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K Kitoh

Publications and source records attributed to K Kitoh.

80 records · Page 5Linked to original sources

E-0702, a new cephalosporin, is incorporated into Escherichia coli cells via the tonB-dependent iron transport system.

E-0702, a new cephalosporin with a potent antipseudomonal action, was synthesized. In the study of the mode of action of this antibiotic in Escherichia coli, it was found that mutants which acquired resistance to E-0702 were isolated spontaneously and could be shown to be susceptible to its closely related derivatives, E-0702-060 and E-0702-061, and other representative beta-lactam antibiotics. In these mutants, no increased production of beta-lactamase was detectable. No apparent differences between the resistant mutants and the parental strains were observed in the affinity of E-0702 for penicillin-binding proteins. Furthermore, no significant reduction in or loss of both OmpF and OmpC porin proteins in the outer membrane was observed. The mutation was mapped to the tonB gene, which is known to be essential for the iron transport system of bacteria. The bactericidal action of E-0702 was rapidly expressed against iron-starved cells in which the iron transport system was induced, whereas the bactericidal action against iron-supplemented cells was ineffective. It is suggested that E-0702 is incorporated into bacterial cells as a chelator of iron via the tonB-dependent iron transport system, after which its strong and rapid bactericidal action is manifested.

Bacterial Outer Membrane Proteins↗

Enhancement of resistance to Escherichia coli infection in mice by dihydroheptaprenol, a synthetic polyprenol derivative.

The effect of a chemically synthesized polyprenol derivative, dihydroheptaprenol (DHP), on the nonspecific resistance of mice to infection with Escherichia coli was investigated. Mice that had been injected intramuscularly with 100 mg of DHP per kg of body weight, prepared as a microemulsion with lecithin, 1 to 4 days before infection showed enhanced resistance to subcutaneous (s.c.) infection with E. coli. When DHP-injected mice were inoculated s.c. with 3 X 10(8) E. coli, which induces fatal acute systemic infection in normal mice, propagation of bacteria in the blood, liver, and spleen was significantly inhibited. Enhanced resistance of athymic (nude) mice to E. coli infection was also induced by DHP. DHP markedly stimulated the generation of peripheral blood neutrophils, significantly enhanced clearance of E. coli from the bloodstream, and activated neutrophils and peritoneal macrophages for H2O2 generation. DHP restored the resistance to E. coli infection in cyclophosphamide-treated mice over the normal level. Furthermore, DHP shortened the period of the recovery of neutrophils and also enhanced clearance of E. coli from the bloodstream in cyclophosphamide-treated mice. DHP was nontoxic for mice and rats (400 mg/kg intramuscularly and 800 mg/kg s.c.) and nonpyrogenic at a dose of 30 mg/kg when administered intravenously to rabbits. These results suggest that the mechanism of action of DHP for enhancing resistance in mice may be, at least in part, its ability to stimulate the generation of potent neutrophils and to activate macrophages in the reticuloendothelial system.

Animals↗

A newly designed model for infection-induced bladder stone formation in the rat.

A newly designed urolithiasis model for rats, inducing a mild urinary tract infection, exhibiting reduced renal damage without pyelonephritis and causing reliable stone formation, was established. This was accomplished by implanting a zinc disc in the bladder and then performing transvesical inoculation of Proteus mirabilis into the bladder. Five days after challenge with 10(7) colony forming units (CFU) of P. mirabilis in each rat, the number of organisms in the bladder urine reached a level of over 10(5) colony forming units per ml. The infection was mostly restricted to the urinary tract organs. Infectious bladder stones were formed 5 days after infection and developed day by day, weighing 88.3 +/- 18.8 mg. on the 21st day. Blood urea nitrogen values stayed in the normal range in all test animals during this experiment. The main composition of the stones formed was shown to be struvite (MgNH4PO4 X 6H2O).

Animals↗

In vitro antibacterial activity of E-0702, a new semisynthetic cephalosporin.

E-0702 is an antipseudomonal cephalosporin derivative which has a broad spectrum of antibacterial activity against clinical isolates of gram-positive and gram-negative bacteria. Its in vitro antibacterial activities were less than those of cefoperazone and cefotaxime against Staphylococcus aureus and Staphylococcus epidermidis, but were significantly high against gram-negative bacteria including the Pseudomonas group. It was most characteristic that E-0702 showed high antibacterial activity against Pseudomonas aeruginosa. E-0702 was relatively stable to inactivation by plasmid-mediated penicillinases and cephalosporinases produced by gram-negative bacteria.

Anti-Bacterial Agents↗

Therapy for urolithiasis with hydroxamic acids. IV. Prevention of infected urinary stone formation with N-(pivaloyl)glycinohydroxamic acid.

With the aim of finding a prospective therapeutic compound with a promising potential for the treatment of urolithiasis, we evaluated the effectiveness of a new potent inhibitor of urease, N-(pivaloyl)glycinohydroxamic acid. The present study revealed that N-(pivaloyl)glycinohydroxamic acid effectively inhibited the alkalinization of urine and the stone formation in vitro and in vivo, due to its strong inhibitory potency against the ureolytic activity of intact Proteus mirabilis. The possibility of the clinical application of this compound in the prevention of struvite stone formation caused by infection of urea-splitting bacteria awaits evaluation of the safety of this compound.

Animals↗

Phenotypic analysis of peripheral T cell lymphoma among the Japanese.

From 1980 to 1990, 174 peripheral T cell lymphomas were studied morphologically and immunophenotypically with a panel of monoclonal antibodies which were reactive with T cell differentiation antigens in cryostat sections and/or cell suspensions. Histologically, 57% of the lymphomas were categorized into low-grade tumors according to the updated Kiel classification, while 41% were high-grade tumors. By immunologic studies, 50% of the lymphomas were of helper/inducer (CD4) phenotype, 6% were of cytotoxic/suppressor (CD8) phenotype, 3% expressed both CD4 and CD8, 3% lacked both CD4 and CD8, and 36% were phenotypically undetermined because of an admixture of a fairly even number of CD4 and CD8-positive cells. The phenotypically undetermined cases were more frequently noted in the low-grade groups than in the high-grade group, and the latter often showed a loss of pan-T antigens, although there was no definite correlation between the histologic category and the immunophenotype. CD25, which is strongly manifested in anti-HTLV-1 antibody-positive cases, was negative or only weakly expressed in anti-HTLV-1 antibody-negative cases. Anaplastic large cell lymphomas (LC-Ana) strongly expressed CD30, which was also detectable in only large blast-like cells in the low-grade tumors. Seventy-one per cent of the lymphomas expressed Ia antigens. In this series, the clinical data were available on 154 patients. For individual markers, the expression of CD30 and HLA-DR were associated with a longer actuarial survival (P < 0.01 and P < 0.05 by the generalized Wilcoxon test). The absence of CD25 or the presence of CD3 on tumor cells correlated with a relatively favorable prognosis, but not significantly. The detection of CD4 and CD8 had relatively little prognostic value. In the cases excluding LC-Ana, a significant difference was also recognized between the groups with and without CD25, CD30 and HLA-DR (P < 0.05 by the generalized Wilcoxon test). These results suggest that the immunophenotypic analysis of peripheral T cell lymphoma provided its use as an adjunct to a histopathologic diagnosis and was related to prognostic prediction.

Biomarkers↗