Search PubMed⌕ Search

Biomedical subjects

S Ohya

Publications and source records attributed to S Ohya.

85 records · Page 5Linked to original sources
PubMed1983

Effect of 7 alpha substitution of cephems on their beta-lactamase stability and affinity for penicillin-binding proteins in Morganella morganii.

Cephamycins, which have a methoxy group at the 7 alpha position of their cephalosporin nuclei, were highly stable against hydrolysis by a beta-lactamase purified from a clinical isolate of Morganella morganii, whereas their 7 alpha-H analogs were rapidly hydrolyzed by the enzyme. The high stability of the cephamycins was not due to their low affinity for the enzyme, since the cephamycins strongly inhibited the enzyme in a competitive manner. In cases in which the 7 alpha-methoxy group was substituted by OC2H5, SCH3, CN, or CH3 groups, the substituted compounds still showed high stability against enzymatic hydrolysis but significantly reduced both their affinities for the enzyme and their antibacterial activities. These 7 alpha-substituted cephalosporins, except for cephamycins, also had greatly reduced affinities for target proteins, i.e., penicillin-binding proteins, of beta-lactam antibiotics. Therefore, the 7 alpha position of cephalosporins was considered to play an important role in both beta-lactamase stability and antibacterial activity.

Bacterial Proteins↗
PubMed1983

Release of lipoteichoic acid from Staphylococcus aureus by treatment with cefmetazole and other beta-lactam antibiotics.

The effect of cefmetazole on the growth together with the release of cellular lipoteichoic acid from cefazolin-resistant strains of Staphylococcus aureus was compared with that of cefazolin, cefotiam, cefoxitin and cefuroxime. Bacteriolytic actions were measured by turbidity and bactericidal actions were followed by viable cell count. Release of cellular lipoteichoic acid was measured by the radioactivity in the supernatant of the cultures. Cefmetazole exerted more potent effects on the bacterial growth and induced more marked release of cellular lipoteichoic acid from resistant strains as compared with other beta-lactams.

Anti-Bacterial Agents↗
PubMed1982

Penem derivatives: beta-lactamase stability and affinity for penicillin-binding proteins in Escherichia coli.

Penem derivatives, a new group of beta-lactam antibiotics with potent activities against a wide range of bacteria, including Pseudomonas aeruginosa, were tested for their stability against hydrolysis by beta-lactamases purified from clinical isolates of Morganella morganii. Proteus vulgaris, and Escherichia coli and by a penicillinase from Bacillus cereus. Penems having 6 alpha substituents, such as hydroxyethyl, hydroxymethyl, and ethyl groups, were very stable against hydrolysis by each of the enzymes. Penems having no 6 alpha substituents were easily hydrolyzed by P. vulgaris and E. coli enzymes, whereas they were rather stable against hydrolysis by M. morganii and B. cereus enzymes, a typical cephalosporinase and penicillinase, respectively. Affinity of the penems for E. coli penicillin-binding proteins (PBPs) was also tested. beta-Lactamase-stable penems having a 6 alpha-hydroxyethyl group showed high affinity for PBP-4, -5, and -6 as well as for PBP-1A, -1Bs, and -2. However, the penems having no 6 alpha substituents showed a far lower affinity for PBP-4, -5, and -6 than that shown by the corresponding 6 alpha-hydroxyethyl penems. Among the penems tested, affinity for PBP-4, -5, and -6 was closely related to their beta-lactamase stability, as was the case among cephamycins and cephalosporins. Effects of the penems on the morphology of a strain of E. coli are also described.

Anti-Bacterial Agents↗
PubMed1982

Potent cephalosporinase inhibitors: 7 beta-[2-(1, 3-dithiolan-2-ylidene) acetamido] cephalosporins and related compounds.

Cephalosporins possessing a 1, 3-dithiolane, 1, 3-dithiane, or 1, 3-dithietane ring on their 7 beta-substituents showed potent inhibitory activity against cephaloridine hydrolysis by cephalosporinases purified from proteus morganii, Proteus rettgeri, and Proteus inconstans, which were not inhibited by clavulanic acid, a well-known beta-lactamase inhibitor. The mode of inhibition was competitive. The dithiolane cephalosporins themselves were stable against hydrolysis by the beta-lactamases tested. A combination of a dithiolane cephalosporin and cephaloridine synergistically inhibited in vitro growth of strains of P. morganii, P. rettgeri, P. inconstans, Enterobacter aerogenes, Enterobacter cloacae, and Serratia marcescens.

Cephaloridine↗
PubMed1980

Purification and some properties of beta-lactamases from Proteus rettgeri and Proteus inconstans.

Two beta-lactamases were isolated from strains of Proteus species and purified, one from a strain of P. rettgeri and the other from a strain of P. inconstans. Each enzyme preparation gave a single protein band on polyacrylamide gel electrophoresis. Molecular weights of P. rettgeri and P. inconstans enzymes were found to be 42,000 and 43,000, and their isoelectric points pH 8.7 and 8.6, respectively. The two enzymes presented typical cephalosporinase profiles. Cefmetazole (CS-1170) and cefoxitin, both cephamycin antibiotics, not only resisted hydrolysis by both of the enzymes, but also inhibited their activities competitively. Rabbit antiserum against purified P. rettgeri enzyme inhibited the activity of both purified and crude enzyme preparations from other strains of P. rettgeri so far tested. None of the beta-lactamases produced by other species of Proteus including P. inconstans was inhibited by the antiserum, thus showing that the purified cephalosporinase was of the species-specific types. The enzymological properties of the preparations were compared with those of beta-lactamases derived from other gram-negative enteric bacteria.

Amino Acids↗
PubMed1979

Penicillin-binding proteins in Proteus species.

Penicillin-binding proteins in three species of Proteus, Proteus mirabilis, P. morganii, and P. rettgeri, were investigated by sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis. Penicillin-binding proteins in these Proteus species were compared with those in Escherichia coli K-12. An approximate correlation between penicillin-binding proteins in E. coli and those in Proteus species was shown by several criteria: electrophoretic mobilities; affinities of several beta-lactam antibiotics which show characteristic patterns of binding to penicillin-binding proteins in E. coli; relation between affinities of antibiotics to the proteins and effects on morphological changes in Proteus species; location of beta-lactamase activity among penicillin-binding proteins; and thermostability. The electrophoretic mobilities and several other characteristics of penicillin-binding proteins among the Proteus species examined were found to be similar from species to species and differed only slightly from those of E. coli.

Bacterial Proteins↗
PubMed1978

New cephamycin antibiotic, CS-1170: binding affinity to penicillin-binding proteins and inhibition of peptidoglycan cross-linking reactions in Escherichia coli.

The binding activity of CS-1170, a new cephamycin antibiotic, to penicillin-binding proteins (PBPs) in Escherichia coli and Proteus species and the potency of this antibiotic in vitro to inhibit enzymes involved in peptidoglycan cross-linking in E. coli were tested. Similar experiments were carried out with the 7alpha-H analog of CS-1170, R-45656, and the results were compared with those obtained with CS-1170. CS-1170 showed high affinities (compared with that of penicillin G) for E. coli PBP-1A, -1Bs, and -3, the PBPs of higher molecular weight, but not PBP-2. It also inhibited the in vitro peptidoglycan cross linking reaction and concomitant release of d-alanine at very low concentrations (approximately its minimal inhibitory concentration). This antibiotic also showed very high affinity for PBP-4, -5, and -6, the PBPs of lower molecular weight, and at extremely low concentrations it inhibited d-alanine carboxypeptidases IA and IB, corresponding to PBP-5/6 and PBP-4, respectively. CS-1170 seemed to be resistant to the beta-lactamase activity of PBP-5 and -6 in E. coli and Proteus species. R-45656 showed as high an affinity for PBP-1A, -1Bs, and -3 as CS-1170, but unlike CS-1170, it had low affinities for PBP-4, -5, and -6. The concentrations of R-45656 required for inhibition of d-alanine carboxypeptidases IA and IB were also much higher than those of CS-1170. R-45656 showed rather low activities in inhibiting the in vitro cross-linking reaction of peptidoglycan and concomitant release of d-alanine. Synergism was observed in 9 of 22 strains examined between CS-1170 and mecillinam, which bound specifically to PBP-2.

Amdinocillin↗
PubMedDate not supplied

Effects of AF64A on the mRNA levels of muscarinic receptor subtypes in the rat iris sphincter.

The reduction of parasympathetic nerve activity by the treatment with ethylcholine mustard aziridinium ion (AF64A) in vivo induced both specific and non-specific supersensitivities in the rat iris sphincter (Tanaka et al., 1999). Changes in the expression of muscarinic receptor subtypes, which could be a cause of specific supersensitivity induced by the treatment with AF64A, were examined using competitive PCR techniques. Muscarinic receptor population is composed of m2, m3, and m4 subtypes in the rat iris (Furuta et al., 1998). Interestingly, m4 mRNA was much more abundantly expressed than m2 and m3 in the rat iris sphincter. The treatment with AF64A significantly increased the mRNA levels of m2 and m3 subtypes to 370 and 330% of the control but not that of m4 (approximately 90% of the control). In addition, the total protein contents were increased to approximately 125% of the control. The up-regulation of the mRNA levels of m2 and m3 subtypes by the treatment with AF64A was significant when they were compensated for the increase in total protein contents. The down regulation of m4 mRNA expression was not significant even after being corrected for the protein content. These results suggest that the up-regulation of the mRNA levels of m2 and m3 subtypes may be, at least in part, responsible for the supersensitivity to muscarinic agonists after the treatment with AF64A in vivo.

Animals↗