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K Kawaharajo

Publications and source records attributed to K Kawaharajo.

At least 19 recordsLinked to original sources
PubMed1991

In-vitro and in-vivo antimicrobial activities of a novel cephalosporin derivative, CP6162, possessing a dihydroxypyridone moiety at the C-3 side chain.

The antibacterial activity of a novel cephalosporin derivative, CP6162, possessing a dihydroxypyridone moiety at the C-3 side chain, was evaluated in vitro and in vivo, with ceftazidime, aztreonam and cefoperazone as the reference antibiotics. CP6162 showed weak or little activity against Gram-positive bacteria, but potent activity against clinical isolates of the Gram-negative species including strains of Pseudomonas aeruginosa, Ps. cepacia, Acinetobacter sp., Xanthomonas maltophilia, Serratia marcescens, Enterobacter cloacae and Citrobacter freundii, which were resistant to the reference antibiotics. The MICs of CP6162 were only slightly affected by the high producers of beta-lactamases except for cephalosporinase-producing C. freundii. It was, however, affected by the presence of ferric ion. CP6162 showed in-vivo activity paralleling the in-vitro activity, and also showed pharmacokinetic parameters similar to those of ceftazidime in mice and rats.

Animals↗
PubMed1990

[In vitro combined effects of pirarubicin (THP) and various antitumor drugs on human tumor cell lines].

The combined effects of pirarubicin (THP) and various antitumor drugs on HeLa S3 human uterine cervix carcinoma and K562 human myelocytic leukemia cells were determined by enhancement of their cytotoxic activities. The combination of 0.15 microgram/ml THP with cisplatin (CDDP), mitomycin C (MMC), peplomycin (PEP), 5-fluorouracil (5-FU), methotrexate (MTX), enocitabine (BH-AC) or etoposide showed synergistic effects on HeLa S3 cells. Also, the combination of 0.01 microgram/ml THP with CDDP, BH-AC or etoposide showed synergistic effects on K562 cells. Especially, the combined effects of THP with MMC or MTX were remarkable, and the combination under almost all concentrations of MMC or MTX showed synergistic effects on HeLa S3 cells. On the other hand, the combination of adriamycin (ADM) with MMC or MTX did not show such a remarkable effects on HeLa S3 cells.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Production and some properties of monoclonal antibodies against serotype strains of Pseudomonas aeruginosa.

A set of 16 serotype specific monoclonal antibodies (MoAbs) against Pseudomonas aeruginosa classified by Homma were obtained by the mouse hybridoma technique. This set of MoAbs was useful for classification of their serotypes especially O-antigen groups G and M. MoAb obtained from serotype 15 of Homma's classification reacted with serotype 17 of the same classification. We also obtained two MoAbs which reacted with 7 Homma's serotypes of 6 different O-antigen groups and one MoAb which recognized all 4 Homma's serotypes of O-antigen group B. These MoAbs were also useful in mice for the preventive effect against the infections of P. aeruginosa.

Animals↗
PubMed1984

In vitro and in vivo antibacterial activities of MT-141, a new semisynthetic cephamycin, compared with those of five cephalosporins.

The in vitro and in vivo antibacterial activities of MT-141 were compared with those of cefoxitin, cefmetazole, moxalactam, cefotaxime, and cefoperazone. The MICs of MT-141 for 90% of bacterial isolates were lower than the reference drugs against clinical isolates of Campylobacter jejuni, Clostridium difficile, and Bacteroides fragilis, whereas against clinical isolates of other gram-positive, gram-negative, and anaerobic bacteria, the MICs of MT-141 were similar to or higher than those of the reference drugs. In contrast, the bactericidal activity of MT-141 after 6- and 24-h exposures was superior to all of the reference drugs against 9 to 10 of the 12 bacterial strains studied, including Escherichia coli, Klebsiella pneumoniae, Salmonella enteritidis, indol-positive Proteus species, Serratia marcescens, Yersinia enterocolitica, Pseudomonas cepacia, and Clostridium perfringens. In the treatment of systemic infections in mice, MT-141 was again superior against 9 of the 12 strains tested, showing a good correlation with the bactericidal activity. It was found that the 50% effective doses of the six cephalosporins studied correlated better with the MBCs than with the MICs. As the serum levels of MT-141 in mice after subcutaneous administration were similar to those of the reference drugs, it was concluded that the bactericidal activity of MT-141 was a dominant factor in its in vivo activity.

Animals↗
PubMed1984

Therapeutic efficacy of a new cephamycin, MT-141, in compromised mice.

The antibacterial activity of MT-141 against Escherichia coli and Proteus morganii in compromised mice was investigated and compared with that of latamoxef, cefmetazole and cefoxitin. The bactericidal activity of MT-141 in short-term contact with E. coli and P. morganii was markedly enhanced when combined with mouse serum, and the activity of MT-141 was greater than the activities of the three reference drugs. The antibacterial activities of MT-141 in the liver, spleen and kidney of neutropenic and Sarcoma 180 tumor-bearing mice infected with E. coli and P. morganii were superior to the activities of the reference drugs. MT-141 was more potent than cefmetazole and cefoxitin, and similar to latamoxef in potency against systemic P. morganii infection in Sarcoma 180 tumor-bearing mice.

Animals↗
PubMed1981

In vitro and in vivo antibacterial activity of 9,3"-Di-o-acetyl midecamycin (Mom), a new macrolide antibiotic.

9,3"-Di-O-acetyl midecamycin (Mom) showed in vitro antibacterial activity against clinical isolates of Staphylococcus aureus and was effective against some of the strans resistant to erythromycin (Em) and josamycin (Jm). The distribution pattern of the level of drug-sensitivity of the isolates to Mom was similar to that of Jm but different from that of Em. Mom- or Jm-resistant strains gradually or rapidly developed among S. aureus strains, that were sensitive or resistant to other macrolide antibiotics. There was no significant difference between Mom and Jm as regards the rate of development of resistant strains. These mutants were always resistant to both Mom and Jm. Mom, like Jm, was effective against Em-inducible strains of S. aureus. The in vivo study demonstrated that Mom was more potent than Jm, similar in its potency to Em against systemic staphylococcal infections, and that it was effective against the infection due to an Em-resistant clinical isolate of S. aureus. Mom was more effective than either Jm or Em against a staphylococcal kidney infection in mice.

Animals↗
PubMed1980

Effects of somatic component of Pseudomonas aeruginosa on protective immunity in experimental mouse burn infection.

In the mouse burn model of Stieritz and Holder [19], a three-component vaccine consisting of elastase toxoid, protease toxoid and the common antigen (OEP) of P. aeruginosa was found significantly effective on protection against subcutaneous injection with strain IFO 3455, but not with strains M2 or PF 2243. Investigating the differences, it was clarified that somatic antigens of strains M2 and PF 2243 did not contain serological antigens cross-reacting with OEP. Accordingly, the protective effects of the somatic antigen of strains M2 were investigated with the result that both formalin and heat-killed antigens demonstrated significant protection against challenge with strain M2 in the mouse burn model. As strains PF 2243 and M2 were found to belong to the same serotype 16 of Homma's schema [23], it is presumed that somatic antigens of serotype 16 are devoid of OEP. At the same time, it is suggested that the somatic component of P. aeruginosa is essential to the effects of the multi-component vaccines on protective immunity.

Animals↗
PubMed1979

Combined action of semisynthetic penicillin and macrolide antibiotic on Pseudomonas aeruginosa in vitro and in vivo.

For the purpose of studying therapy for pseudomonas infection, the synergistic effect of carbenicillin and midecamycin or 9,3''-di-O-acetyl midecamycin on Pseudomonas aeruginosa were studied in vitro and in vivo. Midecamycin and 9,3''-di-O-acetyl midecamycin were effective against spheroplasts of P. aeruginosa induced by carbenicillin treatment. As a result of investigating treatment using a combination of both carbenicillin and macrolide antibiotics on mouse infection model caused by subcutaneous injection of carrageenan solution containing viable cells of P. aeruginosa, the combined treatment was demonstrated to be significantly more effective than the control's single treatment by carbenicillin or the macrolide antibiotic alone.

Animals↗
PubMed1977

Effects of elastase, protease and common antigen (OEP) from Pseudomonas aeruginosa on protection against burns in mice.

For the purpose of studying the role of elastase and protease of Pseudomonas aeruginosa in bacterial infection in burns, the effects of the vaccines made from each enzyme, their toxoids and OEP on protection against infection in burned mice were studied. Elastase, protease, toxoids of the enzymes, two- or three-component-mixed vaccines and OEP demonstrated significant protection. Toxoids of elastase and protease produced effects similar to those of the enzymes themselves but no synergistic effect in mixed vaccine was detected. Elastase was significantly more effective than protease, the three-component-mixed vaccine or OEP in protecting mice against P. aeruginosa infection in burns.

Animals↗
PubMed1976

Synergistic effect of immune gamma-globulin fraction on protection by antibiotic against corneal ulcers in experimental mice infected with Pseudomonas aeruginosa.

Synergistic effects of immune gamma-globulin fraction containing antibodies of OPE, protease and elastase of Pseudomonas aeruginosa on the activities of antibiotic, dibekacin (DKB), in the cornea of mice were examined for the purpose of studying therapy for corneal ulcers due to Pseudomonal infection. In the case of the intramuscular injection, a medium effective dose (ED50) of DKB alone against corneal ulcers caused by strain IID 1210 of P. aeruginosa in experimental mice was 620 mug per mouse. When 15.6 to 18.7 mg of gamma-globulin fraction was subcutaneously given to each mouse prior to the infection with strain IID 1210, opacity instead of severe ulcers was observed only in the central area of cornea. The immune gamma-globulin fraction was far more effective in the protection of cornea from the infection than the calf serum that showed no antibody titer against OEP, protease and elastase. The ED50 values of DKB's combined with the immune gamma-globulin, Fr. 1 and Fr. 2, and the calf serum were 34 and 73, and 480 mug per mouse respectively. There was found no statistical difference in ED50 value between DKB combined with the calf serum and one without it. There was, however, significant difference in ED50 value between DKB's combined with Fr. 1 and Fr. 2, and one with the calf serum. When DKB alone is dropped in the eye of mouse for the protection, the ED50 value was 15 mug per mouse. When 1.56 to 1.87 mg of the immune gamma-globulin fraction was dropped in the eye after the infection with P. aeruginosa, there was observed no protection against corneal ulcers. the ED50 values of DKB's combined with Fr. 1, Fr. 2 and the calf serum were 0.96, 0.94 and 13 mug per mouse, respectively. There was no significant difference between the ED50 values of 0.96 and 0.94 mug, and between 15 and 18 mug. There was, however, significant difference between the former ED50 values (0.96 and 0.94 mug) and the latter ones (15 and 18 mug). The combination of DKB and the immune gamma-globulin fraction was found to be superior to the combination of DKB and the calf serum in the therapeutic effect on corneal ulcers caused by strain IID 1210 of P. aeruginosa.

Abscess↗
PubMed1976

Studies on the pathogenicity of Pseudomonas aeruginosa by the use of ligated rabbit intestines (the De test).

The De test was used as a test to assess the pathogenicity of Pseudomonas aeruginosa in vivo. The test was positive in rabbits inoculated intraintestinally with the protease and elastase-producing strain IFO 3455 of P. aeruginosa whereas it was negative in those inoculated with the nonproducing strains NC-5 or PA103. Animals similarly injected with not less than 2.0 mg of protease or elastase showed positive De tests. The intestinal lesions produced in the animals with positive reaction to the inoculation with the enzyme-producing strain IFO 3455 was histopathologically characterized by atrophy, detachment and flattening of the mucosa with submucosal hemorrhage and atrophy of the Auerbach's plexus, which were nearly comparable to a sum of the microscopic findings found in the animals inoculated with respective enzymes singly. Namely, villi were noted to be atrophic and hemorrhage from the submucosal blood vessels was prominent with atrophy of the mesenteric plexus in the rabbits inoculated with protease alone, whereas in those injected with elastase alone, submucosal hemorrhage was less prominent besides the atrophy of the villi and mesenteric plexuses were markedly atrophic. These experimental findings are considered to suggest that the two enzymes liberated from P. aeruginosa, protease and elastase, may be implicated in the pathogenesis of P. aeruginosa enteritis.

Animals↗
PubMed1975

Effects of protease and elastase from Pseudomonas aeruginosa on skin.

Protease and elastase were inoculated intracutaneously in rabbits, the process of which was followed. Of the enzymes, 50 mug caused circumscribed hemorrhage at the inoculated local and subcutaneous part, and ulcerating lesions of skin and extensive hemorrhagic lesion at the subcutaneous tissues were observed in the case of inoculation with 250 mug. The doses amounting to 500 to 1000 mug of the enzymes caused extensively ulcerating, necrotic lesions at the skin and extensive hemorrhage at the subcutaneous tissue, and a large amount of hemorrhage was observed in the abdomen. It was observed microscopically that cellular infiltration and hemorrhage in the subcutaneous tissue and muscular layer were caused by administration of 2 to 10 mug of the enzymes, and that degeneration of endothelial cells was caused by 2 mug of them.

Animals↗
PubMed1975

In vivo studies on protease and elastase from Pseudomonas aeruginosa.

Protease and elastase from Pseudomonas aeruginosa were inoculated in female mice by intravenous, intraperitoneal, intrapleural and intranasal route, and the lethality and damage of various organs were examined. The protease and elastase exhibited respectively the following minimum lethal dose (MLD) values in 24 hr; 300 and 375 mug inoculated intravenously; 200 and 125-250 mug intraperitoneally; and 100 and 62.5 mug intrapleurally. The instillation of a defined dose of the enzyme by the intranasal route was difficult to control, therefore the MLD could not be defined exactly. The protease and elastase were capable of eliciting hemorrhage at various organs of mice according to the route of inoculation. Of protease, intravenous injections elicited petechial hemorrhage at the lungs and parietal bone-area, and severe one in the medullary area of kidney. The intraperitoneal injection resulted in petechial hemorrhage of the lungs, diaphragm, peritoneum and gastrointestinal serosa. Intrapleural injections and intranasal instillation resulted in confluent pulmonary hemorrhage. Of elastase, intravenous injections elicited confluent pulmonary hemorrhage, hemorrhage in the medullary area of kidney and cerebral ventricles, and petechial hemorrhage at the stomach-walls. The intraperitoneal injections resulted in petechial hemorrhage at the lungs, diaphragm, peritoneum and gastointestinal serosa. Intrapleural injections resulted in confluent pulmonary hemorrhage, and petechiae at the diaphragm and pleura. Intranasal instillation resulted in confluent pulmonary hemorrhage.

Animals↗
PubMed1975

Pathogenesis of the mouse keratitis produced with Pseudomonas aeruginosa.

For the purpose of studying the pathogenesis of corneal infection of Pseudomonas aeruginosa, was examined virulence of elastase and protease producing strains or non-producing strains of the bacteria by using the cornea of mouse. The cornea of mouse was experimentally incised, and then P. aeruginosa cultures were dropped once onto it. As a result serious ulcers were caused over the entire cornea, and abscesses in its central area, by 10(5) and 10(7) viable cells of the enzymes producing strains IID 1210 and NO-5 of P. aeruginosa, respectively. Histological destruction, enlargement and cellular infiltration were observed in the corneal epithelium and stroma. On the other hand, P. aeruginosa strains NC-5 and N-10, enzymes non-producing ones, could not cause corneal lesions such as ulcers or abscesses. However, strain PA-103, which is considered to produce neither of the enzymes, could not cause corneal ulcers but cause uveitis even with 10(5) viable cells per mouse. Histologically, concentrated serous exudatation and severe cellular infiltration were noted in the anterior chamber. Necrosis was observed in the entire layer of the cornea. However, the corneal damage caused by strain PA-103 was clearly different from one due to the enzymes producing strains. Additive synergistic effect of protease on the virulent degree of strain NC-5 against the cornea was detected.

Animals↗