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Biomedical subjects

P Gergely

Publications and source records attributed to P Gergely.

At least 73 records · Page 4Linked to original sources
PubMed1993

Dephosphorylation of distinct sites on microtubule-associated protein MAP1B by protein phosphatases 1, 2A and 2B.

Rat brain microtubule-associated protein MAP1B has been tested as a substrate for Ser/Thr protein phosphatases (PP). The dephosphorylation reactions were followed by specific antibodies recognizing phosphorylated and phosphorylatable epitopes. One set of phosphorylation sites on MAP1B are referred to as mode I sites, and their phosphorylation is presumably catalyzed by proline-directed protein kinases. These mode I sites are efficiently dephosphorylated by PP2B and 2A but not by PP1. Another set of phosphorylation sites on MAP1B are named mode II sites, and their phosphorylation is possibly due to casein kinase II. These mode II sites are dephosphorylated by PP2A and PP1, the PP2B being ineffective. The selectivity of phosphatases for different sites within the same protein indicates the complexity of the dephosphorylation reactions regulating the functionality of MAP1B in neurons.

Animals↗
PubMed1993

ATP induces a conformational change of the 90-kDa heat shock protein (hsp90).

The 90-kDa heat shock protein (hsp90) is a well conserved, abundant cytosolic protein believed to be a "chaperone" of most steroid receptors. We have recently demonstrated that hsp90 has an ATP-binding site and autophosphorylating activity (Csermely, P., and Kahn, C. R. (1991) J. Biol. Chem. 266, 4943-4950). Circular dichroism analysis of highly purified hsp90 from rat liver shows that ATP induces an increase of beta-pleated sheet content of hsp90. Vanadate, molybdate, and heat treatment at 56 degrees C induce a similar change in the circular dichroism spectrum. Fourier transformed infrared spectroscopy reveals an ATP-induced increase in the interchain interactions of the 90-kDa heat shock protein due to an increase in its beta-pleated sheet content. In further studies we found that ATP: 1) decreases the tryptophan fluorescence of hsp90 by 11.6 +/- 1.9%; 2) increases the hydrophobic character of the protein as determined by its distribution between an aqueous phase and phenyl-Sepharose; and 3) renders hsp90 less susceptible to tryptic digestion. Our results suggest that hsp90 undergoes an "open-->closed" conformational change after the addition of ATP, analogous in many respects to the similar changes of the DnaK protein, the immunoglobulin heavy chain binding protein (BiP/GRP78), and hsp70. The ATP-induced conformational change of hsp90 may be important in regulating its association with steroid receptors and other cellular proteins.

Adenosine Triphosphate↗
PubMed1993

Interaction between immunity to Bordetella bronchiseptica and infection of pig herds by Bordetella bronchiseptica and Pasteurella multocida.

The dynamics of toxigenic Bordetella bronchiseptica and Pasteurella multocida infection and the B. bronchiseptica specific antibody content of the blood and nasal secretion were studied in three Hungarian and three Dutch pig herds. In both countries, the studies involved young sows that had farrowed once or twice (YS), old sows that had farrowed more than four times (OS), and their piglets. The results indicate that Dutch sows are characterized by a lower prevalence of B. bronchiseptica and P. multocida infection than Hungarian sows. In Dutch sows and in their piglets, the rate of P. multocida infection was higher than that of B. bronchiseptica infection. The opposite was found for the Hungarian sows and their piglets. B. bronchiseptica infection commenced at 3 and 4 weeks of age in piglets of young and old Dutch sows, respectively, followed by the emergence of P. multocida infection at 5 (YS) and 6 weeks of age (OS). In Hungarian piglets, B. bronchiseptica infection was first demonstrable at 1 (YS) and 3 (OS) while P. multocida infection at 3 (YS) and 5 (OS) weeks of age. The serological tests demonstrated higher B. bronchiseptica specific antibody levels in the Dutch sows and piglets as compared to the Hungarian ones. According to the ELISA results, the levels of IgA and IgG in the serum and those of sIgA, IgA and IgG in the nasal secretion of Dutch sows were significantly (p < 0.001) higher in the Dutch than in the Hungarian piglets up to 3 and 4 weeks of age, respectively.

Animals↗
PubMed1993

Attenuated veterinary virus vaccine for the treatment of cancer.

Attenuated (nonpathogenic) avian viruses have been used as a form of nonspecific immunological treatment for advanced human cancer. For this study, we used Newcastle disease virus (NDV) vaccine MTH-68/N in an open phase II/B, placebo-controlled (26 patients), multicenter clinical trial for the treatment of 33 patients with advanced cancers. NDV (4000 U/day) or placebo was administered by inhalation twice weekly. During the 6-month trial, the size and presence of primary tumors and metastases were objectively monitored at five institutions by radiologists unaware of the type of treatment that was given. Regression of tumor(s) and/or metastases were observed in eight cases treated with virus (vs. none in the placebo group; p < 0.01). Ten additional patients treated with NDV had no further progression of their tumor sizes, whereas tumor stabilization was noted in only two control patients. Objective, favorable responses (regressions plus stabilization) to virus therapy thus occurred in a total of 18 patients (55%) compared to 2 patients in the placebo group (8%; p < 0.01). Two cases of complete remission were noted in the group treated with NDV. Patients receiving virus therapy had a higher rate of survival at 1 to 2 years. Of 33 patients receiving virus vaccine, 22 survived 1 year, compared to only 4 of 26 patients in the control group (p < 0.02). After 2 years, all seven survivors in the study were in the virus therapy group. There were no 2-year survivors in the control group (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Purification and characterization of three distinct types of protein phosphatase catalytic subunits in bovine platelets.

The catalytic subunits of bovine platelet protein phosphatases were separated into three distinct forms by chromatography on heparin-Sepharose. Each phosphatase was further purified to apparent homogeneity as judged in sodium dodecyl sulfate-polyacrylamide gel yielding single protein bands of 37, 41, and 36 kDa. The 37-kDa phosphatase was excluded from heparin-Sepharose and preferentially dephosphorylated the alpha-subunit of phosphorylase kinase. It was stimulated by polycations (polybrene or histone H1) and was inhibited by okadaic acid (IC50 = 0.3 nM), but its activity was not influenced by inhibitor-2 or heparin. The 41-kDa phosphatase was eluted from heparin-Sepharose by 0.20-0.25 M NaCl and preferentially dephosphorylated the beta-subunit of phosphorylase kinase. It was stimulated by polycations and inhibited by okadaic acid (IC50 = 2 nM), but its activity was not affected by inhibitor-2 or heparin. The 36-kDa phosphatase was eluted from heparin-Sepharose by 0.45-0.50 M NaCl and preferentially dephosphorylated the beta-subunit of phosphorylase kinase. It was inhibited by inhibitor-2, heparin, histone H1, and okadaic acid (IC50 = 70 nM). The 37- and 36-kDa phosphatases can be classified as type-2A and type-1 enzymes, respectively. The 41-kDa phosphatase does not precisely fit the criteria of either type, showing only partial similarities to both type-1 and type-2A enzymes and it may represent a novel type of protein phosphatase in bovine platelets.

Animals↗
PubMed1992

Phosphorylation-induced conformational changes in the phosphorylase ab hybrid as revealed by resolution of pyridoxal 5'-phosphate with imidazole citrate and cysteine.

The accessibility of pyridoxal 5'-phosphates of the phosphorylase ab hybrid to resolution by imidazole citrate and cysteine was studied and compared with that of the b and a forms. Promotion of resolution of phosphorylated forms by raising the temperature or in the presence of glycogen indicates that the resistance of phosphorylase a and ab to resolution at 0 degrees C is due rather to their tetrameric state than their phosphorylation-related active conformation. The pattern of resolution of the ab hybrid was similar to that of the a and differed from that of the b forms in that it occurred at 30 degrees C and 37 degrees C but not at 0 degrees C, moreover, it did not show first-order kinetics. On the other hand, inhibition of resolution by ligands binding to the nucleotide site of phosphorylase reflected an intermediate sensitivity of the ab form between that of the b and a forms. We conclude that partial phosphorylation of phosphorylase b elicits conformational change(s) in both subunits which influence the monomer-monomer interactions and resolution of pyridoxal 5'-phosphates. Resistance of ab hybrid to monomerizing agents as imidazole citrate, comparable to that of other forms, argues for its stability, ruling out its reshuffling into mixtures of phosphorylase b and a.

Adenosine Monophosphate↗
PubMed1992

Synthetic peptides comprising defined sequences of CH-2 and CH-3 domains of human IgG1 induce prostaglandin E2 production from human peripheral blood mononuclear cells.

Synthetic peptides Y48 and Y75 comprising sequences at exposed sites within the CH-2 and CH-3 domains of human IgG1 at a concentration of 10(-5) M, increase PGE2 production by human peripheral blood mononuclear cell (PBMC) cultures. An increase of leukocyte migration inhibitory factor (LMIF) production in PBMC cultures--as a result of synthetic peptide treatment--was also observed. This LMIF activity, to some extent, is attributed to the PGE2 production by the cells; the inhibition of leukocyte migration being abolished by the presence of indomethacine or antibody to PGE2.

Cell Migration Inhibition↗
PubMed1992

The pathogenesis of autoimmune disease.

The mechanisms of autoimmune pathology are normally described on a disease-by-disease basis. Taking a novel angle, Peter Gergely here examines the role of different types of leucocytes across a spectrum of autoimmune diseases, combining the results from a number of Hungarian laboratories.

Animals↗
PubMed1992

Comparative characterization of liver glycogen metabolism in rat and guinea-pig.

1. Guinea-pig liver contained more phosphorylase in the active (phosphorylated) form and less synthase in the active (dephosphorylated) form when compared with rat liver. 2. Activities of cyclic AMP-dependent protein kinase and Ca(2+)-dependent phosphorylase kinase were the same in rat and guinea-pig livers. 3. Activities of phosphorylase phosphatase and synthase phosphatase in the extract and glycogen plus microsomal fraction of guinea-pig liver were significantly lower than those of rat liver. 4. The existence of inhibitor-1 in the liver of guinea-pig can maintain a lower activity of type-1 protein phosphatase, especially when inhibitor-1 is phosphorylated by cyclic AMP-dependent protein kinase.

Animals↗
PubMed1992

Effect of human IgG1 peptides on the antigen-specific antibody response of mice in vivo.

The effect of synthetic peptides--corresponding to the amino acid sequences 289-301 (Y48) and 293-301 (Y91) within the CH-2 domain in the human IgG1 was studied on the oxazolone-specific primary and secondary antibody response isotype distribution and on the sheep erythrocyte (SRBC)-specific primary IgM response. High responder (Balb/c) and low responder (C57Bl/6) mice to oxazolone hapten were treated intraperitoneally with various doses of peptides simultaneously with the first and second contact sensitization. The relative levels of oxazolone-specific IgM, IgG3, IgG1, IgG2a and IgG2b antibodies were determined by a solid phase radioimmunoassay. Y48 and Y91 peptides in a dose range of 10(-5) - 10(-8) M/animal enhanced the oxazolone-specific antibody response. This effect was more striking under suboptimal conditions: using smaller antigen dose for sensitization, cyclophosphamide pretreatment or using genetically low responder mice. SRBC-specific primary IgM response was enhanced by Y91 peptide, Y48 was ineffective.

Animals↗
PubMed1991

[Cytokine production in patients with systemic lupus erythematosus].

The production of different cytokines, namely interleukin-2, interleukin-1 and tumor necrosis factor-alpha produced by peripheral immunocompetent cells was evaluated in patients with systemic lupus erythematosus in active and inactive stage of the disease. The results obtained were compared to healthy controls. It has been found that lymphocytes from both groups of SLE patients produced similarly less interleukin-2 activity. Interleukin-1 activity of monocytes was significantly reduced only in patients with active stage of the disease, whereas tumor necrosis factor-alpha production was diminished even in cases of inactive SLE. The simultaneous detection of the above mentioned cytokines may indicate further details concerning immunoregulatory disturbances of systemic lupus erythematosus.

Adult↗
PubMed1991

Modulatory effect of synthetic human IgG Fc peptides on the in vitro immune response of murine spleen cells.

Synthetic peptides representative of defined surface-exposed sequences within the CH-2 and CH-3 domains of human IgG1 induce IgM production by murine spleen cells, even in cultures depleted of T-lymphocytes. This stimulation was not altered by simultaneous administration of dextran sulphate in suboptimal concentration, its effect being additive to that of the peptides. Cell proliferation was augmented only at 10(-4) M doses of peptides. IL-1 production by adherent cells was also increased as a result of peptide treatment; whilst administration of exogenous IL-1, 4 h later, seemed to abrogate the effect of peptide treatment on the augmentation of IgM production. Peptide treatment failed to induce IL-2 and/or IL-4 production. The effect of IgG peptides seems to be exerted directly on B-cells at an early step of activation and to be mediated at least in part by IL-1.

Adjuvants, Immunologic↗
PubMed1991

The effect of D-penicillamine on CCl4-induced experimental liver cirrhosis.

The effect of D-penicillamine (Pe) on liver fibrosis-cirrhosis induced by chronic CCl4 and phenobarbital (Pb) administration in Fischer 344 male rats was studied. Morphometric analysis did not reveal a decrease in the amount of connective tissue fibers after Pe-treatment. Compared to the CCl4 and Pb-treated control groups, Pe had no significant effect on the concentrations of hydroxyproline, a parameter of collagen degradation, either; however, it increased the glycosaminoglycan concentrations. Lymphocyte stimulation by Con-A in the Pe-treated groups did not differ from that of the CCl4 and Pb-treated ones. According to our studies, Pe-treatment was ineffective in rats with liver fibrosis-cirrhosis induced by CCl4 and Pb administration. It seems that Pe can be effective only in the cirrhosis types accompanied by a considerable copper accumulation due to suppression of the toxic effects of copper.

Animals↗
PubMed1991

Effect of the bioflavonoid silymarin on the in vitro activity and expression of superoxide dismutase (SOD) enzyme.

Superoxide dismutase activity and expression of the erythrocytes and lymphocytes of patients suffering from chronic alcoholic liver disease and those of healthy controls were investigated after in vitro incubation with silymarin. It was concluded that silymarin treatment in a concentration achievable by in vivo treatment (10 micrograms/ml) significantly increased the SOD activity of both the erythrocytes and lymphocytes of patients with liver disease, whereas the SOD expression of the lymphocytes enhanced to a considerable extent. These results indirectly indicate that the scavenger silymarin is able to increase the antioxidant protection of the cells by ameliorating the deleterious effects of free radical reactions.

Adult↗
PubMed1991

Long term use of piroxicam in the treatment of systemic lupus erythematosus.

Twelve patients suffering from systemic lupus erythematosus (SLE) were treated with piroxicam (Hotemin-EGIS) for 9-18 (mean: 13.7) months. At the beginning, the patients were in a moderately active stage of the disease, 10 patients also received low dose corticosteroid treatment. After the study was completed, clinical and immunological improvement was seen in 10 cases. The average daily dose of prednisolone could be reduced (from 10.5 mg to 5 mg). These patients tolerated the treatment well, no adverse effect was seen. No elevation of serum transaminase, creatinine or change in blood cell count and glomerular filtration rate were observed. Piroxicam, therefore, is recommended for the treatment of mildly active SLE.

Adult↗
PubMed1990

[Vaccine therapy of malignant tumors].

Vaccine therapy of neoplasms increases anti-tumor immune responses by enhancing the immunogenicity of tumor cells. One possible way of vaccine therapy is treatment with live apathogenic virus vaccines, in particular with Newcastle disease virus and other apathogenic avian viruses. Frequent regression of tumors and subjective improvement by vaccine therapy of patients may be explained by: a) infection of tumor cells by the virus and so enhancing their immunogenicity, b) activation of cells of the immune system, increased production of interferons, tumor necrosis factor-alpha and other cytokines, c) increased production of ACTH and beta endorphin by monocytes and lymphocytes resulting in an improvement in the general well-being. According to the previous results and the experimental data, extended trials with avian virus vaccines seem to be promising.

Humans↗
PubMed1990

[The interleukins ].

Immune response is regulated by a number of soluble mediators. Interleukins belong to these mediators, as a well defined group of regulatory molecules. Interleukins are necessary for the differentiation and activation a T and B lymphocytes and other cells. They play an important role in inflammation: they cause fever, leukocytosis etc. Some interleukins are being used as therapeutic agents.

Adjuvants, Immunologic↗