PubMed Health⌕ Search

Biomedical subjects

D S Feingold

Publications and source records attributed to D S Feingold.

At least 109 records · Page 6Linked to original sources

Selective membrane toxicity of the polyene antibiotics: studies on natural membranes.

The effect of polyene antibiotics on Candida albicans, human erythrocytes, and Acholeplasma laidlawii was studied. The results sustain the observations made with lecithin-sterol liposomes. The distribution of double bonds in the membrane sterol nucleus appears to be of major importance in conferring polyene susceptibility; those sterols with the ergosterol nucleus are far more effective than those with a nucleus similar to cholesterol. Different polyenes vary in their membrane selectivity. The clinical implications of these observations are discussed.

Acholeplasma laidlawii↗

Prevention of gram-negative bacillary pneumonia using aerosol polymyxin as prophylaxis. I. Effect on the colonization pattern of the upper respiratory tract of seriously ill patients.

A prospective study used polymyxin B by aerosol to reduce colonization of the upper respiratory tract with nosocomial gram-negative bacilli. 58 high-risk patients from the Respiratory-Surgical Intensive Care Unit entered the trial. 33 were randomly selected to receive 2.5 mg/kg/day of polymyxin B by hand atomizer into the pharynx, and tracheal tube if present. 17 of 25 control patients became colonized with gram-negative bacilli as compared with 7 of 33 polymyxin-treated patients (p < 0.01). Control patients became colonized with a total of 33 gram-negative bacilli: 3 were Pseudomonas aeruginosa, 21 were species of Enterobacteriaceae. The polymyxin-treated patients became colonized with a total of 11 gram-negative bacilli: no P. aeruginosa and only 3 species of Enterobacteriaceae were recovered. Colonization increased with duration in Respiratory-Surgical Intensive Care Unit and with time of required controlled ventilation. Polymyxin most effectively prevented the increase in colonization in treated patients who stayed in the Respiratory-Surgical Intensive Care Unit for longer than 1 wk and who required controlled ventilation for at least 72 h.

Adult↗

Effect of polymyxin B on antibiotic-resistant Proteus mirabilis.

The surface properties of polymyxin B-resistant Proteus mirabilis are markedly altered by the antibiotic. The effects include the development of susceptibility to surface-active agents such as deoxycholate or tris(hydroxymethyl)aminomethane and a marked increased osmotic fragility. However, cell wall impermeability to various agents such as erythromycin, actinomycin D, bacitracin, lysozyme, and triphenyltetrazolium chloride apparently remains intact. These results support the concept that the actions of the polymyxins on gram-negative bacteria are multiple; the action(s) of the antibiotic responsible for lethality in vitro, presumably at the level of the cytoplasmic membrane, may represent only a portion of the potential therapeutic effects of the antibiotic in vivo.

Deoxycholic Acid↗

Locus of divalent cation inhibition of the bactericidal action of polymyxin B.

The bactericidal effect of polymyxin B upon two Pseudomonas aeruginosa strains and two Escherichia coli strains was studied as a function of the concentration of the divalent cations Ca(2+) and Mg(2+). Lipid spherules in aqueous suspension (liposomes) were prepared from the bacterial phospholipids and were examined for the release of trapped glucose induced by polymyxin B under similar conditions of divalent cation concentration. In contrast to the bacteria, which were protected markedly from the bactericidal action of polymyxin B by Ca(2+) or Mg(2+) at concentrations of 2 x 10(-3)m or less, neither cation had any protective effect on bacterial liposomes at concentrations up to 2 x 10(-2)m. These observations suggest that divalent cations antagonize the bactericidal effect of polymyxin B indirectly through interaction with the cell wall rather than at the primary membrane locus of action. The interaction of the divalent cations with the cell wall prevents access of the antibiotic to the cytoplasmic membrane by mechanisms that remain unclear.

Calcium↗

Nucleoside diphosphate-sugar 4-epimerases. II. Uridine diphosphate arabinose 4-epimerase of wheat germ.

Uridine diphosphate (UDP)-arabinose 4-epimerase (EC 5.1.3.5) has been purified at least 20-fold from wheat germ by MnCl(2) treatment, (NH(4))(2)SO(4) fractionation, dialysis, and Sephadex and diethylaminoethyl cellulose column chromatography. The enzyme has no action on UDP-d-glucose, UDP-d-glucuronic acid, or TDP-d-glucose. The pH optimum is 8.0. Km values are 1.5 mM for UDP-d-xylose and 0.5 mm for UDP-l-arabinose. The equilibrium constant, K, for the reaction UDP-l-arabinose left arrow over right arrow UDP-d-xylose is 1.25. The enzyme is neither activated by nicotinamide adenine dinucleotide nor inhibited by reduced nicotinamide adenine dinucleotide. It is completely inhibited by p-chloromercuri-phenylsulfonate; the inhibition is reversed by cysteine.

Isomerases↗

D-glucaric acid and galactaric acid catabolism by Agrobacterium tumefaciens.

Cell-free extract (crude extract) of Agrobacterium tumefaciens grown on d-glucuronate or d-glucarate converts d-glucarate and galactarate to a mixture of 2-keto-3-deoxy- and 4-deoxy-5-keto-d-glucarate. These compounds are then converted by partially purified crude extract to an intermediate tentatively identified as 2,5-diketoadipate. The same enzyme preparation further decarboxylates this intermediate to alpha-ketoglutarate semialdehyde, which is subsequently oxidized in a nicotinamide adenine dinucleotide-dependent reaction to alpha-ketoglutaric acid. Since A. tumefaciens converts d-glucuronic acid to d-glucarate, a pathway from d-glucuronate to alpha-ketoglutarate in A. tumefaciens was determined.

Adipates↗

Mechanism of polymyxin B resistance in Proteus mirabilis.

The lipids from three types of organisms-a Proteus mirabilis wild type highly resistant to polymyxin B, a polymyxin B-sensitive mutant derived from the wild type, and the wild type grown in the presence of sulfadiazine resulting in phenotypic conversion to polymyxin B sensitivity-were examined to determine the nature of polymyxin B resistance. The phospholipid compositions were nearly identical; each organism contained similar small amounts of N-methyl phosphatidylethanolamine in addition to comparable quantities of phosphatidylethanolamine, phosphatidylglycerol, and cardiolipin. the fatty acid compositions were similar in the exponential phase of growth; in the stationary phase, sulfadiazine markedly inhibited the synthesis of cyclopropane fatty acids. Liposomes prepared from the dried lipids of the three types of organisms were extensively and similarly disrupted by the polymyxin. These findings suggest that polymyxin B resistance in P. mirabilis is determined by the cell envelope which prevents access of the antibiotic to the susceptible lipid target sites.

Chromatography↗