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Biomedical subjects

Y Kazuno

Publications and source records attributed to Y Kazuno.

At least 19 recordsLinked to original sources

Development of a flow system for the microscopic observation of cultured nerve cells and its application to the neurite growth control of PC12h-R.

A flow system has been developed for the continual microscopic observation of cultured nerve cells. The undefined effects of coexisting cells could be efficiently reduced by the continuous flow of a medium. The present flow system was useful also for the experiments requiring medium exchanges. Its performance was demonstrated by the repeated actions of NGF or db-cAMP to PC12h-R cells. The neurite projection and its retraction were repeatedly observed by the supply and the removal of those factors.

Animals↗

Effect of coexisting cells on the NGF-inducing neurite growth from PC12h-R.

Possible roles of coexisting cells in inducing neurite growth from a nerve cell were studied. Nerve growth factor (NGF)-inducing neurite growth from PC12h-R (a cell line derived from cultured nerve cells) was investigated at various cell densities. At the cell density 10(2)-10(4) cells/ml neurites appeared even without NGF. In contrast, no neurite appeared without NGF in single cell culture. The neurite growth observed in plural cell culture without NGF was only partially inhibited by antibody to NGF receptor (Ab-NGFR). However, the effect of the used medium alone was mostly inhibited by Ab-NGFR. These results suggest that the neurite inducing potency of coexisting cells is via different sites than the NGF receptor.

Animals↗

A simple method for predicting modes of actions of antitumor agents.

Modes of actions of antitumor agents can be predicted by comparison of antitumor activities against L1210 cells in the presence and absence of some nucleosides. 1) Deoxyribonucleic acid (DNA) inhibitors were mainly antagonized by thymidine. 2) Both DNA and ribonucleic acid (RNA) inhibitors were mainly antagonized by adenosine and uridine. 3) Uridine antagonized the activities of an RNA inhibitor. 4) None of these nucleosides tested antagonized the antitumor activities of an inhibitor of protein synthesis. 5) A mitotic inhibitor was weakly antagonized by thymidine, adenosine and uridine. This method is useful for approximating the modes of actions of antitumor agents without using radioactive precursors.

Adenosine↗

[Antibacterial activity of cefminox in human urine].

The antibacterial activity of cefminox (CMNX) was compared to those of cefotaxime (CTX) and latamoxef (LMOX) in human urine using 11 clinical isolates from complicated urinary tract infections. When the inoculum size was increased from 10(4) (or 10(3)) to 10(8) (or 10(7)) CFU/ml, MIC values increased in general, but the increment of average MICs of CMNX was the smallest of the 3 drugs: 4 approximately 8 fold with CMNX, 32 approximately 64 fold with CTX and 8 approximately 32 fold with LMOX. MICs also increased when the urinary pH was altered from 8.5 to 5.5, but again the increment of MICs of CMNX was the smallest. Using 5 clinical isolates of Gram-negative bacteria as test organisms, the bactericidal activity of CMNX was compared to those of CTX and LMOX. In spite of the inferior activity of CMNX as determined by the MIC values, CMNX showed killing activity equal to or better than CTX and LMOX, particularly at low concentrations (2 approximately 20 micrograms/ml). The bacteriolytic activity of CMNX was also equal or superior to those of CTX and LMOX against 6 test organisms. These results suggest the usefulness of CMNX in the treatment of urinary tract infections, particularly when dense bacterial populations are present.

Bacteria↗

[Antibacterial activities of arbekacin, a new aminoglycoside antibiotic, against methicillin-cephem-resistant Staphylococcus aureus].

The in vitro and in vivo antibacterial activities of a new aminoglycoside antibiotic, arbekacin (HBK), against methicillin-cephem-resistant Staphylococcus aureus (MRSA) were compared with those of gentamicin (GM), netilmicin (NTL) and amikacin (AMK). The results obtained were summarized as follows: Compared to other aminoglycoside antibiotics, HBK had the highest antibacterial activities against clinically isolated MRSA (46 strains). Therapeutic effects of HBK against experimental systemic infections with MRSA in mice, were superior to those of GM, NTL and AMK. The ED50's of GM, NTL and AMK were more than 2 mg/mouse. Therapeutic effects of HBK against experimental subcutaneous infections with MRSA in mice were also superior to those of GM, NTL and AMK.

Abscess↗

In vitro activity of ME1401, a new antifungal agent.

The in vitro antifungal activity of ME1401, a potential topical antifungal agent, was compared with that of haloprogin, clotrimazole, miconazole, tolnaftate, and ciclopirox olamine by using an agar dilution procedure. ME1401 showed a broad antifungal spectrum and inhibited all of the 428 strains of 52 species of pathogenic yeasts and filamentous fungi tested at concentrations ranging from 0.01 to 12.5 micrograms/ml. In general, the activity of ME1401 was comparable or superior to that of clotrimazole and was greater than that of haloprogin and the other reference drugs under the conditions used. Only tolnaftate was superior to ME1401 in its activity against clinical isolates of Trichophyton rubrum. ME1401 showed no cross-resistance with any of the reference drugs and exhibited potent fungicidal activity.

Antifungal Agents↗

The antibacterial activity of ticarcillin/clavulanic acid (BRL28500) against ticarcillin-resistant bacteria.

The efficacy of BRL28500, a formulation of ticarcillin (TIPC, 15 parts) and clavulanic acid (CVA, 1 part), against TIPC-resistant strains of Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae was studied both in vitro and in vivo. The MICs of BRL28500 against these beta-lactamase producing strains were lower than those of TIPC or CVA alone against such strains. When BRL28500 was added during the logarithmic growth phase of bacteria at a concentration equivalent to the MIC, it demonstrated marked lytic activity. Cells treated with BRL28500 underwent morphological change, becoming filament-like, similar to those treated with TIPC alone. With CVA alone at concentrations above the MIC the cells assumed a stable round form. In bacterial cultures of the beta-lactamase-producing strains, TIPC was protected from hydrolysis by the presence of CVA. The in vivo activity of BRL28500 against experimental infections in mice caused by beta-lactamase-producing strains of bacteria was superior to that of TIPC alone. TIPC and CVA were found to be well distributed in peritoneal fluid following subcutaneous administration of BRL28500 into mice with peritoneal infections. The residual TIPC concentrations achieved were higher than when TIPC alone was administered. These results suggest that BRL28500 will be effective in the treatment of human infections due to TIPC-resistant bacteria.

Animals↗

In vitro evaluation of SF-2103A, a novel carbapenem antibiotic, as a beta-lactamase inhibitor.

SF-2103A, a new carbapenem antibiotic, exhibited a broad antibacterial spectrum and a potent inhibitory activity against a wide range of beta-lactamases, in particular, against cephalosporinases, with lower I50 values than those displayed by sulbactam and clavulanic acid. Using a fixed combination and checkerboard titration, in vitro synergy against the majority of the beta-lactamase-producing strains tested was demonstrated between SF-2103A and various beta-lactam antibiotics, especially cefotaxime, ceftizoxime, and cefoperazone. The synergistic effect of SF-2103A was more pronounced than that of sulbactam. The in vitro synergy was also confirmed by bactericidal and bacteriolytic activities and morphological effects.

Anti-Bacterial Agents↗

Therapeutic effect of SF-2103A, a novel carbapenem antibiotic, in combination with cefotaxime, cefoperazone and other cephalosporins.

Combinations of SF-2103A with cefotaxime, cefoperazone or cefazolin showed synergistic efficacy at a wide range of combination ratios against experimental infection in mice due to Proteus vulgaris GN76/C-1, producing type Ic cephalosporinase, Escherichia coli No. 29/36 RGN823, producing type IIIa (TEM-2) penicillinase and E. coli GN206, producing type Ib cephalosporinase. These effects by SF-2103A were greater than those seen with sulbactam. The in vitro and in vivo synergistic activities were roughly correlated. Potent in vivo activity of SF-2103A was related to good pharmacokinetic properties, with blood half-life of 30 minutes and urinary recovery of 55.2% after parenteral administration to rats. Furthermore, SF-2103A was stable to rat kidney homogenate. The high stability of SF-2103A in aqueous and biological media was correlated with the sulfonate group at C-3.

Animals↗

In-vitro and in-vivo activities of a novel cephamycin MT-141 against the Bacteroides fragilis group in comparison with six cephem antibiotics.

MT-141 inhibited 90% of the clinical isolates of Bacteroides fragilis at 3.13 mg/l, whereas six reference cephem antibiotics inhibited them at 12.5- greater than 100 mg/l. MT-141 was stable to the Bacteroides beta-lactamases, but the stability alone could not explain the potent activity of MT-141 against the other Bacteroides spp., which produced only small amounts of beta-lactamase, but were resistant to other cephem antibiotics. MT-141 exhibited a higher killing rate and more potent in-vivo efficacy than the reference cephem antibiotics against Bact. fragilis No. 36 combined with Escherichia coli No. 29. In conclusion, the in-vitro and in-vivo anti-bacteroides activities of MT-141 ranked first among those of the cephem antibiotics compared.

Animals↗

In vitro and in vivo antibacterial activities of dactimicin, a novel pseudodisaccharide aminoglycoside, compared with those of other aminoglycoside antibiotics.

When compared with astromicin, amikacin, gentamicin, and sisomicin, dactimicin was similar to astromicin in in vitro activity and was more active than amikacin and gentamicin against the clinical isolates of Serratia marcescens, but less active against Pseudomonas aeruginosa. Dactimicin and astromicin were active against many gentamicin- and amikacin-resistant bacteria expressing aminoglycoside-modifying enzymes, with the exception of aminoglycoside 3-acetyltransferase. However, dactimicin was more resistant than astromicin to inactivation by aminoglycoside 3-acetyltransferase, probably owing to the protective action of the formimidoyl group. The in vivo activity of dactimicin, assessed by the 50% effective doses against systemic infections in mice, was similar or superior to that of astromicin and was superior or inferior to that of amikacin depending on the strains tested.

Acetylation↗

Comparative in vitro and in vivo activity of cefminox (MT-141), cefotaxime and cefoperazone against gram-negative bacteria.

Against 17 Gram-negative bacteria, excluding Proteus species, the difference between cefminox and cefotaxime was significant in terms of MIC distribution, in favour of cefotaxime, but was not significant in terms of ED50 distribution. Against 22 Proteus species, the difference between cefminox and cefotaxime was not significant in terms of MIC distribution, but was significant for ED50 distribution, in favour of cefminox. The difference between cefminox and cefoperazone was not significant for either MIC or ED50 distribution against 17 Gram-negative bacteria, but was significant against 22 Proteus species, in favour of cefminox. The distribution of rank of the ED50/MIC ratios for cefminox was significantly lower than those for cefotaxime and cefoperazone, indicating that cefminox showed lower ED50 values than expected from the MIC values.

Animals↗

Comparative bactericidal and morphological effects of five cephamycins on cells of three gram-negative bacilli at decreasing drug concentrations.

The bactericidal and morphological effects under drug-decreasing conditions of cefminox (MT-141), cefoxitin, cefmetazole, cefotetan and latamoxef were compared on Klebsiella pneumoniae PCl-602, Escherichia coli No. 29 and Serratia marcescens No. 1 cells. A new drug-decreasing method was developed by the use of an antibiotic removal device. Cefminox displayed an earlier onset and a higher rate of bactericidal action than the other cephamycins against the test organisms, although the minimum inhibitory concentrations of cefminox were similar to or higher than those of the other drugs. Morphologically, cefminox caused rapid lysis of the cells without filamentation, whereas the reference cephamycins caused mainly elongation of the cells under the test conditions. Frequent formation of multiple bulges on cells exposed to cefminox was observed in an isotonic medium.

Cephamycins↗

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↗

Structure-activity relationships on the terminal D-amino acid moiety of a novel cephamycin MT-141.

The effect of chemical modification of the D-amino acid function, which represents the C-7 beta substituent of cephamycin MT-141 on in vitro antibacterial activity was examined. MT-141 was more active on Gram-negative organisms than Gram-positive ones. It showed strong bacteriolytic activity on Gram-negative organisms. Lysis of Escherichia coli K-12 strain JE1011 treated with a low concentration of this antibiotic was preceded by frequent formation of multiple bulges from the cells. Amidation or decarboxylation, removing the acidic function from the D-amino acid of MT-141, resulted in an increase in activity against Gram-positive bacteria, and a decrease against Gram-negative ones. Cells treated with the amide or the decarboxylate did not form multiple bulges but formed single bulges. N-Acetylation of the D-amino acid moiety removing the basic function, caused a marked drop in activity against both Gram-positive and Gram-negative bacteria. The bacteriolytic activity on E. coli was reduced, and cells treated with the N-acetate became filamentous. Conversion of the D-amino acid function of MT-141 to the L configuration caused a moderate drop in activity against both Gram-positive and Gram-negative organisms. Both bacteriolytic and bactericidal activities against E. coli were reduced in the L-congener. Cefoxitin, cefmetazole and latamoxef used as reference antibiotics were less active than MT-141 in the bactericidal activity against E. coli, and induced single bulge formation or filamentation of the cells around MIC levels. Cell-surface permeability, stability to beta-lactamases, and binding affinity to PBPs of E. coli did not differ between MT-141 and its derivatives.

Bacteria↗