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Biomedical subjects

S Mitsuhashi

Publications and source records attributed to S Mitsuhashi.

At least 307 records · Page 17Linked to original sources

Drug resistance in Streptococcus pyogenes isolated in Japan.

Drug resistance of Streptococcus pyogenes strains isolated during 1974 and 1975 in various districts in Japan were surveyed and compared with an earlier survey of 1970 to 1973. Of 1,021 strains, tetracycline-, macrolide antibiotic-, lincomycin-, and chloramphenicol-resistant strains were demonstrated at frequencies of 80.3, 62.3, 60.8, and 57.9%, respectively. Distinct group resistances to penicillin and aminoglycoside antibiotics could not be identified among the strains examined. It was characteristic that quadruple and triple resistances were manifested among the strains resistant to macrolide antibiotics, lincomycin, tetracycline, and chloramphenicol, and they were confined to the T-type 12. The emergence of multiply resistant streptococcal strains was due mostly to the rapid increase in isolation frequency of macrolide antibiotic- or macrolide antibiotics-lincomycin-resistant strains.

Anti-Bacterial Agents↗

In vitro and in vivo antibacterial activity of T-1220, a new semisynthetic penicillin.

T-1220, sodium 6-[d-(-)-alpha-(4-ethyl-2,3-dioxo-1-piperazinylcarbonyl-amino)- alpha-phenylacetamido] penicillanate, is a new semisynthetic penicillin derivative that possesses a broad spectrum of in vitro antibacterial activity against gram-positive and gram-negative bacteria. T-1220 is more effective than carbenicillin (CB-PC) against Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus species, and Serratia marcescens. Addition of human serum to culture media did not significantly alter the antibacterial activity of T-1220. Greater bactericidal activity toward various strains of gram-negative bacteria was demonstrated with T-1220 than with CB-PC. T-1220, like penicillin G, was hydrolyzed by penicillinase, but was sable to a type IV penicillinase produced by P. aeruginosa strains. In vivo antibacterial activities of T-1220, ampicillin (AB-PC), and CB-PC were compared, using systemic infections of mice with P. aeruginosa, K. pneumoniae, and Escherichia coli. The 50% effective doses (milligrams per kilogram) of T-1220 were consistently lower than those of AB-PC and CB-PC.

Ampicillin↗

Inhibition and facilitation of transfer among Pseudomonas aeruginos R plasmids.

Esamining 12 plasmids in Pseudomonas aeruginosa, we found two types of interaction in their transfer (inhibition and facilitation), using donor cells carrying two compatible plasmids. (i) Ten plasmids representing incompatibility groups P-1, P-2, P-5, P-6, and P-7 were all transmissible at a high frequency, 10-2 to 10-1, except for one with a lower frequency of about 10-3. The transfer of P-5 plasmids was inhibited by P-2 plasmids reciprocally or unilaterally, and the unilateral transfer inhibition was observed in other combinations between plasmids belonging to groups P-1, P-2, P-6, and P-7. It was characteristic of Pseudomonas plasmids that most plasmids with high transferability inhibited the transfer of other coexisting plasmids without distinct inhibition of their own transfer. (ii) Two plasmids, Rms149 of P-8 group and Rlb679, which was not classified, were transmissible at an exceptionally low frequency of 10-7 to 10-6, but their transfer was facilitated by plasmids with high transferability.

Anti-Bacterial Agents↗

Conjugation in lysogenic, multiple-drug resistant, nosocomial strains of Pseudomonas aeruginosa producing a hemolytic toxin.

From incubators and children in a premature-born unit, a number of red-pigmented Ps. aeruginosa strains, resistant to kanamycin, streptomycin and lividomycin and producing haemolytic toxin II, were isolated and investigated for transfer of resistance in mixed cultures. Streptomycin, kanamycin and lividomycin resistance was co-transferred, from some strains, together with the ability of toxin production. Transfer ability was also co-transferred which might have genetic as well as epidemiological significance. Strains do produce "Autoplaques" and transferability of this property as well as of lysogeny is under investition.

Animals↗

Transduction, by phases F116 and G101, of gentamicin-tobramycin resistance, and of "autoplaque formation" property in Pseudomonas aeruginosa.

Pseudomonas aerugionsa phages F 116 and G 101, propagated on ML 4262 strain into which gentamicin-tobramycin resistance determinants have been increased by means of conjugation, from wild-type strains Vy 28, 29 and 34, were capable to transduce R determinants to PAO 1670 strain. Transfer ability was co-transduced as well, with exception of transductants selected with streptomycin. "Autoplaque formation" ability, occurring in original wild-type strain Vy 28, could be co-tranduced with all tobramycin-resistant determinants by F116 but not G 101 phage.

Anti-Bacterial Agents↗

Antimicrobial evaluation of cefoxitin: a new semisynthetic cephamycin. Comparative studies with cefazolin and cefalotin.

Antimicrobial activity of 3-carbamoyloxymethyl-7-alpha-methoxy-7-[2-(2-thienyl)-acetamido]-3-cephem-4-carboxylic acid (cefoxitin), a new semisynthetic cephamycin antibiotic, was studied in comparison with that of cefazolin and cefalotin. Cefoxitin exhibited antibacterial activity against both gramnegative and gram-positive bacteria, and its action was bactericidal. Against gram-negative bacteria, cefoxitin was highly active as well as cefazolin, and more active than cefalotin. Especially, cefoxitin was highly active not only against strains of clinical isolates of indole-positive Proteus and S. marcescens but also against those of E. coli and P. mirabilis which were resistant to cefazolin and/or cefalotin, respectively. In addition, cefoxitin was effective against the strains resistant to beta-lactam antibiotics including cefazolin and cefalotin. Cefoxitin was hardly active against the strains of E. cloacae and P. aeruginosa, similar to cefazolin and cefalotin. Against gram-postive bacteria, cefoxitin was less active than cefazolin and cefalotin. In protection tests in mice, cefoxitin and cefazolin were more effective against infection with E. coli than cefalotin. Furthermore, cefoxitin was more active against infections with S. marcescens and P. morgani than the other antibiotics. Cefoxitin, like cefalotin, was less effective against infection with S. aureus than cefazolin. Cefoxitin was highly resistant to hydrolysis by beta-lactamases derived from the organisms insusceptible to the antibiotic. This fact revealed that the resistance of the organisms to cefoxitin may be in part due to factors other than beta-lactamase inactivation.

Animals↗

Classification of R plasmids by incompatibility in Pseudomonas aeruginosa.

R plasmids identified in Pseudomonas aeruginosa strains isolated in our laboratories were classified by their incompatibility characters by using intraspecies conjugation in P. aeruginosa. The fertility factor, FP2, was compatible with R plasmids belonging to all groups, and was classified in a new group. From these data, the plasmids examined have been placed into seven or eight incompatibility groups.

Anti-Bacterial Agents↗

Inhibition of conjugal transfer of R plasmids by pipemidic acid and related compounds.

It was found that pipemidic acid and related compounds have the common property of inhibiting the conjugal transfer of R plasmids carried by Escherichia coli and Pseudomonas aeruginosa. This inhibition was not due to bactericidal activity of the compounds against donors, recipients, or R(+) transconjugants. However, it was correlated inversely with their minimal inhibitory concentrations, depending especially upon sensitivity of donors to the compounds. The inhibition was generally observed in mating systems using various combinations of 14 R plasmids and 9 bacterial strains. The pretreatment of a donor or a recipient strain with pipemidic acid showed only a small inhibitory effect on the transfer of an R plasmid, whereas the presence of the compound during an active mating caused a marked inhibitory effect.

Anti-Bacterial Agents↗

Plasmid-mediated penicillin beta-lactamases in Pseudomonas aeruginosa.

A penicillin beta-lactamase (PCase) was extracted from Pseudomonas aeruginosa Rms139(+) and purified by means of column chromatography. The isoelectric point of Rms139 PCase was 5.7 and its molecular weight was 22,500 +/- 1,000. The optimal pH for the hydrolysis of benzylpenicillin was 7.0 to 7.5 and the optimal temperature was 45 C, with the PCase also showing high activity against carbenicillin. It is concluded that this enzyme is a new type of penicillin beta-lactamase different from the type I, II, or III R plasmid-mediated PCases reported previously.

Bacterial Proteins↗

Drug resistance and distribution of R factors in Salmonella strains.

Drug resistance and the distribution of R factors in Salmonella strains were surveyed using 1,980 strains isolated in Japan from 1955 to 1973. Resistances were mostly restricted to sulfanilamide (SA), tetracycline (TC), and streptomycin (SM), and combinations thereof. The demonstrated frequency of strains resistant to chloramphenicol (CM) was very low as compared with that in Escherichia coli and Shigella strains. In relation to resistance to TC, CM, SM and SA, the frequency of isolation of single resistance was the highest, followed by triple, double, and quadruple resistance in that order. Low frequency of isolation of quadruple resistance was due to the low frequency of CM resistance in Salmonella strains and differed from the E. coli or Shigella group. R factors with single TC resistance was most common, followed by those with TC,SM,SA; SM,SA; TC,CM,SM,SA; and single (SM and SA) resistance, in that order. Kanamycin and ampicillin resistance was unusual and mostly transmissible.

Anti-Bacterial Agents↗

Quantitative and qualitative determinations of the combined effect of tetracycline and oleandomycin. II. In vivo effect.

The combination effect of tetracycline (TC) and oleandomycin (OM) on acute infection of mice with four strains of Staphylococcus aureus including TC or OM resistant ones was examined by the quantitative determination of protective potencies of single and combined drugs. The grade of synergism was expressed by the synergistic ratio (SR), a ratio of experimentally determined potency of the combined drug over a hypothetical potency in which additive effect of the both drugs is assumed. With 3 out of the 4 strains of S. aureus synergism between TC and OM or triacetyloleandomycin (TAO) was demonstrated by the determination of the 50% effective dose and by statistical examination of the SR. The grade of synergistic protection by these drugs varied with the strains infected and it did not depend upon the sensitivity to antibiotics or grade of synergism in vitro. There was no synergistic enhancement of acute toxic action in the combined administration of TC and OM to mice.

Animals↗

Ribonucleic acid-dependent ribonucleic acid polymerase in the immune response.

Ribonucleic acid (RNA)-dependent RNA polymerase activity was demonstrated in the microsomal and ribosomal fraction from the spleen cells of immunized mice. The enzyme activity was solubilized by Triton X-100 from the fraction and partially purified by Biogel A 1.5 m column chromatography. The RNA-dependent RNA polymerase activity was eluted in a single peak from the column. High activity was demonstrated with an RNA polymerase activity was eluted in a single peak from the column. High activity was demonstrated with an RAN preparation (iotaRNA) as template made from the spleens of immunized mice but very low activity was found with an RNA preparation made from the spleens of normal mice. Incorporation of 3H-UTP markedly decreased in the presence of RNase but not in the presence of DNase. DNA preparations made from the spleens of immunized mice were inactive as template for this enzyme. The iotaRNA preparation was fractionated by sucrose density gradient centrifugation. A fraction corresponding to 12-13 S was most active as a template. It was followed by a fraction corresponding to 6-7 S. Sucrose gradient analysis of the 3H-UTP-labeled product was attempted. Some properties of this enzyme are described.

Animals↗

Acetylation of amikacin, a new semisynthetic antibiotic, by Pseudomonas aeruginosa carrying an R factor.

A clinical isolate Pseudomonas aeruginosa GN315 resistant to amikacin (AK), a new semisynthetic antibiotic, inactivated AK by acetylation. The acetylating enzyme was purified approximately 146-fold from a crude extract of GN315 by affinity chromatography. Fractionated samples obtained by affinity chromatography showed almost the same inactivation curves toward 3',4'-dideoxykanamycin B (DKB) and AK. Partially purified AK-acetylating enzyme inactivated DKB and kanamycin A but could not inactivate gentamicin C(1). The optimal pH for their inactivation was 6.0 to 7.0, and the pH curves for the inactivation of both drugs were almost the same. These facts indicate that AK and DKB are inactivated by the same aminoglycoside-acetylating enzyme. Through elemental analysis, the inactivated AK was found to be a monoacetylated product of AK. A sample of inactivated AK was purified and compared with a synthetic 6'-N-acetyl AK by thin-layer chromatography, and the results indicated that AK was inactivated by acetylation of the 6'-NH(2) group. The ultraviolet, infrared, and nuclear magnetic resonance spectra of the inactivated AK showed that AK was inactivated by the enzyme through acetylation of the amino group of 6'-amino-6'-deoxy-d-glucose moiety of AK. This enzyme, mediated by R factor, is capable of conferring resistance to AK, DKB, kanamycin, gentamicin, and sulfanilamide.

Aminoglycosides↗