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Biomedical subjects

S Mitsuhashi

Publications and source records attributed to S Mitsuhashi.

At least 163 records · Page 9Linked to original sources
PubMed1985

In vitro and in vivo activities of DN-9550, a new broad-spectrum cephalosporin.

DN-9550 [(6R, 7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(1H-imidazol-4-yl) methoxyiminoacetamido]-3-[(1-pyridinio)methyl]-8-oxo-5-thia -1-azabicyclo methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate hydrochloride] is a new semisynthetic cephalosporin with a broad spectrum of antibacterial activity against gram-positive and gram-negative bacteria. The activity of DN-9550 against most species of the family Enterobacteriaceae was roughly comparable to that of ceftazidime, slightly lower than that of cefotaxime, and far exceeded that of cefoperazone. Against Citrobacter freundii, Enterobacter cloacae, and Serratia marcescens, DN-9550 was more active than ceftazidime and cefotaxime. DN-9550 and ceftazidime were significantly more active than cefotaxime against Pseudomonas aeruginosa, but DN-9550 and cefotaxime were clearly more active than ceftazidime against staphylococci and streptococci. Haemophilus influenzae and Neisseria gonorrhoeae were also highly susceptible to DN-9550, but Bacteroides fragilis was generally not susceptible to the compound. DN-9550 was stable to various types of beta-lactamases and had high affinities for penicillin-binding protein 3 of both Escherichia coli and P. aeruginosa. When DN-9550 was administered subcutaneously to mice experimentally infected with Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, or Pseudomonas aeruginosa, its efficacy well reflected its in vitro potency.

Animals↗
PubMed1985

Purification and properties of inducible penicillin beta-lactamase isolated from Alcaligenes faecalis.

An inducible penicillin beta-lactamase was purified from a strain of Alcaligenes faecalis resistant to beta-lactam antibiotics. The purified enzyme preparation gave a single protein band on polyacrylamide gel electrophoresis, and its molecular weight was 29,000 based on sodium dodecyl sulfate-acrylamide gel electrophoresis. Its isoelectric point was 5.9. The enzyme more rapidly hydrolyzed penicillins, such as penicillin G, ampicillin, carbenicillin, piperacillin, and cloxacillin, than it hydrolyzed cephalosporins. For the hydrolysis of penicillin G, the optimal pH was 5.5, and the optimal temperature was 35 degrees C. The enzyme activity was inhibited by iodine, Cu2+, Hg2+, and EDTA but was not inhibited by clavulanic acid and sulbactam.

Alcaligenes↗
PubMed1985

Biochemical properties of beta-lactamase produced by Flavobacterium odoratum.

A constitutively produced beta-lactamase was purified from Flavobacterium odoratum GN14053. The purified enzyme gave a single protein band on polyacrylamide gel electrophoresis. The isoelectric point was 5.8, and the molecular weight was estimated to be about 26,000. The enzyme activity was inhibited by EDTA, iodine, p-chloromercuribenzoate, HgCl2, and CuSO4 but not by clavulanic acid, sulbactam, imipenem, and cephamycin derivatives. The enzyme showed a broad substrate profile, hydrolyzing oxyiminocephalosporins, cephamycins, imipenem, and some penicillins.

Anti-Bacterial Agents↗
PubMed1985

In vitro antibacterial activity of Sch 34343 and its stability to beta-lactamases and renal dehydropeptidase 1.

The in vitro antibacterial activity of Sch 34343 against 1,328 strains of clinical isolates was compared with those of imipenem and ceftazidime. Sch 34343 had a broad spectrum of antibacterial activity against both gram-positive and gram-negative bacteria but was inactive against Pseudomonas aeruginosa and Pseudomonas maltophilia. Sch 34343 was quite stable to hydrolysis by beta-lactamases, including both penicillinases and cephalosporinases. However, Sch 34343 was slightly hydrolyzed by a new type of beta-lactamase (oxyiminocephalosporin beta-lactamase), as was imipenem. Sch 34343 was slightly hydrolyzed by renal dehydropeptidase 1 but was somewhat more stable than other carbapenems.

Animals↗
PubMed1985

Cephamycin inactivation due to enzymatic hydrolysis by beta-lactamase from Bacteroides fragilis.

The susceptibility of 53 clinical isolates of Bacteroides fragilis to cephamycins was examined. Judging from the MICs for 50% of the strains tested, moxalactam was the most active, however, judging from the MICs for 90% of the strains tested, cefbuperazone was more effective than moxalactam. A correlation was observed between in vitro activity of benzylpenicillin and cephaloridine and beta-lactamase production. Inactivation due to enzymatic hydrolysis of cephamycins over a short time was not observed; however, inactivation was detected by a double disk diffusion test, and moxalactam was most easily inactivated. We conclude that inactivation due to enzymatic hydrolysis of cephamycins over a long time may play an important role in resistance to some cephamycins in strains of B. fragilis.

Bacteroides fragilis↗
PubMed1985

[Clinical studies of intravenous drip infusion of micronomicin. 1. Pharmacokinetics (Part 2). Intravenous Micronomicin Research Group].

Following the previous report on pharmacokinetics of micronomicin (MCR) in healthy volunteers, pharmacokinetic studies were made again in patients with different degree of renal impairment, and a nomogram was obtained. MCR at a dose of 60 mg/time was given by 1-hour drip infusion to 14 inpatients who consented to receive MCR (age: 35 to 84 years, Ccr: 17.96 to 104.35 ml/min). The blood collection was performed in accordance with the schedule made upon the degree of renal impairment, and the serum concentration was determined by HPLC method. The results were analyzed by MULT program using two- or one-compartment open model. The serum concentration (Cmax) just after administration of MCR was 5.8 +/- 0.9 microgram/ml (mean +/- S.D.). The biological half-life was 1.81 to 12.35 hours. Taking the above results into consideration together with the previous ones of healthy males, the following correlation was obtained between the elimination constant (Kel or beta) and Ccr calculated from S-Cr.: Kel or beta = 0.0038 X Ccr - 0.0097. Further, no side effect was observed in these studies. Elimination of MCR from blood was dependent on renal function like other aminoglycosides, and so it was possible to estimate the elimination constant from Ccr. From these results, a nomogram for the optimum dosage regimen of MCR was obtained.

Adult↗
PubMed1984

Microbial kinetics of beta-lactam antibiotics against Escherichia coli.

Microbial kinetics of Escherichia coli NIHJ JC-2 and E. coli B/r were investigated in the presence of beta-lactam antibiotics. To maintain a constant drug concentration during the experiment, a novel technique, using a dialysis membrane tube containing the drug solution, was successfully employed. The drug-affected generation curves of E. coli exhibited common features. After the addition of drug, an apparent lag period was noted, followed by a first-order decrease of the sensitive organisms and, 6 h later, by a regrowth of resistant organisms, depending on the antibiotic concentration used. The relationship between the apparent generation rate constant, kapp, and the antibiotic concentration was found to be nonlinear. This phenomenon is consistent with a saturable receptor site model for the drug action. A good linear free energy relationship was observed between the microbial kinetic parameter, kmax, and the alkaline degradation rate constants, kOH, of the cephalosporins studied.

Anti-Bacterial Agents↗
PubMed1984

Kinetic analysis and characterization of the bacterial regrowth after treatment of Escherichia coli with beta-lactam antibiotics.

The generation curves of Escherichia coli B/r and E. coli NIHJ JC-2 in the presence of several beta-lactam antibiotics were studied from the kinetic point of view. Apparent first-order regrowth of resistant organisms was observed approximately 6 h after addition of these antibiotics. The time courses of apparent viable counts could be interpreted in terms of the sum of the viable counts of sensitive and resistant organisms. To clarify the nature of the regrowth, experiments involving a second addition of antibiotic, single colonization by subculture, and synchronous cell culture were carried out. Several possible explanations for the results are discussed, including beta-lactamase production, selection in terms of membrane permeability, and mutation to acquire drug resistance. A selection process or a modification of membrane permeability caused by contact with the drug seems to be the most probable reason for the regrowth of the organisms.

Ampicillin↗
PubMed1984

Cells participating in immunologic memory induced with RNA from the spleens of immunized mice.

Ribonucleic acid (immune RNA, iRNA) extracted from the spleens of mice immunized with heterologous red blood cells induced antigen-specific immunologic memory. The type of cells (T cells, B cells) which participate in immunologic memory induced with iRNA was investigated. Immune RNA-primed T cells cooperated with normal, iRNA-primed or antigen-primed B cells and induced a high IgM response. Immune RNA-primed B cells did not cooperate with normal T cells, but did with iRNA- or antigen-primed T cells. The activities of iRNA-primed T and B cells were antigen-specific.

Animals↗
PubMed1984

Purification and properties of an inducible cephalosporinase from Pseudomonas maltophilia GN12873.

An inducible cephalosporinase was purified from Pseudomonas maltophilia GN12873. The pI was 8.4, and the molecular weight was ca. 56,000 by gel filtration or 27,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, suggesting that this enzyme had two subunits. The optimal pH and optimal temperature were 7.5 and 45 degrees C, respectively. Enzyme activity was inhibited by clavulanic acid, sulbactam, cephamycin derivatives, carbapenem antibiotics, iodine, HgCl2, and p-chloromercuribenzoate. The enzyme showed a broad substrate profile, hydrolyzing cephaloridine, cefazolin, cefsulodin, penicillin G, ceftizoxime, and ampicillin at a high rate.

Anti-Bacterial Agents↗
PubMed1984

In vitro and in vivo antibacterial activities of K-4619, a new semisynthetic aminoglycoside.

The antibacterial activities of K-4619 (3-de-O-methylsporaricin A sulfate) were compared with those of sporaricin A, amikacin, dibekacin, and gentamicin. K-4619 exhibited a high order of activity against gram-positive and gram-negative bacteria, including Pseudomonas aeruginosa. Its activity against Providencia species and Serratia marcescens was the highest of all drugs tested. K-4619 was highly effective against bacteria that produce various aminoglycoside-inactivating enzymes, except for 3-acetyltransferase I. The bactericidal activity of K-4619 was somewhat greater than that of amikacin. The activity of K-4619 against gram-negative bacteria increased at alkaline pH and was hardly affected by inoculum size, addition of horse serum, and composition of the medium. The in vivo protective effect of K-4619 against infections with Klebsiella pneumoniae, S. marcescens, and P. aeruginosa in mice was greater than that of sporaricin A. K-4619 was also active in mice infected with gentamicin- or amikacin-resistant strains bearing some of the aminoglycoside-inactivating enzymes.

Amikacin↗
PubMed1984

Gastrointestinal motor-stimulating activity of macrolide antibiotics and analysis of their side effects on the canine gut.

For clarification of the nature of the side effects of macrolide antibiotics on the gastrointestinal tract, the motor-stimulating activity of these agents was studied in unanesthetized dogs. The results showed that erythromycin and oleandomycin, the 14-membered macrolides with two side chain sugars combined at C3 and C5 in a glycosidic linkage in parallel, strongly stimulate gastrointestinal motor activity, an action accompanied by vomiting at large doses. On the other hand, leucomycin, acetylspiramycin, and tylosin, belonging to a 16-membered macrolide with two side chain sugars in series combined at C5 of the lactone ring, did not induce contractions of the gastrointestinal tract. Motor-stimulating activity by erythromycin and oleandomycin was greatly inhibited by atropine sulfate. These results point to structure-physiological activity relationships.

Aminoglycosides↗