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Biomedical subjects

K Tateda

Publications and source records attributed to K Tateda.

At least 55 records · Page 3Linked to original sources

Primary Shewanella alga septicemia in a patient on hemodialysis.

We report the first Japanese case of primary septicemia with Shewanella alga and also describe the bacteriological characteristics of and results of antibiotic susceptibility tests of the isolate. S. alga was repeatedly isolated, at times simultaneously with Escherichia coli, from the blood of a 64-year-old female undergoing hemodialysis. The isolated organism was determined to be S. alga based on recently published identification criteria, such as hemolysis on sheep blood agar, no acid production from carbohydrates, and growth on agar containing 6. 5% NaCl. Results of antibiotic susceptibility tests demonstrated that the isolate was sensitive to levofloxacin and cefpirome (MICs, </=0.063) but resistant to cefazolin, ceftizoxime, and imipenem (MICs, >128, 64, and 8 microg/ml, respectively). Although the role of S. alga as a human pathogen has not been fully determined, accumulating data suggest that this organism may be a potential pathogen, especially in compromised hosts.

Anti-Bacterial Agents↗

Acute induction of interleukin-6 and biphasic changes of serum complement C3 by carrageenan in mice.

Carrageenan has been widely used as an irritant to evoke inflammation in animals or to selectively deplete macrophages in vivo. Although precise understanding of carrageenan activity is a prerequisite for the experimental use of this polysaccharide, the effects of this agent on host-biological systems are still poorly understood. We investigated the effect of carrageenan on serum concentrations of complement C3 and interleukin (IL)-6, a potent complement-inducing factor. Intraperitoneal administration of carrageenan (4 mg) in mice resulted in an initial fall in serum C3 (70% of control, P < 0.05) between 3 and 6 h, but was followed by a significant rise (180% of the control, P < 0.05) at 24h. Prior to the rise in complement C3, a sharp peak of serum IL-6 was observed at 6h after carrageenan treatment. These results indicate potential of carrageenan to enhance host complement systems, which may be associated with, at least in part, an acute induction of IL-6.

Animals↗

Antibacterial activity of AM-1155 against penicillin-resistant Streptococcus pneumoniae.

AM-1155, a novel fluoroquinolone, exhibited potent activity against Streptococcus pneumoniae, including penicillin-resistant strains; the MIC90 for 48 clinical isolates was 0.25 mg/L. The antibacterial activity of AM-1155 against S. pneumoniae was higher than that of levofloxacin (MIC90 1 mg/L) and comparable with that of sparfloxacin. The MIC90s of penicillin G and erythromycin were 2 and > 4 mg/L, respectively. AM-1155 showed no cross-resistance to penicillin or erythromycin. For experimental murine pneumonia with S. pneumoniae intermediately resistant to penicillin, oral administration of AM-1155 showed efficacy higher than that of levofloxacin and equal to that of sparfloxacin. The efficacy of AM-1155 was also equal to that of subcutaneous penicillin G administration at the same dosage.

Animals↗

Effect of immunisation with Pseudomonas aeruginosa on gut-derived sepsis in mice.

The protective efficacy of immunisation with heat-killed Pseudomonas aeruginosa on murine gut-derived sepsis was evaluated. Mice were immunised intraperitoneally six times with heat-killed bacteria. This induced mean (SEM) serum IgG and IgM antibodies of 1792 (374.7) and 37.3 (8.9) ELISA units, respectively. Specific pathogen-free mice given P. aeruginosa strain D4 orally died of bacteraemia after administration of cyclophosphamide. Immunisation with heat-killed bacteria significantly increased the survival rate compared with that of control mice immunised with bovine serum albumin. Macroscopic observation revealed marked production of liver abscesses in mice immunised with bovine serum albumin but not in those immunised with heat-killed bacteria. Only low titres of antibody against the exoenzymes alkaline protease, elastase and exotoxin A were observed, and no significant difference between antibody titres to boiled and unboiled suspensions of sonicated P. aeruginosa was detected. This suggests that the main protective antibodies might be those specific to the heat stable antigen (lipopolysaccharide). Immunisation with heat-killed bacteria provided complete protection against death from gut-derived P. aeruginosa sepsis.

ADP Ribose Transferases↗

Efficacies of alkaline protease, elastase and exotoxin A toxoid vaccines against gut-derived Pseudomonas aeruginosa sepsis in mice.

The protective efficacies of vaccines prepared from Pseudomonas aeruginosa alkaline protease, elastase and exotoxin A toxoids against gut-derived P. aeruginosa sepsis in mice were evaluated. Specific pathogen-free mice given P. aeruginosa strain D4 orally followed by cyclophosphamide (to promote translocation across the gut wall) died of bacteraemia. Mice immunised with one of the three individual toxoid vaccines were not significantly protected when compared to control mice immunised with bovine serum albumin. Combined immunisation with alkaline protease and elastase toxoids likewise showed no significant protective activity. However, combined immunisation with alkaline protease and exotoxin A toxoids significantly increased the survival rate, which reached 60% (compared with a 7.1% survival rate in the control group). These results show that alkaline protease and exotoxin A play important roles as pathogenic factors in gut-derived sepsis and that a combination of the two exoenzyme toxoids represents a logical candidate for vaccination against P. aeruginosa sepsis.

ADP Ribose Transferases↗

Evaluation of clinical usefulness of the microplate agglutination test for serological diagnosis of legionella pneumonia.

Recently, a microplate agglutination test (MPAT) was established for the serological diagnosis of legionella pneumonia. To evaluate its usefulness, this study examined antibody titres in 121 serum samples serially obtained from 40 patients with pneumonia, including 17 cases of confirmed legionella pneumonia. Six of the 17 proven cases became serologically positive within 4 weeks of the onset of pneumonia as assayed by MPAT (cut-off value: four-fold rise to > or = 128 in paired sera or > or = 256 in a single serum specimen), whereas the remaining 11 cases were serologically negative despite serial examination. Four proven cases who were treated with corticosteroids in the acute phase had antibody titres <8 during the first 4 weeks of infection, after which one case showed an elevation in antibody titre for the first time, 13 weeks after the onset of disease. In contrast, all non-proven cases had antibody titres of < or = 64, and only one case developed a four-fold or greater rise in titre. These results indicate that MPAT is a useful method for the laboratory diagnosis of suspected legionella pneumonia, although several false-negative cases were observed. This suggests that the previously established MPAT criteria may require modification, possibly to slightly lower values. These data also indicate that serial examination over the first month of infection may be necessary for serodiagnosis of legionella pneumonia, especially in patients treated with corticosteroids.

Agglutination Tests↗

Effect of interleukin-10 on gut-derived sepsis caused by Pseudomonas aeruginosa in mice.

We evaluated the protective effect of interleukin-10 (IL-10) against murine gut-derived sepsis caused by Pseudomonas aeruginosa. Gut-derived sepsis was induced by administering cyclophosphamide and ampicillin while feeding P. aeruginosa to specific-pathogen-free mice. Treating mice with recombinant human IL-10 (rhIL-10) at 1.0 or 5.0 microg/mouse twice a day following the second cyclophosphamide administration significantly increased the survival rate compared to that of control mice treated with saline; however, treatment with rhIL-10 at 0.1 microg/mouse did not result in significant protection. Bacterial counts in the liver, spleen, and blood were all significantly lower in mice treated with rhIL-10 than in saline-treated control mice. Treatment with rhIL-10 significantly suppressed tumor necrosis factor alpha, interleukin-1beta, interleukin-6, and gamma interferon levels in the serum of mice following induction of gut-derived sepsis. We also studied the effect of IL-10 on leukocyte recovery after cyclophosphamide treatment of mice. Administration of rhIL-10 intraperitoneally at 1. 0 microg/mouse significantly accelerated the recovery of leukocytes in comparison with that of the group of saline-treated controls. These results indicate that IL-10 shows a protective effect against gut-derived P. aeruginosa sepsis. We suspect that the mechanism of this effect is that IL-10 regulates in vivo production of inflammatory cytokines. Furthermore, acceleration of leukocyte recovery by IL-10 after cyclophosphamide-induced depression may also play an important role in this protection.

Animals↗

In vitro and in vivo antibacterial activities of CS-834, a new oral carbapenem.

CS-834 is a prodrug of the carbapenem R-95867, developed by Sankyo Co., Ltd., Tokyo, Japan. To investigate the possibility that CS-834 may be the first carbapenem usable in an oral dosage form, its in vitro antibacterial activity (as R-95867) and in vivo antibacterial activity were compared with those of cefpodoxime proxetil, cefditoren pivoxil, cefdinir, ofloxacin, imipenem, and amoxicillin. R-95867 had high levels of activity against methicillin-susceptible staphylococci and streptococci, including penicillin-resistant Streptococcus pneumoniae, as well as Neisseria gonorrhoeae, Moraxella catarrhalis, the members of the family Enterobacteriaceae (with the exception of Serratia marcescens), Haemophilus influenzae, and Bordetella pertussis; for all these strains, the MICs at which 90% of tested strains are inhibited (MIC90s) were 1.0 microg/ml or less. Against methicillin-resistant staphylococci, enterococci, Serratia marcescens, Burkholderia cepacia, Stenotrophomonas maltophilia, and Acinetobacter calcoaceticus, R-95867 showed activity comparable to or slightly less than that of imipenem, with MIC90s ranging from 2 to >128 microg/ml. The in vivo efficacy of oral CS-834 against experimental mouse septicemia caused by gram-positive and gram-negative bacteria was better than that of comparative drugs. In murine respiratory infection models, the efficacy of CS-834 reflected not only its potent in vitro activity but also the high levels present in the lungs.

Animals↗

In vivo antibacterial activities of sanfetrinem cilexetil, a new oral tricyclic antibiotic.

The in vivo antibacterial activities of a new oral trinem, sanfetrinem cilexetil (a prodrug of sanfetrinem), were evaluated in comparison with those of cefdinir and amoxicillin. Sanfetrinem cilexetil showed potent efficacy against experimental murine septicemia caused by Staphylococcus aureus, Streptococcus pyogenes, and Escherichia coli and against murine respiratory infections caused by Streptococcus pneumoniae. Likewise, in murine models of respiratory infection by penicillin-susceptible and penicillin-resistant S. pneumoniae, sanfetrinem cilexetil was more effective than amoxicillin in reducing the number of bacteria in infected lungs. These results were reflected in its potent in vitro activity and high levels in plasma.

Animals↗

Serum cytokines in patients with Legionella pneumonia: relative predominance of Th1-type cytokines.

Serum samples from 14 patients with Legionella pneumonia were examined for the presence of cytokines. In spite of high levels of serum C-reactive protein in all patients during the acute phase in only four cases (one involving interleukin-1beta [IL-1beta], three involving IL-6, and none involving tumor necrosis factor alpha) was the concentration of cytokines more than 100 pg/ml. Th2 cytokines IL-4 and IL-10 were detected in only one patient each. In contrast, significant increases of serum gamma interferon (IFN-gamma) and IL-12 levels were observed during the acute phase in 6 and 11 cases, respectively. Interestingly, although serum IFN-gamma levels diminished thereafter, in seven cases IL-12 levels remained high or increased further during the convalescent phase. In an additional 22 cases clinically suspected to be but not diagnosed as Legionella pneumonia, increases of serum IL-12 levels were observed in 16 cases, whereas the remaining 6 cases showed no detectable IL-12. Our results demonstrate the relative predominance of Th1 cytokine production in Legionella pneumonia. Although the role and significance of prolonged increases in IL-12 levels in Legionella disease are unknown, our results should prompt further investigation of the host immune response in terms of Th1 and Th2 balance in legionellosis.

Cytokines↗

[Legionella pneumonia--epidemiology, clinical characteristics and development of diagnosis].

We have characterized clinical and diagnostic features in 18 cases of Legionella pneumonia. Age average of patients was 62.0 years old (male: female = 14:4) and underlying diseases were observed in 12 patients. Legionella pneumonia were diagnosed in 3, 5, 7 and 9 cases by culture, serum antibody measurement, urinary antigen detection and PCR, respectively. Sixteen cases were caused by L. pneumophila, while the other 2 cases were due to L. bozemanii and L. pneumophila or L. dumoffii. Chest X-rays of those patients showed multiple pneumonia shadows in 14 cases, alveolar shadows in 10 cases, pleural effusion in 5 cases. Blood-gas analysis on admission indicated hypoxemia in all cases with abnormal A-a DO2. Laboratory findings showed abnormal data in WBC, CRP, LDH, CPK and liver function tests (ex. GOT, GPT) in most cases. Serum antibody testing showed positive by 5 weeks after onset of pneumonia, but 10 cases of Legionella pneumonia diagnosed by other techniques were judged to be negative. In urinary antigen detection test, 6 and 2 cases showed positive 1 and 4 weeks after onset of pneumonia, respectively. Macrolide antibiotics were administered in all cases during the episode, but delay of macrolide administration was observed in 3 of 4 cases of dead outcome. Serum antibody measurement, urinary antigen detection and PCR, in addition to culture of bacteria, may be required for exact diagnosis of Legionella infection.

4-Quinolones↗

Adverse effects of tumour necrosis factor in cyclophosphamide-treated mice subjected to gut-derived Pseudomonas aeruginosa sepsis.

To evaluate the role of tumour necrosis factor (TNF) in gut-derived sepsis, mice were given Pseudomomas aeruginosa strain D4 by bacterial suspension in their drinking water during which time ampicillin (200 mg/kg) was given to disrupt the normal indigenous bacterial flora. Cyclophosphamide was additionally administered to induce bacterial translocation of the P. aeruginosa that had colonized the gastrointestinal tract, and thereby to cause gut-derived sepsis. In this model, TNF-alpha was detected in serum from the next day after the second cyclophosphamide administration, increasing to level of 3 ng/ml in lethal conditions. Average serum TNF-alpha level was significantly higher in mice with bacteraemia than in those without bacteraemia. Treatment with 0.8 microg/kg of recombinant human TNF-alpha (rhTNF-alpha) did not affect the mortality, whereas administration of either 4 and 20 microg/kg of rhTNF-alpha significantly increased the mortality rate in comparison with saline-treated mice. Bacterial counts in liver and blood were significantly higher in 20 microg/kg of rhTNF-alpha treated mice than in saline-treated mice. Treatment with murine anti-TNF-alpha monoclonal antibody significantly reduced the mortality from septic infection. We conclude that TNF-alpha may facilitate bacterial translocation and causes deterioration of gut-derived sepsis due to P. aeruginosa in mice.

Animals↗

New murine model of bronchopneumonia due to cell-bound Haemophilus influenzae.

This murine model of nontypeable (unencapsulated) Haemophilus influenzae (NTHI) bronchopneumonia used organisms bound to mouse fetal lung (MFL) cells as an inoculum. Pretreatment of the mice with 40 microL of 1% formalin 3 days before intranasal instillation of the bacteria was necessary to allow infection. The number of NTHI recovered from the lungs plus trachea on day 7 after instillation was >100 times the number originally inoculated. Later, however, the number of recovered bacteria diminished gradually, and by day 14 it was almost identical to the original inoculum size. Serum IgM also peaked on day 7 after infection, after which IgG increased while IgM decreased. Histologically, bronchoalveolar infiltration of neutrophils was observed on day 3 after inoculation and continued at least for the following 4 days. The present experiment demonstrates that MFL cells can protect bacteria that have invaded the cells from the opsonizing and killing activities of host humoral defense mechanisms.

Animals↗

Antibiotic MICs and short time-killing against Helicobacter pylori: therapeutic potential of kanamycin.

We compared the susceptibility of Helicobacter pylori to several antibiotics, expressed as MICs and as bactericidal effectiveness in short (3 h) time-killing studies. Of the antimicrobial agent tests, clarithromycin and amoxycillin had the lowest MIC50, 0.063 and 0.125 mg/L respectively, for 24 strains of H. pylori. Minocycline, levofloxacin and lansoprazole followed, with MIC50s of 0.5, 1, and 2 mg/L, respectively. Three-hour time-killing studies using a standard strain demonstrated a different pattern. At 4 x MIC, kanamycin, metronidazole and clarithromycin produced 4.4, 2.6 and 2.1 log decreases in viability, whereas the remaining seven antibiotics (including amoxycillin) were less bactericidal. Amoxycillin's lack of bactericidal activity during brief incubations was confirmed by examining several different clinically isolated H. pylori strains. Clarithromycin's effect, on the other hand, was strain- and concentration-dependent. Kanamycin was the most potent antibiotic in short time-killing studies, with concentrations of 1 x MIC and 4 x MIC producing a reduction of more than 2 and 4 log respectively in all ten strains. Our data suggest that the MIC of antimicrobial agents against H. pylori does not necessarily predict their activity in short time-killing studies. Furthermore, our short time-kill data suggest kanamycin as a potential therapeutic choice for H. pylori infection, even though this agent's MIC would suggest limited activity.

Amoxicillin↗

[Clinical and diagnostic characteristics of Legionella pneumonia].

We have characterized clinical and diagnostic features in 18 cases of Legionella pneumonia. Age average of patients was 62.0 years old (male:female = 14:4) and underlying diseases were observed in 12 patients. Legionella pneumonia were diagnosed in 3, 5, 8 and 9 cases by culture, serum antibody measurement, urinary antigen detection and PCR, respectively. Sixteen cases were caused by L. pneumophila, while the other 2 cases were L. bozemanii pneumonia and L. pneumophila or L. dumoffii pneumonia. Chest X-rays of those patients showed multiple pneumonia shadows in 14 cases, alveolar shadows in 10 cases, pleural effusion in 5 cases. Blood-gas analysis on admission indicated hypoxemia in all cases with abnormal A-a DO2. Laboratory findings showed abnormal data in WBC, CRP, LDH, CPK and liver function tests (ex. GOT, GPT) in most cases. Serum antibody testing showed positive by 5 weeks after onset of pneumonia, but 10 cases of Legionella pneumonia diagnosed by other techniques were judged to be negative. In urinary antigen detection test, 6 and 2 cases showed positive 1 and 4 weeks after onset of pneumonia, respectively. Macrolide antibiotics were administered in all cases during the episode, but delay of macrolide administration was observed in 3 of 4 cases of dead outcome. Serum antibody measurement, urinary antigen detection and PCR, in addition to culture to bacteria, may be required for exact diagnosis of Legionella infection.

Adult↗

In vitro and in vivo antibacterial activities of CS-940, a new fluoroquinolone, against isolates from patients with respiratory infections.

We compared the in vivo and in vitro activities of CS-940, a new fluoroquinolone, with those of a group of other drugs. The activities of CS-940 against gram-positive cocci and gram-negative rods, including methicillin-susceptible Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae, were comparable to those of tosufloxacin, with MICs at which 90% of the strains were inhibited (MIC90s) of 0.5 microg/ml or less. Against methicillin-resistant S. aureus, CS-940 was as active as tosufloxacin, with a MIC90 of 16 microg/ml. The efficacy of CS-940 against murine respiratory infections due to S. pneumoniae or Haemophilus influenzae was better than those of tosufloxacin and sparfloxacin. The efficacy of oral doses of CS-940 reflected not only potent in vitro activity but also a high transmigration ratio from the bloodstream to lung tissues.

Animals↗

Immunomodulating effect of fosfomycin on gut-derived sepsis caused by Pseudomonas aeruginosa in mice.

We evaluated the protective effect of fosfomycin (FOM) and an enantiomer of fosfomycin [FOM (+); an isomer of FOM with no bactericidal activity] on murine gut-derived sepsis caused by Pseudomonas aeruginosa. Endogenous bacteremia was induced by administering cyclophosphamide (CY) and ampicillin to specific-pathogen-free mice fed P. aeruginosa. Treatment of mice with FOM at 250 mg/kg of body weight per day twice a day after the second CY administration significantly increased the survival rate compared to that for control mice treated with saline. Treatment with FOM (+) at 20 and 100 mg/kg also significantly increased the survival rate (from 30% for control mice to 80% for treated mice). The bacterial counts in the liver and blood were both significantly lower in FOM(+)-treated mice in comparison with those in liver and blood of saline-treated control mice. FOM(+) administration affected neither the bacterial colonization in the intestinal tract nor the leukocyte counts in the peripheral blood of the mice. After intravascular inoculation of P. aeruginosa, treatment of mice with FOM (+) did not enhance bacterial clearance from the blood of mice pretreated or not enhance bacterial clearance from the blood of mice pretreated or not pretreated with CY, FOM(+) significantly suppressed tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 levels in the serum of mice after gut-derived sepsis. These results indicate that both FOM and FOM(+) have protective effects against P. aeruginosa bacteremia, despite a lack of specific activity of FOM(+), and suggest that FOM may possess immunomodulating activity and that it induces a protective effect. The protective mechanism is speculated to be that FOM modulates the vivo production of inflammatory cytokines.

Adjuvants, Immunologic↗

Role of tumor necrosis factor alpha in pathogenesis of pneumococcal pneumonia in mice.

The production and role of tumor necrosis factor alpha (TNF-alpha) in pneumococcal pneumonia were investigated in a mouse pneumonia model. When approximately 10(6) CFU of Streptococcus pneumoniae TUM19 were used to inoculate CBA/J mice intranasally, TNF-alpha levels in the lungs and serum began to increase from 1 and 3 days after infection, respectively, concomitantly with the increase in bacterial counts in the lungs. Anti-TNF-alpha antibody accelerated bacterial proliferation in the blood and the death of the mice. Although serum levels of immunoglobulin G antibody against the infecting bacteria were not affected by the anti-TNF-alpha antibody treatment, neutrophil counts in the blood were decreased by the treatment. These results suggest that TNF-alpha produced in the course of pneumococcal pneumonia prevents bacteremia by increasing the number of neutrophils in the blood.

Animals↗