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Biomedical subjects

K Tateda

Publications and source records attributed to K Tateda.

At least 19 recordsLinked to original sources
PubMed2001

Lipoolygosaccharide indirectly enhances inflammatory lesions in lungs as a primary infection site by non-encapsulated and type B Haemophilus influenzae through production of cytokines.

We investigated the role of cytokines in differences in histopathologic changes in the lung between bronchopneumonia caused by non-encapsulated Haemophilus influenzae strain 770235f(0)b(0)and systemic disease caused by type b H. influenzae strain 770235f(0)b(+). Tumour necrosis factor-alpha (TNF-alpha), interleukin-(IL)-6 and IL-1 beta levels in bronchoalveolar lavage fluid (BALF) samples of mice infected with strain 770235f(0)b(0)were higher than in those infected with strain 770235f(0)b(+)until 24 h post-infection. Serum IL-6 rapidly increased in strain 770235f(0)b(0)infection after 72 h post-infection. Serum TNF-alpha level in strain 770235f(0)b(0)infection appeared earlier than in strain 770235f(0)b(+)infection. IL-1 beta production in strain 770235f(0)b(+)infection was later than in strain 770235f(0)b(0)infection. Moreover, a biphasic concentration pattern of TNF-alpha and IL-6 was noted in BALF of mice with strain 770235f(0)b(0)infection.

Animals↗
PubMed2001

Early recruitment of neutrophils determines subsequent T1/T2 host responses in a murine model of Legionella pneumophila pneumonia.

The contribution of neutrophils to lethal sensitivity and cytokine balance governing T1 and T2 host responses was assessed in a murine model of Legionella pneumophila pneumonia. Neutrophil depletion by administration of granulocyte-specific mAb RB6-8C5 at 1 day before infection rendered mice approximately 100-fold more susceptible to lethal pneumonia induced by L. pneumophila. However, this treatment did not alter early bacterial clearance, despite a substantial decrease in neutrophil influx at this time point. Cytokine profiles in the lungs of control mice demonstrated strong T1 responses, characterized by an increase of IFN-gamma and IL-12. In contrast, neutrophil-depleted mice exhibited significantly lower levels of IFN-gamma and IL-12, and elevation of T2 cytokines, IL-4 and IL-10. Immunohistochemistry of bronchoalveolar lavage cells demonstrated the presence of IL-12 in neutrophils, but not alveolar macrophages. Moreover, IL-12 was detected in lavage cell lysates by ELISA, which was paralleled to neutrophil number. However, intratracheal administration of recombinant murine IL-12 did not restore resistance, whereas reconstitution of IFN-gamma drastically improved bacterial clearance and survival in neutrophil-depleted mice. Taken together, these data demonstrated that neutrophils play crucial roles in primary L. pneumophila infection, not via direct killing but more immunomodulatory effects. Our results suggest that the early recruitment of neutrophils may contribute to T1 polarization in a murine model of L. pneumophila pneumonia.

Animals↗
PubMed2001

The in vivo activity of olamufloxacin (HSR-903) in systemic and urinary tract infections in mice.

The in vivo activity of olamufloxacin (HSR-903), a new fluoroquinolone, was evaluated and compared with ciprofloxacin, sparfloxacin and levofloxacin. Olamufloxacin was active against systemic infection in mice inoculated with both Gram-positive and -negative bacteria. Olamufloxacin had equal efficacy for experimental urinary tract infections in mice caused by Pseudomonas aeruginosa.

Animals↗
PubMed2001

Efficacy of azithromycin, clarithromycin and beta-lactam agents against experimentally induced bronchopneumonia caused by Haemophilus influenzae in mice.

Azithromycin is an azalide with potent activity against Haemophilus influenzae including ampicillin-resistant strains. We evaluated the efficacy of azithromycin, clarithromycin and three beta -lactams when used for 1 day only and for 3 days for the treatment of a murine model of bronchopneumonia, using three strains of H. influenzae, two of which were ampicillin resistant. MICs of azithromycin (1-2 mg/L) and clarithromycin (4-8 mg/L) were similar for the three strains. The MICs of cefdinir and cefcapene for beta-lactamase-negative ampicillin-resistant (BLNAR) H. influenzae were 32 times higher than those for beta-lactamase-positive ampicillin-resistant and ampicillin-susceptible strains. The viable counts in the infected tissues of azithromycin-treated mice with bronchopneumonia caused by the susceptible strain TUM8, beta-lactamase-positive strain TUH36 and BLNAR strain TUH267 were less than the counts obtained with the other antibiotics used, irrespective of MIC. At a dose of 50 mg/kg, the area under the concentration curve and the half-life of azithromycin in the lungs were respectively three times higher and six times longer than those of clarithromycin. Our results indicate that azithromycin may be useful for both ampicillin-susceptible and ampicillin-resistant bronchopneumonial infections caused by H. influenzae.

Animals↗
PubMed2001

[Susceptibility testing of clinical strains of Legionella spp. isolated in Japan].

We determined antimicrobial susceptibilities of 23 strains of Legionella spp. clinically isolated in Japan, between September 1994 through November 1999 by using Etest. The MICs of all isolates against macrorides, fluoroquinolones and rifampicin showed 1 microgram/ml or less. Especially rifampicin showed the most potent activity, of which the MICs of all isolates showed 0.064 microgram/ml or less. Although we could not find resistant strains against any antibiotics tested in this study, we think it is important to follow up the susceptibilities of clinical isolates of Legionella.

4-Quinolones↗
PubMed2001

[Drug susceptibility of clinically isolated strains of Neisseria gonorrhoeae].

We investigated the drug susceptibilities of Neisseria gonorrhoeae by using 98 strains of clinical isolates at Toho University Omori Hospital from 1994 to 1998. Minimum Inhibitory Concentrations (MICs) of 15 antimicrobial agents were determined with agar dilution methods according to the guidelines of NCCLS. Among these isolates, only 4 strains (4.1%) were found to be penicillinase producing N. gonorrhoeae. Ceftriaxone showed the most potent activity of which MICs of all strains were 0.06 microgram/ml or less. Macroride antimicrobial agents and minocycline also showed strong activities of which MICs of most of the strains were 0.06 microgram/ml or less. With the criteria of NCCLS, 10 strains (10.2%) were found to be resistant to ciprofloxacin and these 10 strains also showed cross resistance to other fluoroquiolones we tested. Our results also revealed that the number of resistant strains against fluoroquiolones abruptly increased from 1996 and indicate the needs of further surveillance of antimicrobial resistance in clinical isolates of N. gonorrhoeae.

Drug Resistance, Microbial↗
PubMed2001

In vitro and in vivo antibacterial activities of L-084, a novel oral carbapenem, against causative organisms of respiratory tract infections.

L-084 (a prodrug of LJC 11,036 [L-036]) is a new oral carbapenem. Here we compared the in vitro and in vivo antibacterial activities of L-036 with those of imipenem, faropenem, ceditoren-pivoxil, cefdinir, amoxicillin, and levofloxacin. The MICs at which 90% of the isolates were inhibited of L-036 against methicillin-susceptible staphylococci, Streptococcus pneumoniae including penicillin-resistant organisms, Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae including ampicillin-resistant organisms, Legionella pneumophila, and Moraxella catarrhalis were equal to or less than 1 microg/ml. In pharmacokinetics studies of L-084 in lungs of mice, the maximum concentration in serum, half-life, and area under the concentration-time curve of this drug were 9.09 microg/g of tissue, 6.18 h, and 31.0 microg. h/ml, respectively. In murine respiratory infection models of penicillin-susceptible and -resistant S. pneumoniae and H. influenzae, the efficacies of L-084 were better than those of reference drugs. Our results indicate that the in vitro high potency and good distribution in the lungs might be the underlying mechanisms of its efficacy in the murine model of pneumonia.

Animals↗
PubMed2001

In vivo efficacy of telithromycin (HMR3647) against Streptococcus pneumoniae and Haemophilus influenzae.

The in vivo activity of telithromycin against erythromycin A- and penicillin G-resistant Streptococcus pneumoniae was superior to that of azithromycin, clarithromycin, cefdinir, and levofloxacin. In respiratory tract infections caused by erythromycin A-susceptible S. pneumoniae or Haemophilus influenzae in mice, telithromycin was more effective than clarithromycin and comparable to azithromycin.

Animals↗
PubMed2001

Azithromycin inhibits quorum sensing in Pseudomonas aeruginosa.

We report that 2 microg of azithromycin/ml inhibits the quorum-sensing circuitry of Pseudomonas aeruginosa strain PAO1. Addition of synthetic autoinducers partially restored the expression of the trancriptional activator-encoding genes lasR and rhlR but not that of the autoinducer synthase-encoding gene lasI. We propose that azithromycin interferes with the synthesis of autoinducers, by an unknown mechanism, leading to a reduction of virulence factor production.

Anti-Bacterial Agents↗
PubMed2001

Transient transgenic expression of gamma interferon promotes Legionella pneumophila clearance in immunocompetent hosts.

Gamma interferon (IFN-gamma) and T1-phenotype immune responses are important components of host defense against a variety of intracellular pathogens, including Legionella pneumophila. The benefit of intrapulmonary adenovirus-mediated IFN-gamma gene therapy was investigated in a nonlethal murine model of experimental L. pneumophila pneumonia. Intratracheal (i.t.) administration of 10(6) CFU of L. pneumophila induced the expression of T1 phenotype cytokines, such as IFN-gamma and interleukin-12 (IL-12). Natural killer cells were identified as the major cellular source of IFN-gamma. To determine if enhanced expression of IFN-gamma in the lung could promote pulmonary clearance of L. pneumophila, we i.t. administered 5 x 10(8) PFU of a recombinant adenovirus vector containing the murine IFN-gamma cDNA (AdmIFN-gamma) concomitant with L. pneumophila. We observed a 10-fold decrease in lung bacterial CFU at day 2 in the AdmIFN-gamma-treated group compared to controls (P < 0.01). Alveolar macrophages isolated from AdmIFN-gamma-treated animals displayed enhanced killing of intracellular L. pneumophila organisms ex vivo. Similar improvements in bacterial clearance were observed with i.t. recombinant IFN-gamma treatment. The transient transgenic expression of IL-12, a known inducer of IFN-gamma and promoter of T1-type immune responses, resulted in more modest improvement in bacterial clearance (sixfold reduction; P < 0.05). These results demonstrate that, even in immunocompetent hosts, exogenous administration or transient transgenic expression of IFN-gamma, and to a lesser extent IL-12, may be of potential therapeutic benefit in the treatment of patients with Legionella pneumonia.

Animals↗
PubMed2001

Alveolar macrophage deactivation in murine septic peritonitis: role of interleukin 10.

Sepsis predisposes the host to a number of infectious sequelae, particularly the development of nosocomial pneumonia. Mechanisms by which sepsis results in impairment of lung antibacterial host defense have not been well defined. Alveolar macrophages (AM) represent important immune effector cells of the lung airspace. In this study, we examined the effects of cecal ligation and puncture (CLP) on murine AM function ex vivo, including the expression of proinflammatory cytokines and AM phagocytic activity. AM were harvested from mice subjected to a sham operation and CLP 24 h after laparotomy, adherence purified, and challenged with lipopolysaccharide (LPS) or left unstimulated. Both unstimulated and LPS-stimulated AM from mice subjected to CLP (CLP mice) produced significantly smaller amounts of proinflammatory cytokines tumor necrosis factor alpha and interleukin (IL-12) and C-X-C chemokines KC and macrophage inflammatory protein 2 than similarly treated AM from animals subjected to a sham operation. Furthermore, AM isolated from CLP mice displayed a marked impairment in phagocytic activity, as determined by flow cytometry, with this defect persisting to 48 h post-CLP. Induction of peritoneal sepsis syndrome resulted in a time-dependent increase in IL-10 in plasma and peritoneal fluid. Interestingly, the impairment in AM proinflammatory-cytokine production and phagocytic activity observed in AM from CLP mice was partially reversed by the in vivo neutralization of IL-10 prior to AM harvest. These observations suggest that abdominal sepsis syndrome results in significant impairment in AM effector cell function, which is mediated, in part, by sepsis-induced expression of IL-10.

Animals↗
PubMed2001

Chemokine-dependent neutrophil recruitment in a murine model of Legionella pneumonia: potential role of neutrophils as immunoregulatory cells.

The roles of CXC chemokine-mediated host responses were examined with an A/J mouse model of Legionella pneumophila pneumonia. After intratracheal inoculation of 10(6) CFU of L. pneumophila, the bacterial numbers in the lungs increased 10-fold by day 2; this increase was accompanied by the massive accumulation of neutrophils. Reverse transcription-PCR data demonstrated the up-regulation of CXC chemokines, such as keratinocyte-derived chemokine, macrophage inflammatory protein 2 (MIP-2), and lipopolysaccharide-induced CXC chemokine (LIX). Consistent with these data, increased levels of KC, MIP-2, and LIX proteins were observed in the lungs and peaked at days 1, 2, and 2, respectively. Although the administration of anti-KC or anti-MIP-2 antibody resulted in an approximately 20% decrease in neutrophil recruitment on day 2, no increase in mortality was observed. In contrast, the blockade of CXC chemokine receptor 2 (CXCR2), a receptor for CXC chemokines, including KC and MIP-2, strikingly enhanced mortality; this effect coincided with a 67% decrease in neutrophil recruitment. Interestingly, anti-CXCR2 antibody did not affect bacterial burden by day 2, even in the presence of a lethal challenge of bacteria. Moreover, a significant decrease in interleukin-12 (IL-12) levels, in contrast to the increases in KC, MIP-2, and LIX levels, was demonstrated for CXCR2-blocked mice. These data indicated that CXCR2-mediated neutrophil accumulation may play a crucial role in host defense against L. pneumophila pneumonia in mice. The increase in lethality without a change in early bacterial clearance suggested that neutrophils may exert their protective effect not through direct killing but through more immunomodulatory actions in L. pneumophila pneumonia. We speculate that a decrease in the levels of the protective cytokine IL-12 may explain, at least in part, the high mortality in the setting of reduced neutrophil recruitment.

Animals↗
PubMed2001

Selective inhibition of COX-2 improves early survival in murine endotoxemia but not in bacterial peritonitis.

Prostaglandins of the E series are believed to act as important mediators of several pathophysiological events that occur in sepsis. Studies were performed to evaluate the effect of cyclooxygenase (COX)-2-specific inhibition on the outcome in murine endotoxemia and cecal ligation and puncture (CLP). We observed a significant time-dependent upregulation of PGE(2) production in both blood and lung homogenates of mice administered lipopolysaccharide intraperitoneally, which was nearly completely suppressed by the administration of the COX-2 inhibitor NS-398. Treatment with NS-398 significantly improved early but not late survival in lipopolysaccharide-challenged mice. On the contrary, elevated PGE(2) levels were found in bronchoalveolar lavage fluid but not in plasma of mice subjected to CLP (21 gauge). Pretreatment with NS-398 failed to significantly improve survival in CLP mice. No significant differences were noted in plasma or lung homogenate proinflammatory cytokine levels or lung neutrophil sequestration between the NS-398-treated and control groups. These results demonstrate that selective COX-2 inhibition confers early but not long-term benefits without affecting the expression of proinflammatory cytokines or the development of lung inflammation.

Animals↗
PubMed2001

[A case of severe Legionella pneumonia monitored with serum SP-A, SP-D, and KL-6].

A 67-year-old man was admitted for acute pneumonia on July 20th, 1999. Chest radiographs disclosed dense consolidation in the right lower lung fields. After admission, the pneumonia underwent rapid advance. On the basis of serological findings and cultures of pleural effusion and sputum, the patient was given a diagnosis of acute pneumonia caused by Legionella pneumophila 1 a. He gradually recovered from the pneumonia by means of chemotherapy using EM, RFP, Mino, gammaglobulins and steroids. The serum SP-A, SP-D, and KL-6 peaked on July 23rd, July 30th, and August 12th, respectively.

Aged↗
PubMed2001

[Opportunistic pneumonia after kidney transplantation].

This study was conducted to evaluate clinical features at the onset of pneumonia and the usefulness of methods for diagnosing pneumonia in patients who have undergone kidney transplantation. From January 1990 to December 1998. 174 kidney transplantations were performed, and were followed by 22 cases of pneumonia. Of the 22 pneumonia patients, 16 were male and 6 were female. The median age of the 22 patients was 37.2 +/- 13.3 years. All the patients received cyclosporin A and corticosteroids. In 11 cases, the organisms were identified in the microbiology or pathology laboratory, either during life or at autopsy. Six cases were due to Pneumocystis carinii (PC), three to PC and Cytomegalovirus (CMV), one to Aspergillus, and one resulted from miliary tuberculosis. Pneumonia occurred within 4 months after kidney transplantation in most cases. The mean interval between the transplantation and the appearance of pneumonia was 77.3 +/- 34.3 days, except in the cases of Aspergillosis and miliary tuberculosis, where the intervals were 46 and 50 months, respectively. The mean interval from the appearance of symptoms to the detection of pulmonary infiltration was 3.3 +/- 4.3 days. The clinical features present when pulmonary infiltration was detected by CT were fever (91%), cough (32%), and crackles (27%). However, at this time, 55% of the cases had no symptoms other than fever. Chest radiographs were positive for pulmonary infiltration in 64% of the cases at the same time that the pulmonary infiltrates were detected by CT. Eighty percent of the cases exhibited diffuse interstitial infiltrates. Organisms were detected in 7 of 9 cases examined with bronchofiberscopy (BF). But in only one of 13 cases that did not undergo BF. Increased values of serum beta-D-glucan were detected in the early phase of three PC pneumonia cases, suggesting that beta-D-glucan is useful as a marker of PC pneumonia. The use of bronchofiberscopy was more frequent in survivors of PC pneumonia than in non-survivors, whereas the mean age was higher and coexisting CMV infections were identified more frequently in the non-survivors. We concluded that fever is important as an initial symptom of pulmonary infection. In addition, we find that CT is very useful for the detection of interstitial infiltrates, and BF is an excellent method for detecting organisms in the pneumonia patient after kidney transplantation.

Adult↗
PubMed2000

Intrapulmonary TNF gene therapy reverses sepsis-induced suppression of lung antibacterial host defense.

Sepsis syndrome is frequently complicated by the development of nosocomial infections, particularly Gram-negative pneumonia. Although TNF-alpha (TNF) has been shown to mediate many of the pathophysiologic events in sepsis, this cytokine is a critical component of innate immune response within the lung. Therefore, we hypothesized that the transient transgenic expression of TNF within the lung during the postseptic period could augment host immunity against nosocomial pathogens. To test this, mice underwent 26-gauge cecal ligation and puncture (CLP) as a model of abdominal sepsis, followed 24 h later by intratracheal (i.t.) administration of Pseudomonas aeruginosa. In animals undergoing sham surgery followed by bacterial challenge, Pseudomonas were nearly completely cleared from the lungs by 24 h. In contrast, mice undergoing CLP were unable to clear P. aeruginosa and rapidly developed bacteremia. Alveolar macrophages (AM) recovered from mice 24 h after CLP produced significantly less TNF ex vivo, as compared with AM from sham animals. Furthermore, the adenoviral mediated transgenic expression of TNF within the lung increased survival in CLP animals challenged with Pseudomonas from 25% in animals receiving control vector to 91% in animals administered recombinant murine TNF adenoviral vector. Improved survival in recombinant murine TNF adenoviral vector-treated mice was associated with enhanced lung bacterial clearance and proinflammatory cytokine expression, as well as enhanced AM phagocytic activity and cytokine expression when cultured ex vivo. These observations suggest that intrapulmonary immunostimulation with TNF can reverse sepsis-induced impairment in antibacterial host defense.

Adenoviruses, Human↗