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Biomedical subjects

D S Feingold

Publications and source records attributed to D S Feingold.

At least 19 recordsLinked to original sources

Detection of 3-hydroxy fatty acids at picogram levels in biologic specimens. A chemical method for the detection of Neisseria gonorrhoeae?

A method for the detection of 3-hydroxy dodecanoic acid at low picogram levels is described. The procedure involves preparation of a heptafluorobutryl derivative of the butyl ester of the fatty acid and its detection by gas-liquid chromatography using an electron capture detector. The method was adapted for use with biological specimens. Potential of the method for screening for gonococcal infection is discussed. Limitations of the method are that about 105 Neisseria gonorrhoeae cells are required for detection and that interfering substances are a major problem working at maximum sensitivity of the electron capture detector necessitating complex purification procedures. The method eliminates the need to maintain the viability of cells in specimens, thus facilitating collection and transport of specimens.

Bacteriological Techniques

Lipid composition and sensitivity of Prototheca wickerhamii to membrane-active antimicrobial agents.

The lipid composition of Prototheca wickerhamii ATCC 16529 is presented and discussed in relation to the unique susceptibility of the organism to drugs of three membrane-active antimicrobial classes: the polyenes, the polymyxins, and the imidazoles. The presence of ergosterol in the neutral lipid fraction of the membrane is likely responsible for the exquisite susceptibility to amphotericin B. The presence of a large quantity of free fatty acids in the membrane appears responsible for imidazole susceptibility. The membrane determinants of polymyxin B susceptibility are less well defined.

Anti-Infective Agents

Effect of free fatty acids on liposome susceptibility to imidazole antifungals.

The presence of free fatty acids in liposome model membranes sensitizes these membranes to the action of the imidazole antifungals, clotrimazole, micronazole, and sulconazole. Unsaturation of the fatty acids is an important variable; the effect of linoleic and oleic acids is much greater than that of stearic acid. The imidazoles differ somewhat in action, with clotrimazole potency greatest both on membranes with and without fatty acids. Sulconazole has very little activity on membranes without fatty acids even at the highest concentrations tested. The data are discussed with reference to the susceptibility of various cells to the imidazoles and the specificity of imidazole action. A modification of the enzymatic method generally used for assay of marker glucose with liposome systems is also presented.

Antifungal Agents

Enhancement of resistance to murine osteogenic sarcoma in vivo by an extract of Brucella abortus (Bru-Pel): association with activation of reticuloendothelial system macrophages.

The administration of an aqueous-ether extracted residue of Brucella abortus (Bru-Pel) inhibits development of transplanted osteogenic sarcomas in mice as evidenced by a decrease in mortality. At least one mechanism through which Bru-Pel modulates host resistance is activation of macrophages of the reticuloendothelial system. Peritoneal macrophages harvested from mice receiving Bru-Pel were cytotoxic for osteogenic sarcoma cells in vitro, limited the replication of vaccinia virus in cell cultures, and demonstrated enhanced emittance of chemiluminescence during phagocytosis of zymosan particles of Candida albicans. The concept of reticuloendothelial system activation was further supported by the evidence that administration of Bru-Pel enhanced resistance of mice to challenge with a lethal inoculum of Listeria monocytogenes. These observation support the hypothesis that Bru-Pel shares a number of characteristics with recognized immunomodulating agents and that one mechanism by which it modulates host resistance to tumors, to virus infections, and to challenge with L. monocytogenes is through activation of macrophages.

Animals

Induction of colitis in hamsters by topical application of antibiotics.

Syrian hamsters are exquisitely sensitive to clindamycin; as little as 1 mg/kg of clindamycin given systemically causes a fatal colitis. Clindamycin and erythromycin were applied topically daily to the shaved backs of Syrian hamsters in a hydroalcoholic vehicle. A daily dose of 0.1 mg of clindamycin was lethal to more than half the hamsters and 1 mg to all the animals. The antibiotic-associated toxin from Clostridium difficile was present in their cecal material. Based on body surface areas and estimated usual volumes applied, the lethal dose in hamsters is not dissimilar to that given humans for acne. Oral tetracycline therapy protected the animals from clindamycin toxicity, but the animals died three days after stopping tetracycline if topical clindamycin applications were continued.

Administration, Topical

Dissociation between ion permeability and the lethal action of polyene antibiotics on Candida albicans.

Kinetic data on potassium release from and killing of Candida albicans by the four polyene antibiotics amphotericin B, amphotericin B methyl ester hydrochloride, nystatin, and nystatin methyl ester hydrochloride are presented. The nystatins were relatively more effective than the amphotericins in causing potassium release rather than killing. These data suggest that the aqueous channels or pores formed by the polyene antibiotics are not central to the lethal action of the drugs.

Amphotericin B

Activation of reticuloendothelial system macrophages and enhancement of host resistance to a transplantable osteogenic sarcoma in mice by an extract of Brucella abortus.

An aqueous-ether extract of Brucella abortus, Bru-Pel, enhanced resistance of mice to a transplantable osteogenic sarcoma (OGS). The results presented in this report suggest that Bru-Pel is an effective immunomodulator and that one mechanism through which it enhances host resistance is activation of phagocytic cells of the reticuloendothelial system. Peritoneal macrophages from mice inoculated with Bru-Pel 14 days previously were cytotoxic for OGS cells in vitro, limited the multiplication of vaccinia virus in cell cultures, and demonstrated increased chemiluminescence during phagocytosis. Furthermore, Bru-Pel enhanced host resistance to Listeria monocytogenes, in addition to viral infections and a transplantable tumor. These results support the hypothesis that Bru-Pel shares a number of characteristics with other recognized immunomodulating agents and suggest that further studies are warranted to better define the potential of Bru-Pel for immunotherapeutic regimens in man.

Animals

Overview of the activity of a Brucella abortus preparation, Bru-Pel.

The properties of a nonviable, aqueous ether-extracted Brucela abortus preparation, Bru-Pel, are described. In addition to inducing a "virus-type" interferon response and protecting mice against challenge with otherwise lethal doses of Semliki Forest virus, Bru-Pel is demonstrated to have potent antitumor properties in mice. These antitumor effects appear to be mediated by an increase in nonspecific resistance similar to that seen with other experimental antitumor agents.

Animals

Antitumor activity of a Brucella abortus preparation.

Mice injected intraperitoneally with sarcoma-180 cells develop ascites and eventually die. Intraperitoneal injection of a nonviable, aqueous... ether-extracted Brucella abortus preparation (BRU-PEL) as early as 7 days before or as late as 7 days after injection of tumor cells significantly inhibited development of ascites and protected against death. BRU-PEL was not effective if injected after ascites was grossly apparent. BRU-PEL was significantly more active than a Corynebacterium parvum preparation administered in the same way.

Animals

UDP-glucose dehydrogenase from Escherichia coli. Purification and subunit structure.

UDPglucose dehydrogenase from Escherichia coli has been purified 330-fold with an overall yield of 27%. A single homogeneous subunit was demonstrated by ultracentrifugation in 6 M guanidium chloride and by dodecyl sulfate-polyacrylamide gel electrophoresis. Since the molecular weight of the intact dehydrogenase is in the order of 86 000 and the subunit weight determined by the dodecyl sulfate-polyacrylamide gel electrophoresis is 47 000, the enzyme consists of two polypeptide chains. The sole amino terminal acid shown by the dansylation technique was arginine. Forty-four tryptic peptides were obtained by peptide mapping, in agreement with the number of arginine and lysine residues/mole protein [43] determined by amino acid analysis. The data are consistent with the presence of two identical or very similar polypeptide chains in E. coli UDPglucose dehydrogenase.

Alcohol Oxidoreductases

L-Rhamnose dehydrogenase of pullularia pullulans.

Growth of Pullularia pullulans on L-rhamnose induces formation of L-rhamnofuranose dehydrogenase, whichreversibly converts L-rhamnofuranose to L-rhamnono-gamma-lactone with the concomitant reduction of NAD, but not of NADP. The dehydrogenase was purified 100-fold by MnCl(2) treatment...

Alcohol Oxidoreductases