Biomedical subjects

F Antoni

Publications and source records attributed to F Antoni.

At least 37 records · Page 2Linked to original sources

PubMed1991

Accumulation of phenols in isolated hepatocytes after pretreatment with methylglyoxal.

The effects of a single intraperitoneal injection of methylglyoxal (50-800 mg/kg body wt.) in mice were investigated in the liver after 24 h. The administration of methylglyoxal (400 mg/kg body wt.) resulted in an increase in aniline hydroxylase activity in liver microsomes. At the same time an accumulation of p-amino-phenol, the hydroxylated product of aniline, was observed in isolated hepatocytes upon addition of aniline similarly to conditions (starvation, diabetes mellitus, pyrazole pretreatment) when aniline hydroxylase was induced. Methylglyoxal also decreased the reduced glutathione content in the liver, while the activity of serum glutamate pyruvate transaminase was increased, suggesting the onset of liver injuries. It is assumed that the increased oxidation of aniline hydroxylase combined with decreased glutathione levels after methylglyoxal treatment favours the formation of potentially hazardous phenol derivatives in the liver.

Aminophenols↗

PubMed1991

Morphological studies on the effect of L-leucine methyl ester on mouse peritoneal macrophages in vitro.

Mouse peritoneal macrophages (MO) were treated in culture with 5 mM L-leucine methyl ester (L-Leu-OMe), for 5, 10, 20, 40, and 60 min. The treatment resulted in rapid vacuolisation of the cytoplasm due to the dilatation and disruption of lysosomes. Autophagy caused by lysosomal enzymes destroyed most of the cytoplasmic organelles by 40 minutes after L-Leu-OMe treatment, but the cell membrane and nucleus were in many MOs resistant to the damage. 60 min after L-Leu-OMe treatment most of the MOs were killed. It is supposed that the disruption of the lysosomes is caused by formaldehyde produced by the hydrolysis of L-Leu-OMe.

Animals↗

PubMed1990

[DNA-based diagnosis].

DNA diagnostics is rapidly developing and gaining ground especially in the identification of genetic, malignant and infectious diseases as well as in the identification of individuals by means of DNA finger-printing. Present review deals with these and with the technical aspects of DNA diagnostics. The rapidly expanding field of diagnostics is contrasted by gene therapy which is recently not yet adaptable for human use.

Antibodies, Antinuclear↗

PubMed1990

Effect of emetine on the plasma cell population of chicken's gland of Harder.

The emetine effectively abolished the plasma cell population in the chicken's gland of Harder by day 3 of treatment. The plasma cell content regenerated by day 5 following emetine injection, possibly from a metabolically inactive, resting B cell population which was resistant to the emetine treatment. By day 7 extracellular substance in a very large quantity appeared among the plasma cells and epithelial cells which might represent a hyperactive plasma cell secretion. The changes in the circulating antibodies measured by hemagglutination well-correlated with the plasma cell content in the gland of Harder. The gland of Harder (GH) is an accessory lacrimal gland. Its main function is to lubricate the nictitating membrane and keep the surface of the eyeball wet. The presence and regulatory function of cAMP dependent histone kinase was showed. Since it has been published that in chicken the interstitium of this gland contains a proper amount of plasma cells, this observation called the attention of many investigators to study the role of GH in the immune response. The B cell maturation in the chicken GH has been studied. The surface marker studies have proved that beside the B cells the gland contains functionally adequate number of T cell which exert stimulatory effect on B cells to promote their transformation to plasma cells. In addition to T and B cells small number of macrophages also occur. In the 9 H the number of plasma cells is age dependent. At hatch only a few plasma cells occur in the interstitium of the gland but by 3 weeks of age they become predominant. Different isotypes of immunoglobulins are secreted by these plasma cells.

Animals↗

PubMed1990

Bilirubin and morphine glucuronidation is not inhibited by a cyclic-AMP mediated mechanism in murine liver.

Several reactions of the Ist and IInd phase of biotransformation have been reported to be under a negative cyclic-AMP dependent control. Conjugation of bilirubin and glucuronidation of morphine were investigated in isolated mouse hepatocytes and in mouse hepatocyte microsomes, respectively. N6,O2-dibutyryl cyclic-AMP did not inhibit conjugation of bilirubin in isolated hepatocytes. ATP and the dissociated catalytic subunit of the cyclic-AMP dependent protein kinase did not influence the glucuronidation of morphine, while inhibited the formation of p-nitrophenol glucuronide in microsomes prepared from isolated mouse hepatocytes.

Animals↗

PubMed1990

The role of the neuroendocrine system in determining genetic susceptibility to experimental allergic encephalomyelitis in the rat.

Experimental allergic encephalomyelitis (EAE) can be induced in some strains of rat but not others, by the injection of guinea-pig myelin basic protein in Freund's complete adjuvant. In the susceptible Lewis strain, spontaneous recovery from paralysis occurs and previous studies have shown that this recovery is dependent on the production, during the course of the disease, of high levels of corticosterone from the adrenal glands. Adrenalectomy completely abrogates the recovery phase and the disease becomes uniformly fatal unless steroid replacement therapy is given, which reproduces the serum levels of hormone that develop in intact animals with EAE. The PVG strain is not susceptible to EAE, but here it is shown that PVG rats that had been adrenalectomized developed severe disease from which they do not recover. As in the adrenalectomized Lewis rat, steroid replacement therapy could prevent the fatal outcome and in this case the disease course resembled that seen in intact Lewis animals. By a number of parameters PVG rats appear to make a more vigorous steroid response to stress than do Lewis. A comparison of the ratio of adrenal weight to body weight between these strains indicated that this ratio is larger in PVG, and serum corticosterone levels, in response to stress, were also found to be higher in this strain. Furthermore, basal levels of corticosterone were much more labile in PVG rats and had a higher mean value than those found in the age- and sex-matched Lewis animals with which they were compared. Genetic analysis using congenic rat strains showed that a high adrenal weight to body weight ratio was not linked to the major histocompatibility complex (MHC). It appears that the resistance to EAE of PVG rats depends on an enhanced stress response that mediates its immunosuppressive effect via the adrenal glands. While this stress response plays an essential part in the recovery of Lewis strain rats from EAE, it is sufficiently potent in PVG rats to virtually completely prevent signs of disease. Resistance to the induction of EAE could not be abrogated by adrenalectomy in all strains of rats studied. In particular, congenic PVG.RT1u rats, with the same background genes as PVG but with RT1u rather than the RT1cMHC genes of PVG, did not develop EAE when the adrenal glands were removed.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenalectomy↗

PubMed1989

Association of thrombin, plasmin, thrombin-antithrombin III complex and plasmin-antithrombin III complex with isolated hepatocytes.

The interaction of thrombin, plasmin or their antithrombin III complexes with isolated mouse hepatocytes was studied. Plasmin bound to hepatocytes in a concentration-dependent manner with an apparent Kd of 6.4.10(-8) M, attaining equilibrium within 10 min, and the interaction was inhibited by 6-amino-n-hexanoic acid. Plasmin treated with diisopropylfluorophosphate (DFP) bound to the cells in similar way as the untreated form of the enzyme. Thrombin bound also to hepatocytes, in a concentration-dependent manner, with a Kd of 5.4.10(-8) M reaching a steady state after 180 min. Thrombin inactivated with DFP, however, was inhibited in its binding to these cells. These data suggest that, whereas the kringle domains of plasmin are responsible for the enzyme-cell interaction, the active center of thrombin may be involved in the binding of this enzyme to hepatocytes. Plasmin-antithrombin III and thrombin-antithrombin III complexes were also associated with hepatocytes in a time-dependent manner, reaching a plateau after 180 min, and the two complexes competed in the interaction. While the interaction of active proteinases plasmin or thrombin with hepatocytes did not result in their internalization, the antithrombin III complexes were taken up by the cells, and thrombin-antithrombin III complex was degraded. These results indicate that hepatocytes may participate in the elimination of proteinase-antithrombin III complexes from the plasma, while the association of plasmin and thrombin with hepatocytes could imply distinct biological importance.

Animals↗

PubMed1989

Two components of type III protein kinase C with different substrate specificities and a phospholipid-dependent but Ca2+-inhibited protein kinase in rat brain.

The activities of rat brain protein kinase C isoenzymic fractions separated by hydroxyapatite chromatography were measured with histone H1 or the oligopeptide Ala-Ala-Ala-Ser-Phe-Lys-Ala-Lys-Lys-amide as substrates. The oligopeptide was a better substrate than histone H1 for nearly all of the protein kinase C fractions. Two subfractions of type III isoenzyme were resolved (IIIa and IIIb); type IIIb was characterized by a very low histone kinase activity compared to its peptide kinase activity. In some brain extracts a phospholipid-dependent but Ca2+-inhibited protein kinase was also observed which was eluted from the hydroxyapatite column between type II and III isoenzymes of protein kinase C.

Animals↗

PubMed1989

Isoenzyme patterns of protein kinase C and a phospholipid-dependent but Ca2+-inhibited enzyme fraction in the crude extracts of different tissues.

We compared the protein kinase C isoenzyme patterns of crude extracts of rabbit brain, cerebellum, spleen, thymus and human and pig granulocytes. The isoenzymes were fractionated by hydroxyapatite chromatography and the protein kinase C activity was determined with a synthetic oligopeptide substrate. In the extracts of several tissues we also observed an enzyme fraction which was activated by phosphatidylserine + diacylglycerol but inhibited by Ca2+.

Animals↗

PubMed1989

Cellular regulation of ADP-ribosylation of proteins. III. Selective augmentation of in vitro ADP-ribosylation of histone H3 in murine thymic cells after in vivo emetine treatment.

Thymic cells were isolated at intervals of between 0 and 144 h from mice that received one intraperitoneal injection of emetine (33 mg/kg), and thymus weight, incorporation of [14C]leucine into proteins and [3H]thymidine into DNA in intact thymic cells, as well as initial rates of protein ADP-ribosylation in permeabilized cells [A. Sóoki-Tóth, F. Asghari, E. Kirsten, and E. Kun (1987) Exp. Cell Res. 170, 93] were simultaneously monitored. The effect of emetine as an inhibitor of protein synthesis [F. Antoni, N. G. Luat, I. Csuka, I. Oláh, A. Sóoki-Tóth, and G. Bánfalvi (1987) Int. J. Immunopharmacol. 9, 333] corresponds to the induction of sequential cellular events, such as cell exit and remigration, by other antimitotic agents [C. Penit and F. Vasseur (1988) J. Immunol. 140, 3315] and produces an activation of proliferation of cells reentering into this organ. Proliferation, as demonstrated by a large increase in DNA synthesis and entrance into S phase, was kinetically related to an apparent increase in poly(ADP-ribose) polymerase activity in thymic cells and a highly significant in vitro ADP-ribosylation of histone H3. Since no DNA fragmentation occurred in thymic cells, as tested by a fluorometric technique [C. Birnboim and J. J. Jevac (1981) Cancer Res. 41, 1889], it is probable that a selective activation of poly(ADP-ribose) polymerase may have been induced in cells that undergo differentiation and proliferation while repopulating the thymus.

Adenosine Diphosphate Ribose↗

PubMed1989

Follicular cells of tonsils metabolise more deoxycytidine than other cell populations.

Nine subpopulations of tonsillar lymphocytes and the unseparated cells were compared in their utilization of exogenous deoxycytidine ([5-3H]CdR) and thymidine ([3H]TdR). Uptake phosphorylation and incorporation of labeled precursors were determined in B and T lymphocytes, in low density (LD; enriched in S phase cells) and in high density (HD; enriched in G0/G1 phase cells) cell fractions as well as in LD and HD subfractions of B and T lymphocytes, and in cells isolated from follicles of tonsils. As expected, LD cells and B lymphocytes were more active in TdR incorporation than HD cells and T lymphocytes. However, the ratio of [5-3H]CdR to [3H]TdR in their total phosphorylation and incorporation into DNA was much lower than the expected value of 1: about 0.5 for total phosphorylation and about 0.3 for incorporation in all subpopulations, except for the follicular cells, where these ratios were 1.0 and 0.7, respectively. These results show that the relative utilization of the two pyrimidine deoxyribonucleoside precursors varies among different lymphocyte subpopulations. However, this variation is not due to the different rate of DNA synthesis; rather, it depends on the differentiation stage of lymphocytes occurring in the germinal center of the follicles.

Cell Differentiation↗

PubMed1989

Changes of prostacyclin and thromboxane synthesis in the course of mouse liver perfusion. Stimulated thromboxane A2 synthesis of freshly prepared isolated mouse hepatocytes.

The formation of prostacyclin and thromboxane A2 (measured as 6-keto PGF1 alpha and TXB2 by radioimmunoassay) was investigated during a 30 min perfusion of mouse liver in a recirculation system. After cannulation of the portal vein an immediate increase of de novo synthesis and secretion of PGI2 occurred followed by a sharp decrease. Increased PGI2 synthesis was also followed by a continuous increase of TXA2 synthesis and secretion reaching a maximum at the end of the 30 min perfusion. Elevated TXA2 synthesis was also shown in freshly isolated hepatocytes investigated in the course of a 20 min incubation period immediately after the perfusion. However, the elevated TXA2 formation was not observed when it was measured after a 120 min preincubation of the cells. Both PGI2 and TXA2 production could be provoked to a similar extent by the addition of arachidonate and A 23187 immediately after the perfusion or after a 120 min preincubation.

6-Ketoprostaglandin F1 alpha↗

PubMed1989

The effect of L-leucine methyl ester on the phagocytosis and amino acid incorporation of murine peritoneal cells.

Murine peritoneal macrophages were treated in vitro with L-leucine methyl ester (0.25-5.0 mM). This treatment resulted in an inhibition of the amino acid incorporation into the cells both at 4 degrees C and 37 degrees C during a relatively short incubation period. The adherence of macrophages was not changed by the treatment. Bacterial phagocytosis was partly influenced: Leu-OMe did not change the binding but the engulfment of opsonized bacteria was blocked. Damage of the plasma membrane caused by Leu-OMe was not so serious as that produced by specific anti-PEC antiserum. Leu-OMe is a lysosomotropic agent accumulated preferentially by lysosomes. The vacuolization of the cells and the dilatation of the vacuoles are evidences for the intracellular damage. In the early phase this damage is characterized only by the leakage of the cytoplasm, later the damage of the plasma membrane can also be demonstrated.

Animals↗

PubMed1989

Ethanol treatment inhibits the development of diethylnitrosamine-induced tumors in rats.

Effect of ethanol (20% in drinking water) or acetone (1% in drinking water) treatment was investigated on N-diethylnitrosamine (DEN), acetyl-aminofluorene (AAF) and partial hepatectomy (PH) induced hepatic tumors in rats. Simultaneously with the morphological detection of foci and nodules in the liver of the sacrificed rats, the activities of isozymes of cytochrome P450IIE gene subfamily responsible for the oxidation of ethanol or acetone (as aniline hydroxylase) and also the activity of aminopyrine N-demethylase were determined. Nodules could be detected after DEN, AAF and PH treatment with and without combination with acetone, however nodules did not developed in ethanol treated animals even 6 months after the DEN injection. As expected acetone or ethanol selectively increased the activity of aniline hydroxylase without a general induction of P-450 enzymes. It is suggested that the induction of P-450IIE isoenzymes per se is not connected to the preventive effect of ethanol on DEN induced carcinogenesis.

Animals↗

PubMed1988

Glycogenolysis--and not gluconeogenesis--is the source of UDP-glucuronic acid for glucuronidation.

Differences in cofactor (NADPH and UDP-glucuronic acid) supply for various processes of biotransformation were studied by investigating the interrelations between glucose production (gluconeogenesis and glycogenolysis) and drug (p-nitrophenol, aminopyrine, phenolphthalein) biotransformation (hydroxylation and conjugation) in isolated murine hepatocytes. In glycogen-depleted hepatocytes prepared from animals fasted for 48 h (i) p-nitrophenol conjugation was decreased by 80% compared to the fed control, while aminopyrine oxidation was unaltered, (ii) addition of glucose or gluconeogenic substrates failed to increase the rate of p-nitrophenol conjugation, while the rate of p-nitrophenol and also aminopyrine oxidation was increased and (iii) gluconeogenesis was inhibited by 80% by aminopyrine oxidation: it was moderately decreased by p-nitrophenol oxidation and conjugation and remained unchanged by phenolphthalein conjugation. In hepatocytes prepared from fed mice (i) p-nitrophenol conjugation was independent of the extracellular glucose concentration, (ii) it was linked to the consumption of glycogen--addition of fructose inhibited p-nitrophenol glucuronidation only, while sulfation was unaltered and (iii) p-nitrophenol oxidation was not detectable: aminopyrine oxidation was not affected by fructose addition. It is suggested that UDP-glucuronic acid for glucuronidation derives predominantly from glycogen, while the NADPH generation for mixed function oxidation is linked to glucose uptake and/or gluconeogenesis in the liver.

Aminopyrine↗

PubMed1988

Accumulation of phenols and catechols in isolated mouse hepatocytes in starvation or after pretreatment with acetone.

Conditions leading to the accumulation of unconjugated phenols and catechols were investigated in mouse livers. The formation of unconjugated hydroxylated products of added p-nitrophenol and aniline was investigated in isolated hepatocytes prepared from 48 hr fasted or fed mice or from fed mice after acetone pretreatment. 4-Nitrocatechol and p-aminophenol--the hydroxylated products of p-nitrophenol and aniline--were accumulated in cells prepared from fasting animals, while in cells prepared from fed mice these unconjugated derivatives were not detectable. The accumulation of 4-nitrocatechol and p-aminophenol was also shown in isolated hepatocytes prepared from acetone pretreated fed mice. Inhibition of glucuronidation by N6,O2-dibutyryl cAMP or by D-galactosamine increased the accumulation of 4-nitrocatechol upon addition of p-nitrophenol in cells prepared from fasted mice. Both 48 hr starvation and acetone pretreatment enhanced the activity of microsomal p-nitrophenol and aniline hydroxylase by 300% and 600%, respectively, whereas p-nitrophenol conjugation in isolated hepatocytes as well as in hepatocyte homogenates was decreased by about 80% after 48 hr starvation. Acetone pretreatment did not alter the rate of p-nitrophenol conjugation measured in liver homogenates. It is suggested that a shift from conjugation toward hydroxylation in starvation gives rise to the formation of hazardous metabolites.

Acetone↗

PubMed1988

Cyclic AMP-dependent phosphorylation in the control of biotransformation in the liver.

The possibility of a short-term cAMP-dependent regulation of mixed-function oxidation and of glucuronide formation was investigated in isolated mouse hepatocytes and in mouse liver microsomal membranes. N6, O2-dibutyryl cAMP (in accordance with its increasing effect on gluconeogenesis) decreased aminopyrine oxidation and p-nitrophenol conjugation in isolated hepatocytes, while the phenolphthalein conjugation remained unaltered. Similar to dibutyryl cAMP the Ca2+ ionophore A 23187 also decreased aminopyrine oxidation. In cell-free systems the phosphorylation of isolated microsomal membranes by the exogenous cAMP-dependent protein kinase was inhibitory on aminopyrine oxidation and p-nitrophenol glucuronide formation but aniline oxidation and phenolphthalein glucuronidation were not affected. The correlation between the negative cAMP-dependent control of certain processes of biotransformation and the positive cAMP-dependent regulation of gluconeogenesis is discussed.

Aminopyrine↗

PubMed1988

Interrelationship between drug oxidation ureogenesis and gluconeogenesis in isolated hepatocytes.

1. The effect of increased ureogenesis--provoked by NH4Cl and ornithine--on gluconeogenesis and aminopyrine oxidation was studied in isolated hepatocytes prepared from 24 hr starved mice; lactate or fructose was used as gluconeogenic precursor. 2. Increased ureogenesis caused about 40% inhibition both on aminopyrine oxidation and gluconeogenesis when lactate was added as gluconeogenic substrate. 3. On the other hand, only 10% inhibition of aminopyrine oxidation and about 15% inhibition of gluconeogenesis were observed when fructose was used as gluconeogenic precursor. 4. Aminopyrine has been reported to inhibit gluconeogenesis from fructose by 30% and from lactate by 85%. The inhibitory effect of the combined addition of aminopyrine, NH4Cl and ornithine on gluconeogenesis was also dependent on the applied gluconeogenic precursor. 5. The provoked ureogenesis by ammonia and ornithine was not inhibited by aminopyrine. N6, O2-dibutyryl cAMP known to cause an increase of gluconeogenesis a decrease of aminopyrine oxidation enhanced the inhibitory action of increased ureogenesis on aminopyrine oxidation and on gluconeogenesis further. 6. The role of NADPH in the regulation of drug oxidation and ureogenesis is underlined.

Aminopyrine↗