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Biomedical subjects

H Gershon

Publications and source records attributed to H Gershon.

At least 55 records · Page 3Linked to original sources

Antifungal properties of 2-n-alkyn-1-ols.

Fourteen 2-n-alkynols (C3-C14, C16, and C18) were tested against Aspergillus oryzae, Aspergillus niger, Trichoderma viride, and Myrothecium verrucaria in Sabouraud dextrose agar at pH 5.6 and 7.0. Toxicity to Candida albicans, Candida tropicalis, 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. Fungitoxicity was strongly influenced by chain length, slightly by the pH of the medium, and significantly by the presence of beef serum. 2-n-Undecyn-1-ol was the most active member of the series, and there was marked synergism between it and ketoconazole.

Alkynes↗

Induction of interleukin-2 and colony-stimulating factors in lymphoid cell cultures activated by mitogenic mycoplasmas.

Mycoplasmal infections often result in chronic inflammatory diseases that involve both local cell proliferation and chemotactic phenomena. To clarify the mechanisms responsible for these inflammatory reactions, we have examined whether nonspecific activation of host lymphocytes by mitogenic mycoplasmas triggers the production of lymphokines, which influence differentiation and proliferation of lymphocytes, macrophages and granulocytes. Mycoplasma pulmonis and M. neurolyticum were tested for their ability to induce production of interleukin-2 (IL-2) and colony-stimulating factors (CSF) by activated lymphoid cells. Mitogenic doses of membranes purified from M. pulmonis, as well as concanavalin A (ConA), induce rat lymphocytes to produce IL-2. Stimulation with the T cell mitogen ConA induces twice the level of IL-2 than does stimulation with M. pulmonis, which activates both rat B- and T-lymphocytes. Unlike these T cell mitogens, M. neurolyticum, which stimulates rat and mouse B-lymphocytes, lacks the ability to induce production of IL-2. Nevertheless, M. neurolyticum stimulates mouse spleen cells to produce in vitro factors capable of stimulating differentiation of bone marrow cells into colonies of macrophages and granulocytes.

Animals↗

In vitro induction of malignant transformation and in vivo resistance to tumor growth in the X/Gf mouse.

Inbred X/Gf mice are reported to have a very low incidence of spontaneous and induced tumors. Experiments were performed to determine whether the cells of the X/Gf mouse are themselves resistant to in vitro oncogenesis or the organism as a whole is surveyed by a homeostatic mechanism that prevents the expression of potential neoplasia. Cultures of X/Gf or C57BL/6J embryonic fibroblasts were exposed to the chemical carcinogens 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene to test whether the cells of the X/Gf mouse are themselves resistant to oncogenesis. The chemical carcinogens caused transformation of both X/Gf and C57BL/6 fibroblasts into cells that demonstrated altered growth patterns in liquid culture and grew in a clonal fashion in soft agar. Cloned transformed cells were shown to be malignant and resulted in the growth of sarcomas in vivo. X/Gf mice were decidedly more resistant than were C57BL/6 mice to their respective clones of transformed cells. The resistance to neoplastic growth demonstrated by the X/Gf mice was inherited by (C57BL/6J X X/Gf)F1 mice that were resistant to the growth of X/Gf-transformed and C57BL/6-transformed cells at cell doses at which the parental X/Gf mice had survived but at which the C57BL/6 had succumbed to progressively growing tumors. It has thus been established that the tumor resistance of the X/Gf mice is not based on the resistance of isolated cells from these animals to malignant transformation, but rather is attributable to an in vivo homeostatic mechanism that prevents tumor growth.

9,10-Dimethyl-1,2-benzanthracene↗

The effect of donor and cell age on several characteristics of rat erythrocytes.

Erythrocytes from young and old WF rats were separated by discontinuous density gradient centrifugation. The density and mean life span of the erythrocytes were correlated with cell age by 59Fe pulse labeling. A mean half-life of 40 and 25 days was measured for erythrocytes in young and old animals, respectively, with a corresponding 4-fold increase of young cells and a 2.3-fold increase in circulating reticulocytes in old animals. Thus, the old rat has a chronologically younger population of circulating erythrocytes than the young animal. The mean hemoglobin concentration of red cells from old, but not young animals, was found to decrease from 18.5 +/- 2.1 pg to 11.8 +/- 1.8 pg per cell with increasing cell age. Premature exposure of a surface antigen, which is recognized by antibodies present in the serum, was observed in cells of old animals. This antigen-antibody complex is presumed to trigger sequestration by phagocytosis of senescent erythrocytes. The contribution of the observed age-related changes to early erythrocyte sequestration in old animals is discussed.

Aging↗

Effect of 2-alkynoic acids on in vitro growth of bacterial and mammalian cells.

3-Decynoyl-N-acetylcystamine is known to inhibit the in vitro growth of Escherichia coli but not of yeasts or mammalian cells. Neither the free acid nor the 2 positional isomer is active (L. R. Kass, J. Biol. Chem. 243:3223-3228, 1968). Other studies have shown that 2-hexadecynoic acid is fungitoxic whereas most of the shorter chain isomers are inactive (H. Gershon and L. Shanks, Can J. Microbiol. 24:591-597, 1978). Since these studies suggested that positional or chain length isomers of the acetylenic acids may selectively inhibit the growth of microorganisms, the effect of the alkynoic acids on the in vitro growth of gram-positive and gram-negative bacteria was evaluated. 2-Hexadecynoic acid was found to be the most active species. This acid was bacteriostatic for all gram-positive bacteria tested. The acid was readily taken up by the treated cells and incorporated into the phospholipid fraction. When added to the culture medium, 2-hexadecynoic acid inhibited the growth of HeLa cells, but when mixed with an equivalent amount of palmitic acid, growth inhibition was not observed.

Bacteria↗

Reversal of fungitoxicity of 8-quinolinols and their copper(II) bischelates. II. Reversal of the action of 8-quinolinol by DL-alpha-lipoic acid.

The effect of amino acids and derivatives, Krebs cycle acids and related compounds, fatty acids, and vitamins and related compounds on the toxicity of 8-quinolinol and bis(8-quinolinolato)copper(II) to Aspergillus oryzae (ATCC 1011) was studied. Only aliphatic thiol-containing compounds (cysteine, glutathione, dithioerythritol, and dithiothreitol) and DL-alpha-lipoic acid protected against 8-quinolinol but not its copper(II) bischelate. It is suggested that 8-quinolinol inhibits lipoic acid biosynthesis, and the mode of fungitoxicity of 8-quinolinol is different from that of bis(8-quinolinolato)copper(II).

Amino Acids↗

Antifungal properties of n-alkanols, alpha, omega-n-alkanediols, and omega-chloro-alpha-alkanols.

Fourteen n-alkanols (C1-C12, C14, and C16), 13 alpha,omega-n-alkanediols (C2-C12, C14, and C16), and 13 omega-chloro-alpha-alkanols (C2-C12, C14, and C16) were tested against Aspergillus niger, Trichoderma viride, and Myrothecium verucaria in Sabouraud dextrose agar at pH 4.0 and 5.6. Toxicity to Candida blbicans, 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 fungitoxicity of these alcohols was influenced by chain length and insignificantly by the pH of the medium and the presence of beef serum. The C10-member of each series was most active; the order of activity of the three groups was chloroalkanols greater than alkanols greater than alkanediols. Compared to the fatty acids, the order of fungitoxicity on a weight basis was 2-alkynoic acids greater than 2-alkenoic acids greater than omega-chloralkanols greater than alkanoic acids greater than 2-bromoalkanoic acids greater than 2-fluoroalkanoic acids greater than n-alkoxyacetic acids greater than n-alkanols greater than alpha,omega-n-alkanediols.

Alcohols↗

Effect of methyl 2-hexadecynoate on hepatic fatty acid metabolism.

Normal and hepatoma bearing rats were fed a low level of methyl 2-hexadecynoate in a low fat diet for one month. The effect of the acetylenic acid on lipid metabolism as derived from mass analysis of lipid classes, fatty acids and positional monoene isomers isolated from the major lipid classes of liver and hepatoma has been assessed. Methyl 2-hexadecynoate caused a 25% decrease in body weight and the appearance of essential fatty acid deficiency symptoms within one week. Non-tumor-bearing animals contained a seven-fold increase in all neutral lipid classes, except cholesterol, while host animals did not contain fatty livers. The apparent protective effect of the host animal by the hepatoma also resulted in only marginal changes in the fatty acid and positional monoene isomers from host liver and hepatoma lipids. In contrast to host liver and hepatoma, methyl 2-hexadecynoate caused a massive accumulation of palmitate and hexadecenoates with a concomitant decrease in stearate and octadecenoates in most of the lipid classes from non-tumor-bearing animals. These changes were accompanied by a shift from the higher molecular weight triglycerides to lower molecular weights corresponding to carbon number 48. The high concentrations of hexadecenoates consisted predominantly of the delta 9 isomer. Despite the high concentrations of cis delta 9 hexadecenoate, precursor of cis delta 11 octadecenoate (vaccenate), total vaccenate levels of the five major lipid classes were lower than control values. All of these data strongly suggest that long-chain 2-ynoic acids inhibit elongation of saturated and monoene fatty acids.

Animals↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗