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Biomedical subjects

K Tomono

Publications and source records attributed to K Tomono.

143 records · Page 8Linked to original sources
PubMed1993

[A case of pulmonary aspergilloma successfully treated with combination therapy of intracavitary injection of amphotericin B and intravenous administration of urinastatin].

A 57-year-old man with pulmonary tuberculosis underwent left upper lobectomy in 1984. In 1987, chest X-ray showed a fungus ball, and Aspergillus species was isolated from sputum. He was treated by intracavitary injection of amphotericin B (AMPH) in June, 1992. However, no change was observed in the chest CT scan after a total dose of 1,000 mg of AMPH. Combination therapy of intravenous administration of 100,000 units of urinastatin and intracavitary injection of AMPH resulted in complete disappearance of the fungus ball on chest CT scan. This report describes case of pulmonary aspergilloma successfully treated with the combination of AMPH and urinastatin.

Amphotericin B↗
PubMed1992

Efficacy of erythromycin lactobionate for treating Pseudomonas aeruginosa bacteremia in mice.

We induced endogenous Pseudomonas aeruginosa bacteremia by administering cyclophosphamide and ampicillin to specific pathogen-free mice fed P. aeruginosa. Using this model, we evaluated the efficacy of erythromycin lactobionate (EML) in treating P. aeruginosa bacteremia. Treatment with EML at 50 and 100 mg/kg of body weight per day twice a day for 14 days significantly increased the survival rate. The most effective dose was 100 mg/kg/day, with a survival rate of 80% compared with a 20% survival rate in the control. However, the administration of EML at 500 mg/kg/day rather decreased the survival rate. In a model of intravenous infection, treatment with EML at 100 mg/kg/day twice a day for 7 days before the bacterial challenge also enhanced the survival rate. EML levels in serum, liver, and stool were apparently lower than the MIC (512 micrograms/ml). These observations suggest that EML is effective against P. aeruginosa bacteremia despite a lack of specific activity for this pathogen. Although the protective mechanism is still unclear, it is possible that a subinhibitory level of EML may affect the virulence of P. aeruginosa and enhance the host defense system.

Animals↗
PubMed1991

[Effect of erythromycin on neutrophil function in chronic respiratory tract diseases with Pseudomonas infection].

The "low dose and long term" erythromycin (EM) therapy has been reported as effective (or useful) in chronic respiratory tract disease with pseudomonas (P.) infection including diffuse panbronchiolitis (DPB), however the mode of action is still obscure. Therefore in this study we have examined the effect of EM on the interaction between P. aeruginosa and human polymorphonuclear leukocyte (PMN) in vitro. The efficiency of intracellular killing and the ability of superoxide production were employed to evaluate the PMN functions. For the first step, the following results were obtained; 1) Pretreatment of PMN with 20 micrograms/ml EM did not affect the killing ability of PMNs against opsonized P. aeruginosa of standard and clinical isolate from DPB patient. 2) Superoxide production from PMNs was observed by phagocytosis of P. aeruginosa in the presence of serum. This was not affected by exposure of PMNs to 20 micrograms/ml EM even with increased ratios of bacteria to cells. 3) Pretreatment of P. aeruginosa with 20 micrograms/ml EM before opsonization enhanced the killing ability of PMNs in both standard and clinical isolate. 4) Pretreatment of P. aeruginosa with 20 micrograms/ml EM resulted in no effect on superoxide production from PMNs by phagocytosis of the bacteria. These results indicate that EM may modify a certain step of the interaction between bacteria and intracellular host defence mechanisms. Therefore for the second step, we have investigated the susceptibility of EM-exposed bacteria to killing by the cell free (glucose oxidase-glucose) system, which will detect the enzymatic generation of hydrogen peroxide (H2O2). The following results were observed; 1) EM-exposed bacteria was more susceptible to killing than control bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchiolitis↗
PubMed1991

Role of bacterial association with Kupffer cells in occurrence of endogenous systemic bacteremia.

Bacteremia in immunocompromised hosts often arises from their endogenous intestinal flora. We produced experimental endogenous bacteremia by administering cyclophosphamide and ampicillin to conventional and specific-pathogen-free mice. The frequencies of bacteremia and mortality in the conventional mice were significantly higher than for the specific-pathogen-free mice. Pseudomonas aeruginosa was the major pathogen causing systemic bacteremia in conventional mice and was associated with a high mortality rate. Morganella morganii caused systemic bacteremia in both conventional and specific-pathogen-free mice. In contrast, Escherichia coli, enterococci, or other species most often caused portal bacteremia only. To determine the mechanism of occurrence of systemic bacteremia, we investigated bacterial blood clearance in mice and association with murine Kupffer cells, using several bacterial strains isolated from mice with bacteremia. Blood clearance rates and the abilities of isolated Kupffer cells to associate with bacteria were significantly greater for the organisms causing portal bacteremia than for those causing systemic bacteremia. There were no significant differences between the blood clearance rates in carrageenan-treated mice and that in normal mice. Moreover, association at 4 degrees C was not different from that at 37 degrees C. The results suggest that blood clearance of bacteria reflects bacterial adherence to Kupffer cells and that the resistance of bacteria to association with Kupffer cells plays an important role in the occurrence of overwhelming systemic bacteremia in this animal model.

Agglutination↗
PubMed1990

[Investigation on the etiology of sepsis by using experimental mouse model with leukocytopenia. 3. The role of Kupffer cells in the etiology of bacteremia].

In the previous report, we showed that the reticuloendothelial system (RES), especially the liver, played an important role in the etiology of bacteremia or sepsis as the major protective system. In this study, to investigate the role of Kupffer cells in the etiology of bacteremia, we isolated and cultured murine Kupffer cells using a technique involving perfusion with collagenase and DNase. We compared the adherence and phagocytosis rate of two groups of isolated bacteria from bacteremic mice by these cells. One group was bacteria causing systemic bacteremia consisted of P. aeruginosa and M. morganii, and the other was bacteria causing portal bacteremia consisted of E. coli, E. cloacae, K. pneumoniae and Enterococci. As a consequence, the following facts were revealed. 1. The bacterial phagocytosis and adherence rate by Kupffer cells were significantly higher in bacteria causing portal bacteremia than in bacteria causing systemic bacteremia. These data were correlated to each blood clearance rate from mice. 2. Blood clearance rate reflected mainly adherence of Kupffer cells to bacteria, and it was suggested that these adherence were one of the most important factor to protect the hosts from the advance of bacteremia from the portal to the systemic. 3. In the case of using peritoneal macrophage, we couldn't find the same correlation, so the possibility was suggested that the above phenomenon was specific to Kupffer cells.

Animals↗
PubMed1990

[Studies on defence effects of recombinant human granulocyte colony-stimulating factor (G-CSF) to infections. I. Induction of neutrophil polarization by G-CSF].

It is well known that recombinant human granulocyte increases dramatically the number of granulocytes in peripheral blood. It is interesting to see if G-CSF enhances the functions of neutrophil since the neutrophil is one of the most important factors of host defence mechanism against infections. In this study, we have demonstrated that G-CSF induced the polarization of neutrophil while it could not be chemoattractant for the cell. Polarization is considered to be the initial reaction of chemotaxis. Therefore, G-CSF might enhance the defence effect of the neutrophils+ to infections in this point.

Cells, Cultured↗
PubMed1990

[Studies on defense effects of recombinant human granulocyte colony-stimulating factor (G-CSF) to infections. II. Priming effect for superoxide production by human neutrophil].

In present study, we have investigated superoxide (O2-) production from human neutrophils by recombinant human granulocyte colony-stimulating factor (G-CSF) using the microtiter plate for the purpose of being close to the inflammatory site. G-CSF by itself did not induce the release of O2- in human neutrophil on either Fetal Bovine Serum (FBS)-coated plate or plate uncoated with FBS, even if neutrophils were exposed for maximum 3 hr. However, the optimal concentration of G-CSF (50 ng/ml) was able to prime human neutrophils with enhance of O2- release stimulated by the chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP) from 10(-6) to 10(-8) M, but not by the non chemoattractant such as phorbol myristate acetate (PMA), concanavalin A, and ionomycin. These findings indicate that G-CSF might enhance bactericidal activity of neutrophils by priming them penetrating into the inflammatory site.

Cells, Cultured↗
PubMed1990

[Studies on defence effects of recombinant human granulocyte colony-stimulating factor (G-CSF) to infections. III. Protective effect on pulmonary and systemic infections of P. aeruginosa in neutropenic mice].

In the prior two reports, we demonstrated that G-CSF induced the polarization of neutrophils by itself, and also enhanced superoxide production from neutrophils stimulated by the chemotactic peptides. In this study, we have examined the protective effect of G-CSF in vivo on Pseudomonas pneumonia and septicemia in mice. Cyclophosphamide (CY) induced severe reduction of the number of peripheral leukocytes and weakened resistance for Psuedomonas aeruguinosa infection of mice. However, in mice receiving recombinant human G-CSF four daily subcutaneous injection, the number of leukocytes, particulary neutrophils, increased more rapidly than in controls receiving saline. Moreover G-CSF enhanced a protective effect to pulmonary and systemic pseudomonas infections. When G-CSF was administered together with antibiotics, significant synergism in the protection against pulmonary infection of Pseudomonas was observed. Carrageenan treatment decreased the protective effect of G-CSF. These results suggested that the protective effect of G-CSF against P. aeruginosa infection depends not only on PMN but also another complexed host defence mechanism.

Animals↗
PubMed1990

Effect of diethyl-beta-cyclodextrin on the release of nitroglycerin from formulations.

The complex-forming abilities of 2,6-di-O-ethyl-beta-cyclodextrin (DE-beta-CD), and its effect on the release of nitroglycerin (TNG) from formulations of the compound, were studied and compared with corresponding properties of beta-cyclodextrin (beta-CD) and 2,6-di-O-methyl-beta-cyclodextrin (DM-beta-CD). Complex formation was confirmed by differential scanning calorimetry and infrared absorption spectroscopy. In an accelerator test involving temperature and reduced pressure, marked depression of the volatility of TNG was observed as a result of CD complex formation. Dissolution rates of TNG from powdery TNG/DE-beta-CD complex and its tablets were retarded in comparison with the rates from other CD complexes. The release rate of TNG from ointments was accelerated by complexation with DE-beta-CD, and retarded by complexation with beta-CD. To evaluate their in vivo percutaneous absorption, samples were applied to the inside tip of the cheek pouch of male golden hamsters. The amount of TNG remaining in the cheek pouch was lowest in the case of the TNG/DE-beta-CD complex ointment, and relatively high in the case of the TNG/beta-CD complex ointment, in agreement with the in vitro results. We suggest that the combination of DE-beta-CD complex and beta-CD complex might be applicable to sustained-release preparations for percutaneous administration.

Animals↗
PubMed1989

[Investigations on the etiology of sepsis by using experimental mouse model with leukocytopenia. 1. Influence of antibiotics].

Investigation on the etiology of septicemia occurring among the immunocompromised patients was performed by using experimental model of the mouse with leukocytopenia. The ddY conventional mice of 4 weeks of age were inoculated with cyclophosphamide (CPM) intraperitoneally 3 to 5 times every other day with a dose of 3 mg/mouse once to make an agranulocytic status. Then, intraperitoneal administrations of various antibiotic regimens consisting of ampicillin (ABPC) alone, ABPC + ceftazidime (CAZ), ABPC + CAZ + cloxacillin (MCIPC), ABPC + CAZ + MCIPC + minocycline (MINO) and saline as a control to these immunosuppressed mice were begun once every day for 10 days after the second inoculation of CPM. The mortality rate of the mice given saline as a control was very high with a frequency of 43.3% and there were significant differences between the saline group and another antibiotic groups other than ABPC (p less than 0.01). On the other hand, the mortality rate of the group given APBC showed the highest rate of 70% and it was significantly higher than that of the saline control group (p less than 0.05). The main cause of most of the dead mice was septicemia due to P. aeruginosa and which were isolated from the feces of all these mice and serotype of the strains isolated from the heart blood and feces in the same host corresponded to each other. Moreover, intestinal bacterial flora in mice treated by saline and ABPC which highly showed Pseudomonas sepsis, was occupied dominantly by P. aeruginosa, although P. aeruginosa was not detectable from the experimental environments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

[Etiology of sepsis occurring in the immunocompromised host and its prevention. 1. Analysis of the bacterial portal of entrance in experimental mice with bacteremia].

Nosocomial infections due to aerobic gram-negative bacilli are life-threatening problems for immunocompromised patients. Most of these infections might arise from the patient's own flora, especially from their faecal flora. The purpose of this study was to investigate the bacterial portal of entry in experimental mice with bacteremia which were treated by cyclophosphamide (CY). It was clarified that almost all of the isolates from blood of CY and antibiotics treated mice were identical with their own faecal flora, and that organisms were isolated in some cases only from the portal vein but not from heart blood. From these results it was concluded that some of the bacteria entered from the intestinal tract through the portal vein to the systemic circulation in the immunosuppressed state. The time course of bacterial translocation were examined with SPF mice which were given Pseudomonas aeruginosa orally prior to CY treatment. Twelve strains of Escherichia coli were isolated, 10 of which were isolated only from mesenteric lymph nodes (MLN). Though six strains of P. aeruginosa were isolated from the heart blood, 4 were not isolated from MLN. It was suggested that translocations of E. coli and P. aeruginosa occurred by lymphogenous and hematogenous routes respectively. And translocation of viable E. coli was observed only after ABPC treatment but before CY inoculation, on the other hand translocation of viable P. aeruginosa was observed after CY inoculation. So only disruption of the normal flora ecology was necessary for translocation of E. coli, but immunosuppression was additionally necessary for translocation of P. aeruginosa.

Animals↗
PubMed1989

[Etiology of sepsis occurring in the immunocompromised host and its prevention. 2. Preventive effect of BRM to experimental Pseudomonas endogenous septicemia and analysis of its immunological etiology].

In the former report, the bacterial portal of entry in experimental mice with bacteremia were analysed in detail. And it was clarified that almost all of the isolates from blood of cyclophosphamide (CY) and antibiotics treated mice were entered by their own flora, especially by their faecal flora. From this point of view, great care must be taken when using antibiotics for immunosuppressed patients, because it easily causes a super-infection, that is one of the most important factors of endogenous infections. In order to potentiate host immunity, we examined the preventative effect of biological response modifiers (BRM) to experimental endogenous septicemia. MDP-Lys (L18), rhG-CSF, and rhIL-1 were effective on experimental Pseudomonas aeruginosa endogenous septicemia of mice. The effect did not depend on the increased number of total leukocytes and PMN. Further experiments using nude mice suggested that the host defence mechanism inhibiting Pseudomonas endogenous infection might not depend on T-cell mediated immunity.

Animals↗
PubMed1989

[Investigations on the etiology of sepsis by using an experimental mouse model with leukocytopenia. 2. The role of the reticuloendothelial system in the etiology of bacteremia].

It has been recognized by clinical data that most of sepsis occurring in the immunocompromised host are endogenous infection. In recent years, we have investigated the mechanism of these bacteremia and sepsis by experimental studies using neutropenic mice treated with cyclophosphamide. And we evidenced that most pathogens causing bacteremia originated in the intestinal flora of the host. It has been shown that bacteria causing bacteremia were divided into two main groups, causing systemic bacteremia and causing portal bacteremia. Pseudomonas aeruginosa and Morganella morganii belonged to the former, on the other hand, Escherichia coli, Enterobacter cloacae and some other bacteria belonged to the latter. In this study, we studied the role of the reticuloendothelial system (RES) in the etiology of bacteremia or sepsis, using various kinds of bacteria isolated from bacteremic mice. As a result, the following facts were revealed. 1. It was suggested that the low blood clearance rate of the bacteria was one of the great risk factor of systemic bacteremia, since the blood clearance rate of bacteria causing systemic bacteremia was significantly lower than those of bacteria causing portal bacteremia. 2. Bacteria in the blood were eliminated by the RES, mainly by the liver, and the level of bacterial clearance by the liver was relative to the type of bacteremia which was systemic or portal. 3. It was suggested that the bacterial clearance by the liver mainly reflected the phagocytosis by Kupffer cells, and especially the adherence of these cells to bacteria as the first step of phagocytosis.

Animals↗
PubMedDate not supplied

Genetic analysis of serotype 23F Streptococcus pneumoniae isolates from several countries by penicillin-binding protein gene fingerprinting and pulsed-field gel electrophoresis.

We characterized 21 strains of serotype 23F Streptococcus pneumoniae isolated in various countries with various levels of penicillin susceptibility by penicillin-binding protein (PBP) gene fingerprinting and pulsed-field gel electrophoresis (PFGE). Pneumococci isolated in Israel, Hungary, Bulgaria, Slovakia, Rumania, France, the United States, Spain and Japan were included. These strains were classified into 12 and 18 groups by PBP gene fingerprinting and PFGE, respectively. Some of the pneumococci isolated in Spain, the United States and France appeared to be genetically related by PFGE, showed the same PBP gene pattern and had similar antimicrobial susceptibility patterns. One penicillin-susceptible Bulgarian strain, with a similar PFGE pattern but a different fingerprinting pattern, may be an ancestral recipient strain that became transformed into the resistant variants. Rumanian and Israeli strains were also genetically related by PFGE. These results indicate the existence of widely spread but related pneumococci in the world. PBP 2X gene profiles of pneumococci with MICs of 0.25 microg/ml were different from each other and from penicillin-susceptible pneumococci (PSP). PBP 2B gene profiles of these resistant strains were identical. PBP 2B gene profiles of pneumococci (penicillin MICs >/=0.5 microg/ml) were different from PSP. PBP gene profiles may not only be useful for genetic analysis but also for presumed penicillin susceptibility.

Bacterial Proteins↗
PubMedDate not supplied

Trends of genetic relationship of serotype 23F penicillin-resistant Streptococcus pneumoniae in Japan.

No data on the genetic analysis of penicillin-resistant Streptococcus pneumoniae (PRP) in Japan has been reported. The SmaI restriction endonuclease digested patterns of chromosomal DNAs from 15 PRP serotyped 23F isolated in Japan were analyzed by pulsed-field gel electrophoresis (PFGE). The isolates were genetically heterogeneous and seven different PFGE patterns were identified. Nine strains were also resistant to erythromycin and tetracycline. Four strains revealed resistance to ceftriaxone. The PFGE patterns of some strains isolated in Nagasaki University Hospital were identical to each other and closely resembled those of isolates from three different areas of Japan. These results indicate a need for additional studies by PFGE to determine the possibility of clonal spread in Japan.

Anti-Bacterial Agents↗
PubMedDate not supplied

Combination therapy with fluconazole and flucytosine for pulmonary cryptococcosis.

We investigated, in vitro, the combined effects of fluconazole (FLCZ) and flucytosine (5-FC) against different strains of Cryptococcus neoformans, and retrospectively analyzed the clinical efficacy of combination therapy of FLCZ and 5-FC in patients with pulmonary cryptococcosis. The minimum inhibitory concentrations (MICs) of antifungal agents and drug interaction were determined by the broth microdilution method and checkerboard titration. FLCZ and 5-FC showed synergistic activity against 8 (32%) of 25 strains of C. neoformans. The clinical efficacy of the 2 drugs when combined together was good in 9 (90%) patients and fair in 1 (10%) patient with pulmonary cryptococcosis. Renal dysfunction occurred in 1 patient. Our results suggest that a combination therapy using FLCZ and 5-FC is clinically useful in patients with pulmonary cryptococcosis who otherwise show a limited response to monotherapy.

Adult↗