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Hajime Kanamori,
Noboru Aso,
Satoko Tadano,
Miyoko Saito,
Hiroo Saito,
Bine Uchiyama,
Noriomi Ishibashi,
Shinya Inomata,
Shiro Endo,
Tetsuji Aoyagi, Masumitsu Hatta,
Mitsuhiro Yamada,
Yoshiaki Gu,
Koichi Tokuda,
Hisakazu Yano,
Hiroyuki Kunishima,
Yoichi Hirakata,
Takao Saijyo,
Miho Kitagawa,
Mitsuo Kaku
[show abstract]
[hide abstract]
ABSTRACT: Tuberculosis was diagnosed in a person who had stayed in a shelter after the 2011 Great East Japan Earthquake. A contact investigation showed that the prevalence of latent tuberculosis infection among other evacuees at the shelter was 20%. Our report underscores the importance of tuberculosis prevention and control after natural disasters.
Emerging Infectious Diseases 05/2013; 19(5):799-801. · 6.79 Impact Factor
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Tetsuji Aoyagi,
Mitsuhiro Yamada,
Hiroyuki Kunishima,
Koichi Tokuda,
Hisakazu Yano,
Noriomi Ishibashi, Masumitsu Hatta,
Shiro Endo,
Kazuaki Arai,
Shinya Inomata,
Yoshiaki Gu,
Hajime Kanamori,
Miho Kitagawa,
Youichi Hirakata,
Mitsuo Kaku
[show abstract]
[hide abstract]
ABSTRACT: ABSTRACT BACKGROUND Past natural catastrophes increased infectious disease morbidity rates. On March 11, 2011, a 9.0-magnitude mega-earthquake struck East Japan, with an associated gigantic tsunami across the Pacific coast. Our aim of this study was is to investigate characteristics of infectious diseases who need for hospitalization after this disaster. METHODS We searched the medical records of 1,577 patients admitted to Tohoku University Hospital in the Sendai area within 1 month (March 11, 2011-April 11, 2011) following the disaster. We examined (1) changes in the rates of hospitalizations with infectious diseases over time and (2) the variety of infectious diseases. RESULTS The number of hospitalized patients with infectious diseases increased after the first week, and the rate of infectious diseases doubled compared to that during the same period in 2010. Pneumonia comprised 43% of infectious diseases, and 12% consisted of skin and subcutaneous tissue infection including tetanus cases. Most pneumonia cases were elderly people (median age: 78 y) with low levels of serum albumin who had comorbid conditions including brain and nervous system disorders. Sputum cultures contained Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae, known pathogens of community-acquired pneumonia in Japan. In addition, 20.5% of patients were positive for urinary pneumococcus antigen. CONCLUSION Among hospitalized patients, infectious diseases were significantly increased after the disaster compared to the same period in 2010, and pneumonia was prominent among infectious diseases. Our analyses suggest that taking appropriate measures for infectious diseases including pneumonia may be useful for disaster preparedness and medical response in future disasters.From Department of Infection Control and Laboratory Diagnostics, Internal Medicine (Drs Tetsuji Aoyagi: tetsujiaoyagi@med.tohoku.ac.jp, Koichi Tokuda: tokuda@med.tohoku.ac.jp, Noriomi Ishibashi: ishibashi@med.tohoku.ac.jp, Masumitsu Hatta: masumitsu-h@med.tohoku.ac.jp, Shiro Endo: ain@med.tohoku.ac.jp, Shinya Inomata: inomata@med.tohoku.ac.jp, Hajime Kanamori: kanamori@med.tohoku.ac.jp, Mitsuo kaku: kaku-m77@med.tohoku.ac.jp and Ms. Miho Kitagawa: miho0077@med.tohoku.ac.jp), Department of Regional Cooperation for Infectious Diseases (Drs Hiroyuki Kunishima: h2kuni@med.tohoku.ac.jp, Mitsuhiro Yamada: yamitsu@med.tohoku.ac.jp, Yoshiaki Gu: ygu@med.tohoku.ac.jp and Mitsuo Kaku) and Department of Clinical Microbiology with Epidemiological Research & Management and Analysis of Infectious Diseases (Drs Hisakazu Yano: yanohisa@med.tohoku.ac.jp, Kazuaki Arai: kazuarai@med.tohoku.ac.jp and Yoichi Hirakata: hiraichi@med.tohoku.ac.jp), Tohoku University Graduate School of MedicineCorresponding author: Mitsuo Kaku, M.D., Ph.D. Department of Infection Control and Laboratory Diagnostics, Internal Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryoumachi, Aobaku, Sendai 980-8574, Japan. E-mail address: kaku-m77@med.tohoku.ac.jp*These authors contributed equally to this work.
Chest 08/2012; · 5.25 Impact Factor
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Shiro Endo,
Mina Sasano,
Hisakazu Yano,
Shinya Inomata,
Noriomi Ishibashi,
Tetsuji Aoyagi, Masumitsu Hatta,
Yoshiaki Gu,
Mitsuhiro Yamada,
Koichi Tokuda,
Miho Kitagawa,
Hiroyuki Kunishima,
Yoichi Hirakata,
Mitsuo Kaku
Journal of Antimicrobial Chemotherapy 06/2012; 67(10):2533-4. · 5.07 Impact Factor
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Hisakazu Yano,
Miho Ogawa,
Shiro Endo,
Risako Kakuta,
Hajime Kanamori,
Shinya Inomata,
Noriomi Ishibashi,
Tetsuji Aoyagi, Masumitsu Hatta,
Yoshiaki Gu,
Mitsuhiro Yamada,
Koichi Tokuda,
Hiroyuki Kunishima,
Miho Kitagawa,
Yoichi Hirakata,
Mitsuo Kaku
[show abstract]
[hide abstract]
ABSTRACT: Carbapenems are the most potent agents for treating Gram-negative infections due to their stability to the majority of β-lactamases and high rate of penetration through the bacterial outer membranes.…
Antimicrobial Agents and Chemotherapy 06/2012; 56(8):4554-5. · 4.84 Impact Factor
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Shiro Endo,
Hisakazu Yano,
Yoichi Hirakata,
Kazuaki Arai,
Hajime Kanamori,
Miho Ogawa,
Masahiro Shimojima,
Noriomi Ishibashi,
Tetsuji Aoyagi, Masumitsu Hatta,
Mitsuhiro Yamada,
Koichi Tokuda,
Miho Kitagawa,
Hiroyuki Kunishima,
Mitsuo Kaku
[show abstract]
[hide abstract]
ABSTRACT: Acinetobacter baumannii presents a clinical challenge when it is non-susceptible to carbapenems. The prevalence of carbapenem-non-susceptible A. baumannii in Japan is unclear, as previous studies have been limited in scope. We investigated the spread of carbapenem-non-susceptible A. baumannii in Japan and performed a comparison with findings from overseas.
A total of 305 non-duplicate clinical isolates of Acinetobacter spp. from 176 medical facilities in all geographical regions of Japan were tested for susceptibility to antimicrobial agents by the agar dilution method. Isolates with MICs of imipenem ≥ 4 mg/L underwent PCR analysis of OXA-type β-lactamase gene clusters and metallo-β-lactamase genes. These isolates were further analysed by sequencing of OXA-type β-lactamases and by multilocus sequence typing (MLST).
Fifty-five of the 305 clinical isolates had MICs of imipenem ≥ 4 mg/L. The OXA-51-like carbapenemase gene was detected in 52 of these 55 isolates. Within the OXA-51-like gene cluster, OXA-66 was found in 43 (82.7%) of the 52 isolates. MLST identified the following sequence types (STs): ST74, ST76, ST92, ST106, ST188 and ST195 in 2 (3.8%), 2 (3.8%), 40 (76.9%), 5 (9.6%), 2 (3.8%) and 1 (1.9%) of the isolates, respectively. In particular, ST92 was found in 31 (91.2%) of the 34 A. baumannii isolates with MICs of imipenem ≥ 16 mg/L.
This is the first report on the molecular epidemiology of A. baumannii with MICs of imipenem ≥ 4 mg/L in Japan. OXA-66 and ST92 were dominant among these isolates.
Journal of Antimicrobial Chemotherapy 03/2012; 67(7):1623-6. · 5.07 Impact Factor
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Shiro Endo,
Mina Sasano,
Hisakazu Yano,
Kazuaki Arai,
Tetsuji Aoyagi, Masumitsu Hatta,
Yoshiaki Gu,
Mitsuhiro Yamada,
Koichi Tokuda,
Miho Ogawa,
Masahiro Shimojima,
Miho Kitagawa,
Hiroyuki Kunishima,
Yoichi Hirakata,
Mitsuo Kaku
Antimicrobial Agents and Chemotherapy 02/2012; 56(5):2786-7. · 4.84 Impact Factor
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Masumitsu Hatta,
Shiro Endo,
Koichi Tokuda,
Hiroyuki Kunishima,
Kazuaki Arai,
Hisakazu Yano,
Noriomi Ishibashi,
Tetsuji Aoyagi,
Mitsuhiro Yamada,
Shinya Inomata,
Hajime Kanamori,
Yoshiaki Gu,
Miho Kitagawa,
Yoichi Hirakata,
Mitsuo Kaku
[show abstract]
[hide abstract]
ABSTRACT: We describe 2 post-tsunami outbreaks of influenza A in evacuation centers in Miyagi Prefecture, Japan, in 2011. Although containment of the outbreak was challenging in the evacuation settings, prompt implementation of a systemic approach with a bundle of control measures was important to control the influenza outbreaks.
Clinical Infectious Diseases 01/2012; 54(1):e5-7. · 9.15 Impact Factor
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[show abstract]
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ABSTRACT: On 11 March 2011, an earthquake measuring 9.0 on the Richter scale off the northeast coast of Honshu Island, Japan, produced a devastating tsunami that destroyed many towns and villages near the coast in Iwate, Miyagi, and Fukushima prefectures. Miyagi Prefecture was the area most severely devastated by the tsunami, with extensive loss of life and property; hundreds of thousands of people lost their houses and were forced to move to evacuation areas. In the days and weeks following devastating natural disasters, the threat of infectious disease outbreak is high. Rapid diagnostic tests can be performed at or near the site of patient care and the tests were very useful in this disaster, because they enabled us to manage patients appropriately in the settings where medical resources were limited. Here we report actual cases where the rapid diagnostic tests for infectious diseases were useful in the patient management.
Rinsho Biseibutsu Jinsoku Shindan Kenkyukai shi = JARMAM: Journal of the Association for Rapid Method and Automation in Microbiology 01/2012; 23(1):39-41.
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Hajime Kanamori,
Hisakazu Yano,
Yoichi Hirakata,
Ayako Hirotani,
Kazuaki Arai,
Shiro Endo,
Sadahiro Ichimura,
Miho Ogawa,
Masahiro Shimojima,
Tetsuji Aoyagi, Masumitsu Hatta,
Mitsuhiro Yamada,
Yoshiaki Gu,
Koichi Tokuda,
Hiroyuki Kunishima,
Miho Kitagawa,
Mitsuo Kaku
[show abstract]
[hide abstract]
ABSTRACT: The incidence of extended-spectrum β-lactamases (ESBLs) has been increasing worldwide, but screening criteria for detection of ESBLs are not standardized for AmpC-producing Enterobacteriaceae such as Enterobacter species. In this study, we investigated the prevalence of ESBLs and/or AmpC β-lactamases in Japanese clinical isolates of Enterobacter spp. and the association of plasmid-mediated quinolone resistance (PMQR) determinants with ESBL producers. A total of 364 clinical isolates of Enterobacter spp. collected throughout Japan between November 2009 and January 2010 were studied. ESBL-producing strains were assessed by the CLSI confirmatory test and the boronic acid disk test. PCR and sequencing were performed to detect CTX-M, TEM, and SHV type ESBLs and PMQR determinants. For ESBL-producing Enterobacter spp., pulsed-field gel electrophoresis (PFGE) was performed using XbaI restriction enzyme. Of the 364 isolates, 22 (6.0%) were ESBL producers. Seven isolates of Enterobacter cloacae produced CTX-M-3, followed by two isolates producing SHV-12. Two isolates of Enterobacter aerogenes produced CTX-M-2. Of the 22 ESBL producers, 21 had the AmpC enzyme, and six met the criteria for ESBL production in the boronic acid test. We found a significant association of qnrS with CTX-M-3-producing E. cloacae. The 11 ESBL-producing Enterobacter spp. possessing bla(CTX-M), bla(SHV), or bla(TEM) were divided into six unique PFGE types. This is the first report about the prevalence of qnr determinants among ESBL-producing Enterobacter spp. from Japan. Our results suggest that ESBL-producing Enterobacter spp. with qnr determinants are spreading in Japan.
PLoS ONE 01/2012; 7(6):e37967. · 4.09 Impact Factor
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ABSTRACT: It is not clear whether antipseudomonal agents can kill cell-associated bacteria within a short time. Madin-Darby canine kidney (MDCK) and A549 cells were infected with Pseudomonas aeruginosa ATCC 27853 and PAO1 and the bactericidal activity of ceftazidime, imipenem, meropenem, gentamicin, and ciprofloxacin against the organisms was investigated. In both MDCK and A549 cells, β-lactams could not kill epithelial cell-associated bacteria within 2 h. Gentamicin at concentrations ≤32 μg/ml killed more than 99% of epithelial cell-associated bacteria. Ciprofloxacin at 0.5 μg/ml killed more than 99.9% of MDCK cell-associated bacteria. Ciprofloxacin has the strongest and most rapid bactericidal activity against epithelial cell-associated bacteria, which may be explained by the combination of potent in-vitro bactericidal activity and high penetration ability into epithelial cells.
Journal of Infection and Chemotherapy 11/2011; 18(3):347-51. · 1.80 Impact Factor
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Hajime Kanamori,
Hisakazu Yano,
Yoichi Hirakata,
Shiro Endo,
Kazuaki Arai,
Miho Ogawa,
Masahiro Shimojima,
Tetsuji Aoyagi, Masumitsu Hatta,
Mitsuhiro Yamada,
Katsushi Nishimaki,
Miho Kitagawa,
Hiroyuki Kunishima,
Mitsuo Kaku
[show abstract]
[hide abstract]
ABSTRACT: Extended-spectrum β-lactamases (ESBLs) have become a problem among AmpC-producing Enterobacteriaceae and the emergence of concomitant quinolone resistance in β-lactamase-producing isolates poses a global threat. In this study we investigated the prevalence and regional variation of ESBLs in Japanese clinical isolates of Citrobacter spp. and analysed plasmid-mediated quinolone resistance (PMQR) determinants in ESBL-producing Citrobacter spp.
A total of 348 clinical isolates of Citrobacter spp. collected throughout Japan were studied. Screening and the boronic acid disc test were performed to detect ESBLs in Citrobacter spp. with chromosomal AmpC β-lactamases. PCR and sequencing were done to identify ESBL and PMQR genes. For ESBL-producing Citrobacter spp., PFGE was performed using the SfiI restriction enzyme.
The number of ESBL-producing isolates confirmed phenotypically was 67 (19.3%). The prevalence of ESBL-producing Citrobacter koseri was significantly higher (32.1%) than that of ESBL-producing Citrobacter freundii (4.6%) (P < 0.01). Moreover, the prevalence of ESBLs was notably higher among C. koseri from southern Japan (60.0%). CTX-M-2 was predominant in C. koseri. Of the ESBL-producing C. koseri analysed, 23.2% possessed PMQR determinants, and there was a significant association between qnrB4 and bla(SHV-12). The 57 ESBL-producing Citrobacter spp. possessing bla(CTX-M), bla(SHV) or bla(TEM) were divided into 18 unique PFGE types.
This is the first report about the prevalence of PMQR determinants among ESBL-producing Citrobacter spp. from Japan. Our data suggest that ESBLs and PMQR determinants are spreading among C. koseri in Japan.
Journal of Antimicrobial Chemotherapy 07/2011; 66(10):2255-62. · 5.07 Impact Factor
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Tetsuji Aoyagi,
Natsuo Yamamoto, Masumitsu Hatta,
Daiki Tanno,
Akiko Miyazato,
Keiko Ishii,
Kazuo Suzuki,
Toshinori Nakayama,
Masaru Taniguchi,
Hiroyuki Kunishima,
Yoichi Hirakata,
Mitsuo Kaku,
Kazuyoshi Kawakami
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ABSTRACT: Invariant NK T (iNKT) cells are known to play a critical role in the regulation of inflammatory responses in various clinical settings. In the present study, we assessed the contribution of iNKT cells to the development of acute lung injury (ALI), which was caused by intra-tracheal administration of LPS. Jα18 gene-disrupted mice lacking these cells underwent neutrophilic inflammatory responses in lungs at an equivalent level as control mice. Next, mice were sensitized intra-tracheally with α-galactosylceramide, an activator of iNKT cells, followed by challenge with LPS. In this model, mice showed severe lung injury, and all mice were killed within 72 h after LPS injection. IFN-γ and tumor necrosis factor (TNF)-α were strikingly elevated in the lungs of these mice. Administration of neutralizing mAb against IFN-γ and TNF-α attenuated lung injury in a histopathological analysis and improved their survival rate. Flow cytometric analysis revealed that IFN-γ was expressed in NK cells, iNKT cells and also Gr-1(dull+)Ly-6C(+) monocytes and TNF-α was detected mainly in Gr-1(bright+)Ly-6G(+) neutrophils and Gr-1(dull+)Ly-6C(+) monocytes. Otherwise, in mice treated with LPS alone, IFN-γ was not detected in the lungs and Gr-1(bright+)Ly-6G(+) neutrophil was a main cellular source of TNF-α production. Anti-Gr-1 mAb resulted in the attenuation of ALI and decrease in the level of these cytokines. These results indicated that activation of iNKT cells led to striking exacerbation of ALI caused by LPS and that Gr-1(+) monocytes were recruited in the lungs with expressing IFN-γ and TNF-α and played an important role in the development of these responses.
International Immunology 02/2011; 23(2):97-108. · 3.41 Impact Factor
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Kazuaki Arai,
Yoichi Hirakata,
Hisakazu Yano,
Hajime Kanamori,
Shiro Endo,
Ayako Hirotani,
Yuko Abe,
Mitsuaki Nagasawa,
Miho Kitagawa,
Tetsuji Aoyagi, Masumitsu Hatta,
Mitsuhiro Yamada,
Katsushi Nishimaki,
Yoko Takayama,
Natsuo Yamamoto,
Hiroyuki Kunishima,
Mitsuo Kaku
[show abstract]
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ABSTRACT: Streptococcus pyogenes causes various diseases in humans. While the prevalence of fluoroquinolone-resistant S. pyogenes isolates has been increasing since 2000 in the USA and Europe, it has remained very low in Japan. We isolated a fluoroquinolone-resistant S. pyogenes strain and analysed its genetics.
TU-296, a strain of S. pyogenes resistant to levofloxacin (MIC 16 mg/L), was isolated from the throat of a patient in their thirties with pharyngitis in autumn 2007. We carried out susceptibility tests for various antimicrobial agents and PCR analysis of the genes gyrA, gyrB, parC and parE in the quinolone resistance-determining region, followed by sequencing of the PCR products to find mutation(s) and the resulting amino acid substitution(s). We then sequenced the PCR product of the emm gene and determined the emm genotype.
S. pyogenes TU-296 was found to have the following mutations and amino acid substitutions: adenine 476 to cytosine in gyrA and cytosine 367 to thymine in parC, resulting in Glu-85→Ala in GyrA and Ser-79→Phe in ParC. The genotype of the isolate was emm11.
Amino acid substitutions in fluoroquinolone-resistant S. pyogenes have already been reported from Europe and the USA, including Ser-81→Phe or Tyr and Met-99→Leu in GyrA, as well as Ser-79→Phe, Tyr or Ala and others in ParC. Numerous point mutations were found in parC and parE of S. pyogenes TU-296. In addition, a new amino acid substitution was detected (Glu-85→Ala in GyrA). To our knowledge, there have been no previous reports of this substitution in a clinical isolate of S. pyogenes.
Journal of Antimicrobial Chemotherapy 12/2010; 66(3):494-8. · 5.07 Impact Factor
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Yoichi Hirakata,
Hisakazu Yano,
Kazuaki Arai,
Shiro Endo,
Hajime Kanamori,
Tetsuji Aoyagi,
Ayako Hirotani,
Miho Kitagawa, Masumitsu Hatta,
Natsuo Yamamoto,
Hiroyuki Kunishima,
Kazuyoshi Kawakami,
Mitsuo Kaku
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ABSTRACT: Pseudomonas (P.) aeruginosa is a major opportunistic pathogen especially in immunocompromised patients. To evaluate the invasiveness of respiratory pathogens, we developed monolayer culture systems and examined the degree of invasion by P. aeruginosa and invasive Salmonella (S.) typhimurium strains using human respiratory cell lines: A549 (derived from lung cancer), BEAS-2B (normal bronchial epithelium), and Calu-3 (pleural effusion of a patient with adenocarcinoma of the lung). Cells were seeded into filter units containing 0.33 cm(2) filter membranes with 3.0 microm pores, and were incubated at 37 degrees C under 5% CO(2) for 4-10 days. By monitoring the trans-monolayer electrical resistance (TER), we judged that BEAS-2B cells (TER values: 436.2 +/- 16.8 to 628.8 +/- 66.3 Omega cm(2)) and Calu-3 cells (TER values: 490.5 +/- 25.2 to 547.8 +/- 21.6 Omega cm(2)) formed monolayers with tight junctions, but not A549 cells. On day 8 of culture, monolayer cultures were infected with bacteria, and the number of microorganisms penetrating into the basolateral medium was counted. Wild-type P. aeruginosa PAO1 (PAO1 WT) and S. typhimurium SL1344 were detected in the basolateral medium of BEAS-2B monolayer system by 3 h after inoculation, while only P. aeruginosa PAO1 WT was detected in the basolateral medium of Calu-3 monolayer, indicating poor invasiveness of S. typhimurium SL1344 in the Calu-3 system. These findings suggest that BEAS-2B or Calu-3 monolayer system could be useful for evaluating the invasiveness of respiratory pathogens. Because of the difference in bacterial invasiveness, we may need to choose a suitable cell system for each target pathogen.
The Tohoku Journal of Experimental Medicine 01/2010; 220(1):15-9. · 1.24 Impact Factor
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Yoichi Hirakata,
Akira Kondo,
Kazuki Hoshino,
Hisakazu Yano,
Kazuaki Arai,
Ayako Hirotani,
Hiroyuki Kunishima,
Natsuo Yamamoto, Masumitsu Hatta,
Miho Kitagawa,
Shigeru Kohno,
Mitsuo Kaku
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ABSTRACT: Efflux systems are thought to contribute to antimicrobial resistance in Pseudomonas aeruginosa. The mexAB-oprM deletion strain of P. aeruginosa PAO1 is compromised in its capacity to invade Madin-Darby canine kidney (MDCK) cells, suggesting that P. aeruginosa exports invasion determinants using a MexAB-OprM system. The influences of efflux pump inhibitors (EPIs), including the broad-spectrum EPI Phe-Arg-beta-naphthylamide (PAbetaN) and MexAB-OprM-specific EPI D13-9001, on the invasion of wild-type (WT) P. aeruginosa PAO1 and its MexAB-OprM-overproducing nalB strain were examined. The invasiveness of PAO1 WT and nalB strains was inhibited in the presence of EPIs in a concentration-dependent manner. Reduction of the invasiveness of both strains was greater for D13-9001 compared with PAbetaN. EPIs are thought to be useful in reducing the invasiveness and antimicrobial resistance of P. aeruginosa and thus may be promising as new anti-infectious agents.
International journal of antimicrobial agents 11/2009; 34(4):343-6. · 3.03 Impact Factor
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Masumitsu Hatta,
Natsuo Yamamoto,
Akiko Miyazato,
Naoto Ishii,
Kiwamu Nakamura,
Ken Inden,
Tetsuji Aoyagi,
Hiroyuki Kunishima,
Yoichi Hirakata,
Kazuo Suzuki,
Mitsuo Kaku,
Kazuyoshi Kawakami
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ABSTRACT: In this study, we elucidated the role of tumor necrosis factor (TNF)-alpha in the host defense to pulmonary infection with Streptococcus pneumoniae and defined the cellular source of this cytokine at an early stage of infection. Administration of anti-TNF-alpha monoclonal antibody (mAb) resulted in the reduced accumulation of neutrophils in bronchoalveolar lavage fluids (BALFs) and severe exacerbation of this infection. In a flow cytometric analysis, the intracellular expression of TNF-alpha was detected in Gr-1(bright+) and Gr-1(dull+) cells during the time intervals postinfection, and F4/80(+) cells expressed intracellular TNF-alpha before Gr-1(dull+) cells appeared. The Gr-1(bright+) and Gr-1(dull+) cells sorted from BALF cells at 24 h were identified as neutrophils and macrophage-like cells, respectively, and the Gr-1(dull+) cells expressing CD11c, partially CD11b and a marginal level of F4/80 secreted TNF-alpha in in vitro cultures. Finally, deletion of Gr-1(+) cells by administration of the specific mAb significantly reduced the concentrations of this cytokine in BALF at 6 and 12 h postinfection, but not the expression of TNF-alpha in F4/80(+) cells. Thus, these results demonstrated that neutrophils, F4/80(+) macrophages and Gr-1(dull+) CD11c(+) macrophage-like cells played an important role in the production of TNF-alpha in lungs at an early stage of infection with S. pneumoniae.
FEMS Immunology & Medical Microbiology 11/2009; 58(2):182-92. · 2.44 Impact Factor
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Masumitsu Hatta,
Natsuo Yamamoto,
Akiko Miyazato,
Naoto Ishii,
Kiwamu Nakamura,
Ken Inden,
Tetsuji Aoyagi,
Hiroyuki Kunishima,
Yoichi Hirakata,
Kazuo Suzuki,
Mitsuo Kaku,
Kazuyoshi Kawakami
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ABSTRACT: In this study, we elucidated the role of tumor necrosis factor (TNF)- in the host defense to pulmonary infection with Streptococcus pneumoniae and defined the cellular source of this cytokine at an early stage of infection. Administration of anti-TNF- monoclonal antibody (mAb) resulted in the reduced accumulation of neutrophils in bronchoalveolar lavage fluids (BALFs) and severe exacerbation of this infection. In a flow cytometric analysis, the intracellular expression of TNF- was detected in Gr-1bright+ and Gr-1dull+ cells during the time intervals postinfection, and F4/80+ cells expressed intracellular TNF- before Gr-1dull+ cells appeared. The Gr-1bright+ and Gr-1dull+ cells sorted from BALF cells at 24 h were identified as neutrophils and macrophage-like cells, respectively, and the Gr-1dull+ cells expressing CD11c, partially CD11b and a marginal level of F4/80 secreted TNF- in in vitro cultures. Finally, deletion of Gr-1+ cells by administration of the specific mAb significantly reduced the concentrations of this cytokine in BALF at 6 and 12 h postinfection, but not the expression of TNF- in F4/80+ cells. Thus, these results demonstrated that neutrophils, F4/80+ macrophages and Gr-1dull+ CD11c+ macrophage-like cells played an important role in the production of TNF- in lungs at an early stage of infection with S. pneumoniae.
FEMS Immunology & Medical Microbiology 09/2009; 58(2):182 - 192. · 2.44 Impact Factor
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Yoichi Hirakata,
Kaori Ohmori,
Miwako Mikuriya,
Takeshi Saika,
Kaoru Matsuzaki,
Miyuki Hasegawa, Masumitsu Hatta,
Natsuo Yamamoto,
Hiroyuki Kunishima,
Hisakazu Yano,
Miho Kitagawa,
Kazuaki Arai,
Kazuyoshi Kawakami,
Intetsu Kobayashi,
Ronald N Jones,
Shigeru Kohno,
Keizo Yamaguchi,
Mitsuo Kaku
[show abstract]
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ABSTRACT: Beta-lactamase-negative ampicillin-resistant (BLNAR) isolates of Haemophilus influenzae have been emerging in some countries, including Japan. The Clinical and Laboratory Standards Institute has only a susceptible MIC breakpoint (< or = 1 microg/ml) for piperacillin-tazobactam and a disclaimer comment that BLNAR H. influenzae should be considered resistant, which was adapted without presentation of data. In addition, fluoroquinolone-resistant H. influenzae isolates have recently been occasionally reported worldwide. To address these problems, we examined susceptibilities to beta-lactams, including piperacillin-tazobactam, and ciprofloxacin by microdilution and disk diffusion (only for piperacillin-tazobactam) methods, against a total of 400 recent H. influenzae clinical isolates, including 100 beta-lactamase-negative ampicillin-susceptible, beta-lactamase-positive ampicillin-resistant, BLNAR, and beta-lactamase-positive amoxicillin-clavulanate-resistant (BLPACR) isolates each. BLNAR and BLPACR isolates were tested by PCR using primers that amplify specific regions of the ftsI gene. We also detected mutations in quinolone resistance-determining regions (QRDRs) by direct sequencing of the PCR products of DNA fragments. Among beta-lactams, piperacillin-tazobactam exhibited potent activity against all isolates of H. influenzae, with all MICs at < or = 0.5 microg/ml (susceptible). A disk diffusion breakpoint for piperacillin-tazobactam of > or = 21 mm is proposed. We confirmed that all BLNAR and BLPACR isolates had amino acid substitutions in the ftsI gene and that the major pattern was group III-like (87.5%). One ciprofloxacin-resistant isolate (MIC, 16 microg/ml) and 31 ciprofloxacin-susceptible isolates (MICs, 0.06 to 0.5 microg/ml) had amino acid changes in their QRDRs. Piperacillin-tazobactam was the most potent beta-lactam tested against all classes of H. influenzae isolates. It is possible that fluoroquinolone-resistant H. influenzae will emerge since several clinical isolates carried mutations in their QRDRs.
Antimicrobial Agents and Chemotherapy 09/2009; 53(10):4225-30. · 4.84 Impact Factor
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Hajime Kanamori,
Keiji Kanemitsu,
Tomomitsu Miyasaka,
Koken Ameku,
Shiro Endo,
Tetsuji Aoyagi,
Ken Inden, Masumitsu Hatta,
Natsuo Yamamoto,
Hiroyuki Kunishima,
Hisakazu Yano,
Koki Kaku,
Yoichi Hirakata,
Mitsuo Kaku
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ABSTRACT: (1-3)-beta-D-glucan (BDG) is a cell-wall polysaccharide component found in most fungi. The measurement of BDG is a useful diagnostic marker for invasive fungal infections. However, it is well known that interfering substances can result in false positive reactions. We encountered a patient who underwent lung transplantation and presented with highly elevated BDG values, despite having no evidence of invasive fungal infection. We therefore hypothesized that elevated BDG values were originated from the gauze products used during surgery. While it is known that gauze products contain BDG, there have been no previous reports to quantitatively correlate amount of gauze usage and BDG levels. In this study, we extracted BDG from various gauze products and measured BDG to better understand the degree of which gauze contributes to elevated BDG values. Six types of commonly used surgical gauze products were selected for our study. Each of the surgical gauze was immersed in sterile, purified water for up to 120 minutes. At set intervals, BDG values in the water extracts were measured. Purified water samples without gauze were used as negative controls (< 4 pg/ml). After 120-minute extraction, BDG levels varied greatly depending on gauze products, ranging from 11.7 pg/ml to 6612 pg/ml. The gauze made of lyocell, which is a fiber produced from wood pulp cellulose, yielded the lowest levels of BDG, and probably would not cause false positive for fungal infections. There is a need for the development of a gauze product that does not contribute to elevated BDG values.
The Tohoku Journal of Experimental Medicine 02/2009; 217(2):117-21. · 1.24 Impact Factor
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Ken Inden,
Jun Kaneko,
Akiko Miyazato,
Natsuo Yamamoto,
Shota Mouri,
Yoshiyuki Shibuya,
Kiwamu Nakamura,
Tetsuji Aoyagi, Masumitsu Hatta,
Hiroyuki Kunishima,
Yoichi Hirakata,
Yoshifumi Itoh,
Mitsuo Kaku,
Kazuyoshi Kawakami
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ABSTRACT: Leukocidin (Luk), an exotoxin of Staphylococcus aureus consisting of LukF and LukS, is a hetero-oligomeric pore-forming cytolytic toxin toward human and rabbit polymorphonuclear leukocytes. However, it is uncertain how Luk affects the host immune response. In the present study, we investigated whether Luk has the ability to stimulate mouse bone marrow-derived myeloid dendritic cells (BM-DCs). LukF activated BM-DCs to generate IL-12p40 mRNA, induce intracellular expression and extracellular secretion of this cytokine and express CD40 on their surface, whereas LukS showed a much lower or marginal ability in the activation of BM-DCs than its counterpart component. Similarly, TNF-alpha was secreted by BM-DCs upon stimulation with these components. Combined addition of these components did not lead to a further increase in IL-12p40 secretion. IL-12p40 production caused by LukF was completely abrogated in BM-DCs from TLR4-deficient mice similarly to the response to lipopolysaccharide (LPS). Polymixin B did not affect the LukF-induced IL-12p40 production, although the same treatment completely inhibited the LPS-induced response. Boiling significantly inhibited the response caused by LukF, but not by LPS. Finally, in a luciferase reporter assay, LukF induced the activation of NF-kappaB in HEK293T cells transfected with TLR4, MD2 and CD14, whereas LukS did not show such activity. These results demonstrate that LukF caused the activation of BM-DCs by triggering a TLR4-dependent signaling pathway and suggests that Luk may affect the host inflammatory response as well as show a cytolytic effect on leukocytes.
Microbes and Infection 01/2009; 11(2):245-53. · 3.10 Impact Factor
