Biomedical subjects

K Tomono

Publications and source records attributed to K Tomono.

At least 19 recordsLinked to original sources

PubMed2004

Acute infection with influenza virus enhances susceptibility to fatal pneumonia following Streptococcus pneumoniae infection in mice with chronic pulmonary colonization with Pseudomonas aeruginosa.

We established a mouse model in which fatal pneumonia was induced by pneumococcal superinfection following influenza virus infection in chronic Pseudomonas aeruginosa infected mice. In this mouse model, influenza virus infection caused a significant increase in inflammatory cells, cytokines and severe tissue damage in the lungs of these P. aeruginosa infected mice, before pneumococcal infection. Intrapulmonary virus titres were significantly increased in mice with chronic P. aeruginosa infection, compared with control mice. Neutrophil function analysis showed significant reduction of myeloperoxidase (MPO) activity and lysozyme secretion by influenza virus infection in these mice. Our results suggest that influenza virus infection may play an important role in inducing pneumococcal pneumonia in chronic P. aeruginosa infected mice. Our results suggested that our mouse model is useful for investigating the pathogenesis of influenza virus infection in patients with chronic lung infection.

Acute Disease↗

PubMed2004

Virulence of metallo-beta-lactamase-producing Pseudomonas aeruginosa in vitro and in vivo.

We evaluated the virulence of Pseudomonas aeruginosa carrying bla(IMP), a metallo-beta-lactamase gene, and the efficacy of ceftazidime, imipenem-cilastatin, and ciprofloxacin in the endogenous bacteremia model. The presence of bla(IMP) did not practically change the virulence of the parent strain, and ciprofloxacin was effective against infection with P. aeruginosa carrying bla(IMP).

Animals↗

PubMed2004

Immunokinetics in severe pneumonia due to influenza virus and bacteria coinfection in mice.

Coinfections of bacteria and influenza are a major cause of excessive mortality during influenza epidemics. However, the mechanism of the synergy between influenza virus and bacteria are poorly understood. In this study, mice were inoculated with influenza virus, followed 2 days later by inoculation with Streptococcus pneumoniae. The kinetics of viral titres, bacterial numbers and the immune response (cytokine and chemokine production) were also analysed. Short-term survival correlated with pathological changes in the lungs of infected mice. Influenza virus or S. pneumoniae infection alone induced moderate pneumonia; however, severe bronchopneumonia with massive haemorrhage in coinfected mice, which caused death of these mice approximately 2 days after inoculation with S. pneumoniae, was noted. Intrapulmonary levels of inflammatory cytokines/chemokines, type-1 T-helper cell cytokines and Toll-like receptors, and the related mitogen-activated protein kinase signalling molecules (phosphorylated extracellular signal-regulated kinase -1 and - 2, p38 and c-Jun N-terminal kinase), were increased in coinfected mice. These results suggest that immune mediators, including cytokines and chemokines, through Toll-like receptors/mitogen-activated protein kinase pathways, play important roles in the pathology of coinfection caused by influenza virus and Streptococcus pneumoniae.

Animals↗

PubMed2003

Long-term efficacy and safety of clarithromycin treatment in patients with diffuse panbronchiolitis.

Diffuse panbronchiolitis (DPB) can now be cured with long-term erythromycin treatment. Our group conducted a prospective open trial of long-term treatment with a macrolide antibiotic, clarithromycin. We studied ten patients who were treated for 4 years with oral clarithromycin (200 mg once a day). Pulmonary function test, blood gas analysis, comprehensive improvement score, and bacterial culture of sputum were examined at 3, 6, 12 months, and at 2, 3, 4 years after the initiation of the therapy. Pulmonary function improved in most of the patients within 6 months: the forced expiratory volume in one second showed a maximal increase from a mean (SE) value of 1.74 (0.12) l at baseline to 2.31 (0.22) l at 6 months (P < 0.01) and the volume (l) of forced vital capacity also showed a maximal increase within 6 months. The partial pressure of arterial oxygen at rest significantly increased at 3-6 months. The comprehensive improvement score also reached maximum within 6 months in nine of the patients. The majority of patients have developed sputum culture in which bacteria were negative within 6 months after the therapy. All of the patients maintained a stable condition with continued therapy, and no side effects of clarithromycin were observed during the study. This prospective study demonstrated that 6-month treatment with clarithromycin might be necessary to improve the clinical conditions of patients with DPB and the drug could be safely used for a long term.

Adult↗

PubMed2003

Detection of Legionella DNA by PCR of whole-blood samples in a mouse model.

A detection system for Legionella DNA in blood samples based on the PCR was developed and evaluated in A/J mice with experimentally induced Legionella pneumonia. Primers were designed to amplify a 106 bp DNA fragment of the 16S rRNA gene specific to Legionella species. The PCR system could detect clinically relevant Legionella species including Legionella pneumophila, Legionella micdadei, Legionella bozemanae, Legionella dumoffii, Legionella longbeachae, Legionella gormanii and Legionella jordanis. The sensitivity of the PCR system was 20 fg extracted DNA. In the mouse model, the blood PCR was compared with results obtained by PCR on bronchoalveolar lavage fluid (BALF) samples, cultures of blood and BALF and detection of Legionella urinary antigen. Blood PCR was positive until 8 days after infection, while BALF PCR became negative on day 4. These results indicate that PCR using blood samples may be a useful, convenient and non-invasive method for the diagnosis of Legionella pneumonia.

Animals↗

PubMed2002

Interaction of iodine with 2-hydroxypropyl-alpha-cyclodextrin and its bactericidal activity.

To obtain an effective iodine solution, the use of 2-hydroxypropyl-alpha-cyclodextrin (2-HP-alpha-CD) as solubilizer was examined in comparison with alpha-cyclodextrin (alpha-CD), beta-cyclodextrin (beta-CD), potassium iodide (KI), and polyvinylpyrrolidone (PVP). The stability constants for inclusion of iodine with cyclodextrin and KI were ascertained by the solubility method. The apparent stability constants increased in the following order: KI < beta-CD < alpha-CD < 2-HP-alpha-CD. This order was nearly in accordance with that of the stabilization ability. The largest volatile depression effect was exhibited by 2HP-alpha-CD. The measurement of the minimum inhibitory concentration (MC) using Escherichia coli NIH-J-2 and Staphylococcus aureus FDA209P suggested that the bactericidal activity of the iodine/2-HP-alpha-CD system was the same as that of the iodine/alpha-CD, iodine/beta-CD, and iodine/PVP systems. The present results suggest that the combination of 2-HP-alpha-CD and iodine is useful for a stable and effective iodine solution.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed2001

Effects of parenterally administered ciprofloxacin in a murine model of pulmonary Pseudomonas aeruginosa infection mimicking ventilator-associated pneumonia.

BACKGROUND AND METHODS: We compared the bacteriological, pharmacological and histopathological effects of parenterally administered ciprofloxacin (CPFX) to those of imipenem/cilastatin (IMP/CS) and cefozopran (CZOP) in a murine model of mucoid Pseudomonas aeruginosa pneumonia mimicking ventilator-associated pneumonia. RESULTS: The minimum inhibitory concentrations (MICs) of CPFX, IMP and CZOP were 1.0, 1.0 and 4.0 mg/l, respectively. Treatment with CPFX resulted in a significant decrease in the number of viable bacteria [control, IMP/CS, CZOP and CPFX (mean +/- SEM): 5.02 +/- 0.20, 4.96 +/- 0.38, 5.44 +/- 0.13 and 3.27 +/- 0.02 log(10) colony-forming units lung, respectively]. Histopathological examination revealed that inflammatory changes in the CPFX-treated group were less marked than in other groups. Of the drugs analyzed, the pharmacokinetic parameters of area under the time-concentration curve (AUC)/MIC, AUC exceeding MIC and the time that lung concentrations of drug remained above the MIC were highest for CPFX. CONCLUSION: Our results suggest that parenterally administered ciprofloxacin is effective in ventilator-associated P. aeruginosa pneumonia.

Animals↗

PubMed2001

High concentrations of beta-chemokines in BAL fluid of patients with diffuse panbronchiolitis.

BACKGROUND: T cells are important cellular components of bronchial inflammation in diffuse panbronchiolitis (DPB). beta-Chemokines such as RANTES (regulated on activation, normal T-cell expressed and secreted) and macrophage inflammatory peptide (MIP)-1alpha are closely related to the migration of inflammatory cells into the lung. In this study, we investigate the contribution of beta-chemokines to the accumulation of T cells in the lungs of patients with DPB. PATIENTS AND METHODS: We determined the levels of beta-chemokines in BAL fluid (BALF) and the correlation between these levels and T-cell subsets in BALF of 23 patients with DPB and 16 healthy subjects by sandwich enzyme-linked immunosorbent assay and flow cytometry. RESULTS: Percentages of CD3+ human leukocyte antigen (HLA)-DR+, CD8+, and CD8+HLA-DR+ cells in BALF of patients were significantly higher than in the control BALF. The absolute number of CD8+HLA-DR+ cells was also higher in BALF of patients than in the control BALF (p < 0.0001). Phenotypic analysis of CD4+ cells in BALF showed a similar percentage of CD4+CD45RA+ cells and CD4+CD29+ cells in patients and normal subjects. The concentrations of RANTES and MIP-1alpha in BALF of patients with DPB were significantly higher than in BALF of normal subjects (p < 0.05). In addition, there was a significant correlation between the absolute number or percentage of CD8+HLA-DR+ cells and MIP-1alpha concentration in BALF. CONCLUSIONS: Our results suggest that the interaction between activated CD8+ T cells and MIP-1alpha may contribute to the pathogenesis of DPB.

Adolescent↗

PubMed2001

Disopyramide-induced pneumonitis, diagnosed by lymphocyte stimulation test using bronchoalveolar lavage fluid.

A 72-year-old man was admitted to our hospital with fever and cough. He had been on disopyramide treatment for nine days to control cardiac arrhythmia. On admission, chest X-ray examination revealed reticulonodular opacities in both lungs, and impending respiratory failure was evident. A differential cell count of the bronchoalveolar lavage fluid (BALF) showed a marked increase of lymphocytes. A lymphocyte stimulation test (LST) for disopyramide using BALF was positive, although the test using peripheral blood was negative. This case suggests that LST using BALF is useful for the diagnosis of drug-induced pneumonitis.

Aged↗

PubMed2001

[Analysis of patients with middle lobe and lingular syndrome complicated with nontuberculous mycobacterosis, chronic sinusitis, or bronchopulmonary tuberculosis].

The clinical characteristics and chest CT scan findings in 77 cases of middle lobe and lingular syndrome, many of which were complicated with nontuberculous mycobacteriosis (21 cases, 27.3%), chronic sinusitis (16, 20.8%), or bronchopulmonary tuberculosis (11, 14.3%) are reported. Sixteen (76.2%) cases complicated with nontuberculous mycobacteriosis and 14 (87.5%) cases complicated with chronic sinusitis had granular shadows with dilated bronchi of both middle lobe and lingular in their chest CT scans. Granular shadows with a thickening of the bronchial wall or dilated bronchi were common characteristics of the chest CT scans of the patients with nontuberculous mycobacteriosis. However, cicatrization atelectasis of either middle lobe or lingular was the most common finding in patients with bronchopulmonary tuberculosis.

Adult↗

PubMed2001

[Two-step tuberculin skin test in nurse students].

The tuberculin skin test (TST) was conducted in 243 nurse students (19.4 +/- 1.3 years old). The second TST were carried out in 240 students who did not show blister or necrosis in the first TST. The size of erythema was 16.5 +/- 9.4 mm in the first TST (T1) and 24.3 +/- 15.6 mm in the second TST (T2). The negative reactors, whose size of erythema was below 10 mm, were decreased from 53 to 25, whereas, the strong reactors, whose size of erythema was more than 30 mm, were increased from 11 to 71. The difference of the size of erythema (T2-T1) was 9.7 +/- 11.9 mm in the group I (190 students) who received the latest TST in junior high school, whereas, that was 0.5 +/- 9.2 mm in the group II (50 students) who received the latest TST 14 months before this study. T2-T1 in the group I was weakly correlated with T1. Twenty-four negative reactors received BCG vaccination, and 23 of them converted to positive. Seventy-one strong reactors were checked by chest X-ray, and none showed the findings of tuberculosis, and required the administration of anti-TB drug. The two-step TST is an essential means to know the baseline reactivity to TST, and to distinguish newly infected tuberculosis from booster phenomenon.

Adolescent↗

PubMed2001

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (1999)].

From October 1999 to September 2000, we collected the specimen from 430 patients with lower respiratory tract infections in 17 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and antibiotics and patients' characteristics. Of 515 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 506 strains were investigated. The breakdown of the isolated bacteria were: Staphylococcus aureus 78, Streptococcus pneumoniae 101, Haemophilus influenzae 104, Pseudomonas aeruginosa (non-mucoid) 58, P. aeruginosa (mucoid) 11, Moraxella subgenus Branhamella catarrhalis 41, Klebsiella pneumoniae 18, etc. Of 78 S. aureus strains, those with 4 micrograms/ml or above of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) occupied 57.7%. Vancomycin and arbekacin showed the most potent activities against MRSA without detection of ABK-resistant strain (MIC: 64 micrograms/ml) and decrease of VCM-sensitive strains those were found in 1998. The frequency of S. pneumoniae exhibiting low sensitivity to penicillin (penicillin-intermediate S. pneumoniae: PISP + penicillin-resistant S. pneumoniae: PRSP) decreased to 34.7% from 46.0% in 1998. The frequency of PRSP was 3.0%, being the least number after 1991. Carbapenems showed strong activities against S. pneumoniae. Especially, panipenem inhibited the growth of all 101 strains with MIC of 0.063 microgram/ml. Generally, all drugs showed strong activities against H. influenzae with MIC80s of 4 micrograms/ml or below. MICs of ofloxacin ranged between 0.063 microgram/ml and 4 micrograms/ml in 1998, however, those were 0.125 microgram/ml or below in all H. influenzae in 1999 showing the strongest activity. Tobramycin and ciprofloxacin showed strong activities against P. aeruginosa (both mucoid and non-mucoid) with MIC80s of 1 microgram/ml. Number of isolated P. aeruginosa (mucoid) was little as 11, however, the susceptibilities to all drugs were better than P. aeruginosa (non-mucoid). K. pneumoniae showed good susceptibilities to all drugs except for ampicillin with decreasing of low-sensitive strains compared to those detected in 1998. Also, all drugs generally showed strong activities against M. (B.) catarrhalis. MIC80s of all drugs were 2 micrograms/ml or below. The drug which showed the strongest activity was imipenem inhibiting all 41 strains with MIC of 0.063 microgram/ml. On the patients' characteristics, the number of patients aged 80 years or older who had been increased was decreased in 1999 in the distribution by age. The percentage of the elderly patients aged 70 years or older was 47.0%, which occupied almost a half number of the total patients as in the last year. As for the incidence by disease, bacterial pneumonia and chronic bronchitis were the highest. They were noted in 37.9% and 30.5% of the patients, respectively. In 1999, bronchial asthma was frequently observed as compared in recent years. It was noted in about 10% of the patients which is the same % as in bronchiectasis. We examined the number of strains from these patients with infections before and after administration of antibiotics. In patients with bacterial pneumonia, the number of isolated strains was almost the same between those before and after administration. However, in patients with chronic bronchitis, the number of strains remarkably decreased to less than the half of the total after administration of antibiotics in the last year, but it decreased to 2/3 of the total in 1999. On the administration of antibiotics and isolated bacteria by the day of administration, the bacteria which were isolated more before administration were H. influenzae in 28.4%, S. pneumoniae in 25.7%, M. (B.) catarrhalis in 12.0% and S. aureus in 10.6%. The frequency of S. aureus after administration over 15 days was almost the same as that before administration, but the frequency of P. aeruginosa (both mucoid and non-mucoid) was 36.8% which was higher than that before administration. The frequency of isolated S. pneumoniae was decreased after administration and none of them was isolated after completion of administration. However, that of H. influenzae was decreased to 7.1% after administration within 3 days, and many H. influenzae were isolated after completion of administration as 21.4%.

Adolescent↗

PubMed2000

Antifungal activity of a new triazole, voriconazole (UK-109496), against clinical isolates of Aspergillus spp.

Voriconazole is a new triazole antifungal agent with potent activity against yeast and molds. We investigated the in-vitro activity of voriconazole compared with that of other antifungal agents against 50 clinical isolates of Aspergillus spp., measured by the National Committee for Clinical Laboratory Standards (NCCLS) reference method described in the M27-A document, and by an alamar blue colorimetric method. Voriconazole was the most potent agent against Aspergillus fumigatus (minimum inhibitory concentration [MIC]90, 0.5 mg/l) and Aspergillus niger (MIC90, 1.0 mg/l). Voriconazole was less active (MIC90, 1.0 mg/l) against Aspergillus flavus than itraconazole (MIC90, 0.5 mg/l). Voriconazole was more active than itraconazole against Aspergillus fumigatus and Aspergillus flavus by the alamar blue indicator method for the measurement of MIC. Based on these results, voriconazole has promising activity against commonly encountered isolates of Aspergillus spp., and its clinical usefulness should be established by further studies.

Antifungal Agents↗

PubMed2000

Synergistic effect of ofloxacin and fluconazole against azole-resistant Candida albicans.

We investigated the combination effects of ofloxacin and fluconazole against azole-resistant Candida albicans strains in vitro and in vivo. Ofloxacin alone showed no efficacy against the azole-resistant C. albicans strain, C26. The in-vitro combination effects were evaluated by the checkerboard method, calculated as the fractional inhibitory concentration (FIC) index, but there was no synergistic effect of the combination. The activity of the drug efflux pump in the azole-resistant C. albicans strains was measured by intracellular rhodamine 6G concentration. When the cells were incubated with ofloxacin or grepafloxacin, the intracellular rhodamine 6G concentration was significantly increased in the azole-resistant C. albicans strain. In-vivo combination effects were evaluated in murine disseminated candidiasis. The survival of the mice was not prolonged, but counts of the yeast cells in the kidney and spleen were reduced following treatment with the combination of ofloxacin (20 mg/kg) and fluconazole (20 mg/kg). The combination of ofloxacin and fluconazole may represent an effective strategy to treat infections caused by azole-resistant C. albicans.

Anti-Infective Agents↗

PubMed2000

Effects of macrophage colony-stimulating factor (M-CSF) on anti-fungal activity of mononuclear phagocytes against Trichosporon asahii.

Trichosporon asahii is an emerging opportunistic pathogen in immunocompromised patients. Little is known about the mechanisms of host defence against T. asahii. We investigated the fungicidal activity of human peripheral blood monocytes and murine peritoneal macrophages against T. asahii isolates, and the effects of M-CSF on the anti-fungal activity of mononuclear phagocytes. We also established a neutropenic mouse model of disseminated trichosporonosis with T. asahii. M-CSF enhanced the phagocytic fungicidal activity of mononuclear cells, and infected mice treated with human M-CSF at 10 x 106 U/kg showed a significant improvement in survival rate, with fewer fungal colony counts in the lung compared with control mice. Mice treated with human M-CSF showed higher concentrations of tumour necrosis factor-alpha (TNF-alpha) in the lung and plasma compared with control mice. The survival rate was significantly reduced in mice treated with anti-mouse TNF-alpha. Our results showed that M-CSF enhanced the fungicidal activity of mononuclear phagocytes partly by production of TNF-alpha, and suggest that the administration of M-CSF to patients with disseminated trichosporonosis may be a useful adjunct to conventional anti-microbial therapy and prophylaxis.

Animals↗

PubMed2000

Intrapulmonary concentrations of inflammatory cytokines in a mouse model of chronic respiratory infection caused by Pseudomonas aeruginosa.

We investigated the role of inflammatory cytokines in a mouse model of chronic Pseudomonas aeruginosa infection mimicking diffuse panbronchiolitis (DPB), and determined the effects of clarithromycin therapy on the production of these cytokines. The concentrations of IL-1beta, IL-2, IL-4, IL-5, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) were measured serially in the lungs of mice with experimentally induced chronic respiratory P. aeruginosa infection until 60 days after inoculation. The concentrations of these cytokines during the course of the disease were significantly higher than baseline (before inoculation, P<0.01 for all cytokines). Clarithromycin significantly inhibited the production of IL-1beta and TNF-alpha in the lung (P<0.01). The same treatment also reduced the levels of other cytokines, albeit insignificantly. Treatment with anti-TNF-alpha antibody significantly reduced the number of pulmonary lymphocytes and concentration of IL-1beta in the lung (P<0.01), but did not change the number of viable bacteria. Our findings resemble those detected in bronchoalveolar lavage fluid of patients with DPB and indicate that inflammatory cytokines play an important role in chronic P. aeruginosa lung infection. Our results also show that macrolides modulated the production of these cytokines, ultimately reducing lymphocyte accumulation in the lung. Our data suggest that anti-TNF-alpha antibody might be a useful new strategy for the treatment of chronic respiratory P. aeruginosa infection.

Animals↗

PubMed2000

Determination of the stability constants in alkanol/alpha-cyclodextrin mixed system.

The simultaneous determination of the stability constants for inclusion of alkanols with alpha-cyclodextrin (alpha-CD) was investigated in a mixed alkanol system using static head-space gas chromatography (SHSGC). The 1:1 stability constants obtained were in fair agreement with those obtained previously using other methods. The time required for determination of the stability constant was markedly reduced using this simultaneous SHSGC method.

Chemical Phenomena↗

PubMed2000

Interaction of antimalarial agent artemisinin with cyclodextrins.

To obtain an effective solution of the poorly water soluble antimalarial agent artemisinin, the use of several kinds of cyclodextrins (CDs) as solubilizers was examined. The following CDs were used in this study: alpha-CD, beta-CD, gamma-CD as parent CDs, 2-hydroxypropyl-beta-CD (HP-beta-CD), sulfobutyl ether beta-CD (SBE7-beta-CD), heptakis (2,6-di-O-methyl)-beta-CD (DM-beta-CD), 2,3,6-partially methylated-beta-CD (PM-beta-CD) as modified CDs, and glucosyl-beta-CD (G1-beta-CD), and maltosyl-beta-CD (G2-beta-CD) as branched CDs. The solubility curves of artemisinin with CDs can all be classified as type AL. The apparent stability constants for artemisinin-parent CD complexes increased in the order of alpha- < gamma- < or = beta-CD. The constants for artemisinin-beta-CD derivative (and beta-CD) complexes increased in the order of G2-beta-CD approximately equal to G1-beta-CD approximately equal to PM-beta-CD approximately equal to beta-CD < HP-beta-CD < SBE7-beta-CD < DM-beta-CD. These results suggest that the addition of CDs enables the solubilization of artemisinin.

Antimalarials↗