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Biomedical subjects

R Shor

Publications and source records attributed to R Shor.

12 recordsLinked to original sources
PubMed1990

Parasite antigens recognized by patients with cutaneous leishmaniasis.

Humoral and cell-mediated responses to crude and purified parasite antigens were examined in patients with active cutaneous leishmaniasis caused by Leishmania major. The patients had serum antibody titres against parasite lysates ranging from 1/500 to 1/10,000 and recognized multiple components by Western blotting with molecular weights between 5000 and greater than 200,000. Several components, particularly at 5 and 50 kD, were recognized by most of the patients. The lymphoproliferative responses to two pure antigens, promastigote surface protease and lipophosphoglycan, both considered potential candidates for the development of a human vaccine were measured. No response to promastigote surface protease was observed even at 10 micrograms/ml; however, weak proliferation to lipophosphoglycan was consistently present. T cell blots examining peripheral blood lymphocyte proliferation, showed antigen-specific responses to a 72-82 kD component in promastigote lysates.

Animals↗
PubMed1987

Antigen-stimulated lymphokines from patients with cutaneous leishmaniasis induce monocyte killing of Leishmania major intracellular amastigotes.

The specific immune response of patients with cutaneous leishmaniasis including the ability of their lymphokines to enhance the monocytes' leishmaniacidal activity was studied. In 16 patients with cutaneous leishmaniasis, their concanavalin A-induced lymphocyte proliferative responses, interferon-gamma and interleukin 2 activities and the ability of their concanavalin A-induced lymphokines to kill monocyte intracellular amastigotes were not different from normal controls. Antigen-stimulated lymphocyte cultures showed that 13 of 13 patients had an increased lymphocyte proliferative response; 11 of 16 produced interleukin 2 and 12 of 13 produced interferon-gamma; in addition, 10 of 11 of these antigen-induced supernatants increased the monocytes' killing of Leishmania major amastigotes. Antibody levels to parasite membrane antigens determined by radioimmunoassay showed that 8 of 13 titers were greater than 10 and 4 of 13 titers were 2 to 10 times higher than control. Our findings demonstrate that patients with cutaneous leishmaniasis elicit a specific immune response to L. major antigens and part of this response is the production of lymphokine capable of promoting monocyte killing of intracellular amastigotes.

Animals↗
PubMed1987

Topical application of human fibroblast interferon (IFN) in cutaneous leishmaniasis.

Fifteen patients with single or multiple lesions of cutaneous leishmaniasis were randomly assigned to apply either IFN-beta-containing cream or a placebo cream base. Despite 8 weeks of therapy no significant improvement of the lesions was achieved. Although topical IFN-beta was not effective in this study, several laboratory studies suggest that IFN, particularly IFN-gamma, may be of therapeutic value in cutaneous leishmaniasis.

Administration, Topical↗
PubMed1986

The enhancing effect of interferon-beta and -gamma on the killing of Leishmania tropica major in human mononuclear phagocytes in vitro.

Both native human IFN-beta or -gamma added to human monocytes in culture increased their leishmaniacidal effect on intracellular Leishmania tropica major (L. major) amastigotes. This effect was dose-dependent, and was apparent if the IFN was added either before or after infection of the monocyte cultures with the promastigote form of the parasite. Compared on the basis of antiviral activity, IFN-gamma was shown to have a leishmaniacidal effect approximately three times greater than IFN-beta. Recombinant IFN preparations showed similar effects. In addition, IFN-gamma increased H2O2 production from human monocytes in culture in a dose-dependent manner. Monoclonal antibody to IFN-gamma abrogated both its effect on the leishmaniacidal capacity and on H2O2 production by the monocytes. These results suggest that IFN-gamma may be of therapeutic value in cutaneous leishmaniasis.

Adjuvants, Immunologic↗
PubMed1986

The effects of Con A-induced lymphokines from the T-lymphocyte subpopulations on human monocyte leishmanicidal capacity and H2O2 production.

The effects of concanavilin A (Con A)-induced lymphokines from human peripheral blood mononuclear cells, enriched helper and suppressor lymphocyte populations and recombinant interferon-gamma (IFN-gamma) on the ability of monocytes to promote killing of intracellular Leishmania major (L. major) amastigotes and to induce the production of hydrogen peroxide (H2O2) was examined. All these mitogen-induced supernatants contained active IFN-gamma. There were no differences in the ability of these supernatants or IFN-gamma to promote the monocyte killing of the L. major amastigotes or H2O2 production. An increase in H2O2 production by monocyte monolayers was observed following the addition of either of these supernatants or IFN-gamma alone. In addition, a marked increase in the production of H2O2 was observed following priming with either of these mitogen-induced supernatants or IFN-gamma and the addition of a second stimulus, phorbol myristate acetate (PMA). Monoclonal antibody to IFN-gamma abrogated the increase in production of H2O2 by all these mitogen-induced supernatants; however, this antibody only resulted in partial inhibition of the leishmaniacidal effect of these lymphokines on human monocytes. These results would suggest that IFN-gamma is the component of the lymphokine that is largely or exclusively responsible for H2O2 production, while other factors in addition to IFN-gamma are important in promoting oxygen-independent mechanisms for the killing of intracellular L. major amastigotes.

Cells, Cultured↗
PubMed1985

Digoxin quinidine interaction: a pharmacokinetic study in the isolated perfused rat liver.

Digoxin-quinidine interaction was studied in the experimental model of isolated perfused rat liver. Neither digoxin nor quinidine were toxic to the isolated rat liver. The clearance of digoxin and quinidine by the liver was directly related to the rate of bile flow and the size of the initial dose of digoxin. In the presence of quinidine, after initial doses of digoxin of 0.5 and 1 micrograms, the concentration of digoxin in the perfusate was increased 2.5 and 3-fold. Its excretion in the bile was reduced by 45% and 20.5%, respectively (all comparisons, p less than 0.01). Digoxin concentration in the liver tissue was calculated and found to be appreciably elevated in the presence of quinidine. A reduction of about 30% (p less than 0.05) in the excretion of quinidine in the bile was observed in the presence of digoxin. Thus, a competition of digoxin and quinidine for biliary excretion was demonstrated as an underlying cause for digoxin-quinidine interaction in the isolated perfused rat liver.

Animals↗
PubMed1985

The formation of genotoxic metabolites of benzo[a]pyrene by the isolated perfused rat liver, as detected by the bioluminescence test.

The kinetics of the formation of mutagenic metabolites of benzo[a]pyrene (BP) in an isolated perfused rat-liver system have been studied. No genotoxic activity was detected in the perfusate using either the Ames test or the new bioluminescence test for genotoxic agents (BLT). The bile excretion showed strong genotoxic activity especially in the presence of the deconjugation enzymes beta-glucuronidase and arylsulfatase. The BLT was 1000-fold more sensitive than the Ames test in detecting the genotoxic activity in the bile excretion.

Animals↗
PubMed1985

Human monocytes infected with Leishmania amastigotes enhance lymphocyte proliferation.

Human monocytes were infected in vitro with Leishmania tropica major (L. major) promastigotes which transformed to intracellular amastigotes. A spontaneous increase in lymphocyte proliferation occurred in mononuclear cell cultures where the monocytes had been infected with L. major organisms. In addition, an apparent additive effect of lymphocyte proliferation was seen in cultures infected with L. major following phytohaemagglutinin stimulation. This effect was apparent after 3 days in culture and the amount of increase in response was dependent on the number of monocytes in the culture. The effect was also dependent on the number of parasites ingested by the monocytes. The presence of monocytes was essential for this effect, as no enhancement was observed with supernatants from infected cells. This enhanced effect of lymphocyte proliferation was observed predominantly in the B lymphocyte subpopulation. These findings may be of relevance in the immunopathogenesis of Leishmania infections.

B-Lymphocytes↗
PubMed1984

Comparison of the effect of various stimuli on the leishmaniacidal capacity of human monocytes in vitro.

Leishmania organisms are obligate intracellular parasites of mammalian mononuclear phagocytes in vivo. In order to study the interactions of these parasites and mononuclear phagocytes, we have used a model of infection of Leishmania major in human monocytes in vitro. The presence of intracellular parasites did not alter the normal secretion of lysozyme or result in increased secretion of prostaglandin E2 (PGE2) or superoxide anion by the monocytes. Addition of concanavalin A (Con A), which binds to a specific membrane receptor, zymosan particles or endotoxin to infected monocyte monolayers, resulted in the expected increase in PGE2 secretion. In addition, the production of superoxide by infected monocytes treated with phorbol myristate acetate was not different from control uninfected cultures. Despite this evidence of biochemical activation, neither endotoxin, zymosan nor Con A had any parasiticidal effect on the intracellular parasites. In contrast, Con A-induced lymphokines from human mononuclear cells resulted in an increased killing of the intracellular amastigotes. These studies have shown that the induction of leishmaniacidal capacity of human monocytes is dependent on the type of stimulus used to induce activation.

Cells, Cultured↗
PubMedDate not supplied

Effect of intralipid on the phagocytic and microbicidal capacity of human monocytes in culture.

We studied the effect of Intralipid (IL) in monocyte cultures based on the ability of the cultures to phagocytose and kill Candida albicans and produce the oxidative burst. The IL was taken up by monocytes in cultures, and these cells phagocytosed more Candida organisms than did the control cells [85 +/- 2.2% in the IL treated (1%) compared to 68 +/- 2.3% after 1 h in the control]. The percentage of killing of Candida albicans, which had been taken up by the IL-treated monocytes measured after 2 h in culture (48.3 +/- 6.0%), was no different when compared to control (47.0 +/- 5.8%). Following ingestion of IL, there was an increase in basal H2O2 production, however, the presence of the IL in the cells had no effect on the expected increase in H2O2 production following stimulation with either phorbol myristate acetate (PMA) or zymosan particles. Compared to untreated cells, a significant increase in the number of monocytes with positive nitroblue tetrazolium staining was observed in monocytes that had ingested IL (when they were stimulated with either PMA or Candida microorganisms). Similar results were obtained in monocyte-derived macrophages (i.e., monocytes in monolayer cultures for 10 days). These findings suggest that the essential monocyte functions of phagocytosis, microbicidal activity, and ability to elicit an oxidative burst are not directly altered by the conventional use of IL in clinical practice.

Candida albicans↗