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Biomedical subjects

H Gershon

Publications and source records attributed to H Gershon.

At least 37 records · Page 2Linked to original sources
PubMed1993

Characterization of circulating erythrocytes from myelodysplastic patients treated with recombinant human erythropoietin.

Age-density fractionation, in-vitro erythrophagocytosis, and enumeration of membrane-bound antibodies were monitored for circulating red blood cells (RBC) from five anemic patients with myelodysplastic syndromes (MDS), in relation to administration of recombinant human erythropoietin (rhEPO). The density distribution patterns of erythrocytes from the patients prior to treatment were in accordance with their inability to produce compensating levels of circulating RBC. The complete response of one patient to rhEPO and partial responses of two other patients were accompanied by shifts to larger proportions of low density (young) RBC. In vitro phagocytosis of density-fractionated RBC from the complete responder was similar to those of age-matched non-anemic donors. Elevated erythrophagocytosis prior to rhEPO administration was observed for the partial responders and further increased during treatment in one, suggesting the stimulation of abnormal progenitors producing highly defective erythrocytes. There was no correlation between levels of erythrophagocytosis and RBC membrane-bound immunoglobulins in this group of patients. Our findings suggest that density distribution analysis of circulating RBC coupled with in vitro erythrophagocytosis may provide useful predictive tools for selecting potential responders to rhEPO administration among anemic MDS patients.

Aged↗
PubMed1993

Recognition and sequestration of young and old erythrocytes from young and elderly human donors: in vitro studies.

Experiments were performed to determine the mechanism of recognition for sequestration of erythrocytes from elderly and young donors and to study in vitro a previously observed shortening of in vivo life span of erythrocytes in elderly donors. Erythrocytes from young and elderly human donors were separated according to their age-density on Stractan gradients. Elderly donors had more low age-density erythrocytes than did young donors. Erythrocytes from elderly donors had higher levels of immunoglobulin G (IgG) on their erythrocytes than did those from young donors. In an in vitro erythrophagocytosis assay, young (low age-density) and old (high age-density) erythrocytes from elderly donors and old but not young erythrocytes from young donors were recognized and sequestered. Phagocytosis of erythrocytes from elderly 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, thus demonstrating that the recognition of the senescent erythrocyte is not due to the direct recognition of a physiologic autoantibody. beta-Galactoside and alpha-galactoside sugars have no inhibitory effect on erythrophagocytosis mediated by IgG anti-Rh-D antibodies. Erythrophagocytosis of young and old erythrocytes from elderly donors and old erythrocytes from young donors are all mediated by a macrophage receptor with lectin-like properties, which can be inhibited by a beta-galactoside-like sugar moiety, and not by an Fc receptor that recognizes erythrocyte-bound IgG.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
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↗
PubMed1990

The specific blocking of an IgG dependent erythrophagocytosis assay by protein G and ELISA determination of in situ bound IgG on erythrocytes of normal donors.

We report the development of an in vitro erythrophagocytosis assay in which the level of phagocytosis reflects the number of IgG molecules bound to the erythrocyte. This assay is sensitive to 300 IgG per erythrocyte above background levels. Blocking the Fc of the bound immunoglobulin with protein G totally blocks macrophage recognition of the opsonized red cell and prevents Fc-gamma-dependent phagocytosis. An accurate, reliable, easily performed CELL-ELISA (cellular ELISA) for the determination of very low levels of IgG on the human erythrocyte membrane has been developed. This CELL-ELISA is based on the use of biotin conjugated to goat anti-human IgG (GaHIgG) and streptavidin conjugated to alkaline phosphatase. The CELL-ELISA can be accurately performed on either fresh or glutaraldehyde fixed erythrocytes. When a population of healthy young adults was studied an average of 126 +/- 14 IgG molecules per erythrocyte were detected.

Adult↗
PubMed1989

Antigen presentation by neonatal murine spleen cells.

The ability of murine neonatal spleen cells to present soluble antigen to T-helper cells and to produce growth factors in response to subsequent cellular interactions was studied. The T-helper-cell line (D10-G4.1) (D10), which is specific for the soluble antigen conalbumin presented on H-2-matched (H-2k) antigen-presenting cells, was used as cooperating and indicator cells in these cellular interactions. The D10 cells are TH2 T-helper cells which secrete the autocrine growth factor IL-4 and can also respond to exogenous IL-2 (T. R. Mosmann and R. L. Coffmann, Immunol. Today 8, 223, 1987). D10 cells require exogenous IL-1 for their proliferation and secrete, in addition to IL-4, IL-1 inducer factor and GM-CSF. The ability of neonatal spleen cells to present antigen and to stimulate D10 cells to produce IL-4 and proliferate is low. During antigen presentation there is an augmentation of IL-1 and IL-2 production by the antigen-presenting spleen cell population. However, neonatal spleen cells do not respond to the same levels as do adult spleen cells. The addition of exogenous IL-1 cannot repair the antigen presentation by neonatal cells. Experiments in which the antigen processing and presentation steps were separated from those requiring growth factor induction and secretion demonstrate that neonatal spleen cells are impaired in their ability to perform adequate antigen processing and presentation. The neonatal spleen cells are as competent as adult cells to cooperate with T-helper cells and secrete growth factors, provided antigen processing and presentation is performed by fully competent adult spleen cells. Experiments in which neonatal and adult antigen-presenting spleen cell populations were mixed, and others in which plastic adherent and nonadherent cells were separated, could not detect any suppressor mechanisms responsible for the low antigen presentation of neonatal cells. Thus, neonatal spleen cells are impaired in the initial stages of antigen processing and presentation. This impairment which leads to low levels of growth factor production is the major determinant in the ineffectual stimulation of T-helper cells by neonatal spleen cells.

Animals↗
PubMed1989

Synergistic antifungal action of 8-quinolinol and its bischelate with copper(II) and with mixed ligand chelates composed of copper(II), 8-quinolinol, and aromatic hydroxy acids.

Antifungal studies were made of mixtures of minimal inhibitory concentrations (MICs) of 8-quinolinol and its bischelates with copper(II), zinc(II), and manganese(II) and with mixed ligand chelates composed of 8-quinolinol, copper(II) and a second ligand including salicylic acid, 3-hydroxy-2-naphthoic acid, 3,5-diiodosalicylic acid, and 4-bromo-3-hydroxy-2-naphthoic acid. Mixtures of the MICs of the bischelates of 8-quinolinol with copper(II) and zinc(II) and copper(II) and manganese(II), as well as 7-iodo-8-quinolinol and its bischelate with copper(II), and 8-quinolinol and 5-iodo-8-quinolinol were also studied against six fungi: Aspergillus niger, Aspergillus oryzae, Trichoderma viride, Myrothecium verrucaria, Mucor cirinelloides, and Trichophyton mentagrophytes. With the exceptions of the mixtures of 8-quinolinol and (8-quinolinolato)(3,5-diiodosalicylato)copper(II) and (8-quinolinolato)(4-bromo-3-hydroxy-2-naphthoato)copper(II) against M. cirinelloides, all of the test organisms were inhibited by 40% or less of each mixture containing 8-quinolinol. Bischelates of 8-quinolinol with copper(II) and zinc(II) and copper(II) and manganese(II) inhibited five fungi at 50% of the mixtures of the MICs. Mucor cirinelloides was not inhibited by bis(8-quinolinolato)copper(II), bis(8-quinolinolato)zinc(II), or by bis(7-iodo-8-quinolinolato)copper(II).(ABSTRACT TRUNCATED AT 250 WORDS)

Antifungal Agents↗
PubMed1989

Interleukin production by neonatal spleen cells during and as a result of antigen presentation: the effect of ultraviolet light.

Antigen presentation by neonatal murine spleen cells and the production of lymphokines and interleukins involved in the stimulation of a T-helper-2 (TH2) cell line (D10-G4.1) were studied as were the effects of ultra violet (UV)-irradiation on this system. Neonatal spleen cells are less capable than adult cells of performing the initial steps of the immune response required for antigen dependent activation of TH2 cells. These steps include soluble antigen processing and presentation and as a result reduced production of IL-4 and IL-1-Inducer Factor ("IL-1-IF") by the T-helper cells and reduced production of IL-1 and IL-2 by the antigen presenting cell population. Spontaneous membrane IL-1 activity is low in the neonate, however, when exposed to "IL-1-IF" they can express adult levels. Ultra-violet (UV) irradiation of the antigen presenting population has a damaging effect on all the above mentioned processes. Antigen processing and presentation, induction of D10 IL-4 production and proliferation, and IL-2 production demonstrate two different age related patterns of UV-irradiation induced damage: a dose dependent inhibition when adult cells are irradiated and an inverse effect in which low doses of irradiation were more inhibitory than higher doses when neonatal cells are irradiated. However, the secretion and membrane expression of IL-1 by both age groups are directly and totally inhibited by the range of UV-irradiation doses used and cannot be reinduced with a supplement of a crude "IL-1-IF". While the capacity to produced IL-1 is totally destroyed by UV-irradiation, the ability to produce IL-2 remains intact and remains responsive to an "IL-2-Inducer" activity during proper antigen presentation. The low responses of neonatal antigen presenting spleen cell populations and the damaging effect of UV on both neonatal and adult responses are not due to the induction of suppressor factors.

Animals↗
PubMed1988

IL-1 secretion and membrane IL-1 expression by neonatal spleen cells during soluble antigen presentation.

Antigen presentation and IL-1 production by neonatal spleen cells were studied in a murine model. The T-helper-cell line (D10-G4.1) (D10), which is specific for soluble antigen presented on syngeneic antigen-presenting cells and dependent on IL-1 for its proliferation, was used as an indicator cell for the ability of syngeneic neonatal or adult spleen cells to present antigen and produce IL-1. The antigen-presenting capacity of neonatal spleen cells is low as attested by D10 proliferation. During antigen presentation there is an augmentation of IL-1 production by the antigen-presenting spleen cell population. However, neonatal spleen cells do not respond to the same levels as do adult spleen cells. These reduced levels of secreted IL-1 cannot be attributed to a low potential for producing IL-1 as attested by the high levels of IL-1 made by these cells after induction by a crude IL-1 inducer factor (IL-1-IF) and by the stimulus of the IL-1-IF produced by D10 cells during antigen presentation by paraformaldehyde-fixed adult cells. The spontaneous expression of membrane IL-1 by neonatal cells is low. Membrane IL-1 levels on neonatal cells can be brought to adult levels by induction with IL-1-IF. Neonatal spleen cells have an impaired capacity to process and/or present soluble antigen. This impairment leads to a decreased stimulus of the T helper cell to produce inducer factors and thus a reduced level of IL-1 production by the neonatal cells during antigen presentation.

Age Factors↗
PubMed1988

Altered enzyme function and premature sequestration of erythrocytes in aged individuals.

Experimentation performed to determine the parameters of the life-span of the erythrocyte in hosts of various ages have determined that, in aged individuals, the rate of turnover of cells is considerably increased over that observed in young individuals. These observations are based on studies in humans, rats, mice, and rabbits in which either in situ 59Fe labelling or age-density gradient separation were used. The mechanisms for the recognition of the effete red cell in the aged host and the nature of the membrane alterations that bring about the premature sequestration are not fully understood. However, it has been consistently observed that the red cells of aged individuals have higher levels of IgG bound to their membranes than do young cells, with the most dense cells having the highest levels of immunoglobulin. Studies of most enzymes, particularly those involved in protection against oxidative damage have shown reduced activity as a function of both cell and donor age. Evidence of enzyme damage has been observed even in the youngest circulating red blood cells of old individuals. This fact leads us to hypothesize that the erythrocyte of the aged individual as it differentiates and is released from the bone marrow is less functional and partially damaged. The erythrocytes of both old and young individuals age in the circulation, accumulating subtle alterations that are recognized by the immune and/or reticuloendothelial systems and lead to sequestration. The cells of the elderly individual accumulate a greater degree of damage due to their initially reduced capacity to protect themselves from environmental stress. These alterations eventually bring them to their early sequestration.

Aging↗
PubMed1986

Natural killer cell activity in post-necrotic cirrhotic patients as related to hepatitis-B virus infection and plasma zinc levels.

In view of the suggested physiological role of natural killer (NK) cells in immunosurveillance and defence against viral infections, we have investigated the relationship between hepatitis B virus (HBV) infection and NK activity against K-562 cells in patients with post-necrotic cirrhosis. Overall, the NK activity in cirrhotic patients did not differ from age- and sex-matched controls. However, cirrhotic males with evidence of HBV infection with or without HBs antigenemia tend to have lower NK activity than controls. Cirrhotic males without evidence of HBV infection do not differ from controls. Such a trend was not observed in the female cirrhotic patients examined. In addition significantly reduced NK activity was observed in cirrhotic patients with low plasma zinc levels. This relationship is of interest because of the known association between zinc deficiency and various immunodeficiencies.

Adolescent↗
PubMed1985

Antifungal properties of 3-n-alkyn-1-ols and synergism with 2-n-alkyn-1-ols and ketoconazole.

Twelve 3-n-alkyn-1-ols (C4-C12, 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 pH of the medium, and significantly but not strongly by the presence of beef serum. 3-n-Decyn-1-ol, 3-n-undecyn-1-ol, and 3-n-dodecyn-1-ol were the most active members of the series. Synergism toward C. albicans and C. tropicalis was observed between 3-n-undecyn-1-ol and ketoconazole, and a mixture of 3-n-undecyn-1-ol, 2-n-undecyn-1-ol, and ketoconazole in Sabouraud dextrose agar at pH 7.0 in the presence of 10% human serum.

Alcohols↗
PubMed1985

An improved sperm immobilization test based on multiple exposure photography.

An improved method for objective evaluation of results in the complement dependent sperm immobilization test, with the aid of the multiple exposure photography (MEP) method is described. With this method it is possible to determine the percentage of residual motility of spermatozoa quantitatively after incubation with sera suspected of having immobilizing activity in the presence of complement. Long term storage of information, reexamination of data and comparison of results after various treatment are routinely possible with this method.

Antibodies↗
PubMed1985

Evidence that the mechanisms of fungitoxicity of 8-quinolinol and its bischelate with copper(II) are different.

The copper(II) contents of the growth media, Sabouraud dextrose and Czapek-Dox broths, and of the spore inocula of Aspergillus niger (ATCC 1004), Aspergillus oryzae (ATCC 1011), Trichoderma viride (ATCC 8678), and Myrothecium verrucaria (ATCC 9095) were determined by atomic absorption spectrophotometry in a graphite furnace. The test systems composed of Sabouraud dextrose broth and spore inocula of the four fungi contained only a little over 3% of the copper(II) required to form a minimal inhibitory concentration of bis(8-quinolinolato)copper(II). The test system of Czapek-Dox broth and A. oryzae contained slightly less than 65% of the copper(II) required to form a minimal inhibitory concentration of the bischelate of 8-quinolinol with copper(II). When the minimal inhibitory concentrations of 8-quinolinol and bis(8-quinolinolato)copper(II) were added simultaneously to the test system of Czapek-Dox broth and A. oryzae, 10% of the combined mixture of toxicants caused complete inhibition of growth indicating synergism between the toxicants. These results together with the observation that alpha-lipoic acid as well as small aliphatic thiol-containing compounds (cysteine, glutathione, dithioerythritol, and dithiothreitol) reversed the toxicity of 8-quinolinol but not the toxicity of bis(8-quinolinolato)copper(II) led to the conclusion that the mechanisms of fungitoxicity of both toxicants are different.

Aspergillus↗
PubMed1985

Some characteristics of the human erythrocyte as a function of donor and cell age.

Erythrocytes from healthy human donors of various ages (18-93 years) were separated on Percoll into four density fractions. Increased cell density has been reported to correlate with the age of the erythrocyte. Aged individuals, while having normal hematocrits, show an increased percentage of low-density young erythrocytes and almost twice as many reticulocytes in their circulation as do young adults. This evidence for increased, well-compensated, red cell turnover in elderly humans is supported by the finding in older individuals of increased levels of erythrocytes bearing autologous IgG on their membranes. Using fluorescent anti-IgG, erythrocytes with bound autologous IgG could be found in all density fractions from donors of all age groups. The old donors had an increased number of fluorescent cells that appeared in all density fractions albeit with a definite skewing toward the more dense cell fractions. Erythrocytes from young donors had higher levels of intact hemoglobin per cell than those from old donors. The relevance of these results to the aging process and the ability of senescing individuals to withstand hematologic stress are discussed.

Adult↗
PubMed1984

Immune reactivity of the tumor-resistant X/Gf mouse.

Parameters of immune reactivity of the tumor-resistant X/Gf mouse have been studied. X/Gf mice show better survival than do control strains following i.p. inoculation with graded doses of YAC lymphoma cells. The natural killer cell activity of X/Gf mice was higher than that of control mice, and this elevated NK activity was inherited by (C57BL/6 X X/Gf)F1 mice. Differences in NK activity of fresh spleen cells from X/Gf, C57BL/6, and (C57BL/6 X X/Gf)F1 mice were not reflected in their ability to lyse in vitro-derived, cloned, transformed cell lines from X/Gf or C57BL/6 mice in an 8 h 51Cr assay; however, the X/Gf-derived malignant cells were more sensitive to lysis than the C57BL/6-derived cells. In order to test whether X/Gf mice demonstrated any exceptional ability to recognize and destroy altered autologous cells, experiments were performed with TNP-modified syngeneic cells. While X/Gf and B10.A effector cells appeared to respond with similar magnitude, hapten-modified X/Gf cells were stronger stimulator cells and more sensitive targets than control strain cells. The ability of X/Gf mice to reject H-2 compatible and incompatible skin grafts is normal, as judged by a comparison of the rejection times with control strains. Allogeneic mixed lymphocyte reactivity, T-cell-mediated lympholysis, delayed-type hypersensitivity reactions, and in vivo phagocytosis of inert particles are of comparable magnitude in X/Gf and control strain mice.

Animals↗