytic cell line, THP-1. Thus. anti-HSP70 autoantibodies in the CSF of multiple sclerosis patients may play a pathophysiological role in enhancing inflammation. (C) 2009 Elsevier B.V. All rights reserved.

Helicobacter pylori Lipopolysaccharides Upregulate Toll-Like Receptor 4 Expression and Proliferation of Gastric Epithelial Cells via the MEK1/2-ERK1/2 Mitogen-Activated Protein Kinase Pathway

Shin-ichi Yokota, Tamaki Okabayashi, Michael Rehli, Nobuhiro Fujii, Ken-ichi Amano

INFECTION AND IMMUNITY ( AMER SOC MICROBIOLOGY ) 78 ( 1 ) 468 - 476 2010.01 [Refereed]

Helicobacter pylori is recognized as an etiological agent of gastroduodenal diseases. H. pylori produces various toxic substances, including lipopolysaccharide (LPS). However, H. pylori LPS exhibits extremely weakly endotoxic activity compared to the typical LPS, such as that produced by Escherichia coli, which acts through Toll-like receptor 4 (TLR4) to induce inflammatory molecules. The gastric epithelial cell lines MKN28 and MKN45 express TLR4 at very low levels, so they show very weak interleukin-8 (IL-8) production in response to E. coli LPS, but pretreatment with H. pylori LPS markedly enhanced IL-8 production induced by E. coli LPS by upregulating TLR4 via TLR2 and the MEK1/2-ERK1/2 pathway. The transcription factor NF-Y was activated by this signal and promoted transcription of the tlr4 gene. These MEK1/2-ERK1/2 signal-mediated activities were more potently activated by LPS carrying a weakly antigenic epitope, which is frequently found in gastric cancers, than by LPS carrying a highly antigenic epitope, which is associated with chronic gastritis. H. pylori LPS also augmented the proliferation rate of gastric epithelial cells via the MEK1/2-ERK1/2 pathway. H. pylori LPS may be a pathogenic factor causing gastric tumors by enhancing cell proliferation and inflammation via the MEK1/2-ERK1/2 mitogen-activated protein kinase cascade in gastric epithelial cells.

Helicobacter pylori の主要な感染経路は母子感染である―random amplified polymorphic DNA fingerprinting法による検討―

今野武津子, 横田伸一, 藤井暢弘

日本ヘリコバクター学会誌 11 ( 2 ) 59 - 65 2010 [Invited]

Nrc of Streptococcus pneumoniae suppresses capsule expression and enhances anti-phagocytosis

Masaya Yamaguchi, Yuki Minamide, Yutaka Terao, Ryutaro Isoda, Taiji Ogawa, Shin-ichi Yokota, Shigeyuki Hamada, Shigetada Kawabata

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS ( ACADEMIC PRESS INC ELSEVIER SCIENCE ) 390 ( 1 ) 155 - 160 2009.12 [Refereed]

Streptococcus pneumoniae is a major pathogen of community-acquired pneumonia and one of its major virulence factors is pneumolysin, which functions as a cholesterol-dependent cytolytic pore-forming toxin. In this study, we identified the ply-like gene spd0729 in a BLAST search. Unexpectedly, hemolytic and cytotoxic assays showed no significant differences between a Delta spd0729 mutant strain and the wildtype strain, whereas the mutant strain exhibited weaker anti-phagocytic activity in human peripheral blood. In addition, real-time RT-PCR analysis revealed that four capsular biosynthesis genes in the mutant strain had expressions 7- to 432-fold greater than those of the wild type, while an enzyme-linked immunoassay showed a mean 3-fold greater amount of total capsular polysaccharide in the mutant strain. These results suggest that Spd0729 is not a cytolysin, though it plays crucial roles in anti-phagocytosis and regulation of capsule expression. Thus, we named Spd0729 as a negative regulator of capsular polysaccharide synthesis (Nrc). (c) 2009 Elsevier Inc. All rights reserved.

Susceptibility and bactericidal activity of 8 oral quinolones against conventional-fluoroquinolone-resistant Streptococcus pneumoniae clinical isolates

Shin-ichi Yokota, Yasuo Ohkoshi, Nobuhiro Fujii

DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE ( ELSEVIER SCIENCE INC ) 65 ( 1 ) 76 - 80 2009.09 [Refereed]

We evaluated the pharmacokinetic/pharmacodynamic parameters of 8 oral quinolones (ciprofloxacin, garenoxacin [GRNX], gatifloxacin, levofloxacin, moxifloxacin, prulifloxacin, sitafloxacin, and sparfloxacin) on 11 fluoroquinolone-resistant Streptococcus pneumoniae strains, screened from 780 strains isolated from various clinical sources in Japan. GRNX showed the highest area under the blood concentration time curve/MIC ratios, which exceeded the target values for bacterial eradication against all fluoroquinolone-resistant S. pneumoniae strains. (C) 2009 Elsevier Inc. All rights reserved,

High prevalence of beta-lactam-resistant Haemophilus influenzae type b isolates derived from respiratory tract specimens in Japanese patients

Shin-ichi Yokota, Yasuo Ohkoshi, Kiyoshi Sato, Nobuhiro Fujii

INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES ( ELSEVIER SCI LTD ) 13 ( 5 ) 584 - 588 2009.09 [Refereed]

Objective: Serotypeable strains of Haemophilus influenzae, which can cause invasive infections, are found in the respiratory tract at low frequencies. We compared the antibiotic resistance of the typeable and nontypeable strains of H. influenzae in respiratory tract specimens obtained in Japan. Methods: We determined the serotypes and the antibiotic susceptibilities of 440 clinical H. influenzae strains isolated from respiratory tract specimens. We also examined the prevalence of genotypes that are associated with P-lactam resistance. Results: The majority of the strains were nontypeable (421 strains, 95.7%). The remainder belonged to serotypes b (10 strains, 2.3%), e (three strains, 0.7%), or f (six strains, 1.4%). The type b strains exhibited the expression of beta-lactamase and resistance mutations in penicillin-binding protein 3 with significantly higher frequencies than other strains. Conclusions: H. influenzae type b strains, which are associated with meningitis and bacteremia, derived from respiratory tract specimens, shared more p-lactam-resistant mechanisms than nontypeable and other serotype strains. (C) 2008 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

RSV replication is attenuated by counteracting expression of the suppressor of cytokine signaling (SOCS) molecules

Koichi Hashimoto, Kei Ishibashi, Ken Ishioka, Dongchi Zhao, Masatoki Sato, Shinichiro Ohara, Yusaku Abe, Yukihiko Kawasaki, Yuka Sato, Shin-ichi Yokota, Nobuhiro Fujii, Ray Stokes Peebles, Mitsuaki Hosoya, Tatsuo Suzutani

VIROLOGY ( ACADEMIC PRESS INC ELSEVIER SCIENCE ) 391 ( 2 ) 162 - 170 2009.09 [Refereed]

Human RSV causes an annual epidemic of respiratory tract illness in infants and in elderly. Mechanisms by which RSV antagonizes IFN-mediated antiviral responses include inhibition of type I IFN mRNA transcription and blocking signal transduction of JAK/STAT family members. The suppressor of cytokines signaling (SOCS) gene family utilizes a feedback loop to inhibit cytokine responses and block the activation of the JAK/STAT signaling pathway. To evaluate the potential of SOCS molecules to subvert the innate immune response to RSV infection, eight SOCS family genes were examined. RSV infection up-regulated SOCS1, SOCS3, and CIS mRNA expression in HEp-2 cells, Suppression of SOCS 1, SOCS3 and CIS by short interfering ribonucleic acid (siRNA) inhibited viral replication. Furthermore, inhibition of SOCS1, SOCS3, or CIS activated type I IFN signaling by inducing STAT1/2 phosphorylation. These results suggest that RSV infection escapes the innate antiviral response by inducing SOCS1, SOCS3 or CIS expression in epithelial cells. (C) 2009 Elsevier Inc. All rights reserved.

Fosfomycin Suppresses Chemokine Induction in Airway Epithelial Cells Infected with Respiratory Syncytial Virus

Tamaki Okabayashi, Shin-ichi Yokota, Yuko Yoto, Hiroyuki Tsutsumi, Nobuhiro Fujii

CLINICAL AND VACCINE IMMUNOLOGY ( AMER SOC MICROBIOLOGY ) 16 ( 6 ) 859 - 865 2009.06 [Refereed]

Respiratory syncytial virus (RSV) infects airway epithelial cells, causing bronchiolitis and pneumonia. Inflammation is mediated by various cytokines secreted from RSV-infected airway epithelial cells, and it promotes the pathogenesis of RSV-related diseases. Fosfomycin (FOF) is approved as a treatment for various bacterial infectious diseases, including respiratory infectious diseases, in Japan. FOF is suggested to exhibit immunomodulatory effects on lipopolysaccharide-stimulated monocytes and T lymphocytes, in addition to its antimicrobial activity. We investigated the effect of FOF on the cytokine production of an airway epithelial cell line, A549, infected with RSV. RSV-induced cytokines, such as regulated on activation, normal T-cell expressed and secreted (RANTES), interleukin-8 (IL-8), and IL-6, in infected A549 cells. We found that FOF decreased the levels of RSV-induced RANTES and IL-8 but not the level of RSV-induced IL-6. The RANTES promoter was activated by RSV infection. Site-directed mutagenesis analysis of the RANTES promoter showed that NF-kappa B-binding motifs had a critical role in RSV-induced RANTES promoter activity. A luciferase reporter gene assay and a DNA-binding assay indicated that FOF suppressed the NF-kappa B activity induced by RSV infection. These results demonstrate that FOF treatment suppresses the RSV-induced transcription of the chemokines RANTES and IL-8 in airway epithelial cells.

High serum concentrations of autoantibodies to HSP47 in nonspecific interstitial pneumonia compared with idiopathic pulmonary fibrosis.

Tomoyuki Kakugawa, Shin-ichi Yokota, Hiroshi Mukae, Hiroshi Kubota, Noriho Sakamoto, Syunji Mizunoe, Yasuhiro Matsuoka, Jun-ichi Kadota, Nobuhiro Fujii, Kazuhiro Nagata, Shigeru Kohno

BMC pulmonary medicine 8 23 - 23 2008.11 [Refereed] [International journal]

BACKGROUND: The pathological diagnosis of idiopathic interstitial pneumonias (IIP) by surgical lung biopsy is important for clinical decision-making. However, there is a need to use less invasive biomarkers to differentiate nonspecific interstitial pneumonia (NSIP) from other IIP such as usual interstitial pneumonia (UIP). Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagen. HSP47 is increased in various fibrotic diseases. We investigated the autoantibodies to HSP47 in IIPs. METHODS: We measured the serum levels of the autoantibodies to HSP47 in 38 patients with various forms of IIP [16 with idiopathic pulmonary fibrosis (IPF), 15 with idiopathic NSIP, 7 with cryptogenic organizing pneumonia (COP)] and 18 healthy volunteers. RESULTS: The serum levels of autoantibodies to HSP47 in patients with idiopathic NSIP were significantly higher than in patients with IPF (P < 0.01), COP (P < 0.05), and healthy volunteers (P < 0.05). In addition, those in fibrosing NSIP were significantly higher than those of cellular and fibrosing NSIP (p < 0.05). CONCLUSION: We found high levels of anti-HSP47 autoantibody titers in sera of patients with idiopathic fibrosing NSIP compared with other IIPs and healthy volunteers.

Predominance of Mother-to-Child Transmission of Helicobacter pylori Infection Detected by Random Amplified Polymorphic DNA Fingerprinting Analysis in Japanese Families

Mutsuko Konno, Shin-ichi Yokota, Toshihiro Suga, Michiko Takahashi, Kohei Sato, Nobuhiro Fujii

PEDIATRIC INFECTIOUS DISEASE JOURNAL 27 ( 11 ) 999 - 1003 2008.11 [Refereed]

Occurrence of norovirus infections unrelated to norovirus outbreaks in an asymptomatic food handler population

Tamaki Okabayashi, Shin-ichi Yokota, Yasuo Ohkoshi, Hironori Ohuchi, Yasuhiro Yoshida, Masayuki Kikuchi, Koichi Yano, Nobuhiro Fujii

JOURNAL OF CLINICAL MICROBIOLOGY 46 ( 6 ) 1985 - 1988 2008.06 [Refereed]

Enhanced Fe ion-uptake activity in Helicobacter pylori strains isolated from patients with iron-deficiency anemia

Shin-ichi Yokota, Mutsuko Konno, Emi Mino, Kohei Sato, Michiko Takahashi, Nobuhiro Fujii

CLINICAL INFECTIOUS DISEASES 46 ( 4 ) E31 - E33 2008.02 [Refereed]

Measles virus P protein suppresses Toll-like receptor signal through up-regulation of ubiquitin-modifying enzyme A20

Shin-ichi Yokota, Tamaki Okabayashi, Noriko Yokosawa, Nobuhiro Fujii

FASEB JOURNAL 22 ( 1 ) 74 - 83 2008.01 [Refereed]

Emergence. of fluoro quinolone-resistant Haemophilus influenzae strains among elderly patients but not among children

Shin-ichi Yokota, Yasuo Ohkoshi, Kiyoshi Sato, Nobuhiro Fujii

JOURNAL OF CLINICAL MICROBIOLOGY 46 ( 1 ) 361 - 365 2008.01 [Refereed]

Antibiotic susceptibility of Haemophilus influenzae strains isolated from various clinical sources in Hokkaido Prefecture, Japan

Yasuo Ohkoshi, Shin-Ichi Yokota, Kiyoshi Sato, Tasuku Hayashi, Keiko Matsuda, Osamu Kuwahara, Hirotsugu Akizawa, Nobuhiro Fujii

Journal of Infection and Chemotherapy ( Springer Japan ) 14 ( 2 ) 93 - 98 2008 [Refereed]

Any increase in β-lactam-resistant Haemophilus influenzae is a serious problem in respiratory and otolaryngology medicine. In this study, we examined the antibiotic susceptibility and genotype of 457 clinical Haemophilus influenzae strains isolated in Hokkaido Prefecture, Japan. Strains with β-lactam-resistant mutations in gene encoding penicillin-binding protein 3 were more frequently found in lower respiratory tract specimens (sputa) than in upper respiratory tract specimens, such as rhinorrhea. The existence of the TEM-1 β-lactamase gene occurred more frequently in adult patients than in pediatric patients. The results suggest that β-lactam-resistant or nonsusceptible strains are more prevalent in adult patients with respiratory diseases. We observed only a very few strains which were nonsuscpetible to third-generation cephalosporins (CEPs) and carbapenems. However, 12%-13% of the strains were shown to be resistant to penicillins and second-generation CEPs, and approximately 4% of the strains were shown to be nonsusceptible to fourth-generation CEPs. In addition, we identified tetracycline-resistant (2.8%), chloramphenicol-resistant (0.6%), clarithromycin-resistant (2.6%), and fluoroquinolone-nonsusceptible (approximately 2%) H. influenzae strains. © 2008 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases.

Remarkably high prevalence of fts I gene mutations in Haemophilus influenzae isolates from upper respiratory tract infections in children of the Sapporo district, Japan

Atsushi Harimaya, Shin-Ichi Yokota, Kiyoshi Sato, Tetsuo Himi, Nobuhiro Fujii

Journal of Infection and Chemotherapy ( Springer Japan ) 14 ( 3 ) 223 - 227 2008 [Refereed]

Highly-purified Helicobacter pylori LPS preparations induce weak inflammatory reactions and utilize Toll-like receptor 2 complex but not Toll-like receptor 4 complex

Shin-ichi Yokota, Takahiro Ohnishi, Masashi Muroi, Ken-ichi Tanamoto, Nobuhiro Fujii, Ken-ichi Amano

FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY 51 ( 1 ) 140 - 148 2007.10 [Refereed]

Suppression of NF-kappa B and AP-1 activation in monocytic cells persistently infected with measles virus

Tomokazu Indoh, Shin-ichi Yokota, Tamaki Okabayashi, Noriko Yokosawa, Nobuhiro Fujii

VIROLOGY 361 ( 2 ) 294 - 303 2007.05 [Refereed]

Contributions of the lipopolysaccharide outer core oligosaccharide region on the cell surface properties of Pseudomonas aeruginosa

Shin-ichi Yokota, Nobuhiro Fujii

COMPARATIVE IMMUNOLOGY MICROBIOLOGY AND INFECTIOUS DISEASES 30 ( 2 ) 97 - 109 2007.03 [Refereed] [International journal]

Evidence of local antibody response against Alloiococcus otitidis in the middle ear cavity of children with otitis media

Atsushi Harimaya, Ryuta Takada, Tetsuo Himi, Shin-ichi Yokota, Nobuhiro Fujii

FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY 49 ( 1 ) 41 - 45 2007.02 [Refereed]

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