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Biomedical subjects

H Gershon

Publications and source records attributed to H Gershon.

At least 19 recordsLinked to original sources
PubMed1991

Evidence of steric factors in the fungitoxic mechanisms of 8-quinolinol and its 5- and 7-halogenated analogues.

Antifungal studies were made of mixtures of minimal inhibitory concentrations (MICs) of 8-quinolinol and its 5- and 7-halo analogues against six fungi: Aspergillus niger, A. oryzae, Trichoderma viride, Myrothecium verrucaria, Mucor cirinelloides, and Trichophyton mentagrophytes. Mixtures of 8-quinolinol with 5- or 7-fluoro-8-quinolinol and of 5- and 7-fluoro-8-quinolinol showed additive activity, and their respective toxicities were reversed by L-cysteine. These results suggested a common mechanism of activity for the three toxicants. Potentiation of the fungitoxicity of mixtures of 8-quinolinol and its 5- and 7-chloro, bromo, and iodo analogues, as well as mixtures of 5- and 7-chloro, 5- and 7-bromo, and 5- and 7-iodo-8-quinolinols, along with the absence of protection of the fungi by L-cysteine from the toxicities of these compounds was observed. This suggested that the modes of action of these compounds were different from each other and from 8-quinolinol and the 5- and 7-fluoro analogues. The geometry of 8-quinolinol as influenced by substituents in the 5- and 7- positions of the molecule determines its site(s) of fungitoxicity.

Antifungal Agents↗
PubMed1991

In vitro sequestration of erythrocytes from hosts of various ages.

Erythrocytes from young and old human donors were separated according to age-density on Stractan gradients. Old donors had more low age-density (young) erythrocytes than did young donors. Levels of IgG bound to old and young erythrocytes were determined by ELISA. Erythrocytes from old donors bore higher levels of IgG on their erythrocytes (123 +/- 55 IgG molecules per young RBC and 196 +/- 43 IgG per old RBC) than did those from young donors (58 +/- 15 IgG per young RBC and 98 +/- 20 IgG per old RBC). In an in vitro erythrophagocytosis assay, young and old erythrocytes from old donors and old erythrocytes from young donors were shown to be recognized and phagocytosed by lymphokine activated human peripheral blood monocytes. Young erythrocytes from young donors were not phagocytosed in this assay. The in vitro erythrophagocytosis of erythrocytes from old and young donors can be specifically blocked by beta-galactoside but not alpha-galactoside sugars. This phagocytosis is not blocked by Protein-G which specifically blocks Fc-gamma mediated erythrophagocytosis of Rh-D+ erythrocytes coated with IgG anti-Rh-D antibodies. beta-galactoside and alpha-galactoside sugars have no inhibitory effect on erythrophagocytosis mediated by IgG anti-Rh-D antibodies coating Rh-D+ erythrocytes. It thus appears that erythrophagocytosis of young and old erythrocytes from old donors and old erythrocytes from young donors are all mediated by a lectin-like receptor on the monocytes which recognizes beta-galactoside-like sugar moiety on the erythrocytes rather than by recognition of IgG on the erythrocyte and an Fc receptor on the macrophage. It also appears that the membrane of both young and old erythrocytes of old donors are marked for phagocytosis whereas only the old erythrocytes from young donors are so marked.

Adult↗
PubMed1979

T-cell division and aging.

The age-dependent drop in mixed lymphocyte reactivity and responsiveness to concanavalin A of lymph node and spleen cells of C57Bl/6J female mice were studied. The relative decrease in mixed lymphocyte reactivity was shown to be the same whether mounted against H-2 or Mls incompatibile stimulator cells. The time of peak response in vitro as well as the sensitivity to stimulator cell concentration are not altered with age. Cell cycle studies demonstrate that those cells which respond in vitro to alloantigens or to concanavalin A do so with a cell cycle which does not change with the age of the lymphocyte donor. In addition, regardless of the age of the donor, those cells which divide in vitro demonstrate identical capacities to redivide. These experiments suggest that the decline in observed T-cell proliferation in mixed lymphocyte and mitogen reactivity of senescent mice is not to a decreased cell generation time or to a reduced capacity to divide and redivide but rather to a smaller population of reactive cells.

Aging↗
PubMed1979

Dipeptides of O-methyl-L-threonine as potential antimalarials.

L-Leucyl-O-methyl-L-threonine, O-methyl-L-threonyl-L-leucine, and O-methyl-L-threonyl-O-methyl-L-threonine were prepared and compared with O-methyl-L-threonine and L-leucine for antimalarial activity against Plasmodium berghei in mice. O-Methyl-L-threonine significantly prolonged survival time at doses of 160, 320, and 640 mg/kg. O-Methyl-L-threonyl-O-methyl-L-threonine was less active, significantly prolonging survival time only at 640 mg/kg. L-Leucine, as well as the other two dipeptides, exhibited no activity in this test.

Animals↗
PubMed1978

Antifungal properties of halofumarate esters.

Alkyl esters (C1--C4) of the four halofumaric acids were tested for antifungal activity against Candida albicans, Aspergillus niger, Mucor mucedo, and Trichophyton mentagrophytes at pH 5.6 and 7.0 in the absence and presence of 10% beef serum in Sabouraud dextrose agar. The most toxic compound to each organism was: C. albicans, ethyl iodofumarate (0.054 mmole/liter); A. niger, methyl bromofumarate (0.090 mmole/liter); M. mucedo, methyl fluorofumarate (0.037 mmole/liter); and T. mentagrophytes, ethyl iodofumarate (0.020 mmole/liter). The order of overall activity of the six most toxic compounds was: ethyl iodofumarate greater than ethyl chlorofumarate greater than methyl iodofumarate = methyl bromofumarate greater than methyl chlorofumarate greater than bromofumarate.

Antifungal Agents↗
PubMed1978

Amino acid analogs IV:4-fluoroisoleucine.

4-Fluoroisoleucine was produced by ammonolysis of 2-bromo-4-fluoro-3-methylpentanoic acid, which resulted from the bromofluorination of 4-methyl-2-pentenoic acid. It did not inhibit Plasmodium berghei in mice at 640 mg/kg and was not toxic to the animals. The fluoroamino acid inhibited Aspergillus niger, Trichoderma viride, Myrothecium verrucaria, Trichophyton mentagrophytes, and Mucor mucedo in Czapek solution agar at a concentration between 10(4) and 10(3) microgram/ml. Growth of Escherichia coli was inhibited 25% at 900 microgram/ml in a defined medium.

Animals↗
PubMed1978

Antifungal properties of 2-alkynoic acids and their methyl esters.

Thirteen 2-alkynoic acids and their methyl esters (C3--C12, C14, C16, and C18) were tested against Aspergillus niger, Trichoderma viride, and Myrothecium verrucaria in Sabouraud dextrose agar at pH 4.0 and 5.6. Toxicity to Candida albicans, Trichophyton mentagrophytes, and Mucro mucedo was determined in the same medium at pH 5.6 and 7.0 in the absence and presence of 10% beef serum. The fungitoxicity of the acids was influenced by chain length, pH of the medium, and absence or presence of adsorbents. The toxicity of the esters was influenced primarily by chain length and to a lesser extent by the pH of the medium and the presence of beef serum. The order of activity of the 2-alkynoic acids is C10=C11=C12 greater than C14=C16 greater than C9 greater than C8 greater than C7. When compared with other fatty acid analogs, the order of fungitoxicity on a weight basis is 2-alkynoic acids greater than 2-alkenoic acids greater than alkanoic acids greater than 2-bromoalkanoic acids greater than 2-fluoroalkanoic acids. There is an inverse relationship between chain length and pKa of the acids, suggesting that partition behavior is a fundamental determinant of fungitoxicity along with the effect of adsorbents.

Alkynes↗
PubMed1977

Reduced in vitro response to concanavalin A and lipopolysaccharide in senescent mice: a function of reduced number of responding cells.

The proliferative capacity of spleen cells from C57BL/6J female mice of various ages (3-28 months) to the polyclonal mitogens concanavalin A (Con A) and lipopolysaccharide (LPS) was examined. It was found that both the T and B cell population of the spleen demonstrate an age-related decrease in their capacity to respond in vitro. Peak responses to both mitogens occurs at about 1 year of age. This age-related reduction in response is expressed in the degree of incorporation of [3H]thymidine into DNA, the total number of cells generated in vitro, the number of labeled cells per culture and the number of blast cells per culture. The day of peak response in vitro does not change with age. Studies of the cell cycle of cells responding to Con A and to LPS from 12 and 28-month-old mice demonstrate that the generation time of individual proliferating cells does not alter with age. Nor does it differ for the B cells responding to LPS or the T cells responding to Con A. These studies also demonstrate that the proliferating cells from senescent mice are equally capable of repeated cell divisions as are the cells from the 1-year-old adult mouse. It is concluded that the defect in senescent mice which leads to a reduced in vitro response to the polyclonal mitogens LPS and Con A is a reduction in the number of responding cells and not an alteration in the capacity of those cells which do respond to divide.

Aging↗
PubMed1977

Nitrophenylated derivatives of epsilon-aminocaproic acid: synthesis and physico-chemical characterization.

Methods for the synthesis of the mono-, di- and tri-nitro derivatives of epsilon-aminocaproic acid are presented. Special attention is given to the purification procedure, as we have found that methods recommended in the literature do not produce a single product. Evidence is presented which shows that recrystallizing the haptens from hot ethanol produces a by-product which is the ethyl ester of the haptens. Characterization methods and physical properties of the nitro-phenylated derivates of epsilon-aminocaproic acid are summarized.

Aminocaproates↗
PubMed1977

Antifungal properties of 2-bromo-3-fluorosuccinic acid esters and related compounds.

Twelve esters (C1-C6) of erythro- and threo-2-bromo-3-fluorosuccinic acid and related compounds were tested for antifungal activity against Candida albicans, Aspergillus niger, Mucor mucedo, and Trichophyton mentagrophytes at pH 5.7 and 7.0 in the absence and presence of 10% beef serum in Sabouraud dextrose agar. At pH 7.0 in the presence of 10% beef serum, no consistent pattern in the fungitoxicity of the erythro- and threo-2-bromo-3-fluorosuccinate esters was seen. Increasing the length of the ester function affects fungitoxicity as follows: C2 greater than C1 greater than C3 greater than C4 greater than C5 greater than C6. The most fungitoxic compound in this study was threo-ethyl 2-bromo-3-fluorosuccinate (C. albicans, 14 mug/ml; A. niger, 30 mug/ml; M. mucedo, 9 mug/ml; T. mentagrophytes, 5 mug/ml). Due to the ease of dehydrohalogenation, the fungitoxicity of 2-bromo-3-fluorosuccinic acid esters may be the result of a mixture composed of the parent compound, the bromo- and fluorofumaric acid esters, and HF and HBr of which part may be formed extracellularly and part within the cell.

Antifungal Agents↗
PubMed1976

Antifungal activity of 4-substituted crotonic acid esters.

Twenty-three 4-substituted crotonic acid esters were tested for antifungal activity against Candida albicans, Aspergillus niger, Mucor mucedo, and Trichophyton mentagrophytes. For the analogues of the methyl ester containing substituents in the 4 position, the following order of fungitoxicity was observed: I greater than Br greater than Cl greater than CH3S greater than CH3O greater than F=H. Of the homologues of the esters of the 4-iodo and 4-bromo compounds which included methyl, ethyl, n-propyl, n-butyl, n-pentyl, and n-hexyl, ethyl 4-iodocrotonate was most toxic to the four fungi at pH 7.0 in the presence of 10% beef serum (C. albicans, 18mug/ml, A. niger, 40 mug/ml, M. mucedo, 5 mug/ml, T. mentagrophytes, 4 mug/ml). It is believed that the mechanism of fungitoxicity is due, in part, to a nucleophilic reaction involving SH-containing compounds. This is based on the correlation of fungitoxicity with the order of leaving groups in the nucleophilic reaction and the protection against the toxicity of the test compounds to the fungi by cysteine and glutathione.

Antifungal Agents↗
PubMed1976

Antifungal properties of alpha,omega-alkanedicarboxylic acids and their dimethyl esters.

Thirteen alpha, omega-alkanedicarboxylic acids (C2-C12, C14, and C16) and their dimethyl esters were tested against Aspergillus niger, Trichoderma viride, and Myrothecium verrucaria in Sabourauc dextrose agar at pH 4.0 AND 5.6. Toxicity to Canadida albicans, Trichophyton mentagrophytes, and Mucor mucedo was determined in the same medium at pH 5.6 and 7.0 in the absence and presence of 10% beef serum. The dicarboxylic acids possessed very poor to no antifungal activity against all six fungi. The fungitoxicity of the dimethyl esters to A. niger, T. viride, and M. verrucaria was C8 = C9 greater than C7 greater than C6 = C5 greater than C10 greater than C4 greater than C11 and to C. albicans, T. mentagrophytes, and M. mucedo C9 greater than C10 greater than C11 greater than C12 = C8 greater than C7 greater than C6 greater than C5 greater than C4 greater than C3. The fungitoxicity of the esters of fatty acids and alpha-omega-alkanedicarboxylic acids was influenced by chain length and not by the pH of the medium or the absence or presence of beef serum.

Animals↗