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Biomedical subjects

A Marton

Publications and source records attributed to A Marton.

At least 37 records · Page 2Linked to original sources

Cardiac electrophysiological effects of levosimendan, a new calcium sensitizer.

1. The conventional microelectrode and the patch-clamp techniques were used to study the electrophysiological effects of levosimendan, a new calcium-sensitizing cardiotonic drug, in cardiac ventricular muscle. 2. Levosimendan (5 microM) did not change the main repolarizing currents, such as the inward rectifier potassium, transient outward and the delayed rectifier outward potassium current, in rabbit ventricular myocytes. 3. In rabbit ventricular muscle, levosimendan, at relatively low concentrations (0.1-1 microM), did not change significantly the amplitude of the inward calcium current but increased the amplitude of the twitch tension. 4. In guinea pig ventricular muscle, levosimendan, at higher concentrations (1-5 microM), significantly increased the amplitude of the inward calcium current and the slow-response action potential parameters. 5. It is concluded that levosimendan, in addition to its calcium sensitizing properties characterized by "silent electrophysiology," exhibits cardiac electrophysiological effects similar to those of phosphodies-terase inhibitors.

Action Potentials↗

Penicillin-binding proteins as resistance determinants in clinical isolates of Streptococcus pneumoniae.

Altered penicillin-binding proteins (PBPs) with reduced affinity for penicillin are encoded by mosaic genes in penicillin-resistant clinical isolates of Streptococcus pneumoniae. Generally, members of one bacterial clone contain the same mosaic gene. We report here on a serotype 19A clone of penicillin- and multiple-resistant S. pneumoniae prevalent in Hungary, members of which are exceptionally diverse in terms of PBP properties. The pbp2x gene of four 19A isolates was sequenced, and a distinct mosaic structure detected in each case. The pbp2x genes also differed from a homologous gene of a high-level penicillin-resistant S. mitis from Hungary. The contribution of PBPs to resistance development was studied on transformation experiments using the laboratory strain R6 as recipient, and PBP genes from the type 19A isolate Hu11. pbp2x and pbp2b function as primary resistance determinants for different beta-lactams. Secondary transformation with pbp1a increased the resistance level considerably for penicillins and cefotaxime. Chromosomal DNA of a high-level penicillin- and cefotaxime-resistant S. mitis from Hungary also transformed the R6 strain to increased resistance levels, and PBP2x and PBP2b functioned as primary resistance determinants as above. In contrast, high-level cefotaxime resistance appeared to be due to a low affinity PBP2a, indicating that this PBP can also function as a resistance determinant.

Aminoacyltransferases↗

In vitro susceptibility of Streptococcus pneumoniae strains to nine beta-lactam antibiotics and the killing kinetics of cephalosporins alone and in combination with vancomycin or gentamicin.

Minimum inhibitory concentrations (MICs) of a total of 68 Streptococcus (S.) pneumoniae strains (21 susceptible, 23 intermediate, and 24 resistant to penicillin) were tested for 9 beta-lactam antibiotics such as penicillin, cefpirome, cefotaxime, ceftriaxone, cefuroxime, ceftazidime, cefpodoxime, cefodizime, and amoxycillin. MICs to penicillin, cefotaxime, cefpirome, and ceftriaxone were also tested on Muller-Hinton blood agar supplemented with 50% human serum. Killing kinetics of 0.5, 2, and 4 times the MIC of cefpirome and cefotaxime and synergistic bactericidal activity of combinations of cephalosporins with vancomycin or gentamicin were investigated. The synergism studies were conducted with drug concentrations half of the MICs. On the basis of MIC50 values cefpirome, cefotaxime, ceftriaxone, and cefpodoxime were 8, 4, 2, and 2 times more active than penicillin, while on the basis of MIC90 values they were 8, 8, 4, and 2 times superior to penicillin for the penicillin-resistant S. pneumoniae. Cefuroxime, cefodizime, and amoxycillin showed an identical or a 2-fold higher MIC50 or MIC90 than penicillin for the same group of isolates. Ceftazidime showed the lowest activity against S. pneumoniae. MIC50 and MIC90 values for ceftriaxone increased 4-fold when human serum was added to the test medium. Cefpirome was the only drug with MIC50 for the penicillin-resistant S. pneumoniae below the new resistance breakpoint of the NCCLS (> or = 2 mg/liter), while these values for cefotaxime and ceftriaxone were identical to or 2-fold higher than the resistance breakpoint. The MIC50 and MIC90 of the other drugs tested exceeded the breakpoint 2 to 16 times. The combination of vancomycin with cefpirome or cefotaxime showed a higher killing activity to two penicillin-resistant strains tested than 2- and 4-fold concentrations of the MICs of the two cephalosporins alone.

Anti-Bacterial Agents↗

Topoisomerase activity associated with polyoma virus large tumor antigen.

Polyomavirus (Py) large tumor antigen (LT) was produced in mammalian or insect cells infected with a suitable viral expression vector, and purified by a procedure combining immunoprecipitation with ion-exchange chromatography. Fractions containing the bulk of LT displayed a DNA-relaxing activity (LT-topo) which could be attributed neither to topoisomerase II (topo II) nor to topoisomerase I (topo I) encoded by the cell or the viral vector. On the one hand, LT-topo relaxed pBR322 DNA in a reaction which, unlike that characteristic of topo II, was ATP-independent and inhibited by camptothecin. On the other hand, serum from scleroderma patients which strongly inhibited calf thymus topo I had no effect on LT-topo, which absolutely required Mg2+ ions to relax DNA. Thus, LT-topo is either inherent to LT or belongs to a LT-bound enzyme similar to, but distinct from, topo I.

Animals↗

Epidemiology of resistant pneumococci in Hungary.

Data on resistance in Streptococcus pneumoniae was analyzed in cohorts of isolates from nasal carriers without respiratory tract infection, nose-throat swabs, and ear fluid specimens of children, from sputum and bronchoalveolar lavage of adults and central spinal fluid, blood, and pleural fluid of patients without a distinction of age group. Colonizing strains in infant carriers showed a higher resistance rate (47.5%) to penicillin than in other children (24.2%). Isolates of inpatients, predominantly infants with respiratory tract infection, presented a higher prevalence of resistance than outpatients in all age groups. Adults showed the lowest resistance rates. Resistance was rarer among S. pneumoniae isolates from patients with systemic infection. The few cases caused by resistant S. pneumoniae should raise concern. Resistance among strains from ear fluid was more prevalent in all investigated population groups than among isolates from throat-nose swabs. The similarity of resistance rates to erythromycin and penicillin was associated with frequent combined resistance. While the prevalent serotype among the resistant strains was 19A, no predominant serotype was found among the susceptible strains.

Adolescent↗

Penicillin-resistant Streptococcus pneumoniae in Germany: genetic relationship to clones from other European countries.

Penicillin-resistant Streptococcus pneumoniae strains isolated in different parts of Germany between 1982 and 1992 were compared with penicillin-resistant isolates, mainly of serogroups 6, 9, 14, 19 and 23, from other European countries. The main clones were recognised by their serotypes, antibiotic resistance patterns and penicillin-binding protein properties, and this typing was confirmed by multi-locus enzyme electrophoresis for a sample of 43 selected isolates. Eleven of the 14 resistant German isolates could be assigned to five genotypes isolated also in other countries. These included representatives of two distinct serotype 23F lineages predominant in Spain and France; a cluster of three serotype 6B isolates identical to clones in Spain, France, Finland and Hungary; and a serotype 9V clone of a type prevalent in Spain and now also in France. Serotype 19A clones of the type found in Hungary were not collected in Germany. The data suggest that two 23F lineages, represented by seven isolates from different locations, have become disseminated in Germany. Several resistant types found in the former West Germany resembled those found elsewhere in Western Europe whereas those from East Germany were distinct or, in one case, resembled a clone from Hungary. These data may reflect pre-unification travel patterns.

Bacterial Proteins↗

Topoisomerase activity associated with SV40 large tumor antigen.

Purified preparations of simian virus 40 (SV40) large tumor antigen (LT) from three different sources, including LT expressed from a recombinant baculovirus, were found to relax negatively supercoiled cyclic DNA molecules, whether or not they contained SV40 sequences. Relaxation was stimulated by MgCl2 but not by ATP, and inhibited by camptothecin, suggesting the involvement of an enzymatic activity similar to that of topoisomerase I (topo I). However, the pH requirements for relaxation by respectively LT and topo I are different. Also, antibodies reacting with LT inhibited relaxation by preparations of LT but not topo I, whereas antibodies inhibiting relaxation by topo I had no effect on relaxation by LT. Reconstruction experiments suggested that both procedures used to purify LT, immunoaffinity chromatography and DEAE-Sepharose chromatography, separate topo I from LT. Finally, relaxing activity was found in over 40 preparations of LT, and in the few instances where activity could not be found, it probably had been lost during storage, rather than absent from the start. Whereas these results seem to exclude that the activity being detected is that of a contaminant of LT, they would be consistent with this activity being that of a stable topo-LT complex, or else intrinsic to LT itself.

Animals↗

[Autonomic neuropathy in chronic liver diseases].

Autonomic neuropathy has been evaluated by various cardiovascular bedside tests in 172 patients with chronic alcoholism (36 alcoholics without liver disease, 50 patients with fatty liver and 86 with cirrhosis), in 21 patients with HBsAg-positive chronic liver disease, in 14 patients with primary biliary cirrhosis, in 14 patients with cirrhosis of other origin and in 86 healthy controls. Parasympathetic integrity was evaluated by beat-to-beat variation during deep breathing, Valsalva manoeuvre and standing up, sympathetic function by blood pressure response to standing and to sustained handgrip test. Autonomic reflex damage was found in all groups examined. Patients with alcoholic cirrhosis exhibited the most severe alterations. Our results suggest, that chronic hepatopathy itself presents a pathogenetic factor of autonomic neuropathy. Autonomic failure has to be considered as a possible cause of symptoms in liver diseases with all its prognostic consequences.

Adult↗

Prevalence of Chlamydia pneumoniae antibodies in Hungary.

Investigation of Chlamydia pneumoniae (TWAR) antibodies in paired sera of 120 patients with various respiratory diseases revealed a prevalence of 4.2% of IgG seroconversion. IgG antibody without seroconversion was found in 83.3%. Sera of ten patients showed titers as high as 512-1024 or above. Children with no respiratory disease and blood donors in Budapest had specific IgG in 46.5% and 75.2% respectively. Prevalence of IgG antibody in children from the rural areas of Hungary was about 50% lower than in children in the capital. The high prevalence of persistent IgG, indicating earlier infection, suggests that Chlamydia pneumoniae infection may be endemic in Budapest. The small number of the serologically confirmed acute infections in hospitalized patients with pneumonia leads to the conclusion that the majority of patients with chlamydial pneumonia responds to the therapeutic regimen administered by the general practitioner and referral to hospital rarely becomes necessary.

Acute Disease↗

Pneumococcal antimicrobial resistance: the problem in Hungary.

An epidemiological survey of penicillin resistance as determined by minimum inhibitory concentrations (MICs) in Streptococcus pneumoniae strains collected from several Hungarian laboratories in 1988-1989 indicated a prevalence of 58% among a total of 135 isolates. A significantly higher resistance rate (69.2%) was found for isolates from pediatric patients than from adult patients (44.0%). Penicillin-resistant strains were more frequently resistant to non-beta-lactam antibiotics (tetracycline, erythromycin, co-trimoxazole, and chloramphenicol) than were penicillin-sensitive strains. On the basis of the MIC50 and MIC90 values of ampicillin and five cephalosporins for penicillin-resistant strains, it was established that ampicillin and cephalexin were not superior to penicillin. The low MIC90 of ceftriaxone and cefotaxime for these organisms reflects promising therapeutic potential, even in septicemia and meningitis caused by penicillin-resistant strains. The therapeutic alternative to penicillin in the treatment of respiratory tract infection may be second-generation cephalosporins such as cefuroxime or cefamandole.

Adult↗

Geographic distribution of penicillin-resistant clones of Streptococcus pneumoniae: characterization by penicillin-binding protein profile, surface protein A typing, and multilocus enzyme analysis.

Examination of several hundred penicillin-resistant clinical isolates of Streptococcus pneumoniae has revealed extensive strain-to-strain variation in the number and molecular size of penicillin-binding proteins (PBPs). This polymorphism has been used to classify resistant isolates into groups (PBP families) that share distinct electrophoretic profiles. We describe herein properties of four such PBP families: two from Spain (and/or Ohio) and one each from Hungary and Alaska. We have discovered that representative isolates assigned to each PBP family also share capsular serotype, antibiotic resistance pattern, pneumococcal surface protein A type, and multilocus enzyme genotype. The results demonstrate independent clonal origin for strains assigned to each PBP family. Each resistant clone occurs with uniquely high incidence within specific geographic areas.

Alaska↗

[The potentialities and results of the etiologic diagnosis of acute pneumonias].

The paper deals with the results of the joint Soviet-Hungarian study for the determination of etiology of acute pneumonias. Study included 617 patients. The bacteriologic and serologic methods were used to reveal the causative agent of the disease. Prevalence of Streptococcus pneumoniae (33-49%) in the etiologic structure of acute pneumonias was established both in the USSR and Hungary. In many cases pneumonia is also caused by Haemophilus influenzae (21-22%). In 15-31% of the cases the causative agent of pneumonia is gram-negative microorganisms. A protracted course of acute pneumonia is due to the complex associations of microorganisms including S. pneumoniae. A conclusion has been drawn to the effect that the initial antibacterial therapy should be started with administration of antibiotics that act effectively on S. pneumoniae.

Acute Disease↗

DNA nicking favors PCR recombination.

We attempted to use the polymerase chain reaction (PCR) to monitor in vitro recombination in a plasmid containing directly repeated sequences. Some of the plasmid preparations which had not been exposed to recombination conditions were however found to behave in the PCR test as if they had undergone homologous recombination. We show here that such false positives are attributable to a small degree of nicking and/or breaking of the DNA template. Presumably, such damage allows the formation of hybrid parental duplexes containing at least one truncated strand, the 3' end of which maps within the homology; extension of this 3' end by the polymerase then results in a linkage of sequences identical to that arising from homologous recombination.

Base Sequence↗

Extremely high incidence of antibiotic resistance in clinical isolates of Streptococcus pneumoniae in Hungary.

An epidemiologic survey of antibiotic resistance among pneumococcal isolates collected during 1988 and 1989 in Hungary indicated that as many as 58% of all isolates and 70% of isolates from children were resistant to penicillin. These figures surpass even the highest values reported thus far for Spain and South Africa for the same period. Almost or more than 70% of the penicillin-resistant isolates were also resistant to tetracycline, erythromycin, and cotrimoxazole and approximately 30% to chloramphenicol. Intravenous administration of ampicillin (30 mg/kg) did not interfere with the growth in the cerebrospinal fluid of three resistant strains introduced into the rabbit model of experimental meningitis. No resistant strain showed beta-lactamase activity. A representative highly resistant strain contained altered penicillin-binding proteins (low penicillin affinities and abnormal molecular sizes) and was also resistant to the lytic and killing effects of penicillin.

Adult↗

[Congenital saccharase-isomaltase defect--diagnostic difficulties].

Seven patients with congenital sucrase-isomaltase deficiency corresponding to the known diagnostic criteria and five patients having combined disaccharidase deficiencies with unusual pattern characterized by more pronounced sucrase than lactase deficiency were found among 505 children investigated by first jejunal biopsy. On the base of the case histories, the complications and the comparative evaluation of patient and control groups' data (the latter consisted of nine untreated coeliacs) the congenital sucrase-isomaltase deficiency was found to make the patients to be especially susceptible to enteral infections and consequently to postinfectious intestinal damages. These complicated cases do not correspond to the classic diagnostic criteria of the congenital enzyme deficiency causing diagnostic errors. In order to avoid the misdiagnoses the authors suggest modification of the diagnostic criteria of congenital sucrase-isomaltase deficiency as follows: the diagnosis of congenital enzyme deficiency might be verified in spite of mild histological signs and hypolactasia if the degree of lactase deficiency repeatedly and significantly is exceeded by the degree of sucrase deficiency.

Biopsy↗

Reduction of Fe(III)ADP complex by liver microsomes.

An NADPH-driven enzymatic reduction of an Fe(III)ADP complex by rat liver microsomes has been demonstrated directly for the first time during the initial phase of lipid peroxidation by using two different analytical methods. The reduction rate increased upon increasing the ratio of ADP to ferric iron. Fe(III)ADP reducing activity of both detergent-solubilized microsomes and purified NADPH:cytochrome-P-450 (cytochrome-c) reductase decreased to about 20% compared to that of the native microsomes. Superoxide dismutase and KCN did not inhibit the reduction.

Adenosine Diphosphate↗