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Biomedical subjects

M J Weinstein

Publications and source records attributed to M J Weinstein.

At least 55 records · Page 3Linked to original sources

Micromonospora-produced sisomicin components.

A sisomicin fermentation carried out in the presence of (methyl-14C)-L-methionine resulted in a crude mixture, composed of methyl-14C-labeled sisomicin as a major component; and two 4''-C-desmethylsisomicin (66-40B and 66-40D) isomer-like components, an unidentified component and a gentamicin A-like antibiotic as minor components. When (methyl-14C)-L-methionine was added in an early stage of the fermentation (24 hours), incorporation of methyl-14C-label into polar components (e.g., gentamicin A-like antibiotic) preceded that into sisomicin. Chromatographic evidence for the bioconversion of (methyl-14C)-gentamicin A to a radioactive sisomicin-like product (possibly (3''-N-methyl-14C)-sisomicin) was seen, when a Micromonospora blocked mutant was incubated in the presence of the former antibiotic.

Anti-Bacterial Agents↗

Isolation, subunit structure, and proteolytic modification of bovine factor VIII.

A new method has been described for the isolation of factor VIII. The method results in a high yield of factor VIII that is homogeneous by several different criteria. The purified protein is very stable and is not dissociated in the presence of 1 M NaCl or 0.25 M CaCl2. The highly purified protein is readily activated and inactivated by various proteolytic enzymes, such as thrombin, plasmin, and trypsin. The molecular events that lead to the activation reaction, however, have not been established.

Aminocaproates↗

Verdamicin, a new broad spectrum aminoglycoside antibiotic.

Verdamicin is a new aminoglycoside antibiotic isolated from fermentation broths of a species of the genus Micromonospora, M. grisea. It has been differentiated from other known related antibiotics by a variety of chemical and biological methods. Its in vitro and in vivo spectrum of activity appears to be similar to those of gentamicin and sisomicin.

Aminoglycosides↗

Binding of aminoglycoside antibiotics to filtration materials.

An investigation to study adsorption of gentamicin and other related aminoglycoside antibiotics to cellulose, diatomaceous earth (Celite), and Seitz filter sheets was carried out. Experiments with five aminoglycosides indicated that 30 to 100% of these antibiotics was adsorbed to cellulose depending on the ratio of antibiotic to adsorbent, and the total quantity could not be removed by acidification. Similarly, a study with gentamicin found adsorption to diatomaceous earth to be in the range of 33 to 98%. Neomycin and gentamicin were also readily adsorbed to Seitz filter sheets. The data indicate that large losses may occur during filtration of these antibiotics under certain conditions, and care should be taken to properly evaluate results during studies with these compounds in the presence of adsorbent materials.

Adsorption↗

BL-P1654: a bacteriostatic penicillin?

In tube dilution studies, large discrepancies between inhibitory and bactericidal concentrations of BL-P1654 against Pseudomonas were observed. To explain these discrepancies which were not observed with carbenicillin, the kinetics of bacterial killing by these two penicillins were evaluated and compared. The kinetics of bacterial killing by both antimicrobial agents were characteristic of a penicillin, with killing initiating simultaneously with growth. Kill curves revealed the presence of a small number of cells resistant to BL-P1654 which were not detectable macroscopically. Studies on microbial resistance also showed the presence of a small but consistent number of cells resistant to BL-P1654 over a broad range of concentrations above its minimal inhibitory concentration. This pattern of resistance was not observed with carbenicillin. Thus, the discrepancies between inhibitory and bactericidal concentrations of BL-P1654 were not due to any unusual bacteriostatic activity but rather due to a small number of resistant cells whose presence could be detected only by sensitive subculturing techniques.

Carbenicillin↗

New polyene antifungal antibiotic produced by a species of Actinoplanes.

A new species of Actinoplanes, which has been deposited with the designation NRRL 5325 at the Northern Utilization Research and Development Division of the U. S. Department of Agriculture, produces a polyene antifungal complex designated as Sch 16656. The complex, consisting of one major and three minor components, is isolated from the fermentation broth by a solvent extraction procedure and purified by precipitation methods. The major component is a heptaene and is highly active in vitro and in vivo against Candida albicans. It is active also against strains of Torulopsis and is significantly more potent orally than candicidin in mice against Candida infections.

Actinomycetales↗

Antibiotic G-418, a new Micromonospora-produced aminoglycoside with activity against protozoa and helminths: fermentation, isolation, and preliminary characterization.

Antibiotic G-418 is a new aminoglycoside produced as the major component by a new species of Micromonospora, M. rhodorangea NRRL 5326. The antibiotic is prepared by submerged fermentation in a soybean-dextrin medium. Antibiotic G-418 is adsorbed on a cationic-exchange resin and separated from other impurities by passing it down a Dowex (1 x 2) resin column. The antibiotic, which contains 2-deoxystreptamine, has broad-spectrum antibacterial activity and is highly active against protozoa, amoebae, tapeworm, and pinworm infections in mice. This report describes the taxonomy of the organism, and fermentation, isolation, and preliminary characterization of antibiotic G-418.

Aminoglycosides↗

Binding of aminoglycosides to feces.

Gentamicin and several other basic antibiotics were examined for their ability to adsorb to dog feces. It was found that 44 to 90% of all antibiotics studied were adsorbed to feces depending on the ratio of antibiotic to fecal material. Attempts to extract these antibiotics by acid treatment after adsorption onto feces were only partially successful since large portions of the bound materials were not removed.

Adsorption↗

Comparative activity of sisomicin, gentamicin, kanamycin, and tobramycin.

Gentamicin, sisomicin, tobramycin, and kanamycin were compared in parallel tests in vitro and in vivo against a variety of bacterial strains and species. A number of differences were seen in vitro, in particular: (i) the lower activity of kanamycin, (ii) the greater activity of tobramycin against Pseudomonas, (iii) the greater activity of gentamicin and sisomicin against Serratia, and (iv) the generally similar results with tobramycin, gentamicin, and sisomicin against species other than Pseudomonas and Serratia, with the ranking in order of decreasing activity being sisomicin, gentamicin, and tobramycin. Analysis of disc test results suggested that the gentamicin disc is not adequate for testing the susceptibility of all bacteria to sisomicin or tobramycin. In vivo tests did not confirm all specifics of in vitro tests; results of in vivo tests indicated that sisomicin may be the most active. It is suggested that the place of each of the antibiotics in human therapy can best be evaluated by more rigorous in vivo tests and clinical studies rather than extensive in vitro comparisons.

Aminoglycosides↗

Biological activity of Sch 14342, an aminoglycoside antibiotic coproduced in the gentamicin fermentation.

Sch 14342 is an aminoglycoside antibiotic coproduced as a minor component in the gentamicin fermentation. Sch 14342 was found to have the same antibacterial spectrum as gentamicin in vitro and in vivo, and was approximately one-third as active in mouse protection tests. Sch 14342 relative to gentamicin was one-third as toxic in acute tests in mice, one-eighth as toxic in renal toxicity tests in dogs, and an estimated one-tenth as toxic in cat ataxia tests. Sch 14342 possesses a significantly improved therapeutic index relative to gentamicin with reference to ataxia potential and renal toxicity.

Aminoglycosides↗