PubMed Health⌕ Search

Biomedical subjects

Ilona Kovács

Publications and source records attributed to Ilona Kovács.

15 recordsLinked to original sources
PubMed2006

[Stromal tumor of the stomach causing life-threatening arterial bleeding].

Stromal tumors of the gastrointestinal tract are rare mesenchymal neoplasms. The majority of them are appearing in the stomach: their quite common first manifestation is bleeding. The authors report a case of polypoid gastric GIST causing severe bleeding which needed urgent surgical intervention and partial resection of the stomach. Although histological analysis of the tumor revealed low proliferation rate, the urgent operation did not result in a complete eradication of the neoplasm, thereby our patient needs further follow-up and treatment.

Aged↗
PubMed2006

Insulin-like growth factor-I-coupled mitogenic signaling in primary cultured human skeletal muscle cells and in C2C12 myoblasts. A central role of protein kinase Cdelta.

In this study, we have investigated the effects of insulin-like growth factor-I (IGF-I) on cellular responses of primary human skeletal muscle cells and mouse C2C12 myoblasts. In human muscle, IGF-I stimulated proliferation and fusion of the cells and the expression of the differentiation marker desmin. These effects were completely inhibited by Rottlerin, the inhibitor of the protein kinase C (PKC)delta, but were not affected by the inhibition of the mitogen-activated protein kinase (MAPK) or the phosphatidylinositide 3-kinase (PI-3K) pathways. Furthermore, IGF-I initiated the selective translocation of PKCdelta to the nucleus. In C2C12 myoblasts, the growth-promoting effects of IGF-I were abrogated by inhibition of PKCdelta, but not by the inhibition of the PI-3K system. However, in contrast to the human data, the MAPK inhibitor PD098059 partially (yet significantly) also inhibited the action of IGF-I and, furthermore, IGF-I induced phosphorylation of the MAPK Erk-1/2. In addition, overexpression of constitutively active form of PKCdelta in C2C12 cells fully mimicked, whereas overexpression of kinase inactive mutant of the isoform prevented the action of IGF-I. Finally, the inhibition of PKCdelta suspended the IGF-I-induced phosphorylation of Erk-1/2 and, moreover, the inhibition of the MAPK pathway partially (yet significantly) inhibited the accelerated growth of C2C12 cells overexpressing PKCdelta. Taken together, these results demonstrate a novel, central and exclusive involvement of PKCdelta in mediating the action of IGF-I on human skeletal muscle cells, with an additional yet PKCdelta-dependent contribution of the MAPK pathway on C2C12 myoblasts.

Animals↗
PubMed2006

Reduced top-down influences in contour detection in schizophrenia.

INTRODUCTION: Chronic schizophrenia patients have previously demonstrated performance deficits in contour integration tasks. The purpose of this study was to investigate whether schizophrenia patients, spanning a range of illness severity, would demonstrate responsiveness to manipulations that recruit top-down processing strategies involving learning and sequencing effects in a contour integration task. METHODS: We administered a contour integration test over four consecutive days and in two different presentation conditions each day. In one condition, the stimuli were administered in order of increasing difficulty, and in the other they were presented in random order. The order in which these two conditions were presented was counterbalanced across days and participants. In addition, a nonschizophrenia psychotic disorders control group was included to determine if past findings of a contour integration deficit in schizophrenia could be replicated in the presence of a symptomatically similar control group. RESULTS: All groups demonstrated similar learning curves across the four days and generally similar overall levels of performance, with the exception of the group of the most chronic schizophrenia patients. In addition, the order in which the stimuli were presented to subjects affected their performance, with higher scores achieved for all groups in the condition where the stimuli were presented in increasing order of difficulty. Interaction effects revealed that the effects of order presentation were greater for nonpatient than for psychotic patients. CONCLUSIONS: These data are further evidence that perceptual organization impairments in schizophrenia are illness severity-related, and that schizophrenia patients as a whole are less sensitive to top-down manipulations in this type of task.

Adult↗
PubMed2005

TASK-3 immunoreactivity shows differential distribution in the human gastrointestinal tract.

The presence and distribution of TASK-3 immunopositivity (a channel with potential oncogenic significance) was investigated in the human gastrointestinal system. The immunohistochemical reactions were performed with two commercially available polyclonal antibodies, targeting different epitopes of the channel protein. Experiments conducted on frozen and formalin-fixed samples indicated that the application of a suitable antigen retrieval (AR) technique was essential to produce consistent, strong and reproducible TASK-3-specific immunolabelling of the formalin-fixed tissue. The lack of or inappropriate selection of the AR resulted in false-negative reactions. As for the distribution of the TASK-3 channels, strong immunolabelling was observed in the gastric and large intestinal mucosa, with particularly prominent immunoreactivity of the epithelial cells. In contrast, the smooth-muscle layers demonstrated weak TASK-3 positivity. Intense TASK-3 expression was noted in both the exocrine and endocrine pancreas, but the islets of Langerhans exhibited more powerful reactions. The ductal apparatus of the submandibular gland and lymphocytes situated in pericolonic lymph nodes were also TASK-3 positive. Strong TASK-3 positivity could also be observed in malignant gastrointestinal tumours, with intense nuclear-perinuclear labelling of some of the tumour cells. The present findings suggest that TASK-3 channels may have roles in the gastrointestinal functions, including insular hormone secretion.

Biomarkers↗
PubMed2004

Novel secoergoline derivatives inhibit both GABA and glutamate uptake in rat brain homogenates: synthesis, in vitro pharmacology, and modeling.

Three of twelve secoergoline derivatives (Z ethyl 4-[(ethoxycarbonylmethyl)methylamino]-2-methyl-3-phenylpent-2-enoate, 8; ethyl 1,6-dimethyl-3-oxo-5-phenyl-1,2,3,6-tetrahydropyridine-2-carboxylate, 9; Z methyl 4-[(methoxycarbonylmethyl)methylamino)-2-methyl-3-phenylpent-2-enoate, 11), containing bioisosteric sequences of GABA and Glu, inhibited both GABA and Glu transport through cerebrocortical membranes specifically. Compounds 8, 9, and 11 appeared to be equipotent inhibitors of GABA and Glu transport with IC50 values between 270 and 1100 microM, whereas derivatives 1-7, 10, and 12 were without effects. In the presence of GABA and Glu transport-specific nontransportable inhibitors, inhibition of GABA and Glu transport by 8, 9, and 11 proceeded in two phases. The two phases of inhibition were characterized by IC50 values between 4 and 180 nM and 360-1020 microM and different selectivity sequences. These findings may indicate the existence of some mechanism possibly mediated by a previously unrecognized GABA-Glu transporter. Derivatives with the cis, but not the trans configuration of bulky ester groups (8 vs 7 and 11 vs 12) showed significant inhibitory effect (IC50 values of 270 microM vs >>1000 microM and 1100 microM vs >>1000 microM on GABA transport, respectively). The cis-trans selectivity can be explained by docking these secoergolines in a three-dimensional model of the second and third transmembrane helices of GABA transporter type 1.

Amino Acids↗
PubMed2004

Tumor grade-dependent alterations in the protein kinase C isoform pattern in urinary bladder carcinomas.

OBJECTIVES: Members of the protein kinase C (PKC) isoenzyme family play central role in the tumorigenesis of several tissues. In this study our goal was to determine the possible alterations in the protein kinase C (PKC) isoform pattern in relation with the different tumor grade in human urinary bladder carcinomas. METHODS: Western blot analysis, followed by quantitative densitometry, was performed to define the expression of PKC isoforms in the epithelial tissue of human urinary bladder carcinomas with various tumor grades and in control samples. RESULTS: The human urinary bladder epithelium expressed five PKC isoforms (PKC alpha, beta, delta, zeta), the levels of which differentially altered as a function of tumor grade. Namely, whereas the expressions of PKC beta and delta decreased with increasing grade of the carcinomas, the levels of PKC alpha, and zeta showed opposite patterns of changes. CONCLUSIONS: These grade-dependent alterations in the PKC isoform pattern strongly argue for the central yet antagonistic roles of certain members of the PKC system in malignant transformation of human urinary bladder epithelium.

Blotting, Western↗
PubMed2004

Cyclothiazide binding to functionally active AMPA receptor reveals genuine allosteric interaction with agonist binding sites.

The agonist, [3H](-)[S]-1-(2-amino-2-carboxyethyl)-5-fluoro-pyrimidine-2,4-dione ([3H](S)F-Willardiine) binding to functional alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors of resealed plasma membrane vesicles and nerve endings freshly isolated from the rat cerebral cortex displayed two binding sites (K(D1)=33+/-7 nM, B(MAX1)=1.6+/-0.3 pmol/mg protein, K(D2)=720+/-250 nM and B(MAX2)=7.8+/-4.0 pmol/mg protein). The drug which impairs AMPA receptor desensitisation, 6-chloro-3,4-dihydro-3-(2-norbornene-5-yl)-2H-1,2,4-benzothiadiazine-7-sulphonamide-1,1-dioxide (cyclothiazide, CTZ) fully displaced the [3H](S)F-Willardiine binding at a concentration of 500 microM. In the presence of 100 microM CTZ (K(I(CTZ))=60+/-6 microM), both the antagonist [3H]-1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo(F)quinoxaline-7-sulfonamide ([3H]NBQX: K(D)=24+/-4 nM, B(MAX)=12.0+/-0.1 pmol/mg protein) and the high-affinity agonist binding showed similar affinity reduction ([3H](S)F-Willardiine: K(D)=140+/-19 nM, B(MAX)=2.9+/-0.5 pmol/mg protein; [3H]NBQX: K(D)=111+/-34 nM, B(MAX)=12+/-3 pmol/mg protein). To disclose structural correlates underlying genuine allosteric binding interactions, molecular mechanics calculations of CTZ-induced structural changes were performed with the use of PDB data on extracellular GluR2 binding domain dimeric crystals available by now. Hydrogen-bonding and root mean square (rms) values of amino acid residues recognising receptor agonists showed minor alterations in the agonist binding sites itself. Moreover, CTZ binding did not affect dimeric subunit structures significantly. These findings indicated that the structural changes featuring the non-desensitised state could possibly occur to a further site of the extracellular GluR2 binding domain. The increase of agonist efficacy on allosteric CTZ binding may be interpreted in terms of a mechanism involving AMPA receptor desensitisation sequential to activation.

Allosteric Regulation↗
PubMed2003

[Lingual thyroid].

Lingual thyroid is a rare embryological aberration with incidence of 1:100,000. It is an ectopic thyroid tissue. In most cases, it is diagnosed in childhood and young adulthood but frequently around menopause. It appears as a mass on the base of the tongue causing mostly local symptoms often with hypothyroidism, rarely with thrive and mental retardation. Authors describe the features, diagnosis and therapy of lingual thyroid with the case of a 23-year-old woman. They analyze the probable pathomechanism and potential risk of malignant transformation of lingual thyroid. In this case, the diagnosis was described at the age of 17, but therapy or further investigation did not take place then. Six years later the patient visited our surgery with local complaints in euthyroid phase. Since the suppression therapy proved to be unsuccessful, the problem was finally solved by operation.

Adult↗
PubMed2003

Exogenous glutamate and taurine exert differential actions on light-induced release of two endogenous amino acids in isolated rat retina.

A dark-adapted isolated rat retina, preloaded with [(14)C]glutamate ([(14)C]Glu) and [(3)H]taurine ([(3)H]Tau), was superfused with artificial cerebrospinal fluid (ACSF) in the absence and presence of Glu (1 mM) or Tau (1 mM), as well as the Glu uptake inhibitors dihydrokainic acid (DHK, 0.04 mM) and trans-L-pyrrolidine-2,4-dicarboxylate (t-PDC, 0.004 mM). After 10 min of light stimulation, the extracellular level of [(14)C]Glu and [(3)H]Tau was reduced to 82 +/- 2% and 65 +/- 4% of the control, respectively. Basal release was enhanced when Tau and t-PDC were applied together, although none of the compounds had any effect when applied individually. Glu and DHK had no effect. The decrease of [(14)C]Glu efflux evoked by light stimuli was enhanced by t-PDC and Tau, either added separately or together, whereas Glu and DHK were without effect. In contrast, [(3)H]Tau efflux variations induced by light stimuli were reduced markedly by both Tau and Glu. These findings suggest distinctly different roles of Tau and Glu in light-induced responses in mammalian retina, including a possible role for Tau in light adaptation processes.

Animals↗
PubMed2003

Characterisation of an uridine-specific binding site in rat cerebrocortical homogenates.

Parameters of [3H]uridine binding to synaptic membranes isolated from rat brain cortex (K(D)=71+/-4 nM, B(max)=1.37+/-0.13 pmol/mg protein) were obtained. Pyrimidine and purine analogues displayed different rank order of potency in displacement of specifically bound [3H]uridine (uridine>5-F-uridine>5-Br-uridine approximately adenosine>>5-ethyl-uridine approximately suramin>theophylline) and in the inhibition of [14C]uridine uptake (adenosine>uridine>5-Br-uridine approximately 5-F-uridine approximately 5-ethyl-uridine) into purified cerebrocortical synaptosomes. Furthermore, the effective ligand concentration for the inhibition of [14C]uridine uptake was about two order of magnitude higher than that for the displacement of specifically bound [3H]uridine. Adenosine evoked the transmembrane Na(+) ion influx, whereas uridine the transmembrane Ca(2+) ion influx much more effectively. Also, uridine was shown to increase free intracellular Ca(2+) ion levels in hippocampal slices by measuring Calcium-Green fluorescence. Uridine analogues were found to be ineffective in displacing radioligands that were bound to various glutamate and adenosine-recognition and modulatory-binding sites, however, increased [35S]GTPgammaS binding to membranes isolated from the rat cerebral cortex. These findings provide evidence for a rather specific, G-protein-coupled site of excitatory action for uridine in the brain.

Adenosine↗
PubMed2003

Visual context integration is not fully developed in 4-year-old children.

Long-range horizontal interactions supporting contour integration were found to be weaker in children than in adults (Kovács et al, 1999 Proceedings of the National Academy of Sciences of the USA 96 12204-12209). In the present study, integration on a larger scale, between a target and its context was investigated. Contextual modulation of the percept of a local target can be directly measured in the case of geometric illusions. We compared the magnitude of a size contrast illusion (Ebbinghaus illusion or Titchener circles) in children and adults. 4-year-old children and adults performed 2AFC size comparisons between two target disks in the classical Ebbinghaus illusion display and in two other modified versions. We found that the magnitude of the illusion effect was significantly smaller in children than in adults. Our interpretation is that context integration is not fully developed in 4-year-old children. Closer-to-veridical-size estimations by children demonstrate that the perception of the local target is less affected by stimulus context in their case. We suggest that immature cortical connectivity is behind the reduced contextual sensitivity in children.

Adult↗
PubMed2002

[Results of mammographic screening at the Mammary Center of Debrecen in 1999 and 2000].

INTRODUCTION: The screening mammography decreases the mortality of female breast cancer. METHODS: A complex, independent centre of screening mammography has been operating in Debrecen since 1999. RESULTS: The number of the examinations were 10,399 in 1999 and 13,800 in 2000. The number of explored breast cancer cases were 43 (0.41%) in 1999 and 62 (0.45%) in 2000. CONCLUSION: Although the mortality reduction can be exactly measured after several years, we are convinced that the chances for a better life of these 107 women operated on with breast cancer in early state increased thanks to our project. The results of the breast cancer screening program in Debrecen fulfilled the professional requirements of mammographic service-screening.

Aged↗
PubMed2002

Light-induced changes in glutamate release from isolated rat retina is regulated by cyclic guanosine monophosphate.

Isolated rat retina was preloaded with [(14)C]glutamate and subsequently superfused to follow release of glutamate (Glu). After 20 min of superfusion in the dark, exposure of the [(14)C]Glu preloaded rat retina to a single train of white light pulses reduced Glu efflux significantly in the absence as well as in the presence of low (4 microM) and high (0.5 mM) concentrations of the Glu uptake inhibitor trans-L-pyrrolidine-2,4-dicarboxylate (t-PDC). The dark-light response was the highest in the presence of 4 microM t-PDC by establishing a plateau at 75% +/- 7% of the tonic Glu release in the dark (100%). Displaying transient to saturating responses with increasing relative luminance, time series of four trains of white light pulses arrived at a plateau of 85% +/- 10%. The cyclic guanosine monophosphate (cGMP) phosphodiesterase inhibitor Zaprinast (200 microM) antagonized the effect of the light series, leading to a plateau of 115% +/- 9%. Exposure of the retina to the guanylyl cyclase inhibitor LY83583 (30 and 100 microM) showed fast, transient responses characterized by peaks at 90% +/- 1% and 80% +/- 3%, respectively.

Aminoquinolines↗
PubMed2002

[EFfect of quinazolone-alkyl-carboxylic acid derivatives on the transmembrane Ca2+ ion flux mediated by AMPA receptors].

The excitatory neurotransmitter, Glu, plays a crucial role in many sensory and motor functions as well as in brain development, learning and memory and it is also involved in the pathogenesis of a number of neurological disorders, including epilepsy, Alzheimer's and Parkinson's diseases. Therefore, the study of Glu receptors (GluRs) is of therapeutical importance. We showed here by fluorescence monitoring of transmembrane Ca2+ ion fluxes in response to (S)-alpha-amino-3-hidroxi-5-metil-4-izoxazol propionic acid ((S)-AMPA) on the time scale of 0.00004-10 s that Ca2+ ion influx proceeds through faster and slower desensitizing receptors. Pharmacological isolation of the slower and faster desensitizing AMPA receptor was possible by fluorescence monitoring of Ca2+ ion translocation in response to (S)-AMPA in the presence and absence of various 2-methyl-4-oxo-3H-quinazoline-3-alkyl-carboxilic acid derivatives (Qxs): the acetic acid Q1 inhibits the slower desensitizing receptor response specifically, while the acetyl-piperidine Q5 is a more potent inhibitor of the faster desensitizing receptor response. In addition, spontaneous interictal activity, as induced by high [K+] conditions in hippocampal slices, was reduced significantly by Q5, suggesting a possible anticonvulsant property of Q5. Substitutions of Qxs into the GluR2 S1S2 binding core were consistent with their effect by causing variable degree of S1S2 bridging interaction as one of the main determinants of AMPA receptor agonist activity. The exploitation of differences between similar receptors will be important in the development and use of drugs with high pharmacological specificity.

Alkylation↗