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Biomedical subjects

P Gergely

Publications and source records attributed to P Gergely.

At least 145 records · Page 8Linked to original sources
PubMed1986

Indomethacin abrogates the suppression by cyclosporin A of lectin-dependent cell-mediated cytotoxicity to HEp-2 cells.

The effects of cyclosporin A, prostaglandin E1 and indomethacin were studied on lectin-dependent cell-mediated cytotoxicity (LDCC) against adherent HEp-2 human epipharynx carcinoma target cells. LDCC activity by human peripheral blood lymphocytes was evaluated by detachment from the monolayer of [3H]thymidine-prelabelled HEp-2 cells in a 24-h assay at 50:1 effector:target cell ratio in the presence of 25 micrograms/ml concanavalin A. Under these conditions, but without concanavalin A, considerable natural cell-mediated cytotoxicity was not elicited although LDCC was significantly augmented in the presence of concanavalin A. Addition of both cyclosporin A (0.1, 1.0 or 10 micrograms/ml) and prostaglandin E1 (10(-8), 10(-7) or 10(-6) M) dose-dependently suppressed LDCC activity. Indomethacin (0.1, 1.0 or 10 micrograms/ml) did not in itself influence LDCC although suppression of LDCC by cyclosporin A, but not prostaglandin E1, was abrogated in the presence of indomethacin. Similar to indomethacin, acetyl salicylic acid also reversed the inhibition of LDCC by cyclosporin A. In parallel experiments, cyclosporin A elicited a more than two-fold increase of prostaglandin E production under LDCC assay conditions as measured by radioimmunoassay. Contrary to LDCC, depression of concanavalin A induced blastogenesis by cyclosporin A was not influenced by indomethacin, suggesting that the inhibition by cyclosporin A of LDCC and concanavalin A-induced blastogenesis proceed via different mechanisms.

Carcinoma, Squamous Cell↗
PubMed1986

Effects on immune reactions of non-steroidal anti-inflammatory drugs and of two new pyrido-pyrimidine derivatives (CHINOIN 127 and CHINOIN 105).

The effect of three non-steroidal anti-inflammatory agents (NSAIs) and of two new pyrido-pyrimidine derivatives, CHINOIN 127 (1-6-dimethyl-4-oxo-1,6,7,8,9)a-hexahydro-4H-pyrido (1,2-2)pyrimidine-3-carboxamide) and CHINOIN 105 (1-6-dimethyl-4-oxo-1,6,7,8-tetrahydro-4H pyrido (1,2-a) pyrimidine-3-carboxamide) was compared in immune tests using human cells in vitro including T and B lymphocyte proliferation induced with mitogens, spontaneous motility of polymorphonuclear leukocytes, lymphokine (LIF) production, antibody-dependent cell-mediated cytotoxicity (ADCC) and natural killer cell (NK) activity. Indomethacin (INDO) at therapeutic concentrations enhanced the proliferation of lymphocytes stimulated by both Con A and PWM. Acetylsalicylic acid (ASA) increased proliferation of lymphocytes stimulated by Con A and at high concentration inhibited DNA synthesis induced by PWM. Phenylbutazone (PhB) increased DNA synthesis induced by PWM but not by Con A. CHINOIN 127 and CHINOIN 105 inhibited the proliferation of T lymphocytes but failed to influence DNA synthesis of B cells. Indomethacin, ASA and PhB inhibited the spontaneous motility (migration) of polymorphonuclear leukocytes. LIF production of lymphocytes was inhibited by INDO, ASA, PhB, CHINOIN 127 and CHINOIN 105. Phenylbutazone and ASA inhibit ADCC and NK. INDO, Chinoin 127 and Chinoin 105 failed to influence the effector cells of ADC and NK cytotoxicity.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1986

Free radicals in tissue damage in liver diseases and therapeutic approach.

In vitro and in vivo effects of four hepatoprotective agents: silymarin (LegalonR), (+)-cyanidanol-3 (CatergenR), 6,6-methylene-bis(2,2,4-trimethyl-1, 2-dihydroquinoline) (MTDQ), and 4,5-amino-imidazole-carboxamide-phosphate (Aica-P) on the expression and activity of superoxide dismutase enzyme and on certain cellular immune reactions were studied in lymphocytes (and erythrocytes) from cirrhotic patients and from healthy control subjects. In vitro incubation with these drugs inhibited lectin-induced lymphocyte transformation and some of them decreased the antibody-dependent, spontaneous, and lectin-induced lymphocytotoxicity. MTDQ, silymarin and Aica-P enhanced the superoxide dismutase activity of erythrocytes and lymphocytes and the two latter and (+)-cyanidanol-3 increased the superoxide expression of lymphocytes as measured by flow cytofluorometry. In vivo treatment with Aica-P restored the originally low lymphocyte transformation values of patients' lymphocytes. Our results indirectly suggest that both antioxidant and immunomodulatory activities might be important factors in the hepatoprotective action of these drugs.

Aminoimidazole Carboxamide↗
PubMed1986

Immunomodulation in autoimmune diseases.

Systemic autoimmune diseases are generally treated with immunosuppressive agents. In some instances immunomodulatory agents have shown promise in the treatment of certain types of autoimmune disorders. The in vitro and/or in vivo effects of some of these agents (glutaurine, ketoconazole, gutimine and its derivative) are demonstrated. Glutaurine exerts moderate immunostimulating activity, but fails to influence the clinical course of systemic lupus erythematosus. Although ketoconazole suppresses immune responses in vitro, it does not influence cellular reactivity of patients in vivo. The immunostimulatory activity of gutimine and its derivative (T 001) have been demonstrated in vitro, and need to be tested also in vivo.

Adjuvants, Immunologic↗
PubMed1986

Quantitative determination of anti-A-dependent cytotoxicity of human peripheral blood monocytes.

A simple test is suggested for the quantitative measurement of the cytotoxic activity of human peripheral monocytes. Adherent cells are separated from non-adherent cells in the wells of the microtiter plates, thus tedious resuspension of effector cells can be omitted. Effector cell number is accurately determined by isotope labelling. Maximum of cytotoxic activity is measured in the enzyme-like kinetic model of cytotoxicity as a function of target cell number. It was found that 34.2-51.2% of unseparated peripheral blood mononuclear cells (PBMC) were adherent. More than 80% of these were shown to be monocytes by monoclonal antibodies and alpha-naphthyl acetate esterase (ANAE) staining. Depletion of SRBC rosette forming cells prior to adherence (PBMC, E-) resulted in enrichment of adherent cells (61.3-82.8%), which were exclusively monocytes. Cytotoxic activity of both adherent populations (PBMC and PBMC, E-) for human red blood cells sensitized with anti-A was determined experimentally and also extrapolated by using the Michaelis-Menten equation. It was estimated that one monocyte was able to lyse more than 4 erythrocytes.

ABO Blood-Group System↗
PubMed1986

Depressed lectin-dependent and enhanced antibody-dependent cell-mediated cytotoxicity in patients with stage I cancer of the larynx.

Lectin-dependent cell-mediated cytotoxicity (LDCC) of peripheral blood mononuclear cells (PBMC) from patients with stage I cancer of the larynx (LC) was evaluated using human adherent 3H-TdR-prelabeled HEp-2 carcinoma cells as targets at 50:1 effector-target ratio with 25 micrograms/ml concanavalin A (Con A) in a 24-hour assay. Under these conditions, but without Con A, no considerable natural cell-mediated cytotoxicity (NCMC) was performed by PBMC either from control or from LC donors. Depressed levels of LDCC, but augmented ADCC to chicken red blood cells were detected in LC patients. Natural killer activity to K562 targets was not different from that of control subjects. In parallel studies, normal Con A-induced blastogenesis and B cell counts, low T, and active T cell counts, as well as high Leu-11a+ cell counts were detected in patients with LC. The relationship between depressed LDCC and low T, and active T cell counts, and enhanced ADCC and high Leu-11a+ cell counts is suggested in stage I LC patients.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1986

Independence of depressed lectin-dependent cell-mediated cytotoxicity from interleukin 2 production in patients with systemic lupus erythematosus.

The relationship of lectin-dependent cell-mediated cytotoxicity (LDCC) to interleukin-2 (IL-2) production was studied in healthy subjects and in patients with systemic lupus erythematosus (SLE). Profoundly depressed levels of LDCC were elicited by peripheral blood mononuclear cells (PBMC) from nine patients with active SLE in comparison to LDCC from seven controls, and eleven inactive SLE donors, using 3H-TdR-prelabelled adherent HEP-2 cells as targets in a 24 h assay with 25 micrograms/ml Con A. In parallel experiments, no individual correlation was found between LDCC activity and IL-2 production for healthy or SLE subjects. Further, no major differences were detected in IL-2 release when the three groups of donors were compared, a tendency observed at the Con A doses (5 and 25 micrograms/ml) and incubation times (24, 48, and 72 h) used to induce IL-2 production. In additional studies, impaired Con A-induced blastogenesis was noted for PBMC from active SLE patients in comparison to the PBMC from the controls or patients with inactive SLE. While strong individual correlation was obtained between blastogenesis and IL-2 secretion in controls and patients with inactive SLE, no such relationship was found in patients with active SLE. While addition of exogenous IL-2 to the cytotoxicity assay considerably enhanced LDCC by healthy donors it failed to improve LDCC by patients with active SLE. These data suggest that depressed LDCC and Con A-induced blastogenesis of patients with active SLE may not be related to impaired IL-2 production but rather to an inherent dysfunction of the effector lymphocytes, including their unresponsiveness to IL-2.

Concanavalin A↗
PubMed1986

Permanent large granular lymphocytosis in the blood of splenectomized individuals without concomitant increase of in vitro natural killer cell cytotoxicity.

Increased numbers of circulating lymphocytes and large granular lymphocytes (LGL) were observed in 115 individuals splenectomized for haematological disease (74 cases) or for trauma (41 cases). LGL lymphocytosis was present in 78.4% of haematologically indicated and in 85.4% of traumatic splenectomies. A 70.5% of these values was above the 97.5 percentile upper tolerance limit of healthy controls (200 cases). In addition, 175 haematological controls were investigated. Forty per cent or more of circulating lymphocytes exhibited LGL morphology in nearly half of repeatedly investigated splenectomized persons. The increase in LGL is not attributable to lymphocytosis. It becomes apparent, and persists after the first postoperative week, irrespective of the cause of surgery. In spite of the two-fold increase in LGL concentration in the blood, in vitro natural killer (NK) and antibody dependent cellular cytotoxic (ADCC) activities did not increase in the investigated 48 (NK) and 31 (ADCC) splenectomized persons, as compared with the appropriate healthy or haematological controls.

Adolescent↗
PubMed1986

Lectin-dependent cell-mediated cytotoxicity and blastogenesis by large granular-enriched and depleted lymphocytes.

The role of larger granular-enriched and depleted lymphocytes was studied in lectin-dependent cell-mediated cytotoxicity (LDCC) against adherent HEp-2 human epipharynx carcinoma target cells. LDCC was evaluated by detachment from the monolayer of 3H-thymidine-prelabelled HEp-2 cells in a 24 h assay at effector-target cell ratios of 25:1 and 50:1 in the presence of 25 micrograms/ml concanavalin A (Con A). Under the aforementioned conditions but in the absence of Con A natural cell-mediated cytotoxicity (NCMC) was not found. However, cytotoxicity was significantly augmented in the presence of Con A (= LDCC) using human peripheral blood mononuclear cells (PBMC) as effectors. Large granular lymphocytes (LGL), which show high natural killer (NK) activity to K 562 target cells, failed to be cytotoxic against HEp-2 targets similar to large granular depleted lymphocytes (LGL-DL). On the other hand, LGL caused only a slight LDCC; whilst LGL-DL induced strong LDCC activity towards HEp-2 targets. In comparison to LDCC using LGL-DL as effector cells, LGL and LGL-DL mixed at a ratio of 1:2, and added to target cells, had no major effect on LDCC, while a lower level of LDCC was observed at LGL/LGL-DL ratios of 1:1, and 2:1, suggesting the dilution of LGL-DL, potential effectors of LDCC to HEp-2 cells, rather than a specific regulatory role of LGL in LDCC. In parallel studies, the proliferation of LGL-DL in response to Con A was less than that observed with PBMC or LGL. The response could be restored by replacing half of LGL-DL per culture with an equal number of LGL, or by the addition of 10% monocytes. Significant functional differences between LGL and LGL-DL in LDCC as well as in Con A-induced blastogenesis are suggested.

Cell Line↗
PubMed1985

Effect of fructose 1-phosphate on the activation of liver glycogen synthase.

The activation (dephosphorylation) of glycogen synthase and the inactivation (dephosphorylation) of phosphorylase in rat liver extracts on the administration of fructose were examined. The lag in the conversion of synthase b into a was cancelled, owing to the accumulation of fructose 1-phosphate. A decrease in the rate of dephosphorylation of phosphorylase a was also observed. The latency re-appeared in gel-filtered liver extracts. Similar latency was demonstrated in extracts from glucagon-treated rats. Addition of fructose 1-phosphate to the extract was able to abolish the latency, and the activation of glycogen synthase and the inactivation of phosphorylase occurred simultaneously. Fructose 1-phosphate increased the activity of glycogen synthase b measured in the presence of 0.2-0.4 mM-glucose 6-phosphate. According to kinetic investigations, fructose 1-phosphate increased the affinity of synthase b for its substrate, UDP-glucose. The accumulation of fructose 1-phosphate resulted in glycogen synthesis in the liver by inducing the enzymic activity of glycogen synthase b in the presence of glucose 6-phosphate in vivo and by promoting the activation of glycogen synthase.

Animals↗
PubMed1985

Contrasting effects of RNA and protein synthesis blocking on natural and lectin-dependent cell-mediated cytotoxicity against adherent HEp-2 cells.

In this study, earlier observations concerning the independence of both natural (NCMC) and lectin-dependent cell-mediated cytotoxicity (LDCC) from DNA synthesis have been confirmed. In addition, blocking of RNA synthesis by actinomycin D and of protein synthesis, reversibly by puromycin (PM) and irreversibly by emetine (EM) had different effects on NCMC and LDCC against 3H-thymidine-prelabeled HEp-2 target cells. Similarly to the Con A-induced proliferation of lymphocytes, LDCC activity was also inhibited by blocking of RNA and protein synthesis. NCMC to HEp-2 target cells was not affected by blocking of RNA synthesis, while both PM and EM strongly enhanced NCMC activity.

Cell Adhesion↗
PubMed1985

Separation of rabbit liver latent and spontaneously active phosphorylase phosphatases by chromatography on heparin-sepharose.

Latent and spontaneously active forms of phosphorylase phosphatase were separated by heparin-Sepharose chromatography of rabbit liver extract. The latent enzyme had an absolute polycation (histone H1, polybrene) requirement for the activity assayed with phosphorylase a and phosphorylase kinase substrates. Ethanol treatment resulted in the activation of both phosphatases by dissociating of 150-180 kDa holoenzymes to 33-38 kDa catalytic subunits as judged by gel filtration. The latent and spontaneously active phosphatases were differentiated according to their abilities to dephosphorylate the alpha and the beta subunits of phosphorylase kinase and sensitivities to inhibition by inhibitor-2 or heparin, and were classified as type-2A and type-1 phosphatases, respectively.

Animals↗
PubMed1985

Effects of acidic and basic macromolecules on the activity of protein phosphatase-1.

The dephosphorylation of phosphorylase a by the catalytic subunit of protein phosphatase-1 obtained from rabbit skeletal muscle is inhibited by heparin in a noncompetitive manner with respect to phosphorylase a (Ki = 8 micrograms/ml). The inhibitory effect of heparin is also observed in the presence of effectors (e.g., glucose and AMP) modifying the dephosphorylation of phosphorylase a. Heat-stable protein inhibitors of protein phosphatase-1 can develop their inhibitory effect of the activity of protein phosphatase-1 even in the presence of heparin. The inhibitory effect of heparin and the heat-stable inhibitor-2 of phosphatase is additive. Polybrene, a heparin antagonist, prevented phosphatase-1 from the inhibition caused by heparin or the inhibitors. Proteins with basic character, histone fractions (H1, H3) and protamine sulfate, can counteract with the inhibitory effect of heparin, but they cannot intercept the actions of inhibitor-1 or -2.

Animals↗
PubMed1985

Depressed lectin-dependent cell-mediated cytotoxicity against HEp-2 cells in patients with metastasizing solid tumour.

Lectin-dependent cell-mediated cytotoxicity (LDCC) of peripheral blood mononuclear cells (PBMC) from tumour patients was evaluated using human adherent 3H-TdR-prelabelled HEp-2 epipharynx carcinoma cells as targets at 50:1 effector-target cell ratio with 25 micrograms/ml concanavalin A (Con A) in a 24h assay. PBMC of nine patients with metastasizing solid tumour failed to exert cytotoxicity against HEp-2 targets. In contrast, increased survival (decreased detachment from the monolayer) of HEp-2 cells was observed in the presence of PBMC from tumour patients that was significantly enhanced by addition of Con A during LDCC assay.

Cell Line↗
PubMed1985

Stimulation by thymopoietin oligopeptides of lectin-dependent cell-mediated cytotoxicity in patients with systemic lupus erythematosus.

The effect of thymopoietin penta- (TP-5), tetra-(TP-4), and tripeptides (TP-3) was studied on the depressed lectin-dependent cell-mediated cytotoxicity (LDCC) against adherent HEp-2 target cells by peripheral blood mononuclear cells from patients with active systemic lupus erythematosus (SLE). LDCC activity was evaluated by detachment from the monolayer of 3H-thymidine-prelabelled HEp-2 cells in the presence of concanavalin A (Con A). While 10(-5)M TP-3 moderated the depression, 10(-5) M TP-5 strongly enhanced LDCC activity in SLE patients up to the normal level. On the other hand, LDCC activity by normal donors was not influenced by TP-3 and TP-5. TP-4 had no major effect either in control or in SLE patients. In parallel experiments none of the thymopoietin peptides affected the Con A-induced suppressor activity on the blastogenesis of lymphocytes. A selective immunostimulatory effect of TP-3 and TP-5 on the generation of LDCC effector cells in patients with SLE is suggested.

Concanavalin A↗