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Biomedical subjects

Yoichi Hirakata

Publications and source records attributed to Yoichi Hirakata.

At least 19 recordsLinked to original sources
PubMed2003

Clinical and bacteriological characteristics of IMP-type metallo-beta-lactamase-producing Pseudomonas aeruginosa.

IMP-type metallo-beta-lactamase-producing bacteria have recently emerged worldwide. We conducted a case-control study in which 69 inpatients harboring bla(IMP)-positive Pseudomonas aeruginosa and 247 control subjects with bla(IMP)-negative pathogens were investigated. Prolonged hospitalization, antineoplastic chemotherapy, corticosteroid therapy (P=.001), and indwelling urinary catheters (P=.04) were risk factors for isolation of bla(IMP)-positive pathogens. The predominant source was urine (P=.001). The duration of antibiotic treatment and the total dose (including of carbapenems) were significantly greater among case patients than among control subjects (P<.01). bla(IMP)-positive P. aeruginosa isolates were more frequently resistant to multiple drugs (P=.001) and caused more infections (P=.001) than bla(IMP)-negative pathogens. There were no significant differences in bacteriological outcome (P=.94); however, infection-related death was more frequent among case patients than among control subjects (P=.023). These results suggest that precautionary measures against the spread of bla(IMP)-positive isolates are needed, because, for most of such pathogens, no antibiotic is potent enough to be used as a single agent in treatment of infection.

Anti-Bacterial Agents↗
PubMed2003

Clarithromycin inhibits overproduction of muc5ac core protein in murine model of diffuse panbronchiolitis.

Long-term treatment of macrolide antibiotics is considered an effective treatment for diffuse panbronchiolitis (DPB). Although hypersecretion is a common feature of this disease, and it is known that macrolides inhibit mucin production, the mechanism of the effect on mucin production is unclear. The aim of our study was to determine the production of muc5ac core protein, a major core protein of mucin in airway secretion, and the effect of clarithromycin treatment on such production in a mouse model mimicking DPB. Alcian blue-periodic acid-Schiff-positive cells were detected in the lungs of Pseudomonas aeruginosa-infected mice. Western blots of these mice showed muc5ac glycoprotein at day 1 and increased progressively from day 4 to day 14 after inoculation of bacteria. Clarithromycin (10 mg. kg-1. day-1 for 7 days) significantly reduced the muc5ac expression at both the mRNA and protein levels. To investigate the role of molecules upstream in muc5ac regulation, we examined the role of mitogen-activated protein kinase. Extracellular signal-regulated kinase 1/2 phosphorylation increased in the infected lung and decreased after treatment. Our results suggest that overproduction of muc5ac plays an important role in the pathogenesis of DPB and that clinical improvement following macrolide therapy seems to involve, at least in part, its inhibition of mucin overproduction, through modulation of intracellular signal transduction.

Animals↗
PubMed2003

Relationship between whole-blood interferon-gamma production and extent of radiographic disease in patients with pulmonary tuberculosis.

The aim of this study was to determine whether whole-blood interferon-gamma (IFN-gamma) production correlates with the radiographic extent of pulmonary tuberculosis before treatment. The subjects were 40 human immunodeficiency virus-negative patients with pulmonary tuberculosis and 36 healthy volunteers. The concentrations of IFN-gamma in whole blood stimulated with Mycobactrium tuberculosis purified protein derivatives (tuberculous PPD) and phytohemagglutinin (PHA) were evaluated. PHA-stimulated IFN-gamma (PHA-IFN-gamma) was lower in the patients than in healthy volunteers (p < 0.05), and inversely correlated with the disease extent (p < 0.01). Tuberculous PPD-stimulated IFN-gamma as a percentage of PHA response (tuberculous PPD-IFN-gamma/PHA-IFN-gamma) was higher in the patients than in healthy volunteers (p < 0.05). However, tuberculous PPD-IFN-gamma/PHA-IFN-gamma did not correlate with the disease extent. Our results indicate that the tuberculous PPD-IFN-gamma/PHA-IFN-gamma may be useful for the diagnosis of tuberculosis but not for evaluating the disease severity, and suggest that PHA-IFN-gamma could be considered as a marker of disease severity.

Adult↗
PubMed2003

Role of elastase in a mouse model of chronic respiratory Pseudomonas aeruginosa infection that mimics diffuse panbronchiolitis.

Pseudomonas aeruginosa frequently colonizes the respiratory tract of patients suffering from cystic fibrosis (CF) and diffuse panbronchiolitis (DPB). However, the relationship between lung inflammation and extracellular products of P. aeruginosa is not well-defined. To assess the role of elastase released by P. aeruginosa in DPB, a murine model of DPB was employed in this study. Mice were inoculated with either P. aeruginosa PAO1 or PAO-E64; the latter produces elastase with greatly reduced enzymic activity. Throughout the 90-day experiments, counts of viable bacteria from the PAO1- and PAO-E64-infected mice were found to be equivalent. However, the number of lymphocytes isolated from the lungs of PAO-E64-infected mice was significantly lower than the number isolated from the lungs of PAO1-infected animals. Histopathological examination of the lungs of mice infected by PAO1 on day 90 revealed an intense accumulation of chronic respiratory cells surrounding the bronchi, in sharp contrast to the more localized inflammatory response found in those mice infected by PAO-E64. These data suggest that P. aeruginosa elastase (PE) is a potent inflammatory factor in a mouse model of DPB and that the control of PE release by P. aeruginosa may be beneficial for patients with DPB.

Animals↗
PubMed2003

Evaluation of newly developed oxygen meters with multi-channels and disposable oxygen electrode sensors for antimicrobial susceptibility testing.

The objective of this study was to investigate the applicability of new oxygen meters with multi-channels and disposable oxygen electrode sensors (DOX-96) on the antimicrobial susceptibility testing of clinical bacterial isolates. The oxygen amount in the wells of 96-well plates was converted into current through electrodes. Bacterial inoculation decreased the oxygen amount in the wells because viable bacteria consume the oxygen. On the other hand, a failure of bacteria to consume oxygen was observed in the presence of potent antimicrobial agents, representing a serious arrest of bacterial metabolism usually leading to stasis or death. Based on these results, the minimum inhibitory concentration was determined by DOX-96 (MICdox). The MICdox showed good agreement with MIC measured by the standard broth microdilution method (98.2%). DOX-96 was also useful for turbid samples such as Mueller-Hinton broth containing 0.1% lipid emulsion. The MICdox in turbid samples showed good agreement with those in clear samples (100.0%). These results indicate that the newly developed DOX-96 is very useful in antimicrobial susceptibility testing even in turbid clinical samples such as colloidal products and turbid biological components.

Anti-Bacterial Agents↗
PubMed2003

[Two cases of Legionella pneumophila pneumonia improved by parenteral ciprofloxacin administration].

We report here two cases of Legionella pneumophila pneumonia that were markedly improved by parenteral ciprofloxacin administration. A 69-year-old man who had previously visited a hot spring was admitted to our hospital with severe pneumonia and a 48-year-old man with dilated cardiomyopathy as an underlying disease was also hospitalized because of heart failure and pneumonia. In both cases a urinary antigen test for L. pneumophila was negative at the incipient stage, and the initial treatment with a beta-lactam agent was ineffective. However, the high titer of L. pneumophila serogroup 6 antigen in the serum at the convalescent stage revealed that these two pneumonia cases were caused by L. pneumophila, and the following intravenous administration of ciprofloxacin was highly effective. We concluded that intravenous treatment with ciprofloxacin could be effective against L. pneumophila pneumonia, which is sometimes hard to diagnose in the acute phase.

Aged↗
PubMed2003

[Three cases of Stenotrophomonas maltophilia pneumonia].

We encountered 3 cases of pneumonia caused by Stenotrophomonas maltophilia between January and June 2001. S. maltophilia is resistant to broad-spectrum antibiotics including carbapenem. Reported studies indicate that excessive use of broad-spectrum antibiotics may induce resistance in this organism. However, our data showed that there was no clear correlation between the amounts of carbapenems used in our hospital and the isolation of the organism. If broad-spectrum antibiotics are ineffective or even actually worsen a case of pneumonia, S. maltophilia may be the sole causative organism, and a potent double- (or triple-) combination therapy consisting of minocyclin and one or two other potent antimicrobial agents should be considered.

Aged↗
PubMed2002

Multidrug efflux systems play an important role in the invasiveness of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an important opportunistic human pathogen. Certain strains can transmigrate across epithelial cells, and their invasive phenotype is correlated with capacity to cause invasive human disease and fatal septicemia in mice. Four multidrug efflux systems have been described in P. aeruginosa, however, their contribution to virulence is unclear. To clarify the role of efflux systems in invasiveness, P. aeruginosa PAO1 wild-type (WT) and its efflux mutants were evaluated in a Madin-Darby canine kidney (MDCK) epithelial cell monolayer system and in a murine model of endogenous septicemia. All efflux mutants except a deltamexCD-oprJ deletion demonstrated significantly reduced invasiveness compared with WT. In particular, a deltamexAB-oprM deletion strain was compromised in its capacity to invade or transmigrate across MDCK cells, and could not kill mice, in contrast to WT which was highly invasive (P < 0.0006) and caused fatal infection (P < 0.0001). The other mutants, including deltamexB and deltamexXY mutants, were intermediate between WT and the deltamexAB-oprM mutant in invasiveness and murine virulence. Invasiveness was restored to the deltamexAB-oprM mutant by complementation with mexAB-oprM or by addition of culture supernatant from MDCK cells infected with WT. We conclude that the P. aeruginosa MexAB-OprM efflux system exports virulence determinants that contribute to bacterial virulence.

Animals↗
PubMed2002

Possible attenuation of fas-mediated signaling by dominant expression of caspase-8 aberrant isoform in adult T-cell leukemia cells.

The Fas up-regulated in adult T-cell leukemia (ATL) cells is usually the wild-type protein and is usually functional, at least in vitro. However, primary ATL cells, in contrast to ATL cell lines, are not necessarily susceptible to anti-Fas-induced apoptosis. To clarify the mechanism tuning the apoptotic signal transduction initiated by the activation caspase-8 in ATL cells and ATL cell lines, we examined the expression profile of caspase-8, of which there are at least 8 isoforms at the messenger RNA (mRNA) level with the potential to finely tune the signal transduction. Reverse transcription polymerase chain reaction disclosed the 2 major mRNA bands of 815 bp (casp-8S) and 951 bp (casp-8L) with different expression profiles among normal CD4 T-cells, primary ATL cells, and ATL cell lines. Casp-8L was the predominant form in primary ATL cells, whereas casp-8S was predominant in ATL cell lines. Casp-8S was structurally intact as shown by nucleotide analysis, whereas casp-8L was shown to be generated by a 136-bp insertion between exons 8 and 9 and to carry a frame shift in the transcript, introducing a premature stop codon and probably resulting in a truncated protein of approximately 30 kd deduced for the casp-8L transcript. These results suggest that an imbalanced expression of casp-8 isoforms, especially the dominant casp-8L in primary ATL cells, is in part responsible for tumor pathology through the modulation of cell death via Fas-mediated signaling.

Caspase 8↗
PubMed2002

Trichosporon asahii-induced asthma in a family with Japanese summer-type hypersensitivity pneumonitis.

BACKGROUND: Trichosporon species frequently induce summer-type hypersensitivity pneumonitis (SHP), which is the most prevalent type of hypersensitivity pneumonitis (HP) in Japan, but have not been reported to induce asthma. OBJECTIVE: Evaluation of a case of asthma induced by Trichosporon asahii. METHODS AND RESULTS: This report describes a 46-year-old Japanese man who developed asthma induced by T. asahii, following symptoms of HP attributable to the same pathogen, in a case of familial occurrence of SHP. This patient lacked typical findings of HP in his radiograph but had an elevated level of eosinophils in his bronchoalveolar lavage fluid. Open lung biopsy, however, revealed typical pathologic findings of HP when he was free of asthmatic symptoms. His serum was also positive for anti-T asahii antibody, as are the sera of SHP patients. Nevertheless, provocation tests, including returning home and inhalations of T. asahii antigen, reproduced asthmatic features such as airway hyperresponsiveness and reversible bronchoobstruction, but not the features of HP. A skin test with the same antigen also evoked an immediate allergic reaction. An IgE mechanism was suspected but could not be proven by radioallergosorbent test. The patient's son and daughter displayed typical features of SHP, associated with compatible results in their radiographs, bronchoalveolar lavage fluid analysis, serologic and pathologic examinations, and provocation and skin tests. CONCLUSIONS: To our knowledge, this is the first case of extrinsic asthma, and of coexistent asthma and HP, induced by T. asahii. The patient initially displayed symptoms typical of SHP, which were subsequently replaced by more typical asthmatic symptoms.

Adolescent↗
PubMed2002

Multiple gammac-receptor expression in adult T-cell leukemia.

Constitutive expression of the IL-2 receptor (IL-2R) on adult T-cell leukemia (ATL) cells and the presence of permanent IL-2-dependent ATL cell lines indicate that the signal transduction system via IL-2R is a key element for the development of this disease. IL-2R is a member of the common gamma-chain (gammac)-receptor family and shares gamma with IL-4R, IL-7R, IL-9R, and IL-15R. In addition to IL-2R, ATL cells express IL-15R and respond to IL-15. In the present study, we examined other members of this receptor family. ATL cells showed various levels of IL-4Ralpha (CD124) and IL-7Ralpha (CD127) expression, and responded to these cytokines. In contrast, ATL cells hardly responded to IL-9. As primary samples were a mixed population and the results may have been modified by contaminating normal cells, we used ATL cell lines as pure ATL cell populations. Here, we report that IL-2-dependent ATL cell lines also express IL-4Ralpha and respond to IL-4, which was verified by the activation of cytoplasmic transcriptional activator Stat6 protein. Moreover, a novel ATL cell line that grows stably in an IL-7-dependent manner was established from one of the cell lines, and IL-7 induced Stat5 activation in this cell line. These results indicated that ATL cells have the potential to express all gammac-receptors except IL-9R. Overlapping and switching of cytokine receptors supported the idea that ATL cells can rapidly select the appropriate gammac-receptor according to conditions.

Adult↗
PubMed2002

Effect of clarithromycin on chronic respiratory infection caused by Pseudomonas aeruginosa with biofilm formation in an experimental murine model.

Fourteen-membered macrolides (e.g. clarithromycin and erythromycin), but not 16-membered macrolides (e.g. josamycin), are effective in diffuse panbronchiolitis. However, there are no studies that have compared the effects of 14- and 16-membered macrolide antibiotics on biofilm formation. Treatment with high-dose clarithromycin (100 mg/kg) resulted in a significant decrease in the number of viable bacteria in an experimental murine model. Josamycin at a dose of up to 100 mg/kg had no effect on the number of viable bacteria in the lung. Our results may explain, at least in part, the clinical efficacy of 14-membered macrolide antibiotics in patients with chronic pneumonia caused by Pseudomonas aeruginosa.

Animals↗
PubMed2002

Increasing prevalence of antimicrobial resistance among isolates of Streptococcus pneumoniae from the PROTEKT surveillance study, and compatative in vitro activity of the ketolide, telithromycin.

The prevalence of resistance to a range of antimicrobials was determined for isolates of Streptococcus pneumoniae examined in the PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) surveillance study (1999-2000) using NCCLS testing methods and interpretative criteria. Of 3362 pneumococcal isolates collected from 69 centres in 25 countries, 22.1% overall were resistant to penicillin G, with the highest rates of resistance found among isolates from Asia (53.4%), France (46.2%) and Spain (42.1%). Erythromycin A resistance occurred in 31.1% of isolates overall with the highest rates found in Asia (79.6%), France (57.6%), Hungary (55.6%) and Italy (42.9%). Marked geographical differences in the prevalence of both penicillin G (the Netherlands 0%; South Korea 71.5%) and erythromycin A (Sweden 4.7%; South Korea 87.6%) resistance were observed. Asia was characterized by the highest prevalence of resistance, overall, with only eight of 19 antimicrobials (co-amoxiclav, linezolid, vancomycin, teicoplanin, quinupristin/dalfopristin, levofloxacin, moxifloxacin and telithromycin) retaining high activity against isolates of S. pneumoniae from this region. Notable rates of resistance to clarithromycin, azithromycin, co-trimoxazole and tetracycline were observed in the majority of countries submitting isolates of S. pneumoniae to the PROTEKT surveillance study. Fluoroquinolone resistance was low (1%), overall, although 14.3% of 70 isolates from Hong Kong were resistant to levofloxacin and moxifloxacin, all but one of these isolates belonging to a single clone of the 23F serotype. Although, at present, apparently limited to pockets of clonal spread, continued vigilance with regard to the evolution of fluoroquinolone resistance is indicated. Telithromycin (MIC(90) 0.12 mg/L; 99.9% of isolates susceptible) and lin- ezolid (MIC(90) 2 mg/L; 100% of isolates susceptible) were the two most active oral agents tested, both compounds retaining activity against isolates of fluoroquinolone-resistant S. pneumoniae. The results of the PROTEKT surveillance study 1999-2000 emphasize the widespread evolution of resistance to a variety of antimicrobials amongst isolates of S. pneumoniae and demonstrate the potential of telithromycin as a therapeutic option for the treatment of community-acquired respiratory tract infections caused by this organism.

Anti-Bacterial Agents↗
PubMed2002

[A successful treatment of Vibrio vulnificus infection].

A 65-year-old male patient with a history of alcoholism visited our outpatient clinic complaining of nausea and diarrhea followed by dizziness. Erythema and swelling with partial exfoliation on the right forearm to hand and right thigh were noticed. Vibrio vulnificus was isolated from the purulent discharge of the skin. Due to urgent and intensive treatment of bacterial shock and antimicrobial drugs, the patient fully recovered three months later. We believe that the patient survived from this fatal infection because; 1) the isolates were highly sensitive to a wide variety of antibiotics, 2) the antibiotic therapy was started immediately, with an alternative usage of different antibiotics, and 3) the liver dysfunction of the patient had not been severely damaged by alcohol before the infection.

Aged↗
PubMed2002

Efficacy of linezolid against methicillin-resistant or vancomycin-insensitive Staphylococcus aureus in a model of hematogenous pulmonary infection.

We investigated the activities of linezolid, vancomycin, and teicoplanin in a murine model of hematogenous pulmonary infection with Staphylococcus aureus. Our results demonstrate that linezolid clearly reduced bacterial numbers in the methicillin-resistant S. aureus hematogenous infection model and significantly improved the survival rate of immunocompromised mice infected with vancomycin-insensitive S. aureus compared with vancomycin and teicoplanin. The pharmacokinetic profiles also reflected the effectiveness of linezolid.

Acetamides↗
PubMed2002

Mycobacterium avium complex pleuritis.

Non-tuberculous mycobacterium infection is rarely accompanied by pleural involvement. We report a very rare case of Mycobacterium avium-intracellurare complex (MAC) pleuritis with massive pleural effusion. The patient was a non-compromised 67-year-old female and had been treated for pulmonary non-tuberculous mycobacterium infection. She was admitted to hospital because of general malaise, low-grade fever and right pleural effusion. Cytological examination of the effusion did not show malignant cells. MAC was only identified by culture and PCR. No other bacteria were detected. Complete resolution of the pleural effusion occurred after administration of anti-tubercular agents (isoniazid, rifampin, ethambutol) and clarithromycin.

Aged↗
PubMed2002

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2000). I. Susceptibility distribution].

The bacterial strains isolated from patients diagnosed as having urinary tract infections (UTIs) in 10 institutions in Japan were supplied between the period of August 2000 and July 2001. Then, the susceptibilities of them to many kinds of antimicrobial agents were investigated. The number of them were 511 strains. The breakdown of these strains was Gram-positive bacteria as 29.0% and Gram-negative bacteria as 71.0%. Susceptibilities of these bacteria to antimicrobial agents were as follows; vancomycin (VCM), ampicillin (ABPC) and imipenem (IPM) showed strong activities against Enterococcus faecalis. No increase in low-susceptible strains of E. faecalis observed against these antimicrobial agents. VCM showed a strong activity against MRSA preventing growth of all strains with 1 microgram/ml. In addition, the activity of arbekacin (ABK) was strong with the MIC90 of 2 micrograms/ml against MRSA and prevented growth of all strains with 4 micrograms/ml. ABK showed a strong activity against Staphylococcus epidermidis preventing growth of all strains with 0.5 microgram/ml. ABPC, cefotiam (CTM) and cefozopran (CZOP) also showed a relatively strong activity against S. epidermidis (MIC90: 4 to 8 micrograms/ml). Against Escherichia coli, carbapenems showed high activities: meropenem (MEPM) prevented growth of all strains within 0.125 microgram/ml; IPM prevented growth of all strains with 0.25 microgram/ml. CZOP and CTM also showed strong activities against E. coli: MIC90 of CZOP was within 0.125 microgram/ml; MIC80 and MIC90 of CTM were 0.25 and 0.5 microgram/ml, respectively. Quinolone resistant E. coli was detected at frequency of 14.0%, which was significantly higher than that in the last year. Almost all drugs showed strong activities against Klebsiella pneumoniae and Proteus mirabilis, and MEPM prevented growth of all strains within 0.125 microgram/ml. Against Pseudomonas aeruginosa, almost drugs were not so active. The MIC90 of carbapenems and gentamicin (GM) were 16 micrograms/ml and those of all other drugs were more than 32 micrograms/ml. Against Serratia marcescens, the MIC90 of IPM and GM were the lowest value being 2 micrograms/ml, and that of MEPM was 4 micrograms/ml.

4-Quinolones↗