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I Csuka

Publications and source records attributed to I Csuka.

30 records · Page 2Linked to original sources

The immunosuppressive effect of acute doses of emetine on murine thymic cells.

Emetine--a general inhibitor of protein synthesis--was investigated for its ability to depress specific immune response in animal models. A single dose (33 mg/kg) of emetine administered subcutaneously to mice markedly decreased thymus weight and thymic cell numbers. DNA, RNA and protein synthesis of thymic cells were reduced by 90, 50 and 65%, respectively. RNA synthesis was the first process to recover followed by the reconstitution of DNA and protein synthesizing capacity. Histological evidence revealed an effect on the cortical region of thymus upon emetine administration. Results suggest that emetine exerts an immunosuppressive effect on T-cell maturation in the thymus. These findings may enhance a therapeutic interest in the drug.

Animals↗

In vitro effect of emetine and chloroquine on the macromolecular biosynthesis of murine thymus cells.

The in vitro effect of antiparasitic agents, emetine and chloroquine on the DNA, RNA and protein synthesis was studied in isolated murine thymocytes. Cytotoxic effect was observed at 10(-4) and 10(-3) M emetine concentrations causing 50% and 70% cell death, respectively. The toxic effect of emetine could be prevented when emetine was removed within 10 min of treatment. Inhibitory concentrations for DNA, RNA and protein biosynthesis were 10(-5), 5 x 10(-5) and 10(-8) M, respectively. The number of living cells decreased by 30 and 50% at 10(-4) and 10(-3) M chloroquine concentrations, respectively. Gradually decreasing rate of DNA synthesis was measured at increasing concentration of chloroquine between 10(-8) and 10(-3) while RNA and protein synthesis were effected at 5 x 10(-5) M concentration. These results indicate that protein biosynthesis is primarily affected by in vitro emetine and chloroquine treatment of murine thymocytes.

Animals↗

Effect of emetine and chloroquine on phagocytic processes of rat macrophages.

Emetine and chloroquine caused a dose-dependent and time-dependent inhibition of bacterial phagocytosis in rat peritoneal macrophages. The effect of emetine was found to be stronger: 50% inhibition was achieved at 5 X 10(-6) M concentration. The inhibition of phagocytosis was irreversible. Neither the binding of bacteria to the surface of phagocytes nor membrane marker 5' nucleotidase was touched by this treatment. The adherence of macrophages to plastic dishes was also impaired by the drugs but only in a smaller extent. Both emetine and chloroquine blocked the amino acid incorporation into macrophage proteins. The effect of emetine was more marked; 10(-6) M decreased the incorporation to 25% of control, while 10(-4) M chloroquine produced a similar inhibition. The block of protein synthesis was also irreversible.

Animals↗

The effect of emetine on the immune response of mice.

Emetine (33 mg/kg body weight) administered intraperitoneally blocked the immune response of mice to 10(9) sheep red blood cells (SRBC). The inhibition was almost complete when the drug was administered simultaneously or 24 hr after immunization, while partial inhibition was caused by treatment at 48 and 72 hr. Incorporation of 14C-leucine and 3H-thymidine by spleen cells isolated 4 hr after emetine injection of the mice was strongly decreased. Incorporation was approaching the control level in cells isolated 72-96 hr after emetine administration. However, the incorporation of labeled precursors was less than after SRBC treatment only, even after 72-96 hr. Emetine apparently blocked the development of immune response at an early stage and, in contrast to macromolecule synthesis, the inhibition of the antibody response was irreversible.

Animals↗

[Analysis and fractionation of human tonsillar lymphocytes].

Among the human tonsillar cells, 28.0 +/- 3.1 and 45.14 +/- 2.16% were found to be E and EAC rosette forming cells, resp. In the course of the separation procedure with nylon cotton, in the authors' modification, the cells failing to form rosettes were almost entirely adhering irreversibly to the nylon wool. The 3H-thymidine incorporation in these cells was very intensive, and we supposed them to be T and B lymphoblasts. On the basis of E and EAC rosette formation, the percentage of T and B lymphocytes in human tonsils--as reported by various authors--is different. It may be supposed that methods employed by these authors did not demonstrate the equal extent of transformed forms of lymphocytes, i.e. lymphoblasts, whose amount may be influenced by the functional condition of tonsils.

B-Lymphocytes↗

Effect of released lymphocyte proteins on human lymphocytes in vitro. II. Protein synthesis of nylon-wool separated cells in the presence of proteins derived from lymphocytes.

Protein synthesis of nylon-wool adherent (B) and non-adherent (T) human tonsillar lymphocytes was examined in the presence of three protein fractions precipitated with ammonium sulfate from the medium of the above lymphocytes incubated in vitro for 4 hours. One fraction precipitated with ammonium sulfate at 0--30% saturation was found to inhibit amino acid incorporation into proteins mainly in unseparated cells while the fraction precipitated at 30--70% saturation decreased the rate of protein synthesis in B cells. The fraction precipitated at 70--100% saturation inhibited protein synthesis slightly in T lymphocytes. Protein synthesis in B and T as well as in unseparated cells was also examined in the presence of proteins obtained from the medium of B and T lymphocytes. It is assumed that proteins released by lymphocytes without mitogenic activation in vitro are involved in the mediation of lymphocyte interactions and may be related to lymphokines synthesized and released by activated cells.

B-Lymphocytes↗

Testing of pesticide toxicity in tissue culture.

The effect of pesticides on cell growth and on the cell layer was examined. The pesticides under study had a similar toxicity for the cell suspension and for the cell layer. Vital staining of the cells allowed a more sensitive determination of the cytotoxic concentrations than did the studies on cell morphology without staining. No correlation was found between the cytotoxic concentrations and LD50 values of mammals. The results were compared with those of earlier experiments on rats in which methods of general toxicology and neurotoxicology were applied. Of the eight compounds tested, in six the tissue culture method proved even more sensitive than did the functional neurotoxicological tests. It is suggested that the in vitro method with cultured cells should be used to complement in vivo functional toxicological procedures.

Animals↗

Myasthenia gravis: mitotic activity of thymus-dependent and blood-lymphocytes.

The thymus and blood lymphocytes of 20 thymectomized patients with myasthenia gravis, including 3 cases of thymoma, have been studied for mitotic activity (spontaneous mitotic activity of native thymocytes, responsiveness of cultured cells to PHA, DNA-polymerase specific activity). The myasthenic thymus gland was found to be the site of a spontaneous DNA-synthesis of similar intensity as the mitotic activity of the thymus in infancy. This was also reflected by the DNA-polymerase activity of the cells. While the thymocyte cultures responded well to PHA stimulation in 50% of the cases, the blood-lymphocytes were found unresponsive. There was a partial correlation between the individual parameters of mitotic activity, but practically none between the mitotic activity and the clinical severity of myasthenia or the histological features of the thymus or of thymoma. Except in the latter cases, a correlation was found between mitotic activity and preoperative immunosuppressive treatment. It is suggested that the T-lymphocytes are not directly involved in the pathomechanism of myasthenia gravis.

Adolescent↗

Elevated nascent DNA content of peripheral blood mononuclear cell compartment in lymphoma patients.

The kinetics of DNA synthesis and the DNA pattern of isolated peripheral blood mononuclear cells from control subjects and lymphoma patients prior to drug treatment were studied as a possible tool in the early diagnosis of lymphoma. Thymidine and [H3]-dTTP incorporation represented the measure of replicative DNA synthesis in permeable murine thymocytes and HT-168 human melanoma cells as described earlier. The kinetic parameters of nucleotide incorporation were compared with the ploidity parameters of the Feulgen-stained smears examined by the DNASK TV-cytophotometric system. For better evaluation and visualization of the S-phase population, the method of silver impregnation of the Nucleolar-Organizer-Region in combination with the Feulgen technique was used. Significant differences were observed among the five determined parameters of healthy and lymphoma patients. Our results allow to explain some of the facts related to T-cell function deficiency in lymphoma.

Adolescent↗