Yasuo Ono

Vice President(General Affairs)
Faculty of Health and Medical Science,Department of Medical Course,Paramedic CourseDean of Faculty/Chair of Department/Professor
Faculty of Health and Medical Science,Department of Medical Course,Medical Engineering CourseDean of Faculty/Chair of Department/Professor
Faculty of Health and Medical Science,Department of Medical Course,Sports Science CourseDean of Faculty/Chair of Department/Professor
Graduate School of Health Sciences,Doctoral Program in Health SciencesProfessor
Graduate School of Health Sciences,Master's and Doctoral Programs in ParamedicProfessor
Last Updated :2025/10/07

■Researcher basic information

Degree

  • ┣DBM(/)-┫DBedical ┣DBD(/)-┫DBoctor, The University of Tokyo

Research Keyword

  • compromised hosts
  • sepsis
  • drug resistance
  • hospital infection
  • cell migration
  • active oxygen
  • neutrophil
  • Antimicrobial chemotherapy
  • Clinical microbiology
  • neutrophil function
  • host defense
  • Infectious diseases

Field Of Study

  • Life sciences, Infectious disease
  • Life sciences, Immunology
  • Life sciences, Internal medicine - General
  • Life sciences, Gastroenterology
  • Life sciences, Bacteriology

■Career

Career

  • Apr. 2021 - Present
    Teikyo Heisei University, Faculty of Health and Medical Science, Professor/ Director,Faculty of Health and Medical Science/ vice president
  • Apr. 2003 - Mar. 2021
    Teikyo University, School of Medicine
  • Apr. 2003 - Mar. 2021
    Department of Microbiology & Immunology, Teikyo University School of Medicine, Professor & Chairman
  • Apr. 2003 - Mar. 2021
  • Apr. 2003 - Mar. 2021
    Teikyo University
  • 1999 - 2003
    Teikyo University, School of Medicine
  • 1999 - 2003
    Department of Microbiology & Immunology, Teikyo University School of Medicine, Associate Professor
  • 1995 - 1999
    Teikyo University, School of Medicine
  • 1995 - 1999
    Department of Internal Medicine, Teikyo University School of Medicine, Assistant Professor
  • 1994 - 1995
    Teikyo University, School of Medicine
  • 1994 - 1995
    2nd Department of Internal Medicine, Teikyo University School of Medicine, Assistant
  • 1993 - 1994
  • 1993 - 1994
    Department of Infectious Diseases, Kansas University Medical Center, Visiting research
  • 1992 - 1993
    The University of Tokyo, The Institute of Medical Science
  • 1992 - 1993
    Department of Bacterial Infection, The Institute of Medical Science, The University of Tokyo, Researcher
  • Apr. 1985 - 1992
    Teikyo University, School of Medicine
  • 1985 - 1992
    2nd Department of Internal Medicine, Teikyo University School of Medicine, Assistant
  • May 1981 - May 1984
    The University of Tokyo, The Institute of Medical Science

Educational Background

  • 1981, The University of Tokushima, Faculty of Medicine, School of Medicine

Member History

  • 1989 - Present
  • 1989 - Present
  • 1988 - Present
  • Jan. 1999 - Dec. 2023
  • Nov. 2012 - Oct. 2022
  • Mar. 2004 - Apr. 2022
  • May 2004 - Mar. 2021
  • Mar. 2013 - Feb. 2017
  • 2000 - 2008
  • 2001 - 2004

■Research activity information

Award

  • 1993
    Japan

Paper

  • Cefmetazole, flomoxef, and meropenem are effective against planktonic cells but not biofilms of extended-spectrum β-lactamase-producing Escherichia coli.
    Nami Hatayama; Yoshinori Sato; Rika Tahira; Toki Hori; Shigeru Tansho-Nagakawa; Yasuo Ono; Yusuke Yoshino
    BMC microbiology, 02 Jul. 2025, [Reviewed]
    BACKGROUND: Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli is a potential  public health threat through its spread into the environment. Cefmetazole (CMZ) and flomoxef (FMOX) are highly effective alternatives to meropenem (MEM) for the management of ESBL-producing E. coli infections. However, their antimicrobial effects on biofilms remain unclear. Therefore, this study aimed to elucidate the inhibitory and bactericidal effects of CMZ, FMOX, and MEM on the biofilms formed by ESBL-producing E. coli. METHODS: Three ESBL-producing E. coli clinical isolates with biofilm-forming abilities (strains F6, F11, and U3) were used in the present study. Biofilm formation and viability assay kits were used to assess the inhibitory and bactericidal effects of these antibiotics on the biofilm-dispersed and biofilm cells of these strains. Scanning electron microscopy (SEM) was used to acquire images of the biofilms treated with these antibiotics. RESULTS: CMZ and MEM exerted significant inhibitory effects on the growth of biofilm-dispersed cells of all three strains at 1 × minimum inhibitory concentration (MIC). FMOX also exerted significant inhibitory effects on the growth of biofilm-dispersed cells of F11 strain at 1 × MIC; however, it exerted inhibitory effects on the growth of biofilm-dispersed cells of strains F6 and U3 in a concentration-dependent manner. CMZ, FMOX, and MEM exerted different bactericidal effects on biofilm-dispersed cells. CMZ exerted significant inhibitory effects on biofilm formation in all strains at 1 × MIC, whereas MEM exerted significant inhibitory effects on biofilm formation in the F6 and F11 strains at 1 × MIC. FMOX induced biofilm formation in F6 and U3 strains at concentrations between 1 × and 4 × MICs. Notably, CMZ, FMOX, and MEM did not exert bactericidal effects on the biofilm cells of any strain. SEM analysis revealed the induction of bacterial filamentation in the presence of CMZ and FMOX and spheroplast formation in the presence of MEM at 1 × MIC. CONCLUSIONS: CMZ, FMOX, and MEM exhibited varying antimicrobial effects against ESBL-producing E. coli biofilms. Notably, FMOX may increase biofilm formation by inducing strong morphological changes. CMZ and FMOX are effective alternatives to MEM for ESBL-producing E. coli infections; however, their use requires the consideration of biofilm formation.
  • Genomic plasticity of extensively drug-resistant and multidrug-resistant Acinetobacter baumannii ST208 isolates from a fatal outbreak.
    Satoshi Nishida; Yasuo Ono
    Journal of infection and public health, 07 Mar. 2025, [Reviewed]
    BACKGROUND: The prevalence of multidrug-resistant Acinetobacter baumannii (MDRA) has rapidly increased and is linked to severe nosocomial infections. MDRA outbreaks in a Japanese hospital were analysed using whole-genome sequencing. METHODS: Antibiotic susceptibility testing was performed on clinical isolates from hospitalised patients before and during the 2009 and 2010 outbreaks. Whole-genome sequencing was conducted to identify acquired antibiotic-resistance genes and genetic mutations. RESULTS: Clinical A. baumannii isolates were resistant to β-lactams (broad-spectrum cephalosporins and carbapenems), aminoglycosides, chloramphenicol, fosfomycin, fluoroquinolones, tetracyclines, and trimethoprim-sulfamethoxazole. MDRA isolates harboured aac(6')-Ib-cr, abaF, armA, blaADC-30, blaTEM-1, and blaOXA-82, or both blaOXA-66 and blaOXA-23, catB8, mphE, msrE, and tet(B). blaOXA-82 genes were recombinationally multiplied. Quinolone resistance was also associated with gyrA S81L and parC S84L mutations. The MDRA isolates belonged to Oxford sequence type (ST) 208 and Pasteur ST2. Three of the 15 isolates developed an extensively drug-resistant (XDR) phenotype, and two isolates harboured an adeS mutation. CONCLUSIONS: We identified molecular resistance markers in three XDR and one MDR isolate and provided a genomic description of resistance and virulence, as well as the origins of the isolates. The isolates are closely related to MDRA Oxford ST208 and Pasteur ST2, identified in Asia and Australia. MDRA isolates are of concern in both hospital and community settings in the Western Pacific region.
  • Immunobiological effects of lipopolysaccharide derived from Helicobacter pylori and influence of a proton pump inhibitor lansoprazole on human polymorphonuclear leukocytes.
    Yoji Koshibu; Tsuneyuki Ubagai; Yusuke Yoshino; Yasuo Ono
    Folia microbiologica, Dec. 2024, [Reviewed]
    Helicobacter pylori colonizes the human gastric mucosa of more than half of the human population and has a unique lipopolysaccharide (LPS) structure. LPS is the most dominant and suitable pathogen-associated molecular pattern that is detected via pattern recognition receptors. Although the priming effect of H. pylori LPS on reactive oxygen species (ROS) production of PMNs is lower than that of Escherichia coli O111:B4 LPS, LPS released from H. pylori associated with antibiotics eradication therapy may activate PMNs and increase ROS production. In addition, we describe the effects of H. pylori and E. coli O111:B4 LPSs on gene expression and the anti-inflammatory effect of lansoprazole (LPZ) in human polymorphonuclear leukocytes. LPS isolated from H. pylori and E. coli O111:B4 alters toll-like receptor 2 (TLR) and TLR4 expressions similarly. However, LPS from E. coli O111:B4 and H. pylori caused a 1.8-fold and 1.5-fold increase, respectively, in CD14 expression. All LPS subtypes upregulated TNFα and IL6 expression in a concentration-dependent manner. Although E. coli O111:B4 LPS upregulated IL8R mRNA levels, H. pylori LPS did not (≦ 100 ng/mL). Gene expression levels of ITGAM demonstrated no significant change on using both LPSs. These different effects on the gene expression in PMNs may depend on variations in LPS structural modifications related to the acquired immunomodulatory properties of H. pylori LPS. Proton pump inhibitors, i.e., LPZ, are used in combination with antibiotics for the eradication therapy of H. pylori. LPZ and its acid-activated sulphenamide form AG-2000 suppress ROS production of PMNs in a dose-dependent manner. These results suggest that LPZ combination with antibiotics for H. pylori eradication reduces gastric inflammation by suppressing ROS release from PMNs.
  • Identification and characterisation of colistin-resistant Acinetobacter colistiniresistens co-producing IMP-1 and OXA-58 carbapenemases.
    Satoshi Nishida; Yasuo Ono
    New microbes and new infections, Dec. 2024, [Reviewed]
    BACKGROUND: Carbapenem-resistant Acinetobacter is of increasing global concern because infections are challenging to treat with standard antibiotics. Here, we identified a previously uncharacterised Acinetobacter sp. clinical isolate as Acinetobacter colistiniresistens co-producing IMP-1 and OXA-58. We also examined expression of genes related to antibiotic susceptibility and drug resistance, including bla IMP. METHODS: The isolate was deposited at the National Institute of Technology and Evaluation (NITE) as Acinetobacter sp. NBRC 110496. Susceptibility was defined according to the Clinical and Laboratory Standards Institute (CLSI) breakpoints. Genomic and clonal analyses were performed to identify species and resistance genes. RESULTS: The isolate was resistant to β-lactams, including broad-spectrum cephalosporins and carbapenems, polymyxins, and trimethoprim/sulfamethoxazole. Genomic analysis identified the isolate as A. colistiniresistens harbouring bla IMP-1, bla OXA-58, bla OXA-670, aac(6')-Ib, aac(6')-Ij, ant(3")-I I, aph(3')-VI, msrE, mphE, and sul1. Colistin resistance was associated with the eptA-like gene, which encodes a lipid A-modifying enzyme. SNP-based phylogenetic analysis revealed that the strain clustered with other strains isolated in Japan. The IMP-1/OXA-58-producing strain described in this study has a novel integron structure surrounding bla IMP-1, aacA and sul1. CONCLUSIONS: Colistin-resistant IMP-1/OXA-58-co-producing A. colistiniresistens was identified in a patient. This isolate could serve as a reservoir for carbapenemase-producing organisms. This study suggests that screening for colistin-resistant isolates is crucial to preserve colistin as a therapeutic agent for multidrug-resistant bacteria. Identification of this MDR isolate in Asia, and the danger of it spreading worldwide, should raise serious concerns.
  • Genomic analysis of extensively drug-resistant Acinetobacter baumannii harbouring a conjugative plasmid containing aminoglycoside resistance transposon TnaphA6.
    Satoshi Nishida; Yasuo Ono
    Journal of infection and public health, 07 Dec. 2023, [Reviewed]
    The occurrence of multidrug-resistant Acinetobacter baumannii (MDRA) has increased rapidly and is associated with severe nosocomial infections. MDRA has emerged in the hospital setting and has evolved into extensively drug-resistant A. baumannii (XDRA). A clinical XDRA isolate obtained from a hospitalised patient in 2016 was evaluated for antibiotic susceptibility and whole-genome sequence. The XDRA isolate was resistant to β-lactams, including broad-spectrum cephalosporins and carbapenems, and to aminoglycosides, fosfomycin, fluoroquinolones, tetracyclines, tigecycline, and trimethoprim-sulfamethoxazole. The isolate harboured abaF, ant(3″)-II-c, aph(3″)-Ib, aph(6)-Id, armA, blaADC-73, blaTEM-1, blaOXA-66, blaOXA-23, mphE, msrE and tet(B). Quinolone resistance was associated with mutations gyrA S81L and parC S84L. Tigecycline resistance was associated with a mutation in adeS. The isolate belonged to Oxford and Pasteur scheme sequence type 1050 and 2, respectively, and harboured a conjugative plasmid containing the aminoglycoside resistance transposon TnaphA6. Our study demonstrates that the isolate is closely related to a recent MDRA identified in Australia and the USA, in which a similar conjugative plasmid is not observed. Although the MDRA in Australia caused an outbreak, our hospital's surveillance protocol managed to prevent a further outbreak. Our finding suggests that this XDRA isolate is of concern in hospital and community care settings. The gpi allele could be a marker for discriminating this isolate from clonal complex 92 isolates.
  • Genetic relatedness of third-generation cephalosporin-resistant Escherichia coli among livestock, farmers, and patients in Japan
    Ryuichi Nakano; Akiyo Nakano; Ryuji Nishisouzu; Kenji Hikosaka; Yuki Suzuki; Go Kamoshida; Shigeru Tansho-Nagakawa; Shiro Endo; Kei Kasahara; Yasuo Ono; Hisakazu Yano
    One Health, Jun. 2023, [Reviewed]
    OBJECTIVES: The third-generation cephalosporin (3GC)-resistant E. coli strains have been detected worldwide in humans and animals. Hence, in this study, we evaluated the prevalence and genetic characteristics of 3GC-resistant E. coli in livestock, farmers, and patients to further analyse if livestock serves as a potential reservoir of antimicrobial-resistant bacteria. METHODS: Faecal samples were collected from 330 healthy livestock (216 cattle and 114 swine), 61 healthy livestock farmers (52 cattle farmers and 9 swine farmers), and 68 non-duplicate 3GC-resistant E. coli isolates were also obtained from the clinical specimens of patients in Japan between 2013 and 2015. Genes associated with resistance in 3GC-resistant E. coli were identified using polymerase chain reaction (PCR) and DNA sequencing. Genotypic diversity was determined by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). RESULTS: We obtained 39 and 17 non-duplicated 3GC-resistant E. coli strains from healthy livestock (33 cattle and six swine) and livestock farmers, respectively. All isolates carried either CTX-M-type extended-spectrum β-lactamase or plasmid-mediated AmpC β-lactamase genes, with CTX-M-14 being the most frequent. CTX-M producers from livestock and patients belonged to 22 and 19 different sequence types (STs), respectively, and only three STs were the same. Among the 3GC-resistant E. coli from livestock and farmers, three types of CTX-M producers have shown similar characteristics (CTX-M genotype, ST, PFGE patterns, and antimicrobial susceptibilities) and were identified as clonal isolates shared among their farms. CONCLUSIONS: Our study findings indicate that CTX-M-14 is predominant in Japan. No distinct relationship was observed between the 3GC-resistant E. coli isolated from livestock and patients; however, some clonal relatedness was observed between the isolates from livestock and farmers due to their close contact.
  • Evaluation of an immunological assay for the identification of multiple carbapenemase-producing Gram-negative bacteria.
    Satoshi Nishida; Yusuke Ihashi; Yusuke Yoshino; Yasuo Ono
    Pathology, Dec. 2022, [Reviewed]
    Carbapenemase-producing Gram-negative organisms (CPOs) frequently gain multidrug-resistant phenotypes and thereby limit the therapeutic options available. Colonisation and infection with CPOs are critical risks for mortality in clinical settings, especially in critical care medicine. Carbapenemase genes on plasmids have transferred to many Gram-negative species, and these species have spread, leading to global concern regarding antimicrobial resistance. A molecular rapid diagnostic test (mRDT) for CPOs is urgently required in critical care medicine. Here, we evaluated a rapid lateral flow immunoassay (LFIA) for CPOs isolated from patients at university hospitals, including intensive care units, and compared the results with those obtained using the multiplex polymerase chain reaction (PCR) method. NG-test CARBA 5 detected multiple carbapenemases, KPC, OXA-48, NDM, VIM, and IMP variants expressed in clinical isolates. Quick Chaser IMP detected IMP variants. The LFIAs exhibited 100% sensitivity and specificity relative to clinical isolates on agar plates. By contrast, the multiplex PCR method exhibited a limited ability to detect IMP-7-producing isolates not belonging to the IMP1 group, which resulted in 97% sensitivity and 100% specificity for IMP-producing isolates. Our results demonstrate that the LFIA is a useful mRDT to identify CPOs and has an advantage over the PCR method for both detection time and sensitivity to the IMP groups. LFIA could complement the nucleic acid amplification test used to identify CPOs. In conclusion, we evaluated sensitive and specific LFIAs capable of detecting carbapenemase production in Gram-negative bacteria. We anticipate that LFIAs will become a point-of-care test enabling rapid detection of carbapenemases in hospital settings, particularly in intensive care units.
  • Tigecycline Suppresses the Virulence Factors of Multidrug-Resistant Acinetobacter baumannii Allowing Human Neutrophils to Act
    Yoshinori Sato; Nami Hatayama; Tsuneyuki Ubagai; Shigeru Tansho-Nagakawa; Yasuo Ono; Yusuke Yoshino
    Infection and Drug Resistance, Jun. 2022, [Reviewed]
  • Histopathological Analysis of Acinetobacter baumannii Lung Infection in a Mouse Model.
    Shigeru Tansho-Nagakawa; Yoshinori Sato; Tsuneyuki Ubagai; Takane Kikuchi-Ueda; G O Kamoshida; Satoshi Nishida; Yasuo Ono
    Polish journal of microbiology, Dec. 2021, [Reviewed]
    Acinetobacter baumannii is the main causative pathogen of nosocomial infections that causes severe infections in the lungs. In this study, we analyzed the histopathological characteristics of lung infection with two strains of A. baumannii (ATCC 19606 and the clinical isolate TK1090) and Pseudomonas aeruginosa PAO-1 in C3H/HeN mice to evaluate the virulence of A. baumannii. Survival was evaluated over 14 days. At 1, 2, 5, or 14 days postinfection, mice of C3H/HeN were sacrificed, and histopathological analysis of lung specimens was also performed. Histopathological changes and accumulation of neutrophils and macrophages in the lungs after infection with A. baumannii and P. aeruginosa were analyzed. Following intratracheal inoculation, the lethality of ATCC 19606- and TK1090-infected mice was lower than that of PAO-1-infected mice. However, when mice were inoculated with a sub-lethal dose of A. baumannii, the lung bacterial burden remained in the mice until 14 days post-infection. Additionally, histopathological analysis revealed that macrophages infiltrated the lung foci of ATCC 19606-, TK1090-, and PAO-1-infected mice. Although neutrophils infiltrated the lung foci of ATCC 19606- and TK1090-infected mice, they poorly infiltrated the lung foci of PAO-1-infected mice. Accumulation of these cells in the lung foci of ATCC 19606- and TK1090-infected mice, but not PAO-1-infected mice, was observed for 14 days post-infection. These results suggest that A. baumannii is not completely eliminated despite the infiltration of immune cells in the lungs and that inflammation lasts for prolonged periods in the lungs. Further studies are required to understand the mechanism of A. baumannii infection, and novel drugs and vaccines should be developed to prevent A. baumannii infection.
  • Optimization and application of silver staining of non-glycosylated and glycosylated proteins and nucleic acids for agarose native gel electrophoresis.
    Masataka Nakagawa; Yui Tomioka; Chiaki Sakuma; Ryo Sato; Takashi Shibata; Yasunori Kurosawa; Yoshinori Sato; Yasuo Ono; Tsutomu Arakawa; Teruo Akuta
    International journal of biological macromolecules, 23 Aug. 2021, [Reviewed]
    Electrophoresis is one of the major techniques to analyze macromolecular structure and interaction. Its capability depends on the sensitivity and specificity of the staining methods. We have here examined silver staining of proteins and nucleic acids separated by agarose native gel electrophoresis. By comparing five commercial kits, we identified Silver Stain Plus from Bio-Rad most adequate, as it provided little background staining and reasonable band staining. One of the disadvantages of the Silver Stain Plus kit is its variable staining of glycoproteins as tested with several model samples, including hen egg white proteins, α1-acid glycoprotein and SARS-CoV-2 Spike protein. One of the advantages of silver staining is its ability to stain nucleic acids as demonstrated here for a model nucleic acid with two kits. It was then used to monitor the removal of nucleic acids from the affinity-purified maltose binding protein and monoclonal antibody. It also worked well on staining proteins on agarose gels prepared in the vertical mode, although preparation of the vertical agarose gels required technological modifications described in this report. With the silver staining method optimized here, it should be possible in the future to analyze biological samples that may be available in limited quantity.
  • A rabbit monoclonal antibody-mediated lateral flow immunoassay for rapid detection of CTX-M extended-spectrum β-lactamase-producing Enterobacterales.
    Satoshi Nishida; Masataka Nakagawa; Yuki Ouchi; Chiaki Sakuma; Yu Nakajima; Hisayo Shimizu; Takashi Shibata; Yasunori Kurosawa; Toshiaki Maruyama; C J Okumura; Nami Hatayama; Yoshinori Sato; Miwa Asahara; Shinobu Ishigaki; Taiji Furukawa; Teruo Akuta; Yasuo Ono
    International journal of biological macromolecules, 12 Jun. 2021, [Reviewed]
    Infections of CTX-M extended-spectrum β-lactamase-producing Enterobacterales are a severe threat in clinical settings. CTX-M genes on plasmids have been transferred to many Enterobacterales species, and these species have spread, leading to the global problem of antimicrobial resistance. Here, we developed a lateral flow immunoassay (LFIA) based on an anti-CTX-M rabbit monoclonal antibody. This antibody detected CTX-M variants from the CTX-M-9, CTX-M-2, and CTX-M-1 groups expressed in clinical isolates. The LFIA showed 100% sensitivity and specificity with clinical isolates on agar plates, and its limit of detection was 0.8 ng/mL recombinant CTX-M-14. The rabbit monoclonal antibody did not cross-react with bacteria producing other class A β-lactamases, including SHV and KPC. In conclusion, we developed a highly sensitive and specific LFIA capable of detecting CTX-M enzyme production in Enterobacterales. We anticipate that our LFIA will become a point-of-care test enabling rapid detection of CTX-M in hospital and community settings as well as a rapid environmental test.
  • Effects of colistin and tigecycline on multidrug-resistant Acinetobacter baumannii biofilms: advantages and disadvantages of their combination.
    Yoshinori Sato; Tsuneyuki Ubagai; Shigeru Tansho-Nagakawa; Yusuke Yoshino; Yasuo Ono
    Scientific reports, 03 Jun. 2021, [Reviewed]
    We investigated the antimicrobial effects of colistin (CST) and tigecycline (TGC), either alone or in combination, on biofilm-dispersed and biofilm-embedded multidrug-resistant Acinetobacter baumannii (MDRAB) strains R1 and R2. The bacterial growth of biofilm-dispersed MDRAB was inhibited by CST or TGC. However, the inhibitory effects were attenuated by a combination of CST and low concentrations of TGC. The bactericidal effects of CST, but not TGC, were observed on biofilm-dispersed MDRAB. Notably, the bactericidal effects increased with a combination of CST and high concentrations of TGC, whereas they were attenuated with the combination of CST and low concentrations of TGC. Although biofilm formation by MDRAB decreased with increasing concentrations of CST or TGC, there was no complete disruption of the biofilms. Additionally, the biofilms increased with a combination of 1-2 μg/mL CST and TGC at 2 μg/mL and 2-4 μg/mL for strains R1 and R2, respectively. Biofilm-embedded MDRAB was eradicated with CST, but not TGC. Notably, the eradication effects increased with a combination of CST and high concentrations of TGC, whereas attenuation happened with the combination of CST and low concentrations of TGC. These results provide information on the combined effects of CST and TGC in the treatment of biofilm-associated MDRAB infection.
  • Prevalence and Relatedness of mcr-1-Mediated Colistin-Resistant Escherichia coli Isolated From Livestock and Farmers in Japan.
    Akiyo Nakano; Ryuichi Nakano; Ryuji Nishisouzu; Yuki Suzuki; Saori Horiuchi; Takane Kikuchi-Ueda; Tsuneyuki Ubagai; Yasuo Ono; Hisakazu Yano
    Frontiers in microbiology, 26 Apr. 2021, [Reviewed]
    Colistin is used to treat infectious diseases in humans and livestock; it has also been used as a feed additive for livestock for approximately 50 years. Since the mcr-1 plasmid-mediated colistin resistance gene was discovered in China in 2015, it has been detected worldwide, mainly in livestock. In this study, we investigated the prevalence and characteristics of mcr-mediated colistin-resistant Escherichia coli in livestock and farmers in Japan. We collected fecal samples from 295 healthy livestock (202 cattle and 93 swine) and 62 healthy farmers from 72 livestock farms (58 cattle farms and 14 swine farms) between 2013 and 2015. Twenty-eight mcr-1-harboring E. coli strains were isolated from 25 livestock (six cattle and 19 swine) and three farmers (two cattle farmers and one swine farmer). The prevalence rates of mcr-1-harboring E. coli in livestock and farmers were 8.47 and 4.84%, respectively. Of the 28 strains, the resistance genes of three were transferable via the mcr-1-coding plasmids to E. coli J53 at low frequencies (10-7-10-8). Six strains coharbored mcr-1 with CTX-M β-lactamases (CTX-M-14, CTX-M-27, or CTX-M-156). Of the isolates obtained from livestock and farmers in four farms (farms C, I, N, and P), nine strains had the same genotypical characteristics (sequence types and pulsed-field gel electrophoresis band patterns), plasmid characteristics (incompatibility group and plasmid transferability), and minimum inhibitory concentrations. Thus, the findings suggested that clonal strains could spread among livestock and farmers within farms. To our knowledge, this is the first study to detect clonal relatedness of mcr-1-mediated colistin-resistant E. coli in livestock and farmers. It is suggested that farmers are at a higher risk of acquiring mcr-1-harboring strains, calling for our attention based on the One Health concept.
  • Development of a rapid scabies immunodiagnostic assay based on transcriptomic analysis of Sarcoptes scabiei var. nyctereutis.
    Teruo Akuta; Daisuke Minegishi; Nobuhide Kido; Keitaro Imaizumi; Shinji Nakaoka; Shin-Ichiro Tachibana; Kenji Hikosaka; Fumi Hori; Masataka; Nakagawa; Chiaki Sakuma; Yuki Oouchi; Yu Nakajima; Sohei Tanaka; Tomoko Omiya; Kouki Morikaku; Minori Kawahara; Yoshifumi Tada; Hiroshi Tarui; Takafumi Ueda; Takane Kikuchi-Ueda; Yasuo Ono
    Scientific reports, 19 Mar. 2021, [Reviewed]
    Scabies is a highly contagious skin disease caused by the mite Sarcoptes scabiei that affects many mammals. However, the sensitivity of traditional tests for scabies diagnosis in humans is less than 50%. To simplify the diagnosis of scabies, methods that are simple, sensitive, specific, and cost-effective are required. We developed an immunodiagnostic test based on S. scabiei var. nyctereutis RNA-seq data collected from Japanese raccoon dogs with sarcoptic mange. Three candidate antigens-a highly expressed hypothetical protein "QR98_0091190," another mite allergen known as "SMIPP-Cc," and an abundant "vitellogenin-like protein"-were evaluated by western-blot analysis. A lateral flow immunoassay, using specific antibodies against the vitellogenin-like protein, successfully detected scabies in the skin flakes of S. scabiei-infected raccoon dogs. This assay can potentially diagnose scabies more accurately in wildlife, as well as in humans.
  • Acinetobacter baumannii LOS Regulate the Expression of Inflammatory Cytokine Genes and Proteins in Human Mast Cells.
    Takane Kikuchi-Ueda; Tsuneyuki Ubagai; Go Kamoshida; Ryuichi Nakano; Akiyo Nakano; Yasuo Ono
    Pathogens (Basel, Switzerland), 03 Mar. 2021, [Reviewed]
    Herein, we investigated the effect of bacterial lipooligosaccharides (LOS), from Acinetobacter baumannii, on the expression of pro-inflammatory genes that play an essential role in bacterial clearance. LAD2 human mast cells were stimulated with LOS derived from two strains of A. baumannii-ATCC 19606 and MDRA T14. LOS exposure induced the expression of genes for pro-inflammatory mediators, including TNF-α, IL-8, LTC4S, CCL4, and TLR4. The mRNA expression levels of a majority of the pro-inflammatory genes, except TLR4, in A. baumannii-LOS stimulated mast cells were increased. Moreover, co-culture of neutrophils with the supernatant obtained from LOS (ATCC 19606 and MDRA T14)-induced LAD2 cells increased the transmigration of neutrophils, which plays a critical role in the early protection against bacterial infections. The results of the present study suggest that LOS could be involved in the pathogenicity of A. baumannii by inducing inflammatory responses via mast cells and that IL-8 is involved in recruiting neutrophils in response to bacterial invasion.
  • Immunomodulatory gene expression analysis in LPS-stimulated human polymorphonuclear leukocytes treated with antibiotics commonly used for multidrug-resistant strains.
    Tsuneyuki Ubagai; Yoshinori Sato; Go Kamoshida; Yuka Unno; Yasuo Ono
    Molecular immunology, 30 Nov. 2020, [Reviewed]
    Conventional antibiotics used for the treatment of severe infections such as sepsis and septic shock confer immunomodulatory benefits. However, the growing problem of multidrug resistant infections has led to an increase in the administration of non-conventional last-resort antibiotics, including quinolones, aminoglycosides, and polypeptides, and the effects of these drugs on immunomodulatory gene expression in activated human polymorphonuclear leukocytes (PMNs) have not been reported. In this study, lipopolysaccharide-stimulated PMNs were incubated with piperacillin, rifampicin, fosfomycin (FOM), levofloxacin (LVFX), minocycline (MINO), colistin, tigecycline, or amikacin, and the mRNA expression levels of pattern recognition receptors (TLR2, TLR4, and CD14), inflammatory cytokines (TNFα and IL6), and chemokine receptors (IL8Rs and ITGAM) in these cells were quantitated using real-time qPCR. Many of the tested antibiotics altered the expression of the investigated cytokines. Notably, FOM, LVFX, and MINO significantly downregulated the expression of IL6, which is associated with pro- and anti-inflammatory defense mechanisms. Treatment of FOM and LVFX reduced IL-6 production as well as observed for IL6 gene expression. These findings indicated transcription and translation cooperation under the used experimental conditions. Therefore, our findings suggest that administration of these antibiotics suppresses the host anti-inflammatory response.
  • Emergence of Enterobacter cloacae Complex Co-Producing IMP-10 and CTX-M, and Klebsiella pneumoniae Producing VIM-1 in Clinical Isolates in Japan.
    Satoshi Nishida; Naohisa Matsunaga; Yuta Kamimura; Shinobu Ishigaki; Taiji Furukawa; Yasuo Ono
    Microorganisms, 18 Nov. 2020, [Reviewed]
    BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE) are an emerging threat in healthcare settings worldwide. OBJECTIVES: We evaluated the presence of carbapenemase genes in CPE in a tertiary care university hospital in Tokyo, Japan. METHODS: Carbapenem-resistant clinical isolates were collected in 2018 at Teikyo University Hospital (Tokyo, Japan). Bacterial species were identified using MALDI-TOF MS. Carbapenemase production was evaluated using a carbapenemase inactivation method. The presence of carbapenemase genes was confirmed by multiplex PCR and DNA sequencing. RESULTS: Four CPE isolates were identified: two Enterobacter cloacae complex strains and Klebsiella oxytoca and Klebsiella pneumoniae strains. Three of the isolates (E. cloacae complex and K. oxytoca) were IMP-1-type producers, including IMP-10 in their produced metallo-β-lactamase, and are epidemic in East Japan. The IMP-10-producing E. cloacae complex strain also produced CTX-M ESBL. The other CPE isolate (K. pneumoniae) is a VIM-1 producer. VIM-1-producing K. pneumoniae is epidemic in Europe, especially in Greece. Accordingly, the VIM-1 producer was isolated from a patient with a medical history in Greece. CONCLUSIONS: This study revealed the emergence of E. cloacae complex co-producing IMP-1-type carbapenemase and CTX-M ESBL, and K. pneumoniae producing VIM-1 carbapenemase in clinical isolates in Japan. Metallo-β-lactamase was the most prevalent type of carbapenemase at Teikyo University Hospital, especially IMP-1-type carbapenemase. The detection of VIM-1-producing K. pneumoniae suggests that epidemic CPE from overseas can spread to countries with low CPE prevalence, such as Japan, highlighting the need for active surveillance.
  • Genomic analysis of a pan-resistant Klebsiella pneumoniae sequence type 11 identified in Japan in 2016.
    Satoshi Nishida; Yasuo Ono
    International journal of antimicrobial agents, Apr. 2020, [Reviewed]
    BACKGROUND: Klebsiella pneumoniae (K. pneumoniae) carbapenemase (KPC)-producing K. pneumoniae has rapidly expanded and is associated with severe nosocomial infections. Last-line antibiotics, such as colistin and tigecycline, remain the only treatment option. This study described the genetic background of a novel pan-resistant KPC-producing K. pneumoniae isolate from Tokyo, Japan. METHODS: The antibiotic susceptibility of clinical isolates from a patient hospitalised in 2016 was tested using a MicroScan WalkAway instrument and the broth microdilution method. Susceptibility was defined according to breakpoints provided by the Clinical and Laboratory Standards Institute. Whole-genome sequencing was performed to detect acquired resistance genes and gene mutations. RESULTS: The isolates were identified as part of a laboratory stool and swab surveillance-screening program for infection control. The carbapenem-resistant strain was resistant to β-lactams, including broad-spectrum cephalosporins and carbapenems, and to aminoglycosides, chloramphenicol, fosfomycin, fluoroquinolones, polymyxins, tetracyclines, and trimethoprim/sulfamethoxazole. The K. pneumoniae isolate harboured a plasmid carrying fosA3, rmtB, blaCTX-M-65, blaSHV-12, and blaKPC-2 in a non-Tn4401 mobile element. Colistin resistance was associated with a mutation in the mgrB gene, which regulates PhoP/PhoQ. The K. pneumoniae isolate belongs to sequence type 11, which is a successful epidemic-type strain. CONCLUSION: This study identified molecular resistance markers in a pan-resistant isolate and provided a genomic description of the pan-resistance and origins of the isolate and plasmid. The isolate is closely related to a recent highly pathogenic carbapenem-resistant K. pneumoniae identified in China; however, it lacks a virulence plasmid (but it could still act as a reservoir for a virulence plasmid). This K. pneumoniae isolate is of concern in hospital and community care settings.
  • Analysis of Immune Responses in Acinetobacter baumannii-Infected Klotho Knockout Mice: A Mouse Model of Acinetobacter baumannii Infection in Aged Hosts.
    Yoshinori Sato; Shigeru Tansho-Nagakawa; Tsuneyuki Ubagai; Yasuo Ono
    Frontiers in immunology, 2020, [Reviewed]
    Acinetobacter baumannii is an important opportunistic pathogen that primarily afflicts elderly people. To clarify the pathogenicity of A. baumannii in the elderly, we investigated immune responses to A. baumannii ATCC 19606 infection in klotho knockout (KO) mice, the mouse model of aging. Following intravenous inoculation, the mice seldom displayed severe symptoms. However, the survival rate was 56% at 7 days post-infection. Bacteria were detected in the lungs of klotho KO mice but not klotho wildtype (WT) mice at 7 days post-infection. Neutrophils, eosinophils, interstitial macrophages, and monocyte/dendritic cell subset in the lungs of klotho KO mice were transiently induced after infection with A. baumannii. The number of alveolar macrophages in klotho KO mice was lower than that in klotho WT mice, except for 1 day post-infection. CD11b expression on neutrophils and alveolar macrophages in the lungs of klotho KO mice was seldom upregulated by the infection. These results suggested that immune functions eliminating bacteria in the lungs of klotho KO mice were insufficient. CD11blow conventional DC cells hardly increased in klotho KO mice infected with A. baumannii. Additionally, the production of interleukin (IL)-10 in the sera of klotho KO mice was significantly higher than that in klotho WT mice, whereas that production of interferon-gamma was not detected in the sera of klotho KO mice. These results suggested that acquired immune responses were hardly induced in klotho KO mice. IL-1β, CXCL1, CXCL2, and CCL2 expression was significantly higher in the lungs of klotho KO mice infected with A. baumannii than in those of klotho WT mice at 1 day post-infection. These results suggested that pulmonary inflammation was elicited in klotho KO mice during early infection. The expression levels of proinflammatory cytokines significantly correlated with TLR9 expression in the lungs of klotho KO mice. The collective results demonstrate an A. baumannii infection state in aged hosts and suggest that pulmonary inflammation and bacterial burden should be noted in aged hosts even in the absence of severe symptoms of A. baumannii infection.
  • Lipopolysaccharide-Deficient Acinetobacter baumannii Due to Colistin Resistance Is Killed by Neutrophil-Produced Lysozyme.
    Go Kamoshida; Takuya Akaji; Norihiko Takemoto; Yusuke Suzuki; Yoshinori Sato; Daichi Kai; Taishi Hibino; Daiki Yamaguchi; Takane Kikuchi-Ueda; Satoshi Nishida; Yuka Unno; Shigeru Tansho-Nagakawa; Tsuneyuki Ubagai; Tohru Miyoshi-Akiyama; Masataka Oda; Yasuo Ono
    Frontiers in microbiology, 2020, [Reviewed]
    Acinetobacter baumannii causes nosocomial infections due to its multidrug resistance and high environmental adaptability. Colistin is a polypeptide antibacterial agent that targets lipopolysaccharide (LPS) and is currently used to control serious multidrug-resistant Gram-negative bacterial infections, including those caused by A. baumannii. However, A. baumannii may acquire colistin resistance by losing their LPS. In mouse models, LPS-deficient A. baumannii have attenuated virulence. Nevertheless, the mechanism through which the pathogen is cleared by host immune cells is unknown. Here, we established colistin-resistant A. baumannii strains and analyzed possible mechanisms through which they are cleared by neutrophils. Colistin-resistant, LPS-deficient strains harbor mutations or insertion sequence (IS) in lpx genes, and introduction of intact lpx genes restored LPS deficiency. Analysis of interactions between these strains and neutrophils revealed that compared with wild type, LPS-deficient A. baumannii only weakly stimulated neutrophils, with consequent reduced levels of reactive oxygen species (ROS) and inflammatory cytokine production. Nonetheless, neutrophils preferentially killed LPS-deficient A. baumannii compared to wild-type strains. Moreover, LPS-deficient A. baumannii strains presented with increased sensitivities to antibacterial lysozyme and lactoferrin. We revealed that neutrophil-secreted lysozyme was the antimicrobial factor during clearance of LPS-deficient A. baumannii strains. These findings may inform the development of targeted therapeutics aimed to treat multidrug-resistant infections in immunocompromised patients who are unable to mount an appropriate cell-mediated immune response.
  • A Novel Mismatched PCR-Restriction Fragment Length Polymorphism Assay for Rapid Detection of gyrA and parC Mutations Associated With Fluoroquinolone Resistance in Acinetobacter baumannii.
    Kakuta N; Nakano R; Nakano A; Suzuki Y; Tanouchi A; Masui T; Horiuchi S; Endo S; Kakuta R; Ono Y; Yano H
    Annals of laboratory medicine, Jan. 2020, [Reviewed]
    BACKGROUND: Mutations in the quinolone resistance-determining regions (QRDRs) of Acinetobacter baumannii DNA gyrase (gyrA) and topoisomerase IV (parC) are linked to fluoroquinolone (FQ) resistance. We developed a mismatched PCR-restriction fragment length polymorphism (RFLP) assay to detect mutations in the gyrA and parC QRDRs associated with FQ resistance in A. baumannii. METHODS: Based on the conserved sequences of A. baumannii gyrA and parC, two primer sets were designed for mismatched PCR-RFLP to detect mutations in gyrA (codons 83 and 87) and parC (codons 80 and 84) by introducing an artificial restriction enzyme cleavage site into the PCR products. This assay was evaluated using 58 A. baumannii strains and 37 other Acinetobacter strains that have been identified by RNA polymerase β-subunit gene sequence analysis. RESULTS: PCR amplification of gyrA and parC was successful for all A. baumannii strains. In 11 FQ -susceptible strains, the gyrA and parC PCR products were digested by the selected restriction enzymes at the site containing gyrA (codons 83 and 87) and parC (codons 80 and 84). PCR products from 47 FQ-resistant strains containing mutations in gyrA and parC were not digested by the restriction enzymes at the site containing the mutation. As for the non-baumannii Acinetobacter strains, although amplification products for gyrA were obtained for 28 strains, no parC amplification product was obtained for any strain. CONCLUSIONS: This assay specifically amplified gyrA and parC from A. baumannii and detected A. baumannii gyrA and parC mutations with FQ resistance.
  • The complete mitochondrial genome of Sarcoptes scabiei var. nyctereutis from the Japanese raccoon dog: Prediction and detection of two transfer RNAs (tRNA-A and tRNA-Y)
    Takafumi Ueda; Hiroshi Tarui; Nobuhide Kido; Keitaro Imaizumi; Kenji Hikosaka; Takashi Abe; Daisuke Minegishi; Yoshifumi Tada; Masataka Nakagawa; Sohei Tanaka; Tomoko Omiya; Kouki Morikaku; Minori Kawahara; Takane Kikuchi-Ueda; Teruo Akuta; Yasuo Ono
    Genomics, Dec. 2019, [Reviewed]
  • Multidrug-resistant Acinetobacter baumannii resists reactive oxygen species and survives in macrophages.
    Yoshinori Sato; Yuka Unno; Chizuru Miyazaki; Tsuneyuki Ubagai; Yasuo Ono
    Scientific reports, 25 Nov. 2019, [Reviewed]
    We investigated the intracellular survival of multidrug-resistant Acinetobacter baumannii (MDRAB) clinical isolates in macrophages, after phagocytosis, to determine their virulence characteristics. After ATCC 19606 and 5 clinical isolates of MDRAB were phagocytosed by mouse and human macrophages, the bacterial count of MDRAB strains, R4 and R5, increased in the mouse macrophages, 24 hours after phagocytosis. Bacterial count of the strains, R1 and R2, was almost equal 4 and 24 hours after phagocytosis. Intracellular reactive oxygen species was detected in the macrophages after phagocytosis of these bacteria. Further, the strains R1, R2, R4, and R5 showed higher catalase activity than ATCC 19606. Additionally, strains R1, R4, and R5 grew more efficiently than ATCC 19606 in the presence of H2O2, whereas growth of strains R2 and R3 was marginally more than that of ATCC 19606 in the presence of H2O2. The MDRAB clinical isolates altered the expression of TNF-α, IL-1β, IL-6, and MIP-2 mRNA induced in J774A.1 cells, 24 hours after phagocytosis. These results provide insights into the renewed virulence characteristics of MDRAB clinical isolates. Finally, tigecycline killed MDRAB phagocytosed by the macrophages more effectively than colistin, although colistin and tigecycline are both considered effective antibiotics for the treatment of MDRAB.
  • Mycobacterium heckeshornense-induced deep abscess in the gluteus maximus muscle: a case report and review of the literature.               
    Kikuchi H; Asako K; Kono H; Asahara M; Tanaka H; Kamosida G; Ueda T; Nagakawa S; Ubagai T; Kazumi Y; Ono Y
    JJA, Mar. 2019, [Reviewed]
  • Prevalence and mechanism of fluoroquinolone resistance in clinical isolates of Proteus mirabilis in Japan.
    Nakano R; Nakano A; Abe M; Nagano N; Asahara M; Furukawa T; Ono Y; Yano H; Okamoto R
    Heliyon, Mar. 2019, [Reviewed]
  • Emergence of Escherichia coli producing OXA-48-like carbapenemase in a patient with percutaneous transhepatic biliary drainage.               
    Infection Prevention in Practice, 2019, [Reviewed]
  • Resolvin E1, but not resolvins E2 and E3, promotes fMLF-induced ROS generation in human neutrophils
    Unno Yuka; Sato Yoshinori; Fukuda Hayato; Ishimura Kohei; Ikeda Hiroyuki; Watanabe Mizuki; Tansho-Nagakawa Shigeru; Ubagai Tsuneyuki; Shuto Satoshi; Ono Yasuo
    FEBS LETTERS, Aug. 2018, [Reviewed]
  • Palmitoyl lactic acid induces adipogenesis and a brown fat-like phenotype in 3T3-L1 preadipocytes.
    Yuka Unno; Hirona Yamamoto; Shuto Takatsuki; Yoshinori Sato; Takefumi Kuranaga; Kazunaga Yazawa; Yasuo Ono; Toshiyuki Wakimoto
    Biochimica et biophysica acta. Molecular and cell biology of lipids, Jul. 2018, [Reviewed]
    Brown adipose tissue is specialized to generate heat by dissipating chemical energy and may provide novel strategies for obesity treatment in humans. Recently, advances in understanding the pharmacological and dietary agents that contribute to the browning of white adipose tissue have been made to alleviate obesity by promoting energy expenditure. Krill oil is widely used as a health supplement in humans. In this study, the components from krill oil that promote adipogenesis of 3T3-L1 cells were screened to reveal palmitoyl lactic acid (PLA) as a promoter of adipogenesis. The PLA-induced adipocytes contained large number of small lipid droplets. Moreover, similar to the peroxisome proliferator-activated receptor (PPAR)γ agonists, pioglitazone and rosiglitazone, PLA significantly enhances adipogenesis in the presence of dexamethasone compared with PLA alone. Treatment with PLA causes a brown fat-like phenotype in 3T3-L1 cells by enhanced expression of various brown/beige cell-specific genes, such as PR domain containing 16 (Prdm16) and peroxisome proliferative activated receptor, gamma, coactivator 1 alpha (Pgc1a), as well as adiponectin gene. The expression profile of the brown/beige cell-specific genes induced by PLA was similar to that of the PPARγ agonist in 3T3-L1 cells. Our findings suggest that PLA induces a brown fat-like phenotype and, thus, likely has therapeutic potential in treating obesity.
  • Improving the quality of a recombinant rabbit monoclonal antibody against PLXDC2 by optimizing transient expression conditions and purification method.
    Hisayo Shimizu; Masataka Nakagawa; Nemuri Todaka; Keitaro Imaizumi; Yasunori Kurosawa; Toshiaki Maruyama; C J Okumura; Takashi Shibata; Yosuke Tanaka; Yoshinori Sato; Yasuo Ono; Teruo Akuta
    Protein expression and purification, Jun. 2018, [Reviewed]
    Rabbit monoclonal antibodies (mAbs) have many advantages over mouse antibodies in biological research and diagnostics applications because they exhibit high affinity and specificity. However, the methods of recombinant rabbit mAb production have not been optimized to the same extent as techniques used to produce mouse and human mAbs. In this study, we sought to optimize the production of a recombinant rabbit mAb against human plexin domain containing protein 2 (PLXDC2), a known cell surface antigen, by culturing HEK293-6E cells transfected with antibody-encoding genes at two different temperatures and by purifying the end-product by three different chromatography methods. The quality and function of purified antibody preparations were checked by electrophoresis and western blot analysis. The secreted rabbit mAb produced by a combination of culturing at 32 °C, purification by ammonium sulfate fractionation, and diethylaminoethyl resin (DEAE) ion exchange chromatography was of high quality. In contrast, the antibody produced by the cells grown at 37 °C for 6 days after transfection and purified by Protein A/G affinity method was low quality. Hypothermic conditions during production reduced protein heterogeneity probably by favorably affecting the levels of glycosylation and aggregation. In particular, according to western blotting data, CIMmultus DEAE chromatography that utilizes monolithic columns not only excluded inferior charge variants resulting from nonspecific reactions but also yielded rabbit mAb that was of better quality than commercially available rabbit polyclonal antibodies. The combination of techniques suggested by us may be a general approach to enhance product quality of rabbit mAbs produced by transient expression systems.
  • Pathogenic bacterium Acinetobacter baumannii inhibits the formation of neutrophil extracellular traps by suppressing neutrophil adhesion
    Go Kamoshida; Takane Kikuchi-Ueda; Satoshi Nishida; Shigeru Tansho-Nagakawa; Tsuneyuki Ubagai; Yasuo Ono
    Frontiers in Immunology, 07 Feb. 2018, [Reviewed]
  • Sub-minimum inhibitory concentrations of colistin and polymyxin B promote Acinetobacter baumannii biofilm formation.
    Yoshinori Sato; Yuka Unno; Tsuneyuki Ubagai; Yasuo Ono
    PloS one, 2018, [Reviewed]
    We investigated the numbers of planktonic and biofilm cells and the expression levels of genes encoding efflux pumps and biofilm-related proteins in 10 clinical isolates of multi-drug resistant Acinetobacter baumannii (MDRA) as well as in its standard strain ATCC 19606 in the presence of colistin (CST), polymyxin B (PMB), minomycin (MIN), and tigecycline (TGC) at their respective sub-MICs. The number of planktonic and biofilm cells of ATCC 19606 decreased in the presence of all aforementioned antibiotics in a dose-dependent manner. Cell number also decreased in two representative MDRA strains, R2 and R3, in the presence of MIN and TGC in a dose-dependent manner. In contrast, the number of biofilm cells in these two strains increased in the presence of CST, while they increased significantly in the presence of PMB in R2 only. Pearson correlation analysis revealed that the number of biofilm cells was positively and significantly correlated with the mRNA levels of genes encoding efflux pumps (adeB and adeG) and autoinducer synthase (abaI) in strain R2 and adeB, adeG, adeJ, poly-acetyl-glucosamine-porin (pgaA), and abaI in strain R3 in the presence of CST. It was positively and significantly correlated with the mRNA levels of genes encoding adeB in strain R2 and an outer membrane protein A (ompA) and biofilm-associated protein (bap) in strain R3 in the presence of PMB. These results provide valuable insights into the biofilm formation potency of clinical isolates of MDRA that depends on efflux pumps and biofilm-related genes and its regulation by antibiotics.
  • Analysis of membrane antigens on neutrophils from patients with pneumonia.
    Tansho-Nagakawa S; Ubagai T; Koshibu Y; Kikuchi-Ueda T; Nakano R; Kamoshida G; Kikuchi H; Ikeda H; Uchida Y; Sakamoto T; Ono Y
    Int J Immunol Immunother, 2018, [Reviewed]
  • Comparative analysis of the pathogenicity between multidrug-resistant Acinetobacter baumannii clinical isolates: isolation of highly pathogenic multidrug-resistant A. baumannii and experimental therapeutics with fourth-generation cephalosporin cefozopran.
    Satoshi Nishida; Yasuo Ono
    Infection and drug resistance, 2018, [Reviewed]
    Introduction: The pathogenicity of fatal-outbreak Acinetobacter baumannii isolates has not been fully investigated. This study aimed to compare the pathogenicity between A. baumannii clinical isolates, including multidrug-resistant A. baumannii (MDRA). Materials and methods: Antibiotic susceptibility was determined by the broth microdilution method, and drug-resistant genes were characterized by PCR and sequencing. The pathogenicity of A. baumannii and antibiotic responses were evaluated using the Galleria mellonella infection model. Clinical isolates from an A. baumannii outbreak at our hospital were categorized using the pulse-field gel electrophoresis. Of the 16 isolated A. baumannii clones, 12 clones were resistant to carbapenems (meropenem and imipenem), of which 10 clones were also resistant to amikacin and ciprofloxacin (MDRAs). MDRAs had OXA-51-like β-lactamase gene harboring an insertion sequence in the promoter region and armA gene encoding 16S rRNA methyltransferase. Results: Carbapenem- and/or amikacin-resistant A. baumannii were more pathogenic than carbapenem- and/or amikacin-sensitive A. baumannii in G. mellonella. MDRA isolate TK1033 was more virulent than other A. baumannii isolates. However, TK1033 was sensitive to the fourth-generation cephalosporin cefozopran in addition to minocycline, tigecycline, and polymyxins (colistin and polymyxins B) in vitro and in vivo in the MDRA-G. mellonella infection model. Conclusion: Differences in pathogenicity among carbapenem-resistant A. baumannii clones are consistent with heterogeneous clinical outcomes. Strain TK1033, isolated frequently during the outbreak, was the most virulent, whereas preoutbreak isolate TK1032 was less virulent than other A. baumannii isolates. Infection by high-virulence isolates may be more prevalent during outbreaks. These strains may prove valuable for investigating MDRA virulence and novel therapeutics.
  • The TNF-alpha of mast cells induces pro-inflammatory responses during infection with Acinetobacter baumannii
    Takane Kikuchi-Ueda; Go Kamoshida; Tsuneyuki Ubagai; Ryuichi Nakano; Akiyo Nakano; Teruo Akuta; Kenji Hikosaka; Shigeru Tansho-Nagakawa; Hirotoshi Kikuchi; Yasuo Ono
    IMMUNOBIOLOGY, Nov. 2017, [Reviewed]
  • Acinetobacter baumannii Lipopolysaccharide Influences Adipokine Expression in 3T3-L1 Adipocytes
    Unno Y; Sato Y; Nishida S; Nakano A; Nakano R; Ubagai T; Ono Y
    Mediators of Inflammation, Jul. 2017, [Reviewed]
  • Spontaneous formation of neutrophil extracellular traps in serum-free culture conditions
    Go Kamoshida; Takane Kikuchi-Ueda; Satoshi Nishida; Shigeru Tansho-Nagakawa; Hirotoshi Kikuchi; Tsuneyuki Ubagai; Yasuo Ono
    FEBS OPEN BIO, Jun. 2017, [Reviewed]
  • Lactobacillus paraplantarum 11-1 Isolated from Rice Bran Pickles Activated Innate Immunity and Improved Survival in a Silkworm Bacterial Infection Model
    Satoshi Nishida; Masaki Ishii; Yayoi Nishiyama; Shigeru Abe; Yasuo Ono; Kazuhisa Sekimizu
    FRONTIERS IN MICROBIOLOGY, Mar. 2017, [Reviewed]
  • New techniques to collect live Sarcoptes scabiei and evaluation of methods as alternative diagnostics for infection
    Nobuhide Kido; Teruo Akuta; Hiroshi Tarui; Keitaro Imaizumi; Takafumi Ueda; Yasuo Ono; Takane Kikuchi-Ueda; Sohei Tanaka; Tomoko Omiya
    PARASITOLOGY RESEARCH, Mar. 2017, [Reviewed]
  • Inhibition of Neutrophil Adhesion and Antimicrobial Activity by Diluted Hydrosol Prepared from Rosa damascena
    Naho Maruyama; Shigeru Tansho-Nagakawa; Chizuru Miyazaki; Kazuyuki Shimomura; Yasuo Ono; Shigeru Abe
    BIOLOGICAL & PHARMACEUTICAL BULLETIN, Feb. 2017, [Reviewed]
  • Virulence characteristics of Acinetobacter baumannii clinical isolates vary with the expression levels of omps
    Yoshinori Sato; Yuka Unno; Sayoko Kawakami; Tsuneyuki Ubagai; Yasuo Ono
    JOURNAL OF MEDICAL MICROBIOLOGY, Feb. 2017, [Reviewed]
  • Acinetobacter baumannii Lipopolysaccharide Influences Adipokine Expression in 3T3-L1 Adipocytes
    Yuka Unno; Yoshinori Sato; Satoshi Nishida; Akiyo Nakano; Ryuichi Nakano; Tsuneyuki Ubagai; Yasuo Ono
    MEDIATORS OF INFLAMMATION, 2017, [Reviewed]
  • A novel bacterial transport mechanism of Acinetobacter baumannii via activated human neutrophils through interleukin-8
    Go Kamoshida; Shigeru Tansho-Nagakawa; Takane Kikuchi-Ueda; Ryuichi Nakano; Kenji Hikosaka; Satoshi Nishida; Tsuneyuki Ubagai; Shouichi Higashi; Yasuo Ono
    JOURNAL OF LEUKOCYTE BIOLOGY, Dec. 2016, [Reviewed]
  • Improving the soluble expression and purification of recombinant human stem cell factor (SCF) in endotoxin-free Escherichia coli by disulfide shuffling with persulfide
    Takafumi Ueda; Teruo Akuta; Takane Kikuchi-Ueda; Keitaro Imaizumi; Yasuo Ono
    PROTEIN EXPRESSION AND PURIFICATION, Apr. 2016, [Reviewed]
  • Lactic acid bacteria activating innate immunity improve survival in bacterial infection model of silkworm.
    Satoshi Nishida; Yasuo Ono; Kazuhisa Sekimizu
    Drug discoveries & therapeutics, Feb. 2016, [Reviewed]
    Lactic acid bacteria (LAB) have been thought to be helpful for human heath in the gut as probiotics. It recently was noted that activity of LAB stimulating immune systems is important. Innate immune systems are conserved in mammals and insects. Silkworm has innate immunity in response to microbes. Microbe-associated molecular pattern (ex. peptidoglycan and β-glucan) induces a muscle contraction of silkworm larva. In this study, we established an efficient method to isolate lactic acid bacteria derived from natural products. We selected a highly active LAB to activate the innate immunity in silkworm by using the silkworm muscle contraction assay, as well. The assay revealed that Lactococcus lactis 11/19-B1 was highly active on the stimulation of the innate immunity in silkworm. L. lactis 11/19-B1 solely fermented milk with casamino acid and glucose. This strain would be a starter strain to make yogurt. Compared to commercially available yogurt LAB, L. lactis 11/19-B1 has higher activity on silkworm contraction. Silkworm normally ingested an artificial diet mixed with L. lactis 11/19-B1 or a yogurt fermented with L. lactis 11/19-B1. Interestingly, silkworms that ingested the LAB showed tolerance against the pathogenicity of Pseudomonas aeruginosa. These data suggest that Lactococcus lactis 11/19-B1 would be expected to be useful for making yogurt and probiotics to activate innate immunity.
  • Loop-mediated isothermal amplification: Rapid and sensitive detection of the antibiotic resistance gene ISAba1-bla(OXA-51-like) in Acinetobacter baumannii
    Xiaoqin Mu; Ryuichi Nakano; Akiyo Nakano; Tsuneyuki Ubagai; Takane Kikuchi-Ueda; Shigeru Tansho-Nagakawa; Hirotoshi Kikuchi; Go Kamoshida; Shiro Endo; Hisakazu Yano; Yasuo Ono
    JOURNAL OF MICROBIOLOGICAL METHODS, Feb. 2016, [Reviewed]
  • Gene expression analysis in human polymorphonuclear leukocytes stimulated by LPSs from nosocomial opportunistic pathogens
    Tsuneyuki Ubagai; Ryuichi Nakano; Akiyo Nakano; Go Kamoshida; Yasuo Ono
    INNATE IMMUNITY, Nov. 2015, [Reviewed]
  • Lactate retards the development of erythrocytic stages of the human malaria parasite Plasmodium falciparum
    Kenji Hikosaka; Makoto Hirai; Keisuke Komatsuya; Yasuo Ono; Kiyoshi Kita
    PARASITOLOGY INTERNATIONAL, Jun. 2015, [Reviewed]
  • Rapid detection of the Klebsiella pneumoniae carbapenemase (KPC) gene by loop-mediated isothermal amplification (LAMP)
    Ryuichi Nakano; Akiyo Nakano; Yoshikazu Ishii; Tsuneyuki Ubagai; Takane Kikuchi-Ueda; Hirotoshi Kikuchi; Shigeru Tansho-Nagakawa; Go Kamoshida; Xiaoqin Mu; Yasuo Ono
    JOURNAL OF INFECTION AND CHEMOTHERAPY, Mar. 2015, [Reviewed]
  • Expression of bioactive soluble human stem cell factor (SCF) from recombinant Escherichia coli by coproduction of thioredoxin and efficient purification using arginine in affinity chromatography
    Teruo Akuta; Takane Kikuchi-Ueda; Keitaro Imaizumi; Hiroyuki Oshikane; Toshio Nakaki; Yoko Okada; Sara Sultana; Kenichiro Kobayashi; Nobutaka Kiyokawa; Yasuo Ono
    PROTEIN EXPRESSION AND PURIFICATION, Jan. 2015, [Reviewed]
  • Acinetobacter baumannii escape from neutrophil extracellular traps (NETs)
    Go Kamoshida; Takane Kikuchi-Ueda; Shigeru Tansho-Nagakawa; Ryuichi Nakano; Akiyo Nakano; Hirotoshi Kikuchi; Tsuneyuki Ubagai; Yasuo Ono
    JOURNAL OF INFECTION AND CHEMOTHERAPY, Jan. 2015, [Reviewed]
  • First Report of Metallo-beta-Lactamase NDM-5-Producing Escherichia coli in Japan
    Ryuichi Nakano; Akiyo Nakano; Kenji Hikosaka; Sayoko Kawakami; Naohisa Matsunaga; Miwa Asahara; Shinobu Ishigaki; Taiji Furukawa; Masato Suzuki; Keigo Shibayama; Yasuo Ono
    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Dec. 2014, [Reviewed]
  • Gene Expression Analysis of TREM1 and GRK2 in Polymorphonuclear Leukocytes as the Surrogate Biomarkers of Acute Bacterial Infections
    Tsuneyuki Ubagai; Ryuichi Nakano; Hirotoshi Kikuchi; Yasuo Ono
    INTERNATIONAL JOURNAL OF MEDICAL SCIENCES, 2014, [Reviewed]
  • Rapid assay for detecting gyrA and parC mutations associated with fluoroquinolone resistance in Enterobacteriaceae
    Ryuichi Nakano; Ryoichi Okamoto; Akiyo Nakano; Noriyuki Nagano; Michiko Abe; Shigeru Tansho-Nagakawa; Tsuneyuki Ubagai; Takane Kikuchi-Ueda; Osamu Koshio; Hirotoshi Kikuchi; Yasuo Ono
    Journal of Microbiological Methods, Sep. 2013, [Reviewed]
  • Effects of antibiotics in immunomodulatory gene expression of LPS-stimulated human polymorphonuclear leukocytes
    T. Ubagai; S. Nagakawa; T. Ueda; R. Nakano; H. Kikuchi; Y. Ono
    INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, Jun. 2013
  • Effects of Erythromycin and Rifampicin on Immunomodulatory Gene Expression and Cellular Function in Human Polymorphonuclear Leukocytes
    Xiaoqin Mu; Tsuneyuki Ubagai; Takane Kikuchi-Ueda; Shigeru Tansho-Nagakawa; Ryuichi Nakano; Hirotoshi Kikuchi; Yasuo Ono
    CHEMOTHERAPY, 2013, [Reviewed]
  • Usefulness of gram-stained sputum obtained just after administration of antimicrobial agents as the earliest therapeutic indicator for evaluating the effectiveness of empiric therapy in community-acquired pneumonia caused by pneumococcus or Moraxella catarrhalis
    Ryuichi Fujisaki; Toshimori Yamaoka; Michiko Yamamura; Sayoko Kawakami; Yasuo Ono; Yukihisa Miyazawa; Tamio Teramoto; Hajime Nishiya
    Journal of Infection and Chemotherapy, 2013, [Reviewed]
  • Case of Mycobacterium tuberculosis meningitis: Gram staining as a useful initial diagnostic clue for tuberculous meningitis
    Sayoko Kawakami; Yasuyosi Kawamura; Kyouhei Nishiyama; Hiroki Hatanaka; Ryuichi Fujisaki; Yasuo Ono; Yukihisa Miyazawa; Hajime Nishiya
    JOURNAL OF INFECTION AND CHEMOTHERAPY, Dec. 2012, [Reviewed]
  • Analysis of membrane antigens on neutrophils from patients with sepsis
    Shigeru Tansho-Nagakawa; Tsuneyuki Ubagai; Takane Kikuchi-Ueda; Osamu Koshio; Yoji Koshibu; Hirotoshi Kikuchi; Yasuo Ono
    JOURNAL OF INFECTION AND CHEMOTHERAPY, Oct. 2012, [Reviewed]
  • Enhancement of interleukin-8-induced chemotactic response and reactive oxygen species production in HL-60 cells expressing CXCR1
    Takane Kikuchi-Ueda; Shigeru Tansho; Yasuo Ono
    JOURNAL OF INFECTION AND CHEMOTHERAPY, Jun. 2012, [Reviewed]
  • Etanercept for the treatment of intractable hemophagocytic syndrome with systemic lupus erythematosus
    Hirotoshi Kikuchi; Tadashi Yamamoto; Kurumi Asako; Maki Takayama; Ryosuke Shirasaki; Yasuo Ono
    MODERN RHEUMATOLOGY, Apr. 2012, [Reviewed]
  • Apoptotic signaling in endothelial cells with neutrophil activation
    Osamu Koshio; Tomokazu Nagao; Ayako Mabuchi; Yasuo Ono; Kazuo Suzuki
    MOLECULAR AND CELLULAR BIOCHEMISTRY, Apr. 2012, [Reviewed]
  • A d-octapeptide drug efflux pump inhibitor acts synergistically with azoles in a murine oral candidiasis infection model
    Kazumi Hayama; Hiroko Ishibashi; Sanae A. Ishijima; Kyoko Niimi; Shigeru Tansho; Yasuo Ono; Brian C. Monk; Ann R. Holmes; David R. K. Harding; Richard D. Cannon; Shigeru Abe
    FEMS MICROBIOLOGY LETTERS, Mar. 2012, [Reviewed]
  • [Effect of oral administration of β-D-glucan from Aureobasidium pullulans ADK-34 on Candida and MRSA infections in immunosuppressed mice].
    Tanioka A; Hayama K; Mitsuya M; Tansho S; Ono Y; Tsubaki K; Abe S
    Medical mycology journal, 2012, [Reviewed]
    We examined the effect of the oral administration of β-D-glucan derived from Aureobasidium pullulans ADK-34 (AP-FBG) on Candida albicans or methicillin-resistant Staphylococcus aureus (MRSA) infection in immunosuppressed mice. Mice pretreated with cyclophosphamide (CY) were intraperitoneally administered AP-FBG for 4 days and then infected with 6×104 C. albicans cells. In a preliminary experiment, the survival time of the Candida-infected mice treated with AP-FBG was clearly prolonged. Similarly, the effect of the oral administration of AP-FBG was examined. Mice were orally given 2.5% AP-FBG in feed for 42 days from 14 days prior to 2×104 C. albicans cells infection. The survival time of mice treated with AP-FBG was significantly prolonged and the viable cell count in the kidneys of the survivors was significantly decreased at 30 days after infection. The effects of the oral administration of AP-FBG on intestinal MRSA infection were also examined. Mice were given 2.5% AP-FBG orally in feed for 30 days before and after oral MRSA infection and treated with CY 12 days after the infection. The number of viable MRSA cells or the IgA production in feces did not significantly change, while AP-FBG administration seemed to relieve temporally the loss of body weight of mice. Conclusions: These results suggest that oral pre-administration of AP-FBG promoted resistance of CY-treated mice to C. albicans and lessened the weight reduction of CY-mice infected by MRSA.
  • Recurrent Helicobacter cinaedi Cellulitis and Bacteremia in a Patient with Systemic Lupus Erythematosus
    Hirotoshi Kikuchi; Kurumi Asako; Shigeru Tansho; Takane Ueda; Osamu Koshio; Tuneyuki Ubagai; Miwa Asahara; Sayoko Kawakami; Yasuo Ono
    INTERNAL MEDICINE, 2012, [Reviewed]
  • The usefulness of changing focus during examination using Gram staining as initial diagnostic clue for infective tuberculosis
    Yoshiko Atsukawa; Sayoko Kawakami; Miwa Asahara; Shinobu Ishigaki; Takashi Tanaka; Yasuo Ono; Hajime Nishiya; Ryuichi Fujisaki; Ichiro Koga; Yasuo Ota; Yukihisa Miyazawa
    JOURNAL OF INFECTION AND CHEMOTHERAPY, Aug. 2011, [Reviewed]
  • Condition for effective inhibition of Candida albicans growth by lactoferricin B and its therapeutic activity with fluconazole against oral candidiasis in mice
    Takashi Tanaka; Takafumi Okutomi; Hiroyuki Wakabayashi; Hiroko Ishibashi; Shigeru Tansho; Kentaro Ninomiya; Hideyo Yamaguchi; Yasuo Ono; Shigeru Abe
    Med Mycol J, 2011, [Reviewed]
  • Complement-mediated bacteriolysis after binding of specific antibodies to drug-resistant Pseudomonas aeruginosa: morphological changes observed by using a field emission scanning electron microscope
    Jun Tanaka; Takashi Nakae; Takatoshi Onoe; Yoshitaka Horiuchi; Hiroyoshi Miyamoto; Jun Adan-Kubo; Hiroaki Adachi; Yasuo Ono
    JOURNAL OF INFECTION AND CHEMOTHERAPY, Dec. 2010, [Reviewed]
  • Aflatoxin B-1 modulates the insulin-like growth factor-2 dependent signaling axis
    Tsuneyuki Ubagai; Takane Kikuchi; Toshio Fukusato; Yasuo Ono
    TOXICOLOGY IN VITRO, Apr. 2010, [Reviewed]
  • Suppression of phosphorylation of extracellular-signal-regulated kinase and p38 mitogen-activated protein kinase in polymorphonuclear leukocytes by the proton pump inhibitor lansoprazole
    Osamu Koshio; Shigeru Tansho; Tsuneyuki Ubagai; Toshio Nakaki; Yasuo Ono
    JOURNAL OF INFECTION AND CHEMOTHERAPY, Apr. 2010, [Reviewed]
  • Downregulation of immunomodulator gene expression in LPS-stimulated human polymorphonuclear leukocytes by the proton pump inhibitor lansoprazole
    Tsuneyuki Ubagai; Yoji Koshibu; Osamu Koshio; Toshio Nakaki; Yasuo Ono
    JOURNAL OF INFECTION AND CHEMOTHERAPY, Dec. 2009, [Reviewed]
  • ZAAPS International Surveillance Program (2007) for linezolid resistance: results from 5591 Gram-positive clinical isolates in 23 countries
    Ronald N. Jones; Shigeru Kohno; Yasuo Ono; James E. Ross; Katsunori Yanagihara
    DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, Jun. 2009, [Reviewed]
  • Complement-mediated bactericidal effect of antibodies in human intravenous preparation against multi-drug resistant Pseudomonas aeruginosa
    Takashi Nakae; Jun Tanaka; Atsushi Nakano; Yasuo Ono
    Japanese Journal of Antibiotics, Dec. 2008, [Reviewed]
  • Multicenter Retrospective Evaluation of Tigecycline Tested Against Clinical Pathogens from Japan (2003-2004)
    S. Kohno; M. Inuoe; Y. Ono; R. Jones; J. Turnidge
    INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, Dec. 2008, [Reviewed]
  • Influences of aflatoxin B-1 on reactive oxygen species generation and chemotaxis of human polymorphonuclear leukocytes
    Tsuneyuki Ubagai; Shigeru Tansho; Tadashi Ito; Yasuo Ono
    TOXICOLOGY IN VITRO, Jun. 2008, [Reviewed]
  • Candida glabrataによる血行播種性肺Candida症の1例
    山岡利守; 川上小夜子; 山村麻倫子; 藤崎竜一; 斧康雄; 西谷肇
    日本臨床微生物学雑誌, 25 Jun. 2007, [Reviewed]
  • Opsonic activity assessment of human intravenous immunoglobulin preparations against Candida albicans               
    Ono Y; Ubagai T; Shigeru T; Koshio O
    2006, [Reviewed]
  • Efficacy of intravenous itraconazole against invasive pulmonary aspergillosis in neutropenic mice
    Shigeru Tansho; Shigeru Abe; Hiroko Ishibashi; Shinichi Torii; Hisaya Otani; Yasuo Ono; Hideyo Yamaguchi
    Journal of Infection and Chemotherapy, 2006, [Reviewed]
  • Regional variation in the prevalence of extended-spectrum beta-lactamase-producing clinical isolates in the Asia-Pacific region (SENTRY 1998-2002)
    Y Hirakata; J Matsuda; Y Miyazaki; S Kamihira; S Kawakami; Y Miyazawa; Y Ono; N Nakazaki; Y Hirata; M Inoue; JD Turnidge; JM Bell; RN Jones; S Kohno
    DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, Aug. 2005, [Reviewed]
  • Activity of a peptide deformylase inhibitor LBM415 (NVP PDF-713) tested against recent clinical isolates from Japan
    JM Bell; JD Turnidge; M Inoue; S Kohno; Y Hirakata; Y Ono; RN Jones
    JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, Feb. 2005, [Reviewed]
  • Evaluation of the contemporary occurrence rates of metallo-beta-lactamases in multidrug-resistant Gram-negative bacilli in Japan: report from the SENTRY Antimicrobial Surveillance Program (1998-2002)
    RN Jones; LM Deshpande; JM Bell; JD Turnidge; S Kohno; Y Hirakata; Y Ono; Y Miyazawa; S Kawakama; M Inoue; Y Hirata; MA Toleman
    DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, Aug. 2004, [Reviewed]
  • Production of anti-Candida antibodies in mice with gut colonization of Candida albicans
    S Tansho; S Abe; H Ishibashi; M Mitsuya; K Wada; T Ikeda; N Suegara; O Koshio; Y Ono; H Yamaguchi
    MEDIATORS OF INFLAMMATION, Jun. 2004, [Reviewed]
  • Opsonophagocytic dysfunction in patients with liver cirrhosis and low responses to tumor necrosis factor-α and lipopolysaccharide in patients' blood
    Yasuo Ono; Takeshi Watanabe; Kaoru Matsumoto; Tadashi Ito; Otohiko Kunii; Elliot Goldstein
    Journal of Infection and Chemotherapy, 2004, [Reviewed]
  • Opsonic activity assessment of human intravenous immunoglobulin preparations against drug-resistant bacteria
    Yasuo Ono; Tadashi Ito; Takeshi Watanabe; Osamu Koshio; Shigeru Tansho; Tatsuo Ikeda; Sayoko Kawakami; Yukihisa Miyazawa
    Journal of Infection and Chemotherapy, 2004, [Reviewed]
  • Transferability of VanA Gene from Vancomycin-Resistant Enterococcus faecalis in the Digestive Tract of Specific Pathogen-Free Mice
    IKEDA Tatsuo; WATANABE Takeshi; MATSUMOTO Kaoru; MURAYAMA Somay Y.; KOSHIO Osamu; TANSHO Shigeru; ONO Yasuo
    Journal of the Japanese Association for Infectious Diseases, 2004, [Reviewed]
    We evaluated the transferability of vanA gene from vancomycin-resistant Enterococcus faecalis (VREF) to vancomycin-sensitive E. faecalis (VSEF) in vitro and in vivo. In vitro conjugal transfer experiment by filter mating, the vanA gene of VREF was transferable at the high frequency to VSEF and a mutant strain which cured vanA gene of VREF. In vivo studies in the digestive tract of specific pathogen-free mice pretreated with oral antibiotics, transconjugants were also detected from the feces of a mouse at the lower frequency. However, the colonization of transconjugants was transient. The vanA gene in the donor and the transconjugant strain was confirmed by using a polymerase chain reaction method.
    These results suggest that VSEF colonizing in the human digestive tract might be developed to VREF by transferring of the vanA gene.
  • 食道癌術後にムーコル創感染を併発し重症化した症例               
    Oct. 2003, [Reviewed]
  • Prophylactic Efficacy of A Basidiomycetes Preparation AHCC against Lethal Candida albicans Infection in Experimental Granulocytopenic Mice
    IKEDA Tatsuo; ISHIBASHI Hiroko; FUJISAKI Ryuichi; YAMAZAKI Masatoshi; WAKAME Kohji; KOSUNA Kenichi; YAMAGUCHI Hideyo; ONO Yasuo; ABE Shigeru
    日本医真菌学会雑誌 = Japanese journal of medical mycology, Apr. 2003, [Reviewed]
  • 手指熱風消毒器の消毒・殺菌効果               
    Mar. 2002, [Reviewed]
  • Modulation of oxidative burst of neutrophils by doxycycline in patients with acute myocardial infarction
    S Takeshita; Y Ono; K Kozuma; M Suzuki; Y Kawamura; N Yokoyama; T Furukawa; T Isshiki
    JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, Feb. 2002, [Reviewed]
  • Destructive pulmonary embolism in a patient with community-acquired staphylococcal bacteremia
    T. Miyashita; Y. Shimamoto; H. Nishiya; Y. Koshibu; H. Sugiyama; Y. Ono; T. Satoh; H. Haraoka; J. Nakano; K. Ohta; T. Sato; N. Morinaga; M. Noda
    Journal of Infection and Chemotherapy, 2002, [Reviewed]
  • Protection of mice from lethal endogenous Candida albicans infection by immunization with Candida membrane antigen
    S Tansho; S Abe; S Mizutani; Y Ono; K Takesako; H Yamaguchi
    MICROBIOLOGY AND IMMUNOLOGY, 2002, [Reviewed]
  • Murine IgE Antibody to Recognize Human Major Allergen, Mal f4
    MITSUYA Masayasu; SUEGARA Nobuo; WADA Kayoko; IKEDA Tatsuo; MURAYAMA Somey Y; TANSHO Shigeru; YAMAGUCHI Hideyo; ONO Yasuo
    日本医真菌学会雑誌 = Japanese journal of medical mycology, 30 Oct. 2001, [Reviewed]
    To elucidate the specificity of murine IgE antibody against Malassezia furfur, the immunoblot patterns of IgE in sera obtained from mice inoculated repeatedly in the nasal cavity with M. f. cells, or injected intraperitoneally with M. f. cells mixed with Al(OH)3 gel were compared with those of IgE antibody detected in sera from patients with AD. Most of the murine IgE anti-Malassezia antibodies shared some antigenic bands with IgE in sera from patients with AD. The IgE antibody of murine also recognized Mal f4, one of the major allergens detected in patients with AD.
  • Four-week Oral Toxicity Studies of the Leaf Powder of Mulberry (Morus alba L.) in Rats
    MITSUYA Masayasu; SUEGARA Nobuo; KOJIMA Yoshihiro; TANIGUCHI Keiichi; ABE Shigeru; YAMAGUCHI Hideyo; ONO Yasuo
    応用薬理, Oct. 2001, [Reviewed]
  • Increased leukocyte activity as a predictor for flow-limiting coronary lesions in patients with angina pectoris
    S Takeshita; H Hashimoto; Y Ono; M Ochiai; N Yokoyama; M Terakura; T Sato; T Isshiki
    ATHEROSCLEROSIS, Oct. 2001, [Reviewed]
  • Survey of antibiotic resistance in Pseudomonas aeruginosa by the Tokyo Johoku Association of pseudomonas studies
    K. Kato; S. Iwai; K. Kumasaka; A. Horikoshi; S. Inada; T. Inamatsu; Y. Ono; H. Nishiya; Y. Hanatani; T. Narita; H. Sekino; I. Hayashi
    Journal of Infection and Chemotherapy, 2001, [Reviewed]
  • A case of infective endocarditis due to methicillin-resistant staphylococcus aureus successfully treated with vancomycin in combination with rifampicin and sulbamethoxazole/trimethoprim
    SHIMAMOTO Yuko; NISHIYA Hajime; YAMAOKA Toshimori; KOSHIBU Yoji; MATSUMOTO Kaoru; SUGIYAMA Hajime; MIYASHITA Taku; ONO Yasuo; KUNII Otohiko; SATO Tomohide
    Jpn.J.Chemother., 2001, [Reviewed]
  • Influence of various antibiotics on B cell immunoglobulin secretion and lymphocyte growth
    Taku Miyashita; Yuko Shimamoto; Yasuo Ono; Toshimori Yamaoka; Yoji Koshibu; Tadashi Ito; Kaoru Matsumoto; Hajime Sugiyama; Hajime Nishiya; Otohiko Kunii
    Jpn.J.Chemother., Dec. 2000, [Reviewed]
  • Ecology of yeast flora of the human intestine based on culture study of fecal specimens from patients and healthy subjects
    ISHIGAKI Shinobu; KAWAKAMI Sayoko; ONO Yasuo; MIYAZAWA Yukihisa; YAMAGUCHI Hideyo
    J.Jpn.society.clin.Microbiology, 25 Oct. 2000, [Reviewed]
  • Prophylactic efficacy of a basidiomycetes preparation AHCC against lethal opportunistic infections in mice
    H Ishibashi; T Ikeda; S Tansho; Y Ono; M Yamazaki; A Sato; K Yamaoka; H Yamaguchi; S Abe
    YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN, Aug. 2000, [Reviewed]
  • Evaluation of a new method for antifungal drugs susceptibility testing to yeasts
    ISHIGAKI Shinobu; KAWAKAMI Sayoko; ONO Yasuo; MIYAZAWA Yukihisa
    J. Jan. Assac. Infect. Die., Mar. 2000, [Reviewed]
  • Bacteremic Moraxella catarrhalis pneumonia in a patient with immunoglobulin deficiency
    Hajime Sugiyama; Eri Ogata; Yuko Shimamoto; Youji Koshibu; Kaoru Matsumoto; Keiko Murai; Taku Miyashita; Yasuo Ono; Hajime Nishiya; Otohiko Kunii; Tomohide Sato
    Journal of Infection and Chemotherapy, 2000, [Reviewed]
  • Susceptibility testing of Mycobacterium avium and Mycobacterium Kansasii-comparison of the E test and an agas dilution method-               
    2000, [Reviewed]
  • Extended-spectrum β-lactamase (ESBL) Produced by Escherichia coli and Klebsiella pneumoniae Isolated from Teikyou University Hospital-The Second Report-
    KAWAKAMI Sayoko; ONO Yasuo; YAMAMOTO Miwa; MATUMURA Mituru; OKAMOTO Ryoichi; INOUE Matuhisa; MIYAZAWA Yukihisa
    J. Jan. Assac. Infect. Die., 2000, [Reviewed]
    We studied the high-level resistant to cefotaxime (CTX, MIC≥512μg/ml) clinical isolates of Escherichiacoli and Klebsiella pneumoniae in Teikyo University Hospital.
    The CTX-resistance could be transferred to E. coli K-12χ 1037 or ML4903 strains from 30 of the33 isolates by cojugation at a frequency of 10-4. When the hydrolysis rate of benzylpenicillin was 100%, the P-lactamases which were extracted from the transconjugants hydrolyzed CTX, CAZ and AZT at the rate of 38-95%, 0-8.6% and 0-56%, respectively. These results demonstrate thatthese enzymes should be categorized into ESBL. The nucleotid sequence of CTX-resistant gene wasidentified to that of the CTX-M2 gene which was first described in Argentina. It was found to have99.9% homology to Toho-1 gene in Japan and 99.6% homology to CMY-2 gene. Using a PCR methodsfor the detection of one of ESBL gene such as CTX-M2, Toho-1 or CMY-2, the DNA was amplifed from all strains (11 isolates of E. coli and 21 isolates of K. pneunoniae).
  • 化学発光酵素免疫測定法によるHCVコア抗体測定の基礎的検討               
    Dec. 1999, [Reviewed]
  • Acidic glycosaminoglycans of abdominal mucin in a case of pseudomyxoma peritonei caused by appendiceal cancer
    T Miyashita; K Murata; E Hoshino; H Nishiya; Y Ono; Akaoka, I; O Kunii
    DIGESTIVE DISEASES AND SCIENCES, Nov. 1999, [Reviewed]
  • Extended-spectrum β-lactamase (ESBL) Produced by Escherichia coli and Klebsiella pneumoniae Isolated from Teikyou University Hospital-The First Report-
    KAWAKAMI Sayoko; ONO Yasuo; YAMAMOTO Miwa; MATUMURA Mituru; OKAMOTO Ryoich; INOUE Matsuhisa; MIYAZAWA Yukihisa
    J. Jan. Assac. Infect. Die., Nov. 1999, [Reviewed]
  • 転移性両側全眼球炎を合併したKlebsiella pneumoniaeによる肝膿瘍の1例               
    Jan. 1999, [Reviewed]
  • 免疫クロマトグラフィー法によるTreponema pallidum抗体の測定               
    Oct. 1998, [Reviewed]
  • Basic study on identification of inactive E. coli which were misjudged as Shigella spp. using commercial identification kits
    NAKAZAWA Naomi
    医学検査 : 日本臨床衛生検査技師会誌 = The Japanese journal of medical technology, Jul. 1998, [Reviewed]
  • Survey of Fungemia Cases During the Past Seventeen Years at Teikyo University Hospital
    KAWAKAMI Sayoko; ONO Yasuo; MIYAZAWA Yukihisa; YAMAGUCHI Hideyo
    感染症学雑誌 : 日本伝染病学会機関誌 : the journal of the Japanese Association for Infectious Diseases, Feb. 1998, [Reviewed]
  • Systemic inflammatory responses in acute coronary syndrome: increased activity observed in polymorphonuclear leukocytes but not T lymphocytes
    S Takeshita; T Isshiki; M Ochiai; T Ishikawa; Y Nishiyama; T Fusano; H Toyoizumi; K Kondo; Y Ono; T Sato
    ATHEROSCLEROSIS, Dec. 1997, [Reviewed]
  • A case of Primary HIV-1 infection
    SUGIYAMA Hajime; KAWAMATA Keiko; KATOH Junko; MIYASHITA Taku; ITOH Tadashi; OHYATSU Isao; AOKI Masumi; ONO Yasuo; NISHIYA Hajime; KUNII Otohiko; SATOH Tomohide
    J. Jap. Assoc. Infect. Dis., 20 Sep. 1997, [Reviewed]
    A previously healthy 28 year old Japanese man came to us with a genital ulcer which appeared 13 days before admission to our hospital. He had subsequently fever (40°C), arthralgia, sore throat and oral aphtha 6 days before admission. He had a history of sexual contact with female commercial sex worker one week before his illness.
    On the day of admission, he had shallow ulcers on the lip, tongue and penis. Initial laboratory test included leukopenia and thrombocytopenia. His fever abated 3 days after admission. His condition and bicytopenia recovered completely after 12 days of admission. Although, his serum HIV-1 antibody was negative when he was admitted, 3 months later the antibody was seroconverted. And p24 antigen and HIV-1 RNA of stocked serum were positive. Diagnosis of primary HIV-1 infection was made. Recently, HIV-1 infection has been increasing in Japan. Consideration ofthis disease in differential diagnosis of acute febrile illness is necessary.
  • Effect of Seihai-to on the active oxygen generated from sputa               
    Kampo and Immuno-allergy, 1997, [Reviewed]
  • The prevalence of Helicobacter pylori positive serology in asymptomatic Japanese children
    KAWAKAMI Sayoko; OHGO Emi; NAKAZATO Yutaka; TAJIMA Takeshi; ONO Yasuo; MIYAZAWA Yukihisa
    J. Jap. Assoc. Infect. Dis., 20 Nov. 1996
  • マイクロパーティクルEIA法によるHCV抗体測定の検討               
    Jun. 1996, [Reviewed]
  • A Case of Schistosomiasis Suspected by Circumoval Precipitin Test and Diagnosed by Rectal Biopsy
    NISHIYA Hajime; MAEDA Ryuichiro; HOSHINO Etsuo; ONO Yasuo; KUNII Otohiko; MIYASHITA Hideo; ARAKI Kunioki; SHIBUYA Toshiro
    感染症学雑誌 : 日本伝染病学会機関誌 : the journal of the Japanese Association for Infectious Diseases, 20 Mar. 1996, [Reviewed]
    A forty-year-old female from Brazil was admitted to Teikyo Hospital because of easy fatigability, fullness of the abdomen and left hyochondralgia. She was anxious about Schistosoma mansoni infection, because three of her relatives died of the infection. Physical examinations revealed a tenderness at the left hypochondrium. Laboratory data showed no abnormal finding. No egg of S. mansoni was found in the stool.
    A circumoval precipitin test (COPT) with the serum showed a deposite around the egg. Enzyme-linked immunosorbent assay (ELISA) revealed the presence of antibody against S. mansoni in the serum. A colonoscopy showed no abnormal finding macroscopically. The rectal biopsy showed the existence of mild procitis. The diagnosis was made by finding the characteristic lateral-spined eggs in the biopsy specimens from the rectum. Treatment of 3 g of prazicantel per day for three days was started. She complained of mild nausea at the first dosing. A month later, another three-day-treatment was given. In the case where there are no eggs found in the stool, COPT and ELISA are usefull in detecting the disease, and colonoscopy is recommended in diagnosing the disease.
  • Clinical effects of balofloxacin on bacterial infections in the field of internal medicine
    KUNII Otohiko; MIYASHITA Taku; ONO Yasuo; MIYASHITA Hideo; KOBAYASHI Hiroyuki; SAKAYORI Susumu; SHIMADA Kaoru; OKA Shinichi; INAMATSU Takashi; ISHIKAWA Kumiko; MASUDA Yoshishige; FUKAYAMA Makiko; MIKI Fumio; YAMAMOTO Toshiyuki; MATSUURA Toru; SUZUKI Kanzo
    CHEMOTHERAPY, Nov. 1995, [Reviewed]
  • Basic and clinical studies on Pazufloxacin
    TOKUMURA Yasuaki; ONO Yasuo; SUGIYAMA Hajime; AOKI Masumi; OHYATSU Isao; NISHIYA Hajime; KUNII Otohiko
    Chemotherapy, Sep. 1995, [Reviewed]
  • Basic and clinical studies on grepafloxacin
    GUJI Atsuko; OHYATSU Isao; ONO Yasuo; MIYASHITA Taku; NISHIYA Hajime; TOKUMURA Yasumasa; SUGIYAMA Hajime; YAMAGUCHI Morimichi; AOKI Masumi; HAGA Toshiaki; KUNII Otohiko; MIYASHITA Hideo
    日本化学療法学会雜誌 = Japanese journal of chemotherapy, Jul. 1995, [Reviewed]
  • A case report of toxic shock-like syndrome due to Group A Streptococcal infection in an alcoholic
    ONO Yasuo; MEGUMI Masako; SUGlYAMA Hajime; TOKUMURA Yasumasa; KATO Junko; OHYATSU Isao; MIYASHITA Taku; NISHIYA Hajime; KUNll Otohiko; MIYASHITA Hideo; KAWAKAMI Sayoko; OKINAGA Kouta; UBUKATA Kimiko; KONNO Masatoshi
    J. Jap. Assoc. Infect. Dis, May 1995, [Reviewed]
  • An autopsy case of Fungal(Mucor) cerebral aneurysm
    TOKUDA Takahiro; ONO Yasuo; NISHIYA Hajime; AOKI Masumi; YAMANOUCHI Shunichi; KUNII Otohiko; MIYASHITA Hideo
    J. Jap. Assoc. Infect. Dis, Apr. 1995, [Reviewed]
  • GLUTATHIONE S-TRANSFERASES AS A CEFPIRAMIDE BINDING-PROTEIN IN RAT-LIVER
    A GUJI; H NISHIYA; M AOKI; OHYATSU, I; M YAMAGUCHI; Y TOKUMURA; H SUGIYAMA; T MIYASHITA; Y ONO; O KUNII
    PHARMACOLOGY & TOXICOLOGY, Mar. 1995, [Reviewed]
  • Useful abdominal Ultrasonography for diagnosis of Fitz-Hugh-Curtis Syndrome : Two case Reports
    SUGIYAMA Hajime; ONO Yasuo; AOKI Masumi; NISHIYA Hajime; TOKUMURA Yasuaki; OHYATSU Isao; KUNII Otohiko; MIYASHITA Hideo
    J. Jap. Assoc. Infect. Dis., Mar. 1995, [Reviewed]
  • A comparative study of tazobactam/piperacillin and piperacillin in bacterial pneumonia
    Kotaro Oizumi; Takayosi Ohno; Masao Kawahara; Shinzo Kawaguchi; Masazumi Saisho; Yoshiyuki Mitutake; Akira Saito; Masumi Tomizawa; Takao Koike; Kazuo Takebe; Toyokazu Tamura; Hiroshi Inoue; Kazuki Konishi; Takashi Mohri; Sakura Katoh; Kenichi Takeuchi; Akiho Ohara; Haruhito Hirano; Hideki Ikeda; Kunio Sirato; Yasuo Tanno; Masato Tohno; Yasuo Ono; Takuya Suzuki; Masahiro Sakamoto; Akira Watanabe; Toshihiro Nukiwa; Kiyoshi Konno; Kuniharu Shida; Tsuneo Sayama; Kazuo Sato; Yoshiyuki Anzai; Yoshiki Anazawa; Susumu Yoshida; Akira Ohishi; Kohtaro Kaneko; Kaoru Shimada; Yasuyuki Sano; Norihisa Akiyama; Yasuo Arai; Mamoru Ohtomo; Koichiro Nakada; Tatsuo Nakatani; Naohiko Tyonabayashi; Koichiro Kudo; Hiroko Arioka; Harumi Shishido; Atsushi Takahashi; Atsuhisa Tamura; Hirofumi Katayama; Motoo Baba; Masaru Koyama; Kohji Murabayashi; Jingoro Shimada; Shoichiro Irimajiri; Yasuo Matsuoka; Mitsuo Obana; Fumio Matsumoto; Takeo Imai; Shigeki Odagiri; Takashi Oguri; Yoshihiro Hirai; Masaaki Arakawa; Shigeyuki Hoshino; Hiroki Tsukada; Nobuki Aoki; Saburo Izumi; Atsuhiko Sato; Tadakazu Hattori; Yutaka Nakano; Kenzo Takagi; Yasunobu Noda; Hideo Gonda; Toshihiko Takeuchi; Yasuo Yamada; Hidekazu Hanaki; Makoto Kawakami; Toshiyuki Yamamoto; Kanzo Suzuki; Toshinobu Yamamoto; Fumiyuki Kuze; Kenji Bando; Shinichiro Ohyama; Shohei Kusaka; Tadashi Ishida; Yoshiro Mochizuki; Rieko Kanan; Kazushige Tsuyuguchi; Kojiro Yasunaga; Seibun Yonezu; Yoshitaka Yamanaka; Nobuhiro Narita; Masayoshi Sawaki; Keiichi Mikasa; Kazuya Higashino; Takashi Nakano; Tetsuya Nishigaki; Yumiko Goto; Hiroshi Sugimoto; Rinzo Soejima; Yoshihito Niki; Osamu Moriya; Akihisa Shindo; Toshiharu Matsushima; Makoto Kimura; Michio Yamakido; Kenji Hasegawa; Osamu Kurimura; Takehiko Hiramoto; Masahide Takii; Masanori Higuchi; Takaoki Ohyama; Katsuhiko Furuumi; Tsuneo Ishibashi; Masahiro Takamoto; Yasuko Harada; Susumu Harada; Kohei Hara; Hironobu Koga; Yoshiaki Ri; Taiji Masuyama; Masahiko Yoshimoto; Kazunori Shimoguchi; Kazuhiro Okuno; Kiyoyasu Fukushima; Keizo Matsumoto; Tsuyoshi Nagatake; Kazunori Oishi; Akihiro Hori; Tasuku Sakamoto; Hirofumi Tanaka; Toshihiro Morito; Mikio Fujishita; Masayuki Ando; Moritaka Suga; Naoki Saita; Masaru Nasu; Tohru Yamasaki; Jun Goto; Kazuo Kitagawa; Atsushi Saito; Hiroshi Fukuhara; Isoko Owan; Jun Inadome; Nobuya Ogawa; Koichi Deguchi
    The Japanese Journal of Antibiotics, 1995, [Reviewed]
  • Clinical evaluation of grepafloxacin in the treatment of various infectious diseases in the field of internal medicine
    Hiroyuki Kobayashi; Hiroaki Takeda; Hidehiro Watanabe; Hiroshi Ohtami; Susumu Sakayori; Akira Saito; Ichiro Nakayama; Kiyoshi Sato; Masumi Tomizawa; Yohmei Hiraga; Mitsuhide Ohmichi; Kazuo Takebe; Seiichi Murakami; Mitsuo Masuda; Kenichi Imamura; Hisashi Nakahata; Miyoko Saito; Takeshi Osonoi; Masashi Tamura; Kazuki Konishi; Kazuo Obara; Taro Chiba; Yoji Aoyama; Akiko Shiba; Akira Watanabe; Kazunao Niizuma; Shigeo Takizawa; Yushi Nakai; Yoshihiro Honda; Masataka Katsu; Akira Ohishi; Morio Nakamura; Kotaro Kaneko; Michihiro Sakauchi; Noboru Aosaki; Kaoru Shimada; Hajime Goto; Mieko Goto; Yasuyuki Sano; Yasufumi Miyamoto; Yasuo Arai; Norio Kikuchi; Osamu Sakai; Koya Shiba; Masaki Yoshida; Seiji Hori; Jingoro Shimada; Kihachiro Shimizu; Koichiro Nakata; Tatsuo Nakatani; Eiyasu Tsuboi; Koji Narui; Yoshitaka Nakamori; Hiroko Inagawa; Kyoichi Totsuka; Yusuke Shibata; Ken Kikuchi; Hiromi Hasegawa; Takeshi Mori; Hiroshi Isonuma; Mayumi Takahashi; Tsukasa Ebe; Masayoshi Inagaki; Otohiko Kunii; Atsuko Guji; Isao Ohyatsu; Yasuo Ono; Taku Miyashita; Hajime Nishiya; Yasumasa Tokumura; Hajime Sugiyama; Morimichi Yamaguchi; Masumi Aoki; Toshiaki Haga; Hideo Miyashita; Yasuo Ikeda; Masahiro Kisaki; Shigehisa Mori; Hiroshi Uchida; Yoshio Kobayashi; Koichiro Kudo; Tadashi Horiuchi; Shunsuke Shoji; Junzaburo Kabe; Harumi Shishido; Hideaki Nagai; Koji Satoh; Atsuyuki Kurashima; Shuji Miyake; Kenji Kawakami; Koji Hayashi; Fumio Matumoto; Takeo Imai; Iwao Sakurai; Koji Yoshikawa; Takayuki Takahashi; Masayuki Morita; Shigeki Odagiri; Kaneo Suzuki; Hiroshi Takahashi; Kenichi Takahashi; Takao Okubo; Hirotada Ikeda; Tamotsu Kaneko; Masaaki Arakawa; Nobuki Aoki; Osamu Sekine; Yasutoshi Suzuki; Katsuji Uno; Motohiro Yagi; Hajimu Takeda; Saburo Izumi; Atsuhiko Sato; Kingo Senda; Takafumi Suda; Ryoji Tamura; Atsushi Yoshitomi; Takeshi Yagi; Toshihiko Takeuchi; Yasuo Yamada; Atsushi Nakamura; Toshinobu Yamamoto; Kazuhide Yamamoto; Hidekazu Hanaki; Toshiyuki Yamamoto; Toru Matsuura; Masahiro Yamagoshi; Kanzo Suzuki; Kaoru Shimokata; Satoshi Ichiyama; Hidehiko Saito; Shuzo Sakai; Shiro Nomura; Kazuyoshi Senda; Takeshi Iwahara; Hironobu Minami; Masashi Yamamoto; Hiroshi Saito; Sadaaki Yamori; Tomohisa Shibagaki; Keisuke Nishiwaki; Kazuo Nakanishi; Nobuhiro Narita; Keiichi Mikasa; Masayoshi Sawaki; Mitsuru Konishi; Koichi Maeda; Kaoru Hamada; Shoji Takeuchi; Masahiro Sakamoto; Masayuki Tsujimoto; Mikikazu Kunimatsu; Fumiyuki Kuze; Mitsuru Kawai; Fumio Miki; Yoshiyasu Ikuno; Akihito Murata; Kazuo Sakamoto; Masato Hiruma; Shinichiro Otani; Yasushi Hara; Koji Nakayama; Satohiko Tanaka; Akihisa Hanatani; Saburo Yano; Masaru Nakagawa; Rinzo Soejima; Niro Okimoto; Osamu Moriya; Yoshihito Niki; Toshiharu Matsushima; Makoto Kimura; Yoshihiro Kobashi; Norifumi Adachi; Jun Tanabe; Yoshihiko Tano; Hiroki Hara; Michio Yamakido; Kenji Hasegawa; Tsuyoshi Ogura; Kanji Asada; Osamu Namikawa; Shinsuke Nishioka; Masahiko Azuma; Mikie Maeda; Minoru Shirakami; Yoshiyuki Niho; Yoshiro Sawae; Kaoru Okada; Koji Takaki; Nobuyuki Shimono; Hiroyasu Misumi; Katsuhiko Eguchi; Kotaro Oizumi; Naoto Tokunaga; Yoichiro Ichikawa; Takafumi Yano; Kohei Hara; Shigeru Kohno; Hironobu Koga; Mitsuo Kaku; Kazunori Tomono; Naomi Ito; Koichi Watanabe; Keizo Matsumoto; Masakazu Takasugi; Mikio Taguchi; Kazunori Oishi; Atsushi Takahashi; Hiroshi Watanabe; Akemi Omori; Kiwao Watanabe; Tsuyoshi Nagatake; Hirofumi Tanaka; Soichiro Yamauchi; Tomoku Ichimiya; Kazufumi Hirai; Hiroshi Kawano; Takayoshi Tashiro; Kiyoshi Shima; Shinobu Takenaka; Atsushi Saito; Hiroshi Fukuhara; Yuei Irabu; Jun Inadome; Nobuchika Kusano; Yoshiko Furugen; Isamu Nakasone; Shinko Taira
    Japanese Journal of Chemotherapy, 1995, [Reviewed]
  • COMPARATIVE-STUDY OF THE EFFECTS OF CEFODIZIME AND HBW-538 IN POTENTIATING THE PRODUCTION OF REACTIVE OXYGEN SPECIES BY HUMAN POLYMORPHONUCLEAR LEUKOCYTES
    Y ONO; O KUNII; OHYATSU, I; Y TOKUMURA; T MIYASHITA; M AOKI; H SUGIYAMA; H NISHIYA; H MIYASHITA; E GOLDSTEIN
    CHEMOTHERAPY, Nov. 1994, [Reviewed]
  • Tazobactam/Piperacillinに関する基礎的・臨床的検討               
    Oct. 1994, [Reviewed]
  • Effect of newer quinolones on the extra- and intra-cellular chemiluminescence response of human polymorphonuclear leucocytes
    Masumi Aoki; Yasuo Ono; Otohiko Kunii; Elliot Goldstein
    Journal of Antimicrobial Chemotherapy, Sep. 1994, [Reviewed]
  • 巨大疣贅の切除および僧帽弁形成術にて治癒した急性感染性心内膜炎の1例               
    May 1994, [Reviewed]
  • Two cases of Campylobacter fetus subsp. fetus sepsis
    J. Jpn. Assoc. Infect. Dis., Feb. 1994, [Reviewed]
  • biapenemに関する基礎的臨床的研究
    山口守道; 斧康雄; 西谷肇; 宮下琢; 国井乙彦ほか
    CHEMOTHERAPY, 1994, [Reviewed]
  • SY5555に関する基礎的臨床的研究
    大谷津功; 斧康雄; 宮下琢; 西谷肇; 国井乙彦ほか
    化学療法学会雑誌, 1994, [Reviewed]
  • Effect of Cefodizime on the Chemiluminescence Response of Phagocytic Cells-A Comparative Study with HBW 538, a Derivative of its Side-chain at Position 3               
    Chemotherapy (Basel), 1994, [Reviewed]
  • OPSONIC ACTIVITY OF SERA AND BLISTER FLUID FROM SEVERELY BURNED PATIENTS EVALUATED BY A CHEMILUMINESCENCE METHOD
    Y ONO; O KUNII; H SUZUKI; H IKEDA; K KOBAYASHI; S KANEGASAKI
    MICROBIOLOGY AND IMMUNOLOGY, 1994, [Reviewed]
  • FK037に関する基礎的臨床的研究
    青木ますみ; 西谷肇、宮司厚子; Yasuo 斧康雄、国井乙彦ほか
    CHEMOTHERAPY, 1994, [Reviewed]
  • Cefozopranに関する基礎的,臨床的検討               
    Dec. 1993, [Reviewed]
  • Temafloxacinの基礎的・臨床的検討               
    Dec. 1993, [Reviewed]
  • 内科領域におけるTeicoplaninの臨床的検討               
    Aug. 1993, [Reviewed]
  • Loracarbef(LCBF)に関する基礎的・臨床的検討               
    Aug. 1993, [Reviewed]
  • S-1108に関する基礎的・臨床的検討               
    Jun. 1993, [Reviewed]
  • A Case of Spontaneous Bacterial Peritonitis with Ascites Caused by Hypoproteinemia after a Massive Bleeding from a Gastric Ulcer
    GUJI Atsuko; NISHIYA Hajime; HAGA Toshiaki; AOKI Masumi; NOZUE Norio; ONO Yasuo; KUNII Otohiko; MIYASHITA Hideo
    Journal of the Japanese Association for Infectious Diseases, 1993, [Reviewed]
    A case of spontaneous bacterial peritonitis (SBP) developed in an old man whose ascitic fluid was related neither to portal hypertension nor nephrotic syndrome, but with severe hypoalbuminemia emerged after a massive bleeding from a gastric ulcer in a malnutrition state. Ascitic fluid, increasing day by day, yielded Enterobacter cloacae and Bacteroides fragilis. Though autopsy was not carried out because of refusal of his family, neither liver necropsy, nor abdominal CT scan nor repeated abdominal ultrasonography showed findings suggesting existence of liver cirrhosis.
    In the presence of his ascites, the extent of a chemiluminescence (CL) response of polymorphonuclear cells from volunteers was significantly lower than that of his serum.
    This report shows that SBP can develop in a patient with ascites unrelated to portal hypertension when ascitic fluid induces little CL response.
  • Evaluation of opsonophagocytic dysfunction in burned patients
    Ono Yasuo; Kunii Otohiko; Kobayashi Kunio; Kanegasaki Shiro
    Microbiology and Immunology, 1993, [Reviewed]
    We compared the luminol-dependent chemiluminescence (CL) response of peripheral blood from severely burned patients with that from normal controls to evaluate the primary defense level against bacterial infection in the patients. The CL was measured upon addition to diluted whole blood of a soluble stimulus, phorbol myristate acetate (PMA) or particulate stimuli such as bacteria or zymosan without special opsonization. In the early post-burn days, the initial rate of whole blood CL induced with the particulate stimulus was much lower than that in the normal controls, whereas the rate was higher when PMA was used as a stimulus. The number of granulocytes in the patients' blood had increased and isolated polymorphonuclear leukocytes (PMNs) from the patients exhibited higher CL responses to the particulate or soluble stimulus as compared with those of normal controls. The results suggest that the PMNs in burn patients were activated and normally mobilized in the early post-burn period but the opsonizing capacity in the blood decreased. In fact, the serum levels of complement, immunoglobulins and fibronectin were found to be lower in the blood from the patients than those from normal controls and a supplement of freshly frozen plasma of human immunoglobulin preparations restored the initial rate of the whole blood CL upon phagocytosis. The prognosis is still poor when severe infection occurs in the patients with decreased CL response of whole blood. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) enhanced the CL response of PMNs from burn patients. The administration of rhG-CSF may be useful for decreasing the morbidity of severe infection following burn injury in the near future.
  • Cefclidinに関する基礎的,臨床的検討               
    Sep. 1992, [Reviewed]
  • Meropenem (MEPM)の基礎的・臨床的研究               
    Apr. 1992, [Reviewed]
  • ME 1207の基礎的,臨床的検討               
    Apr. 1992, [Reviewed]
  • Effect of interferon-γ on human neutrophil chemiluminescence
    Masumi Aoki; Yasuo Ono; Otohiko Kunii
    CHEMOTHERAPY, 1992, [Reviewed]
  • panipenem/betamipronに関する基礎的・臨床的検討               
    Sep. 1991, [Reviewed]
  • Sparfloxacin (SPFX)の基礎的,臨床的検討               
    Aug. 1991, [Reviewed]
  • 重症熱傷患者の好中球機能に及ぼすrhG-CSFの効果               
    Jul. 1991, [Reviewed]
  • Cefpirome (CPR)に関する基礎的・臨床的検討               
    Feb. 1991, [Reviewed]
  • 第二内科のMRSAの現状 臨床例の検討               
    Jul. 1990, [Reviewed]
  • 他剤無効例に対するimipenem/cilastatin sodium (IPM/CS)の臨床的検討               
    Apr. 1990, [Reviewed]
  • Clinical study on cefetamet pivoxil
    Toshiaki Haga; Norio Nozue; Masumi Baba; Atsuko Guuji; Yasuo Ono; Hajime Nishiya
    CHEMOTHERAPY, 1990, [Reviewed]
  • 黄色ブドウ球菌のオプソニン化・貪食作用に及ぼす最小発育阻止濃度以下の抗菌剤の影響               
    Jan. 1990
  • 重症熱傷患者における全血chemiluminescence (CL)の検討               
    Dec. 1989, [Reviewed]
  • 7432-Sのヒト食細胞との協力殺菌作用および基礎的臨床的検討               
    Nov. 1989, [Reviewed]
  • 重症クレブシエラ肺炎による敗血症性ショックの1例と免疫グロブリン製剤の有用性について               
    May 1989, [Reviewed]
  • 院内感染によるAcinetobacter敗血症の3症例               
    Mar. 1989, [Reviewed]
  • Effects of 2(3)-tert-butyl-4-hydroxyanisole pretreatment on cefpiramine binding to mouse glutathione S-transferases
    H. Nishiya; T. Haga; N. Nozue; T. Komatsu; M. Baba; Y. Ueda; Y. Ono; O. Kunii
    Pharmacology, 1989, [Reviewed]
  • Influence of a subinhibitory concentration of antibiotics on opsono-phagocytic functions of klebsiella pneumoniae by human phagocytes
    Yasuo Ono; Yuichiro Ueda; Masumi Baba; Hajime Nishiya; Otohiko Kunii
    Chemotherapy, 1989, [Reviewed]
  • Cefodizime (THR-221)に関する基礎的・臨床的研究               
    Oct. 1988, [Reviewed]
  • ヒト食細胞機能に及ぼすCefodizime (THR-221)の影響               
    Oct. 1988, [Reviewed]
  • TE-031に関する研究 特に食細胞機能に及ぼす効果について               
    Jul. 1988, [Reviewed]
  • CS-807に関する臨床的研究               
    May 1988, [Reviewed]
  • Laboratory and clinical studies on cefotiam hexetil
    Norio Nozue; Yuichiro Ueda; Toshiaki Haga; Akira Muraoka; Yasuo Ono; Hajime Nishiya; Hideo Miyashita
    CHEMOTHERAPY, 1988, [Reviewed]
  • Effect of cefodizime (THR-221) on the function of human phagocytic cells
    Yasuo Ono; Yuichiro Ueda; Masumi Baba; Norio Nozue; Toshiaki Haga; Akira Muraoka; Hajime Nishiya; Otohiko Kunii; Hideo Miyashita
    CHEMOTHERAPY, 1988, [Reviewed]
  • 健康成人に発症したサイトメガロウイルス(CMV)単核細胞症の1例               
    Jul. 1987, [Reviewed]
  • Carumonamに関する基礎的,臨床的研究               
    Jun. 1987, [Reviewed]
  • Laboratory and Clinical Studies of Flomoxef
    Norio Nozue; Yuichiro Ueda; Toshiaki Haga; Akira Muraoka; Yasuo Ono; Hajime Nishiya; Hideo Miyashita
    The Japanese Journal of Antibiotics, 1987, [Reviewed]
  • Cefuroxime axetil (CXM-AX)の臨床的検討               
    Nov. 1986, [Reviewed]
  • BRL 28500 (Clavulanic acid-Ticarcillin)に関する研究               
    Oct. 1986, [Reviewed]
  • BAY o 9867 (Ciprofloxacin)に関する研究               
    Dec. 1985, [Reviewed]
  • Imipenem/Cilastatin sodium (MK-0787/MK-0791)に関する研究               
    Nov. 1985, [Reviewed]
  • Azthreonam (SQ 26,776)に関する研究               
    Apr. 1985, [Reviewed]
  • 肝膿瘍の1例(小膿瘍の検出例)               
    Dec. 1984, [Reviewed]
  • 肝内胆汁うっ滞例における超音波像について               
    Dec. 1984, [Reviewed]
  • 血液疾患における脾腫の超音波学的検討               
    May 1984, [Reviewed]
  • Studies on ceftriaxone (Ro 13-9904)
    Otohiko Kunii; Takashi Komatsu; Hajime Nishiya; Ryuji Ieki; Yasuo Ono; Shiro Miwa
    CHEMOTHERAPY, 1984, [Reviewed]
  • Clinical studies on lenampicillin (KBT-1585)
    Otohiko Kunii; Takashi Komatsu; Hajime Nishiya; Yasuo Ono; Shiro Miwa
    CHEMOTHERAPY, 1984, [Reviewed]
  • Studies on AC-1370
    Otohiko Kunii; Takashi Komatsu; Hajime Nishiya; Yasuo Ono; Jun Yokota; Takenori Takizawa; Shiro Miwa; Kazufuto Fukaya
    CHEMOTHERAPY, 1984, [Reviewed]
  • Studies on sulbactam/cefoperazone
    Otohiko Kunii; Takashi Komatsu; Hajime Nishiya; Masakiyo Hirayama; Yasuo Ono; Shiro Miwa; Masazumi Eriguchi; Hiraku Honda; Genichi Tomori
    CHEMOTHERAPY, 1984, [Reviewed]
  • Studies on MT-141
    Otohiko Kunii; Takashi Komatsu; Hajime Nishiya; Yasuo Ono; Katsuyuki Haranaka; Nobuko Satomi; Akiko Sakurai; Akira Hirono; Takenori Takizawa; Shiro Miwa
    CHEMOTHERAPY, 1984, [Reviewed]
  • 超音波断層法による伝染性単核症とA型肝炎の脾腫の比較検討               
    Dec. 1983, [Reviewed]
  • Studies on ceftazidime (SN401)
    Otohiko Kunii; Takashi Komatsu; Hajime Nishiya; Yasuo Ono; Takenori Takizawa; Shiro Miwa; Kazufuto Fukaya
    CHEMOTHERAPY, 1983, [Reviewed]

MISC

Books and other publications

  • 標準微生物学 改訂第14版
    Contributor
    Mar. 2023
    9784260043311
  • 今日の臨床検査
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    May 2021
    9784524228034
  • アスペルギルス抗原測定.               
    Contributor
    Jun. 2020
  • 細菌性感染症を疑った場合の検査の進め方,検査データの評価をする際のポイント               
    Contributor
    Jun. 2020
  • 感染症検査,レビューアー P369ー373, 今日の臨床検査2019~2020.[櫻林郁之介監修,矢富裕,廣畑俊成,山田俊幸,石黒厚至・編]               
    Feb. 2019
  • レンサ球菌属,腸球菌属, P124-131,標準微生物学第13版.[神谷 茂, 錫谷達夫 編]               
    Contributor
    Mar. 2018
  • 第7章 感染症.P99-146,シンプル内科学 改訂第2版.[寺野彰総編集]               
    Contributor
    Oct. 2017
  • 感染症検査,レビューアー P357ー361, 今日の臨床検査2017~2018.[櫻林郁之介監修,矢富裕,廣畑俊成,山田俊幸,石黒厚至・編]               
    Contributor
    May 2017
  • 抗菌薬とエンドトキシンの遊離,p226-228,感染症専門医テキスト改訂第2版,第I部解説編[日本感染症学会編]               
    Contributor
    2017
  • 宿主寄生体関係,p25-27,感染症専門医テキスト改訂第2版,第I部解説編[日本感染症学会編]               
    Contributor
    2017
  • 病原微生物の病原因子,p22-24,感染症専門医テキスト改訂第2版,第I部解説編[日本感染症学会編]               
    Contributor
    2017
  • 常在菌,p20-22,感染症専門医テキスト改訂第2版,第I部解説編[日本感染症学会編]               
    Contributor
    2017
  • 高齢者感染症ー超高齢社会の課題と特徴               
    Contributor
    May 2016
  • 一発診断一目瞭然.目で診る症例から瞬時に診断. P11,P55, [日本内科学会専門医部会編]               
    Apr. 2015
  • アスペルギルス抗原測定.P920ー923, 臨床検査ガイド2015改訂版.[Medical Practice 編集委員会・編]               
    Mar. 2015
  • 細菌性感染症を疑った場合の検査の進め方,検査データの評価をする際のポイント.P4ー12, 臨床検査ガイド2015改訂版[Medical Practice 編集委員会・編]               
    Mar. 2015
  • 標準微生物学第12版.レンサ球菌属,腸球菌属P176ー184               
    Feb. 2015
  • 今日の臨床検査2015~2016.               
    Contributor
    Jan. 2015
  • 医師・薬剤師のための医薬品副作用ハンドブック.[寺本民生監修]               
    Contributor
    Oct. 2013
  • 抗菌薬の選び方・使い方ハンドブック[戸塚恭一]編               
    Contributor
    Aug. 2013
  • 抗菌薬の選び方・使い方ハンドブック.[戸塚恭一]編               
    Contributor
    Aug. 2013
  • 抗菌薬の選び方・使い方ハンドブック [戸塚恭一]編               
    Contributor
    Aug. 2013
  • 今日の臨床検査2013~2014.[櫻林郁之介監修,矢富裕、廣畑俊成,山田俊幸,石黒厚至・編]               
    Contributor
    Mar. 2013
  • 臨床検査ガイド2013~2014.[Medical Practice 編集委員会・編]               
    Contributor
    Mar. 2013
  • 臨床検査ガイド2013~2014.[Medical Practice 編集委員会・編]               
    Contributor
    Mar. 2013
  • 感染症診断に必要な微生物検査. [菅野治重,川上小夜子 監修]               
    Contributor
    2013
  • 顕微鏡検査ハンドブック. 臨床に役立つ形態学. [菅野重治,相原雅典,伊勢恵子,伊東仁,手島伸一,矢富裕編]               
    Contributor
    2013
  • 静注用免疫グロブリン製剤ハンドブック[正岡 徹監修]               
    Contributor
    2011
  • 感染症専門医テキスト, 第I部解説編[日本感染症学会 編]               
    Contributor
    2011
  • 感染症専門医テキスト, 第I部解説編[日本感染症学会 編]               
    Contributor
    2011
  • 感染症専門医テキスト, 第I部解説編[日本感染症学会編]               
    Contributor
    2011
  • 感染症専門医テキスト,第I部解説編[日本感染症学会編]               
    Contributor
    2011
  • 臨床検査ガイド2011~2012[Medical Practice 編集委員会・編]               
    Contributor
    2011
  • 臨床検査ガイド2011~2012.[Medical Practice 編集委員会・編]               
    Contributor
    2011
  • 外科・救急集中治療における感染症対策.今すぐ実践したい周術期管理と抗菌薬適正使用. [竹末 芳生 編]               
    Contributor
    2011
  • ガイドライン/ガイダンス 成人市中肺炎,こう診る・こう考える.[三笠桂一 編]               
    Contributor
    2010
  • 医薬品副作用ハンドブック第2版[高橋隆一監修]               
    Contributor
    2010
  • 熟練医から日常診療の様々なコツを伝授.[日本プライマリ・ケア学会編]               
    Contributor
    2009
  • 感染症内科クリニカルスタンダード.[前崎繁文編]               
    Contributor
    2008
  • キーワード感染症第2版, [山口恵三,戸塚恭一 編集]               
    Contributor
    2008
  • 最新臨床検査項目辞典.[櫻林郁之介,熊坂一成 監修]               
    Contributor
    2008
  • シンプル内科学 [寺野彰総編集]               
    Contributor
    2008
  • シンプル内科学 [寺野彰総編集]               
    Contributor
    2008
  • シンプル内科学.[寺野彰総編集]               
    Contributor
    2008
  • シンプル内科学[寺野彰総編集]               
    Contributor
    2008
  • 今日の診断基準.[大田健, 奈良信雄編]. 南江堂               
    Contributor
    2007
  • 今日の診断基準.[大田健, 奈良信雄編]               
    Contributor
    2007
  • わが病院の感染対策. [木村 哲 編]               
    Contributor
    2006
  • ベッドサイドで役立つ微生物検査ガイド. [河野茂,平潟洋一 編]               
    Contributor
    2006
  • 生活習慣病クリニックII. 帝京大学医学部附属病院編. [寺本民生監修]               
    2006
  • 日常外来で遭遇する感染症診療ガイド.[舟田 久 編著]               
    Contributor
    2006
  • 食中毒検査・診断のコツと落とし穴. [渡辺治雄編]               
    Contributor
    2006
  • 食中毒検査・診断のコツと落とし穴.[渡辺治雄編]               
    Contributor
    2006
  • Q &Aで読む細菌感染症の臨床と検査[五島 瑳智子監修]               
    Contributor
    2005
  • 実地診療に役立つ実践抗生物質・抗菌薬療法ガイド[Medical Practice 編集委員会・編]               
    Contributor
    2005
  • よりよい感染症診療をめざして-検査報告のありかた-[菅野治重 監修]               
    Contributor
    2005
  • プロフェッショナル英和辞典SPED EOS 生命科学編,初版               
    Contributor
    2004
  • バンコマイシン耐性菌戦略Q&A.[公文裕巳 編] 医薬ジャーナル社               
    Contributor
    2004
  • EBM内科処方指針[黒川清,寺本民生 編]               
    Contributor
    2004
  • 臨床検査ガイド2005~2006.[Medical Practice 編集委員会・編]               
    Contributor
    2004
  • 臨床検査項辞典               
    May 2003
  • 消化器疾患の薬物療法.[星野恵津夫,山岡桂子 編]               
    Contributor
    2003
  • 臨床検査項辞典.[櫻林郁之介,熊坂一成 監修]               
    2003
  • 朝倉内科学. [杉本恒明,小俣政男,水野美邦 総編集]               
    Contributor
    2003
  • 朝倉内科学.[杉本恒明,小俣政男, 水野美邦 総編集]               
    Contributor
    2003
  • 病院感染なるほどABC. [斧 康雄 編]               
    Editor
    2003
  • ヘテロ耐性と臨床効果.バンコマイシン耐性菌戦略〔公文裕巳 編〕               
    Contributor
    2001
  • 抗菌薬.エクセルナース・消化器疾患〔滝川一 編〕               
    Contributor
    2000
  • ワルファリンと抗菌薬               
    Contributor
    2000
  • 日常検査における耐性菌の検出法.VRE(バンコマイシン耐性腸球菌)               
    Contributor
    2000
  • 感染症と抗生物質の使い方 第3版 感染症と炎症反応               
    Contributor
    1999
  • ステロイド.効果的な選び方・使い方 感染症               
    Contributor
    1999
  • 消化管疾患の薬物療法 消化管感染症の薬物療法               
    Apr. 1998
  • カルバペネム薬の使用法.               
    Contributor
    1997
  • 顆粒球コロニー刺激因子(G-CSF)               
    Contributor
    1996
  • 症例に学ぶ内科感染症の抗菌薬使用法 國井乙彦編著               
    Contributor
    1996
  • 再燃する細菌感染症。細菌感染症と好中球の活性化               
    Contributor
    1996
  • MRSA感染症のすべて 紺野昌俊編               
    Contributor
    1991
  • 基礎・臨床からみた日常診療における感染症の現状と対策               
    Contributor

Lectures, oral presentations, etc.

Affiliated academic society

  • May 2025 - Present
    日本呼吸器学会               
  • JAPANESE ASSOCIATION FOR ACUTE MEDICINE               

Works

  • 好中球細胞外トラップ(NETs)に関する研究               
    2013 - Present
  • アシネトバクターの耐性機序と病原性に関する研究               
    2011 - Present
  • 薬剤耐性菌の迅速検出法に関する研究               
    2010 - Present
  • 薬剤耐性菌の耐性機構の解析               
    2010 - Present, Others
  • 細菌や真菌の菌体成分の免疫系に及ぼす作用               
    2006 - Present
  • 分子生物学的手法を用いた好中球能の機能解析               
    2005 - Present, Artistic activity
  • 薬剤耐性菌の耐性機構に関する疫学的,分子生物学的解析               
    2004 - Present
  • 好中球の細胞内シグナル機構の解析               
    2003 - Present
  • 免疫増強物質と免疫抑制物質の食細胞機能に及ぼす影響               
    2002 - Present
  • 薬剤耐性菌の病原性に関する研究               
    2001 - Present
  • 免疫不全患者の感染防御能の解析               
    2001 - Present
  • 好中球の走化能に関する研究               
    2001 - Present
  • 易感染性宿主の食細胞機能に関する研究               
    2000 - Present
  • 抗菌薬の好中球機能に及ぼす効果               
    1999 - Present
  • カンジダ属の病原性に関する研究               
    1995 - Present
  • 全身性炎症反応症候群(SIRS)とセプシスに関する研究               
    1995 - Present
  • アスペルギルスの病原性に関する研究               
    2000 - 2010
  • 好中球遊走能のコンピュータ画像解析               
    2005
  • Study on receptor and gene expression of chemokines and cytokines in neutrophil               
    2005
  • 肝硬変患者の食細胞機能に関する研究               
    1993 - 2004
  • 好中球のサイトカイン,ケモカイン遺伝子発現と疾患               
    2004
  • Study on drug-resistant bacteria               
    2001
  • Analysis of host defense in immunocompromised hosts               
    2001
  • Study of chemotaxis of human neutrophils               
    2001
  • 抗真菌薬の薬剤感受性試験に関する研究               
    1999 - 2000
  • ESBL産生菌の薬剤耐性機構の解析               
    1999 - 2000
  • 薬剤耐性菌の疫学調査               
    1999 - 2000
  • Study of testing for drug sensitivity against fungi               
    1999 - 2000
  • Analysis of drug-resistance mechanism on ESBL producing bacteria               
    1999 - 2000
  • Epidemiological survey on drug-resistant bacteria               
    1999 - 2000
  • Analysis of eosinophil function               
    2000
  • Study of production of active oxygen from human eosinophils               
    2000
  • Study of chemotaxis of human eosinophils               
    2000
  • Study on pathogenesis of Aspergillus               
    2000
  • Study of phagocytic function in Compromised hosts               
    2000
  • Effects of antibiotics on neutrophil function               
    1999
  • ペプチドグルカンのヒト好中球の活性酸素放出能に及ぼす研究               
    1997 - 1998
  • Study of peptidglucan on the production of active oxygen from human neutrophils               
    1997 - 1998
  • β-glucanのヒト好中球の活性酸素放出能に関する研究               
    1996 - 1998
  • Study of β-glucan on the production of reactive oxygen species from human neutrophils               
    1996 - 1998
  • ヘリコバクター・ピロリー感染の疫学調査と活性酸素による胃粘膜細胞障害機序に関する研究               
    1995 - 1998
  • Study on pathogenesis of Candida species               
    1995 - 1998
  • Study of epidemiology of Helicobacter pylori infection and role of active oxygen in H .Pylori- induced gastric mucosalinjury               
    1995 - 1998
  • 抗菌薬の食細胞機能に及ぼす効果               
    1993 - 1998
  • ペニシリン耐性肺炎球菌の病原性に関する研究               
    1995 - 1996
  • Study on pathogenesis of penicillin-resistant Streptococcus pneumoniae               
    1995 - 1996
  • 一酸化窒素と活性酸素の相互作用に関する研究               
    1995
  • Study on the interaction of nitric oxide and active oxygen               
    1995
  • Study of systemic inflammatory response syndrome               
    1995
  • 各種サイトカイン及びエンドトキシンのヒト好中球活性酸素産生能に及ぼす効果               
    1993
  • HIV感染患者における食細胞機能の検討               
    1993
  • 敗血症性ショックに対する抗TNF療法               
    1993
  • 敗血症に対する抗エンドトキシン療法               
    1993
  • Effects of various cytokines and endotoxin on production of reactive oxygen species from human neutrophils               
    1993
  • Study of opsonophagocytic function in patients with liner cirrhosis               
    1993
  • Effects of antibiotics on human Phagocytic cell function               
    1993
  • Study of Phagocytic cell function in HIV-infected patients               
    1993
  • Anti-TNF therapy against Septic shock               
    1993
  • Anti-endotoxin therapy against Septicemia               
    1993
  • 重症熱傷患者における感染症の補助療法に関する研究               
    1990 - 1992
  • MRSA感染症に対する治療に関する研究               
    1990 - 1992
  • Study of supportive therapy on the infection in severely burned patients               
    1990 - 1992
  • Study of treatment against MASA infection               
    1990 - 1992
  • 化学発光法の臨床応用               
    1983 - 1992
  • Clinical application of chemiluminescence               
    1983 - 1992
  • 抗菌薬の最小発育阻止濃度以下の効果に関する研究               
    1989 - 1991
  • Effects of sub-MIC of Antibiotics               
    1989 - 1991

Research Themes

  • Study on the escape mechanism of multidrug-resistant bacteria from host defense mechanism and development of new therapeutic method
    Grant-in-Aid for Scientific Research (C)
    Teikyo University
    01 Apr. 2017 - 31 Mar. 2020
    Acinetobacter baumannii (A.b) suppresses NETs formation in neutrophils. MDRA clinical isolates have high catalase-producing ability and survive and proliferate in the phagosome even after being phagocytosed by macrophages. Co-culture of A.b and its lipopolysaccharide (LPS) with mast cells and adipocytes enhanced the production of inflammatory cytokines and chemokines. The sub-MICs of tigecycline suppressed the biofilm formation of MDRA, while colistin (CL) enhanced it. The virulence of the LPS-deficient A.b strain was reduced. We analyzed the resistance genes of multidrug-resistant strains such as KPC-producing Klebsiella pneumoniae isolated in our hospital. Pathological findings in A.b mouse pneumonia model were compared with Pseudomonas aeruginosa.
    We established a drug efficacy evaluation system for antibacterial drugs using the MDRA insect infection model.
  • Development of basic research data management materials for leadership training seminar (Recording and Analysis)               
    International University of Health and Welfare
    May 2018 - Mar. 2020
  • Elucidation of the prevalence and relevance of drug-resistant bacteria in human and livestock
    Grant-in-Aid for Young Scientists (B)
    01 Apr. 2014 - 31 Mar. 2017
    The aim of this study was to evaluate the prevalence and genetic characteristics of CTX-M-producing Escherichia coli in fecal samples of livestock (bovine and pigs) and compare the relationship to gain insight into transmission routes. Many CTX-M-producing E. coli were isolated from 3rd-generation cephalosporin resistant isolates. The genetic characteristics of the isolates were identified by analyzing genotypic diversity and plasmid incompatibility type. Molecular analysis indicated that the genetic characteristics of the isolates were clearly different and the relevance between human and livestock (healthy bovine and pigs) was low.
    Furthermore, I have developed a loop-mediated isothermal amplification (LAMP) method for rapid detection of carbapenemase producers, KPC producing Enterobacteriaceae and OXA-51 producing Acinetobacter, which is problematic in clinical settings. It may be routinely applied for detection of carbapenemase producers in the clinical laboratory.
  • Immuno-modulator effects of the apyrase derived from Toxoplasma gondii
    Grant-in-Aid for Scientific Research (C)
    Teikyo University
    01 Apr. 2012 - 31 Mar. 2016
    Immuno-modulate effects of T. gondii NTPase on neutrophils or mast cells were examined in this research project. When neutrophils or mast cells were exposed with ATP in vitro, gene expressions of TNF-α and IL-8 were down-regulated. However, presence of NTPase with ATP neutralized those effects of down-regulation. Gene expression of CD39 that is as known as ecto ATPase in neutrophil were also decreased. Neutrophils exposed both of ATP and NTPase showed that the equal CD39 expression with control. The mRNA expression of an adenosine receptor, AdoRA2a was down-regulated by NTPase. No effects of ATP or NTPase were observed in CD73 expression. It is suggested that T. gondii might use NTPase as an immune-modulator to escape from neutrophils or other immune cells in infection.
  • Analysis of the predisposing host factors to severe pathological conditions caused by Acinetobacter baumannii infections and the search the new virulence factors of multi-drug resistant strains
    Grant-in-Aid for Scientific Research (C)
    Teikyo University
    01 Apr. 2012 - 31 Mar. 2015
    1)Acinetobacter baumannii (A.baumannii) were resistant to phagocytosis and bactericidal activity by neutrophils as compared with Pseudomonas aeruginosa, neutrophil extracellular traps (NETs) formation was very little. 2) The lethality in a pulmonary infection mouse model caused by P. aeruginosa was higher than that of A.baumannii infection. 3) When neutrophils were stimulated with the lipopolysaccharides (LPS) derived from an A.baumannii standard strain or a multi-drug resistant strain (MDRA), gene expression levels of inflammatory cytokines in neutrophils were equally upregulated. Membrane vesicles derived from A.baumannii could not stimulate the production of reactive oxygen in neutrophils, but acted as a chemoattractant. 4) A. baumannii-derived LPS enhanced the TNF-α and IL-8 production in mast cells. 5) We have developed a LAMP method to detect MDRA. 6) Humoral immunodeficiency may be a predisposing factor to severe pathological conditions during A. baumannii infections.
  • Establishment of immuno-monitoring system for the infectious disease control and analysis of neutrophil dysfunction in various compromised hosts
    Grant-in-Aid for Scientific Research (C)
    Teikyo University
    2009 - 2011
    Neutrophil chemotaxis was reduced in septic patients and poorly controlled diabetic patients. Neutrophil bactericidal ability in the patients with liver cirrhosis, SLE, AIDS, myeloma, severe burn and elderly persons was significantly lower than that of healthy controls. Expression levels of neutrophil membrane antigens, CD14 and TLR-4 were higher in patients with sepsis ; however, the expression levels of CD11b and CD16 were lower. The gene expression of TREM-1 in neutrophils associated with the severity of sepsis. Analysis of neutrophil functions using these assays may be available as the sensitive and reliable immuno-monitoring tools for determining the capacity of host defense against bacterial infections in compromised hosts.
  • Detection of TNF-α release from mast cells stimulated with Toxoplasma gondii.
    Grant-in-Aid for Scientific Research (C)
    Teikyo University
    2008 - 2010
    Bone marrow derived mast cells (BMMCs) from mice were examined for TNF-α release by stimulating with Toxoplasma gondii tachyzoites. BMMC stimulated with live tachyzoites of T.g (RH) or crude extracts released TNF-α in culture supernatant. TNF-α gene expression was also enhanced after T.g stimuli. Activation of neutrophils were observed in the cells stimulated with BMMC primed with T.g compared to stimulation with BMMC.
  • Activation mechanism of superoxide generating system in neutrophils upon bacterial infection.
    Grant-in-Aid for General Scientific Research (B)
    The University of Tokyo
    1993 - 1994
    1)Cytochrome b558 in phagocytes is a transmembrane protein composed of large and small subunits, and considered to play a key role in O_2^--generation during the respiratory burst. We showed previously that two synthetic peptides corresponding to the COOH-terminal region of each subunit inhibit NADPH-dependent oxygen uptake induced by sodium dodecylsulfate (SDS) in a cell free system consisting of plasma membrane and cytosol. Using a cross-linking reagent containing disulfide bound cleavable under reducing conditions (DTBP), we showed that the cytosolic 47-kDa protein, an essential component of the O_2^--generating system, interacted with the synthetic peptides during activation. We now extend the observations to intact neutorphils. The synthetic peptide corresponding to the COOH-terminal region of the large subunit was introduced into neutrophils by electropolation and the cells were stimulated with chemotactic peptide f-Met-Leu-Phe, phorbolmyristate acetate or SDS.The synthetic peptide but not unrelated peptide was found to inhibit O_2^--generation induced by the simuli. The synthetic peptide conjugaated with a photoreactive cross-linking agent (Sulfo-SADP) was introduced into the cells by the same procedure but under dark conditions. After stimulaltion with the stimuli, the cells were exposed to UV light. Photoaffinity labeled proteins in the cells were analyzed by SDS-PAGE and subsequently by immunoblotting method using antibody against the synthetic peptide. The cytosolic 47-kDa protein was found to be cross-linked with the synthetic peptide. The results cleanly indicate that the cytosolic COOH-terminal region of cytochrome b_<558> subunit is the binding site for the cytosolic 47-kDa protein, and that the binding takes place during activation of the system.
    2)We focused on a hydrophilic region bearing the beta-turn structure near the predicted heme-binding site in the small subunit of the cytochrome (i.e.His-94) and synthesized peptides corresponding to this region. The peptides inhibited superoxide generation in a cell-free system. The shortest sequence that gave a half inhibitory concentration (IC_<50>) lower than 50 muM was TRNYYVRAVL.Substitution of alanine for any of two tyrosine or central valine residues markedly increased IC_<50>, there by indicating that these residues are critical for the activity. Since the inhibition was observed when the peptide was added to the system before but not after the stimulation with sodium dodecylsulfate, the peptides seem to interact irreversibly with the cytochrome molecule and hinder electron transport or alternatively to interfere with the association between cytochrome b_<558> and cytosolic components.
    3)We evaluate activities of neutrophils from immunocompromized hosts by measuring chemiluminescence. Previously, we have shown that the assay is a very sensitive and reliable way for determining the opsonic activity of serum. By using the method, we compared the serum opsonic activity of patients infected with human HIV and that of healthy persons. Sera from the patients exhibited lower opsonic activity than pooled normal serum. The low opsonic activity was found in both asymtomatic HIV-seropositive individuals and patients with acquired immmunodeficiency syndrome.
  • 薬剤耐性菌に関する研究               
    1994
  • Study on antbiotics-resistant bacteria               
    1994
  • Study on antibiotics-resistant bacteria               
    1994
  • Role of active oxygen generated by neutrophils during bacterial infection
    Grant-in-Aid for General Scientific Research (B)
    The University of Tokyo
    1991 - 1992
    1) We purified two cytosolic proteins from neutorphils. Since no prosthetic group such as heme, flavin and non-heme iron was found, we proposed that cytosolic proteins regulate O_<2->- generation.
    2) We analyzed the orientation of cytochrome b_<558>, an essential component of O_<2->- generating sytem in neutrophil membrane and found that the carboxyl temini of the large and small subunits of the cytochrome are exposed to the cytoplasmic side.
    3) We provide direct evidence that the carboxyl temini of two subunits of cytochrome b_<558> interact with the 47-kDa cytosolic protein durig activation of O_<2->-generating sytem.
    4) We showed that all components necessary for O_<2->-generating sytem in neutrophils are also present in peripheral B lymphocytes and some leukemia-lymphoma cell lines.
    5) We found that B lymphocytes generate O_<2-> upon cross-linking of surface Ig's.
  • Mechanism of Active Oxygen Generation in Neutrophils and Its Role in Defense Against Bacterial Infection
    Grant-in-Aid for General Scientific Research (B)
    The Institute of Medical Science, the University of Tokyo
    1989 - 1990
    Previously, we have shown that almost all molecular oxygen consumed during the respiratory burst is converted to superoxide anion, which is released to the outside of neutrophils (or inside of phagosomes). By using spin-trap EPR spectrometry, we confirmed that superoxide anion but not hydroxyl radial was formed during the respiratory burst induced by soluble or particulate stimuli. We have developed monoclonal and polyclonal antibodies against large and small subunits of cytochrome b_<558>, which is considered to be involved in the reaction. Using these antibodies, we found that the cytochrome was present in the plasma membrane of neutrophils, eosinophils, monocytes and macrophages in various tissues and B lymphocytes, all of which could generate superoxide anion upon stimulation. We have also established a method for the prenatal diagnosis of cytochrome b_<558>-deficient chronic granulomatous disease and its carrier state. We found that the antibiotic cerulenin inhibited the respiratory burst in neutrophils and macrophages through inhibition of intracellular calcium mobilization. We monitored whole blood chemiluminescence in severely burned patients and found that the opsonizing capacity in the blood is decreased in these patients due to decreased levels of complement, immunoglobulins and fibronectin. Such monitoring was effective for the determining the contents and quantity of colloidal infusion during the treatments. Introduction of the controlled treatment to burned patients lowered the mortality rate of burned patients to 25% from the 60.9% for the 2 years before the introduction of the treatment.
  • Study on pathogenesis of sepsis               
    1985
  • Study on Phagocytic cell function               
    1983
  • Image analysis of chemotaxis of effector cells               
  • Research on diseases associated with disorder of neutrophil function               
  • Research on drugs which modulate neutrorhil function               

Others

  • 資格など

■Achievement List

Lectures, oral presentations, etc.

  • 22 Apr. 2022, 22 Apr. 2022 - 23 Apr. 2022, Not exist, Domestic conferences, Not International Collabolation, Verbal presentations (general)
    Url
  • 27 Oct. 2021, 27 Oct. 2021 - 29 Oct. 2021, Not exist, Domestic conferences, Not International Collabolation, Verbal presentations (general)
    Url
  • 20 Sep. 2021, 19 Sep. 2021 - 20 Sep. 2021, Not exist, Domestic conferences, Verbal presentations (general)
    Url
  • 20 Sep. 2021, 19 Sep. 2021 - 20 Sep. 2021, Not exist, Domestic conferences, Not International Collabolation, Verbal presentations (general)
    Url
  • 19 Sep. 2021, 19 Sep. 2021 - 20 Sep. 2021, Exist, Domestic conferences, Not International Collabolation, Verbal presentations (keynote)
    Url
  • 19 Sep. 2021, 19 Sep. 2021 - 20 Sep. 2021, Not exist, Domestic conferences, Not International Collabolation, Verbal presentations (general)
    Url
  • Evaluation of multiple methods for determining the linezolid minimum inhibitory concentration in clinical isolates of methicillin-resistant Staphylococcus aureus.
    31st ECCMID, 09 Jul. 2021, 09 Jul. 2021 - 12 Jul. 2021, Not exist, International conferences, Not International Collabolation, Verbal presentations (general)
    Url
  • omparison of two matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry systems for identification of Neisseria spp.
    31st ECCMID, 09 Jul. 2021, 09 Jul. 2021 - 12 Jul. 2021, Not exist, Not International Collabolation, Verbal presentations (general)
    Url
  • Usefulness of a new Acid-fast Bacilli detection method Based on image Usefulness of a new acid-fast bacilli detection method based on image analysis (virtual slide).
    31st ECCMID, 09 Jul. 2021, 09 Jul. 2021 - 12 Jul. 2021, Not exist, International conferences, Not International Collabolation
    Url
  • Detectability of carbapenemase-producing strains using mass spectrometry-based MBT STAR-BL and disk diffusion methods.
    31st ECCMID, 09 Jul. 2021, 09 Jul. 2021 - 12 Jul. 2021, Not exist, International conferences, Not International Collabolation, Verbal presentations (general)
    Url
  • Prevalence and Relatedness of Escherichia coli with mcr-1-plasmid Mediated Colistin-Resistance Isolated From Livestock and Farmers in Japan.
    31st ECCMID, 09 Jul. 2021, 09 Jul. 2021 - 12 Jul. 2021, Not exist, International conferences, Not International Collabolation, Verbal presentations (general)
    Url
  • Whole-genome Sequence of a Pan-resistant Klebsiella pneumoniae Sequence Type 11 Harbouring an IncR-F33A-:B- Plasmid Carrying Mul5ple Resistance Determinants.
    World Microbe Forum 2021., 20 Jun. 2021, 20 Jun. 2021 - 24 Jun. 2021, Not exist, International conferences, Not International Collabolation, Verbal presentations (general)
    Url
  • 07 May 2021, 07 May 2021 - 09 May 2021, Not exist, Domestic conferences, Not International Collabolation, Verbal presentations (general)
    Url
  • 07 May 2021, 07 May 2021 - 09 May 2021, Not exist, Domestic conferences, Not International Collabolation, Verbal presentations (general)
    Url