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Biomedical subjects

M Toth

Publications and source records attributed to M Toth.

At least 73 records · Page 4Linked to original sources
PubMed1988

Activation of the major late promoter in adenovirus transformed cells by 5-azacytidine.

The adenovirus major late promoter (MLP) is normally not active in transformed cells. We investigated if it could be activated with 5-azacytidine. Three days of treatment with 10 microM 5-azacytidine induced transient activation of the MLP as shown by hybridization with an L1 r-strand-specific probe. The po/III-transcribed VA-RNAs were not activated. L1 activation was not accompanied by detectable changes in methylation of HpaII sites at the promoter or in the body of the transcript. Stably activated cell clones could be obtained at 20% frequency after long-term drug treatment.

Adenoviridae↗
PubMed1988

Activation of the human beta interferon gene by the adenovirus type 12 E1B gene.

The transcription of endogenous beta interferon mRNA was activated in human embryo kidney (HEK) cells infected with adenovirus type 12 (Ad12) but was activated only inefficiently or not at all in HEK cells infected with Ad5 and rc-1 (Ad5 dl312 containing the Ad12 E1A region). The analysis with Ad12 mutants showed that Ad12 E1B products, especially the 19K protein, were important for the expression of the endogenous beta interferon gene and Ad12 E1A products were not involved in the expression. The expression of exogenously transfected pIFN-CAT (a hybrid plasmid having the human beta interferon promoter fused with the CAT gene) was activated in HEK and chicken embryo fibroblast (CEF) cells infected with either Ad12 or Ad5. The analysis of cotransfection of CEF cells with pIFN-CAT and plasmids containing fragments of Ad12 or Ad5 DNA showed that Ad12 or Ad5 E1B (possibly the 19K protein) was and E1A was not involved in the expression of the exogenous pIFN-CAT.

Adenoviridae↗
PubMed1988

Trypsin-sensitive neutralization site on VP1 of Theiler's murine encephalomyelitis viruses.

We generated Theiler's murine encephalomyelitis virus mutants resistant to several neutralizing monoclonal antibodies (MAbs) having their epitopes near a trypsin cleavage site of VP1. Neutralization and Western blot (immunoblot) studies suggest that two of the MAbs have identical epitopes that partly overlap the epitope of a third MAb. Sequencing of RNA of the mutants localized the epitopes to a site near the carboxyl end of VP1. The limited diversity of nucleotide changes seen in the mutants and the immunodominance of the site suggest that the carboxyl end of VP1 may have an important function.

Animals↗
PubMed1988

The role of infection in the etiology of preterm birth.

The hypothesis that infection induces or is a precursor to preterm birth or premature rupture of the membranes was examined in a prospective study of 193 randomly selected pregnant women. We investigated the prognostic significance of factors that suggest infection of the uterine cavity before pregnancy, such as a history of pelvic inflammatory disease, a history of intrauterine contraceptive device (IUD) use, multiple sex partners, and the presence of antisperm antibodies, in relation to premature rupture of the membranes and preterm birth. Sexual activity, a potential vehicle for bacterial exchange, was also charted throughout pregnancy via monthly interviews. We performed immunologic tests on each patient and obtained cultures of the cervix for aerobic and anaerobic bacteria and chlamydia at the first visit, occurring at six to 14 weeks' gestation, and again at 36 weeks. The results suggest that infection may indeed play a causative role in premature rupture of the membranes or preterm birth. A strong correlation was found between preterm birth and both a history of pelvic inflammatory disease (P = .004) and a history of IUD use (P = .0015). Amnionitis was associated with the presence of immunoglobulin G (IgG) antisperm antibodies (P = .02), as well as with a history of pelvic inflammatory disease (P = .0006). There was also a correlation between premature rupture of the membranes and a history of multiple sex partners (P = .02). This collective evidence implicates preexisting infection of the uterine cavity as a predisposing factor in premature rupture of the membranes, preterm delivery, and amnionitis.

Chorioamnionitis↗
PubMed1987

Release and regulation of atrial natriuretic peptide (ANP).

Mammalian atrial cardiocytes synthesize and secrete a hormone called atrial natriuretic peptide (ANP), which causes natriuresis, diuresis and inhibition of smooth muscle contraction, aldosterone and renin release. Volume loading, vasoconstrictor agents, immersion in water, atrial tachycardia and high salt diets have been reported to increase the release of cardiac ANP, thereby suggesting that the peptide is released in response to an increase in atrial pressure. That stretch is an important stimulus for ANP release is also suggested by clinical studies demonstrating a direct correlation between secretion rate and atrial pressure. The experiments using isolated perfused rat heart provide direct evidence that distension of the right atrium stimulates the release of ANP. Pharmacological studies in the isolated heart point to roles of cytosolic calcium, the phosphoinositide system and the cyclic AMP pathway in the regulation of ANP release. The concentration of calcium in heart muscle cells, in addition to the length of the muscle fibers, depends on many factors such as the action of humoral substances, cardiac nerve activity and heart rate, which may all contribute to the regulation of ANP secretion.

Acetylcholine↗
PubMed1986

The phorbol ester induced atrial natriuretic peptide secretion is stimulated by forskolin and Bay K8644 and inhibited by 8-bromo-cyclic GMP.

The role of intracellular signals in the regulation of atrial natriuretic peptide (ANP) release was studied using the isolated perfused rat heart. The phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), known to activate the protein kinase C pathway, produced a dose-dependent increase in perfusate ANP immunoreactivity. Bay k8644, a putative calcium channel activator, and forskolin, which stimulates adenylate cyclase, induced a sustained increase in ANP secretory rate. TPA in combination with either Bay k8644 or forskolin induced higher ANP secretion than the calculated additive value for each agent. 8-bromo-cyclic GMP and sodium nitroprusside, when given alone, had no effect on ANP secretion, but delayed the TPA-stimulated increase in perfusate ANP. ANP secretion appears therefore to be mediated both by the phosphoinositide and the cAMP system, whereas the cGMP pathway may be inhibitory.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1986

Atriopeptin III kinetics and pharmacodynamics in normal and anephric rats.

To elucidate the disposition of atriopeptin III in plasma we performed experiments in normal and anephric rats. Bolus, i.v. atriopeptin III (250 ng) was given after which the rats were decapitated at 30-sec intervals. The half-life of atriopeptin III in normal rats was 26.5 sec, the volume of distribution was 352 ml and the plasma clearance was 500 ml/min. In anephric rats the half-life was 56.8 sec, the volume of distribution was 345 ml and the plasma clearance was 206 ml/min. In other rats atriopeptin III was given and urine was collected simultaneously. No atriopeptin III could be measured in the urine. We gave 0.0, 0.067, 0.125, 0.25, 0.5 and 1.0 ng/kg of bolus atriopeptin III to normal rats and measured effects on blood pressure, heart rate and plasma concentration at 30 sec, the time at which maximum effect on blood pressure occurred. Dose, change in blood pressure and plasma concentration were correlated. Heart rate increased, but not in a dose-dependent fashion. We conclude that atriopeptin III is cleared from rat plasma rapidly and that the kidneys account for 59% of its elimination by degradation rather than excretion. Because the effect of atriopeptin III on blood pressure is concentration-dependent, the transient changes exerted by atriopeptin III may be related to its rapid disappearance from plasma.

Animals↗
PubMed1986

Regulation of atrial natriuretic peptide secretion.

To evaluate the role of the autonomic nervous system in the regulation of atrial natriuretic peptide (ANP) secretion, the secretory responses of isolated perfused rat hearts to adrenaline and acetylcholine were studied. Infusion of adrenaline produced a dose-dependent rise in heart rate and contractile force associated with a marked increase in perfusate ANP immunoreactivity. The ANP response was almost completely abolished by the alpha-adrenoceptor antagonist phentolamine (10(-6)) and attenuated by the beta-adrenoceptor antagonist metoprolol (10(-5)). Thus, both alpha- and beta-adrenoceptors may mediate the adrenaline effect on ANP release. Perfusion of the isolated heart with 10(-6) or 10(-5) acetylcholine resulted in a short rise in hormone release followed by a gradual decline. The negative ionotropic and chronotropic effects of acetylcholine and the rise in ANP induced by acetylcholine were blocked by atropine, suggesting that a muscarinic receptor is involved. The finding that both adrenaline and acetylcholine alter ANP secretion rate points to the participation of autonomic nerves in the regulation of ANP release from atrial cardiocytes.

Acetylcholine↗
PubMed1986

Group practice in Yugoslavia.

Group dental practice depends to a considerable extent on the social system of the state in which it exists. In the Socialist Federal Republic of Yugoslavia it is therefore based on the principles of the central system of socialist self-management. Private dental practice is the exception; dentistry is normally practised in particular health care organizations. Within these organizations, the members of the group independently take the decisions relevant to their activity, mutual rights and obligations, and material affairs. Special agreements arrived at and other decisions are taken in a highly democratic manner with this intention. The legislator has provided only certain frameworks or foundations for their decisions.

Dental Health Services↗
PubMed1986

Nonintervention in premature rupture of the amniotic membranes.

One hundred and forty-one instances of premature rupture of the amniotic membranes (PROM), between 25 and 36 weeks gestation and with duration of PROM greater than six hours, were managed by bedrest, observation and no obstetric intervention. Delivery was allowed if the patient had spontaneous labor develop, and delivery was initiated for chorioamnionitis or fetal distress. The perinatal mortality was 25 of 148 infants delivered (168 of 1,000 births). The majority of neonatal deaths (64 per cent) were attributable to complications of prematurity. Neonatal sepsis was uncommon as a cause of death (0.16 per cent). Results indicate that the natural history of PROM is associated with a low incidence of serious maternal and fetal infections and that prematurity is the most serious problem.

Amniocentesis↗
PubMed1985

Atrial natriuretic peptide secretion: synergistic effect of phorbol ester and A23187.

To investigate the role of inositol phospholipid turnover in the atrial natriuretic peptide (ANP) secretion, the secretory responses from isolated perfused rat hearts to the ionophore, A23187, and the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), alone or in combination, were studied. A23187 induced a sharp increase in ANP secretion, whereas TPA caused a slowly progressive increase in secretion rate. 4 alpha-phorbol-12,13-didecanoate, which lacks the ability to activate protein kinase C, had no effect on ANP secretion. The combination of A23187 and TPA stimulated ANP secretion higher than the calculated additive value for each agent. The synergistic effect of the agents suggests a role of calcium-activated protein kinase C in ANP secretion from atrial cardiocytes.

Animals↗
PubMed1985

The structure of adenovirus chromatin in infected cells.

The structure of adenovirus chromatin in infected cells was studied by micrococcal nuclease digestion and hybridization with virus-specific probes. In the early phase of infection (5 h) a significant proportion of viral molecules was organized like actively transcribed cellular chromatin. As expected for a transcriptionally active population of molecules, even at high multiplicity of infection the nucleosomal repeating pattern was less distinct than in a transformed cell which contained the corresponding but less active genomic region. The observed repeating pattern in infected cells was unlikely to be due to integrated molecules since less than 0.07% of input genomes became associated with cellular DNA. After the onset of viral DNA replication, the pool of viral chromatin organized like cellular chromatin rapidly increased. In addition, newly replicated molecules also maintained the cellular chromatin-like organization as measured by [3H]thymidine incorporation after the cessation of cellular DNA synthesis. These data suggest that newly replicated viral molecules are organized by histones into cell-like chromatin throughout the infection cycle. Coincident with the peak of viral DNA and core protein synthesis, and the decline of histone synthesis, the late, core-like non-repeating viral chromatin became dominant, increasingly obscuring the underlying repeating pattern. Experiments suggest that this late chromatin is destined for encapsidation, that the early chromatin persists and that viral core proteins do not displace histones on viral DNA. A model is proposed suggesting that transcription and type I replication occur on histone-condensed templates, while type II replication products late in infection are condensed by core proteins and are destined for encapsidation.

Adenoviruses, Human↗
PubMed1984

Prostaglandin F2 alpha, oxytocin, and uterine activation in hypertonic saline-induced abortions.

Intra-amniotic injections of hypertonic saline at midgestation induce uterine activity, which evolves into a laborlike pattern in less than 24 hours and is associated with progressive increase in uterine oxytocin response. This uterine activation occurred in the absence of a measurable increase in plasma 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM). Only after 25 to 27 hours was a rise in plasma concentration of PGFM detected, which then increased in a parallel manner with cervical dilatation. By contrast, plasma oxytocin levels increased by almost 100% soon after the injection of hypertonic saline, declining to initial levels by 24 to 28 hours. Oxytocin infusion given after the intra-amniotic injection at rates resulting in about a fivefold increase in plasma oxytocin significantly accelerated cervical dilatation and the rise in plasma PGFM. Oxytocin infused before induction of abortion resulted in only a small and transient rise in plasma PGFM. Hypertonic saline injections thus increase the prostaglandin F2 alpha-stimulating action of oxytocin, which in turn may be responsible for the enhanced contractile response to the hormone. Myometrial activation after hypertonic saline injections is probably caused by an interaction of oxytocin and prostaglandin F2 alpha, and cervical dilatation depends on contractile activity and a critical increase in prostaglandin production.

Abortion, Induced↗
PubMed1984

Nuclease sensitivity of adenovirus type 2 chromatin in lytic infection.

We have investigated the sensitivity of adenovirus type 2 naked DNA and chromatin at 5 h and 20 h after infection to digestion by DNase I, micrococcal nuclease and endogenous nuclease between map coordinates 11.3 and 18.0 (SmaI-F fragment) using a terminal labelling method. Infected cell nuclei were gently digested with nucleases, DNA was extracted and digested to completion with SmaI and the fragments shorter than the SmaI-F fragment mapped by hybridization with a 708 base pair probe co-terminal with the SmaI-F fragment. Early chromatin contained hypersensitive sites at 16.0 and 14.3. These sites became minor cleavage sites in late chromatin and new hypersensitive sites appeared at 13.5 and 13.0. The change in the location of the hypersensitive sites in the course of infection correlated with the early to late switch in the transcription pattern in this region and the early to late change in the overall structure of adenovirus chromatin.

Adenoviruses, Human↗