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Biomedical subjects

E Kovacs

Publications and source records attributed to E Kovacs.

At least 19 recordsLinked to original sources
PubMed2005

Orientation behavior of retinal photoreceptors in alternating electric fields.

In alternating electric (AC) fields, particles experience polarizing effects that induce dipoles that orient elongated specimens either parallel or perpendicular to the field lines. In this work we studied the behavior of photoreceptor cells' rod outer segments (ROS) in AC fields of different frequencies. We showed that at low frequencies, ROS orient parallel to the field, whereas at higher frequencies they orient perpendicular to the field lines (in the frequency range from 100 Hz to 10 MHz). We found this behavior to be dependent on the physiological state of cells (due to modifications in their electrical properties). To simulate cell damage, the membrane conductivity was changed by treating the cell with gramicidin A, which resulted in a decrease of cytosol conductivity and, consequently, in a change of the orientation behavior of the treated cells. The change of cell orientation with cytosol conductivity is rather sharp, suggesting the potential of the method for accurate evaluation of the cell physiological status. We modeled the interaction between ROS and AC fields approximating the rod cell by a prolate spheroid with a very long axis. The internal compartment of the ellipsoid was considered to be filled with an inhomogeneous medium consisting of alternating layers of membrane and cytoplasm as media modeling the disks. This theoretical model proved to be in good agreement with the experimental results and enabled the derivation (by fitting with the experimental results) of the membrane and cytosol parameters for normal and damaged cells.

Animals↗
PubMed2003

Association of D4 dopamine receptor gene and serotonin transporter promoter polymorphisms with infants' response to novelty.

Effects of DRD4 and 5-HTTLPR length polymorphisms have been reported on neonatal and infant temperament as well as adult personality traits. The 7-repeat form of the DRD4 III exon VNTR polymorphism has been associated with childhood ADHD, and recently we have reported its link with attachment disorganization in a nonclinical population of infants. Here, we report associations of these polymorphisms with infant temperament at 12 months of age. Maternal accounts of temperament and observed response to novelty were investigated for 90 infants, who were independently genotyped for the DRD4 III exon, and for 5-HTT-linked promoter region length polymorphisms. Maternal rating of temperament was not affected by these polymorphisms, but we found combined genotype effects for infants' observed responses to a novel, anxiety-provoking stimulus: the appearance of, and approach by, a stranger. Infants with at least one copy of both the 7-repeat DRD4 allele and the long variant of 5-HTTLPR (7(+), l/l&l/s) responded with significantly less anxiety than infants with other genotypes. However, infants with the 7-repeat DRD4 allele and homozygous for the short form of 5-HTTLPR (7(+), s/s) showed more anxiety and resistance to the stranger's initiation of interaction. These genotype effects were not redundant with the previously reported association between the 7-repeat DRD4 allele and disorganized attachment behavior. Although both temperament and attachment behavior were affected by the DRD4 repeat polymorphism, the effect on temperament measures was modified by the infants' 5-HTTLPR genotype.

Carrier Proteins↗
PubMed2002

Measurements of IL-6, soluble IL-6 receptor and soluble gp130 in sera of B-cell lymphoma patients. Does viscum album treatment affect these parameters?

Interleukin-6 (IL-6) can be involved in several diseases including lymphoid malignancies. This cytokine binds to soluble IL-6 receptor (sIL-6R) circulating in blood, leading to signal transduction via gp130. Soluble IL-6R shows agonistic activity for IL-6, and the soluble form of gp130 (sgp130) an antagonistic effect against the complex IL-6/sIL-6R. Viscum album extract (Iscador) as an immunomodulator is used in the treatment of malignant disorders. In this study we investigated the effect of this treatment on the serum levels of IL-6, sIL-6R and sgp130 in B-cell lymphoma patients (n = 27), in comparison to healthy controls (n = 28). Twenty-one of 27 patients had been treated previously with chemo/radiotherapy. The patients were divided into two groups; those with short-term (investigated before and during treatment) or those with long-term Viscum album (VA) therapy (investigated during therapy). The serum levels of the three parameters were determined by ELISA. In patients having short-term treatment IL-6 values were similar to those of controls. During long-term therapy the values were significantly lower (P<0.05). The values of sIL-6R were elevated only in long-term treated patients (P<0.05), the values of sgp130 in both short-term (P<0.05) and in long-term treated patients (P=0.001). There is a significant correlation (P<0.05) between levels of sIL-6R and sgp130 in both therapy groups at 24 hours after injection. This indicates that the potent effect of sIL-6R on the biological activity of IL-6 could be inhibited by sgp130 as antagonist. Clinical data show that half of the patients (6/12) with long-term treatment had a continuous complete remission, whereas only 2/15 patients with short-term treatment had a complete remission.

Adult↗
PubMed2002

The effects of rehydration on cycling performance after exercise-induced dehydration.

The effects of 7.6% carbohydrate-electrolyte solution (CES) and placebos (P) on rehydration (R) after exercise-induced dehydration and on a subsequent time-trial (TT) of cycling performance were studied. Thirteen male subjects exercised in a thermally-controlled environment (28 degrees C, 63% RH) until 3% of their body weight was lost. After exercise, the subjects moved to a neutral environment (22 degrees C) and rested for 30 minutes prior to a 2-hour R period. During R, subjects were fed CES or P to a maximum volume of 120% of previous body mass loss at 0, 30, and 60 minutes, in bolus-doses of 50%, 40% and 30% respectively. After R, subjects performed a 1-hour TT with no further fluid intake. % R with CES was significantly higher than with P (70 +/- 3% vs 60 +/- 5%; p < 0.01). During the TT, blood glucose dropped in the CES group but not in the P group. It was found that, despite a more effective R with CES, the performance results did not differ between groups (65.1 +/- 2.2 minutes and 65.2 +/- 2.3 minutes for CES and P respectively). It is suggested that an insulin-mediated rebound effect on CHO metabolism during TT, in which no further CHO was supplied, nullified the benefits of rehydration.

Adult↗
PubMed2001

Analysis of dopamine D4 receptor gene polymorphism using microchip electrophoresis.

A microfabricated electrophoresis device was used for rapid polymerase chain reaction product analysis in genotyping the dopamine D4 receptor gene (DRD4) 48 base pairs repeat polymorphism. An allelic ladder, prepared from homozygous individuals, was used as internal standard during the microchip electrophoresis based analysis. Comparison of this novel separation method with the conventional slab gel and previously reported ultra-thin-layer techniques confirmed the reliability of this new method. Genotyping of 332 healthy Hungarian individuals gave the following allele frequencies: two-repeat: 0.089; three-repeat: 0.026; four-repeat: 0.674; five-repeat: 0.011; six-repeat: 0.002; seven-repeat: 0.189; eight-repeat: 0.011. The genotype frequencies obtained showed no deviation from the Hardy-Weinberg equilibrium (p>0.903), further underlying the reliability of this new genotyping technique.

Base Sequence↗
PubMed2001

High-throughput genotyping of repeat polymorphism in the regulatory region of serotonin transporter gene by gel microchip electrophoresis.

Large-scale genotyping of the repeat polymorphism in the regulatory region of the serotonin transporter gene (5-HTTLPR) was attempted by polymerase chain reaction (PCR) amplification followed by gel microchip electrophoresis analysis. The multilane (96) format of the gel microchip system allowed parallel separation of a large number of samples. The separation and visualization of the PCR amplicons from either the 5-HTTLPR short allele (number of repeats are 14) or the 5-HTTLPR long form (16 repeats) was completed in a few minutes. Genotyping of healthy Caucasian individuals showed that the short allele had a somewhat lower frequency (0.42) than the long form (0.58), and the genotype frequencies fulfilled the criteria of the Hardy-Weinberg equilibrium (chi = 0.012, p = 0.994). Based on these results, gel microchip electrophoresis system proved to be a powerful tool for high throughput genotyping of repeat polymorphism.

Alleles↗
PubMed2001

Analysis of mutations in the plasma cholinesterase gene of patients with a history of prolonged neuromuscular block during anesthesia.

Decreased activity of plasma cholinesterase is responsible for prolonged apnea during anesthesia using neuromuscular blockers such as suxamethonium and mivacurium. More than 20 mutations have been identified so far in the BCHE gene resulting in impaired plasma cholinesterase activity. Biochemical tests are not always able to differentiate between pathological and normal sera; hence in some cases unanticipated complications can still occur during anesthesia even after measurements of enzyme activity and dibucaine numbers within the normal range. Therefore, molecular genetic testing is required for the accurate diagnosis of this deficiency. Here we present a study of plasma cholinesterase activity and BCHE genotyping of patients with a history of prolonged neuromuscular block and most of their pedigrees. All four exons of the BCHE gene were directly sequenced from samples and a number of mutations responsible for the reduction of plasma cholinesterase activity were identified. In most cases the atypical mutation in exon 2 (nt 209A --> G, Asp70 --> Gly) was found together with the K-variant mutation in exon 4 (nt 1615G --> A, Ala539 --> Thr), which is in good agreement with previous data suggesting that these mutations along with two others (at nt -116 and nt 1914) are in linkage disequilibrium.

Adult↗
PubMed2001

The serum levels of IL-12 and IL-16 in cancer patients. Relation to the tumour stage and previous therapy.

In this study the serum levels of the cytokines IL-12 (p40 and p70) and IL-16, and the number of cells which produce them (monocytes, CD8+ T cells, B cells), were measured in 76 cancer patients with different types of cancer (breast > gastrointestinal > uterine/ovarian > renal/bladder) and compared with 28 healthy controls. The patients were divided into four groups: stage I+II without or after chemo/radiotherapy, and stage III+IV without or after chemo/radiotherapy. The distribution of patients in the groups was similar. The levels of cytokines were determined by ELISA, the number of the immunocompetent cells by flow cytometry. The serum values of IL-12 were significantly elevated in each tumour stage both without and after additional chemo/radiotherapy. They correlated positively with the progression (P < 0.02). The serum values of IL-16 were only significantly increased in tumour stage III+IV without or after chemo/radiotherapy. The number of monocytes showed no alteration in any investigated group, chemo/radiotherapy significantly reduced the number of CD8+ T cells at each stage, and the number of B cells was negatively correlated with the disease progression (P < 0.03). The results indicate that there is an increase of IL-12 and IL-16 in sera during tumour progression due only to an alteration in the function of the immunocompetent cells, not to an increased number. This investigation reports for the first time that IL-16 is involved in cancer diseases.

Adult↗
PubMed2001

Investigation of interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R) and soluble gp130 (sgp130) in sera of cancer patients.

The serum levels of interleukin-6 (IL-6), sIL-6R and sgp130 were investigated in 76 cancer patients in comparison with 28 healthy controls. IL-6 is a multifunctional cytokine involved in certain malignant diseases. Soluble IL-6 receptor as agonist enhances the biological effect of released IL-6. Soluble gp130 as antagonist inhibits the effect of the IL-6/sIL-6R complex. Patients with different types of tumour (breast/gastrointestinal/uterine/ovarian/renal/bladder) were divided into four groups according to tumour stage and previous therapy (stage I + II without or after chemo-/radiotherapy, stage III + IV without or after chemo-/radiotherapy). The distribution of different tumour histotypes was similar in each group of patients. The levels of the three serum parameters were determined by ELISA. At each tumour stage either without or after chemo-/radiotherapy, the serum values of IL-6 were found to be not significantly different from those of controls. The values of sIL-6R were significantly elevated in stage I + II (P < 0.02) patients, with a borderline significance in stage III + IV (P = 0.06), in both cases only when no additional therapy was initiated. The serum values of sgp130 increased significantly at each tumour stage both without and after chemo-/radiotherapy (P < 0.001). A significant correlation was found between the values of sIL-6R and sgp130 in stage I + II (P < 0.02) and III + IV (P < 0.004) patients, in both cases without chemo-/radiotherapy. There were no other significant correlations. In conclusion, the simultaneous measurement of IL-6, sIL-6R and sgp130 in sera is an important factor in evaluating the biological effect of IL-6 in malignant disease. This is the first report to investigate sgp130 in cancer patients with different types of tumour.

Adult↗
PubMed2000

Serum levels of IL-12 and the production of IFN-gamma, IL-2 and IL-4 by peripheral blood mononuclear cells (PBMC) in cancer patients treated with Viscum album extract.

A dysregulation between cellular immunity (Th1 cells) and humoral immunity (Th2 cells) is a characteristic of cancerous diseases. Viscum album (VA) extract has an immunomodulatory effect and can be used in the treatment of cancer patients, either following or in combination with chemo- /radiotherapy. In this pilot study, we investigated the effect of VA extract on the serum levels and production of cytokines in a group of cancer patients undergoing treatment (N = 16) in comparison with healthy untreated controls (N = 11). The serum levels of interleukin-12 (IL-12) (p40 and p70), and the production of gamma interferon (IFN-gamma), interleukin 2 (IL-2), and interleukin-4 (IL-4) in peripheral blood mononuclear cells (PBMC) were measured in patients before treatment and on days 3, 5, 8, 15, and 21-29 during therapy, and in the control group at the same time intervals over a two-week period. Cytokine levels were determined by ELISA. In cancer patients, the serum levels of IL-12 (p40 and p70) before therapy were about 3-fold higher than in controls. They increased during therapy, with a borderline significance (Wilcoxon paired signed-rank test, P = 0.06). In PBMC the production of IFN-gamma and IL-2 (before therapy respectively 3-fold and 9-fold lower than in controls) increased significantly (Wilcoxon paired signed-rank test and Mann-Whitney U-test, P < 0.05) during treatment. In PBMC, IL-4 production was in the same range as in controls, and remained unaltered during therapy. In conclusion, the results of this study show that treatment with VA extract leads an increase in Th1 cytokine levels (IFN-gamma and IL-2), which suggests that cell-mediated immunity could be positively affected.

Cells, Cultured↗
PubMed1999

Caffeine improves cognitive performance after strenuous physical exercise.

The effects of three carbohydrate electrolyte solutions (CES) containing different amounts of caffeine on cognitive function and the combined effects of these drinks and exercise on cognitive functions were investigated in a double-blind, cross-over study. On five separate occasions, fifteen endurance trained male athletes (23.3 years) received water placebo, CES placebo (68.8 g/l), and three CES drinks containing low, medium and high dosages of caffeine (150, 225 and 320 mg/l). Each occasion, 8 ml/kg of the drink was consumed before -- and 6 ml/kg of the drink was consumed during an all-out 1 hour time trial on a bicycle ergometer. Cognitive (attentional, psychomotor, and memory) tests were carried out immediately before and immediately after exercise. Before exercise, long term memory was improved by CES plus low dose caffeine compared to both placebos. Immediately after exercise, all cognitive functions were improved by CES plus low- and medium-dose caffeine compared to placebo. These results comprise the first practical demonstration of the cognition improving effects of low amounts of caffeine in CES after strenuous physical exercise.

Adult↗
PubMed1999

Metabolic effects of a protein-supplemented carbohydrate drink in marathon runners.

A field study was performed to investigate the acute influence of a milk protein hydrolysate supplemented drink (CHO+PRO) on metabolism during and after a marathon run compared to the same drink without protein (CHO). Carbohydrate metabolites and hormones were not influenced by CHO+PRO. Levels of plasma free fatty acids were significantly lower and levels of urea and most amino acids were significantly higher with CHO+PRO. Sweat urea and ammonia nitrogen excretion during the run as well as urinary 3-methylhistidine excretion during the entire exercise day was similar in both treatments. Urinary total nitrogen was significantly increased and urinary pH decreased with CHO+PRO. It was concluded that the supplemented protein was absorbed and probably at least partially oxidized during the run and that no obvious negative metabolic effects occurred. CHO+PRO did not acutely affect myofibrillar protein breakdown as assessed by the 3-methylhistidine method; however, total body protein breakdown was not measured.

Adult↗
PubMed1999

Restoration of immunity with interleukin-2 therapy.

HIV replication can now be effectively suppressed using antiretroviral combination regimens. The search continues, however, for ways to restore the immune response and eliminate reservoirs of latent infection. Interleukin-2 (IL-2) may augment the immune response in HIV-infected persons. This article discusses the rationale for using IL-2 in those with HIV disease and reviews key trials of IL-2 treatment regimens.

Antiretroviral Therapy, Highly Active↗
PubMed1996

Pore formation by S. aureus alpha-toxin in liposomes and planar lipid bilayers: effects of nonelectrolytes.

Nonelectrolytes such as polyethylene glycols (PEG) and dextrans (i) promote the association of S. aureus alpha-toxin with liposomes (shown by Coomassie staining) and (ii) enhance the rate and extent of calcein leakage from calcein-loaded liposomes; such leakage is inhibited by H+, Zn2+ and Ca2+ to the same extent as that of nonPEG-treated liposomes. Incubation of liposomes treated with alpha-toxin in the presence of PEG with the hydrophobic photo-affinity probe 3-(trifluoromethyl)-3-m-[125I]iodophenyl) diazirine (125I-TID) labels monomeric and-predominantly-hexameric forms of liposome-associated alpha-toxin; in the absence of PEG little labeling is apparent. At high concentrations of H+ and Zn2+ but not of Ca(2+)-all of which inhibit calcein leakage-the distribution of label between hexamer and monomer is perturbed in favor of the latter. In alpha-toxin-treated planar lipid bilayers from which excess toxin has been washed away, PEGs and dextrans strongly promote the appearance of ion-conducting pores. The properties of such pores are similar in most regards to pores induced in the absence of nonelectrolytes; the differ only in being more sensitive to "closure" by voltage (as are pores induced in cells). In both systems, the stimulation by nonelectrolytes increase with concentration and with molecular mass up to a maximum around 2,000 Da. We conclude (i) that most of the alpha toxin that becomes associated with liposome or planar lipid bilayers does not form active pores and (ii) that the properties of alpha-toxin-induced pores in lipid bilayers can be modulated to resemble those in cells.

Animals↗
PubMed1996

Peripheral blood mononuclear phagocyte subpopulations as cellular markers in hypercholesterolemia.

Mononuclear phagocytes play a major role in the development of vascular lesions in atherogenesis. The goal of our study was to characterize circulating blood monocyte subpopulations as potential cellular markers of systemic immunological abnormalities in hypercholesterolemia. In normal subjects, three-parameter immunophenotyping of whole blood revealed that 61.3 +/- 6.0% of monocytes showed "bright" expression of the lipopolysaccharide receptor (LPSR: CD14) and Fc gamma receptor I (RI: CD64) without expression of Fc gamma-RIII (CD16). Other monocyte subsets (populations 2, 3, 4, and 5) were characterized by the simultaneous expression of both Fc gamma-R's (25.6 +/- 5.0%), isolated expression of Fc gamma-RIII (9.4 +/- 1.7%), or high expression of CD33 (3.7 +/- 1.1%) with only dim expression of CD14, respectively. The smallest subset of monocytes (population 5: 2.1 +/- 0.8%) differed from the predominant population of CD14brightCD64+CD16- monocytes by additional expression of neural cell adhesion molecule (N-CAM: CD56). In a group of hypercholesterolemic patients (n = 19), high density lipoprotein cholesterol levels were negatively correlated to the population size of CD64-CD16+ monocytes. In both healthy subjects (n = 55) and hypercholesterolemic patients, the rare apolipoprotein E3/E4 and E4/E4 phenotypes were associated with a tendency toward a larger population of CD64-CD16+ monocytes. Expression of the variant activation antigen CD45RA by peripheral blood mononuclear phagocytes showed a positive correlation to plasma levels of the atherogenic lipoproteins low density lipoprotein and lipoprotein(a). These data suggest that systemic abnormalities in mononuclear phagocyte subpopulations may play a role in the pathogenesis of atherosclerosis.

Adult↗