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Biomedical subjects

György Szekeres

Publications and source records attributed to György Szekeres.

At least 19 recordsLinked to original sources
PubMed2006

Abnormal neurological signs, visual contrast sensitivity, and the deficit syndrome of schizophrenia.

This study was designed to investigate the relationship between abnormal neurological signs, visual contrast sensitivity, and the deficit syndrome of schizophrenia. Visual contrast sensitivity for counterphase-modulated low spatial frequency gratings was measured in 32 non-deficit and 12 deficit schizophrenia patients and 20 healthy controls subjects. Abnormal neurological signs were evaluated with the Neurological Evaluation Scale (NES). Compared with the controls, patients with schizophrenia displayed impaired visual contrast sensitivity, which was associated with sensory integration deficits, as measured with the NES. The deficit syndrome was predicted by negative symptoms and sensory integration deficits. These results suggest that early-stage perceptual dysfunctions, which may reflect the abnormality of precortical magnocellular visual pathways, are related to a specific group of abnormal neurological signs.

Adult↗
PubMed2006

Correlations between clinical symptoms, working memory functions and structural brain abnormalities in men with schizophrenia.

Thirteen male patients with schizophrenia and thirteen male normal control subjects were compared by magnetic resonance imaging (MRI) on volumes of the straight gyrus (SG), anterior cingulate gyrus, middle frontal gyrus, hippocampus, third ventricle, cavum septi pellucidi, total brain volume and intracranial volume. In addition, neuropsychological tasks were used to measure working memory and executive functions. Healthy volunteers and schizophrenic patients showed no significant differences in mean values for volumes of regions of interests. In the case of the SG, we found a significant difference in laterality: the tendency toward left dominance in healthy volunteers changed to significant right dominance in patients. The schizophrenic patients showed lower performance in working memory tasks, and strongly significant group differences were observed in measures of neurological signs assessed by the Neurological Evaluation Scale (NES). Negative symptoms correlated with the level of spatial working memory and executive functions. Negative symptoms also correlated with the volume of the right hippocampus, while the rate of anhedonia negatively correlated with the relative volume of the left SG.

Adult↗
PubMed2005

Habit learning and the genetics of the dopamine D3 receptor: evidence from patients with schizophrenia and healthy controls.

In this study, the authors investigated the relationship between the Ser9Gly (SG) polymorphism of the dopamine D3 receptor (DRD3) and striatal habit learning in healthy controls and patients with schizophrenia. Participants were given the weather prediction task, during which probabilistic cue-response associations were learned for tarot cards and weather outcomes (rain or sunshine). In both healthy controls and patients with schizophrenia, participants with Ser9Ser (SS) genotype did not learn during the early phase of the task (1-50 trials), whereas participants with SG genotype did so. During the late phase of the task (51-100 trials), both participants with SS and SG genotype exhibited significant learning. Learning rate was normal in patients with schizophrenia. These results suggest that the DRD3 variant containing glycine is associated with more efficient striatal habit learning in healthy controls and patients with schizophrenia.

Adult↗
PubMed2005

Over-expression of dopamine D2 receptor and inwardly rectifying potassium channel genes in drug-naive schizophrenic peripheral blood lymphocytes as potential diagnostic markers.

Schizophrenia is one of the most common neuropsychiatric disorders affecting nearly 1% of the human population. Current diagnosis of schizophrenia is based on complex clinical symptoms. The use of easily detectable peripheral molecular markers could substantially help the diagnosis of psychiatric disorders. Recent studies showed that peripheral blood lymphocytes (PBL) express subtypes of D1 and D2 subclasses of dopamine receptors. Recently, dopamine receptor D3 (DRD3) was found to be over-expressed in schizophrenic PBL and proposed to be a diagnostic and follow-up marker for schizophrenia. In this study we screened PBL of 13 drug-naive/drug-free schizophrenic patients to identify additional markers of schizophrenia. One of the benefits of our study is the use of blood samples of non-medicated, drug-naive patients. This excludes the possibility that changes detected in gene expression levels might be attributed to the medication rather than to the disorder itself. Among others, genes for dopamine receptor D2 (DRD2) and the inwardly rectifying potassium channel (Kir2.3) were found to be over-expressed in microarray analysis. Increased mRNA levels were confirmed by quantitative real-time PCR (QRT-PCR) using the SybrGreen method and dual labeled TaqMan probes. The use of both molecular markers allows a more rapid and precise prediction of schizophrenia and might help find the optimal medication for schizophrenic patients.

Adult↗
PubMed2005

Immunohistochemical distribution of vanilloid receptor, calcitonin-gene related peptide and substance P in gastrointestinal mucosa of patients with different gastrointestinal disorders.

The immunohistochemical distribution of capsaicin/vanilloid (transient receptor potential vanilloid 1, TRPV1) receptors and neuropeptides (CGRP, SP) was studied in the gastrointestinal mucosal biopsies of patients with gastritis, erosions, ulcers, polyps, adenocarcinoma, chronic inflammatory bowel diseases, polyps without and with hyperplasia, dysplasia and adenocarcinoma in colon. The studies were carried out in 127 patients and 30 people with only functional dyspepsia (without any histological alteration). The results were: (1) the positivity of TRPV1 receptor and CGRP was detected, and weak participation of SP was detected in patients with different gastric diseases; (2) the presence of TRPV1, CGRP and SP could be detected in chronic inflammation of bowel disease; (3) SP could not detected in patients with colon polyps, dysplasia and adenocarcinoma; (4) the presence of TRPV1 and CGRP was proved in colon dysplasia and adenocarcinoma. We conclude that (1) the immunohistochemical distribution of TRPV1, CGRP and SP differs in gastrointestinal diseases of the upper and lower tract, and (2) the participation of TRPV1, CGRP and SP differs significantly in these different gastrointestinal diseases.

Adenocarcinoma↗
PubMed2005

Participation of vanilloid/capsaicin receptors, calcitonin-gene-related peptide and substance P in gastric protection of omeprazole and omeprazole-like compounds.

The effects of omeprazole and different omeprazole-like compounds, associated with anti-ischaemic, antioxidant and poly(adenosine-diphosphate-ribose) polymerase (PARP) inhibitory properties, on the gastric acid secretion (4 h pylorus-ligated) and indomethacin-induced gastric mucosal damage connected with the specific immunohistochemical distribution of TRPV1, CRGP and SP during the effects of these compounds, were studied. The observations were carried out in CFY-strain rats (180-210 g), according to the standard methods and the above-mentioned parameters were studied in these experimental circumstances without and with application of different compounds. We found that: (1) all of the compounds dose-dependently inhibited the gastric acid secretion and mucosal damage; (2) the expression of TRPV1 receptor, CGRP and SP decreased significantly in both pylorus-ligated and indomethacin-treated animals and (3) the expression of TRPV1 and CGRP was reduced. Meanwhile, no change was obtained in SP expression during the gastric mucosal protection produced by omeprazole and omeprazole-like compounds. The conclusions were that (1) a functional overlap exists between the capsaicin-sensitive afferent and efferent vagal nerve during omeprazole effects; (2) chemical modification of omeprazole molecule offers a new pathway to obtain a new drug for the introduction in the clinical practice.

Animals↗
PubMed2004

[Are there new possibilities in immunomorphology?].

Immunomorphology, including immunohistochemistry and immunocytochemistry, forms a category of well known, reproducible, cost and environment saving immunodiagnostic methods based on immunological specificity. Both the accurate diagnosis and a better knowledge of biological parameters of diseases, especially of malignant tumors, result from the continual development of technologies and applications concerning at least 60 years of history of immunostaining. This review attempts to summarize the most important steps of development of immunomorphology.

Animals↗
PubMed2004

Role of dopamine D3 receptor (DRD3) and dopamine transporter (DAT) polymorphism in cognitive dysfunctions and therapeutic response to atypical antipsychotics in patients with schizophrenia.

Molecular components of the dopaminergic system may play an important role in the pathophysiology of schizophrenia. In this study, we investigated the relationship of the Ser9Gly (S/G) polymorphism of the dopamine D3 receptor (DRD3) and the variable number of tandem repeats (VNTR) polymorphism of the dopamine transporter (DAT) with therapeutic response to atypical antipsychotics (clozapine, olanzapine, quetiapine, risperidone) and cognitive functions. No associations were found between the DRD3 and DAT polymorphisms and schizophrenia. The S/S genotype and the S allele were more frequent in the non-responder patients (n = 28) than in the group of responders (n = 47) (cut-off: >20-point improvement in Global Assessment of Functioning (GAF) scale). The patients with S/S genotype completed fewer categories and had more perseverative errors in the Wisconsin Card Sorting Test (WCST) compared with the S/G patients. The S/S and S/G patients did not differ in positive and negative symptoms, GAF scores, WCST failure to maintain set, and verbal learning. No differences in symptoms or WCST measures were observed in the patients with different DAT genotypes. These results suggest that the S/S genotype of the DRD3 is associated with worse therapeutic response and more severe executive dysfunctions in patients with schizophrenia.

Adult↗
PubMed2004

The prognostic value of dopamine receptor occupancy by [123I]IBZM-SPECT in schizophrenic patients treated with quetiapine.

BACKGROUND: In the present study D2 receptor occupancy was investigated in quetiapine treated schizophrenic patients for the detection of a relationship between the scintigraphic pattern and clinical signs and symptoms. MATERIAL AND METHODS: In 10 schizophrenic patients [123I]IBZM-SPECTs were performed during the introduction of quetiapine therapy (600-800 mg/day) and during a lower maintenance dose (200-400 mg/day). The patients' clinical follow-up was continued for 1 year. For the evaluation of SPECT images, visual interpretation was performed and striatum/occipital lobe (S/O) activity ratio was calculated. RESULTS: The initial striatum/occipital ratio was significantly higher in patients with relapse compared to the others (1.86 +/- 0.17, 1.53 +/- 0.15, p < 0.01). The decreasing striatum/occipital ratio (increasing D2 receptor occupancy) on the 2nd SPECT was a predictive factor for the relapse. CONCLUSIONS: D2 receptor occupancy and its changes during quetiapine therapy were related to the prognosis of the treatment efficacy.

Adult↗
PubMed2003

The C270T polymorphism of the brain-derived neurotrophic factor gene is associated with schizophrenia.

We investigated a novel polymorphism of single nucleotide substitution (C270T) of the brain-derived neurotrophic factor (BDNF) gene in schizophrenia patients (n=101) and in controls (n=68). The frequency of the C/T genotype and the T allele were significantly higher in the schizophrenia patients (25.7% and 13.9%, respectively) compared with the controls (5.9% and 2.9%). There were no significant differences in Positive and Negative Symptom Scale (PANSS) items and Global Assessment of Functioning (GAF) scores between the patients with C/C and C/T genotypes. Further studies are warranted to elucidate the significance of this finding in the pathophysiology of schizophrenia.

Adult↗
PubMed2003

[Immuno-diagnosis of malignant melanoma].

The diagnosis of malignant melanoma must be followed by treatment shown to be effective. Therefore a correct diagnosis, including staging, that will permit a meaningful prognosis and treatment, is essential. The usefulness and great specificity of immunological methods is based on the detection of antigens characteristic of neoplastic and reactive cells. In cases of malignant melanoma, immunohistochemistry has limited practical value in the routine diagnosis of melanocytic lesions. The method may be important, however, in the differential diagnosis of, for example, malignant melanoma vs. non-melanocytic anaplastic neoplasia, malignant vs. benign melanocytic lesions, etc. Recent advances in relating the immunostaining of antigens to the development of tumor cells, such as proliferation and apoptosis, metastatic potential, etc. have given considerable importance to the immunomorphological evaluation of malignant melanomas. Likewise, immunotherapy requires the immunophenotyping of the reactive cells of the immune system.

Antigens, Neoplasm↗
PubMed2002

[Correlation between the effectiveness of atypical antipsychotics and dopamine D3 receptor polymorphism in schizophrenia].

OBJECT: Numerous relevant variants of dopamine receptors have been identified in schizophrenia. The Ser9Gly gene polymorphism of dopamine D3 receptor is known as a susceptibility factor for the disease. In addition, it has a role in the modification of therapeutic effect of antipsychotics. In this naturalistic study the authors investigated the relationship between this polymorphism and the therapeutic response to atypical antipsychotics. METHOD: 75 patients with schizophrenia according to DSM-IV and 45 healthy controls were recruited. The patients were divided to responder and nonresponder subgroups, cut-off: > 20 point improvement in Global Assessment of Functioning. By polymerase chain reaction the genotype of dopamine D3 receptor of every participant was determined. RESULTS: The Ser9Ser genotype of dopamine D3 receptor was more frequent in the nonresponder subgroup (64%, p = 0.0018). The Ser9 allele was overrepresented among nonresponder patients (82%, p = 0.0172). CONCLUSION: Based on our results, the worse therapeutic response to atypical antipsychotics is associated with Ser9 variant of dopamine D3 receptor.

Adult↗
PubMed2002

Simultaneous presence of neutrophil alveolitis and Ki-67 positivity of alveolar macrophages in dermato-/polymyositis and systemic sclerosis.

OBJECTIVE: The proportion of cell proliferation-associated nuclear Ki-67 antigen positive alveolar macrophages was compared in the bronchoalveolar lavage fluids (BAL) of patients with dermato-/polymyositis (DM-PM), scleroderma-myositis overlap syndrome (Scl-M), systemic sclerosis (SSc), and undifferentiated connective tissue disease (UCTD). PATIENTS AND METHODS: We examined 8 patients with DM-PM, 3 with Scl-M, 11 with SSc, and 10 with UCTD. The patients were selected on the basis of their interstitial lung involvement diagnosed by non-invasive methods. RESULTS: Increased Ki-67 expression in alveolar macrophages was observed in three cases of SSc (27%) and in 4 of myositis (36%). In UCTD and in healthy volunteers a low level of Ki-67 expression was detected (in both groups 5%). A positive correlation was found between the percentage of the Ki-67 positive alveolar macrophages and the percentage of granulocytes in BAL fluid of the investigated patients with different systemic autoimmune diseases and healthy controls, indicating that increased local proliferation of differentiated large alveolar macrophages can be detected in cases with neutrophil alveolitis. There was also a correlation between the extent of ground glass opacity on HRCT and elevated proportion of proliferating alveolar macrophages in BAL fluid.

Adult↗
PubMed2002

[Receptor polymorphism and response to treatment in schizophrenia].

The new molecular genetic methods have generated dynamic changes in the field of schizophrenia research in the last decade. There is increasing knowledge about potential genetic variants affecting the phenotype in terms of response to antipsychotic therapy. It is known that polymorphisms of genes encoding proteins that participate in the metabolism of neuroleptics, alter the pharmacokinetics of drugs. In addition, experience has been emerging about receptor polymorphisms that may play substantial role in the etiology and pharmacotherapy of schizophrenia. These data throw new light upon issue of therapy resistance in schizophrenia. Authors review the literature about polymorphisms of neurotransmitter systems relevant to schizophrenia, and its associations with the response to typical and atypical antipsychotic treatments. They outline the trends of pharmacogenomics and its perspectives in the research of new treatment possibilities in schizophrenia.

Antipsychotic Agents↗
PubMed2002

[Investigation of the dopamine dysregulation hypothesis of schizophrenia with neuroimaging techniques].

The most elaborated biochemical concept of schizophrenia is the dopamine hypothesis. However, this classical theory is based on indirect observations. It has recently become possible to study this theory directly by means of advanced functional neuroimaging techniques, the development of specific radioligands and study protocols that are eligible to monitor dynamic changes in the neurotransmitter systems. According to the early concept, the essence of schizophrenia is the hyperactivity of the dopamine system. Nevertheless, this idea has gone through many modifications. In accordance with the modified dopamine hypothesis, the cognitive deficit and negative symptoms are related to the hypoactivity of the dorsolateral prefrontal cortex while the acute phases of the disease associates with hyperactivity of the ventral striatal elements of the dopaminergic system. Between these dysfunctions there is causality via their exuberant connections. Beyond that, the interactions between the prefrontal and striatal anomalies implicate the involvement of other neurotransmitters than dopamine. Observations from model psychosis induced by N-methyl-D-aspartate antagonists and in vivo neuroimaging investigations in humans support primarily the role of glutamatergic system. Our developing knowledge about the neurochemical mechanism of schizophrenia can significantly affect therapeutic strategies as well.

Amphetamine↗
PubMed2002

Development and characterisation of a monoclonal antibody family against aquaporin 1 (AQP1) and aquaporin 4 (AQP4).

Recent studies have discovered the existence of water-channel molecules, the so called aquaporins (AQP) presumably involved in active, ATP dependent water transport between the intracellular and extracellular compartments. Both genetic and protein sequences and structures of the AQPs are known and crystallographic analyses of some members of the AQP family have been performed. Specific antibodies are required to examine their histological locations and analyse their roles in physiological and pathological pathways of water transportation and osmotic regulation. Until recently some polyclonal antibodies have been developed against certain members of the AQP family. However, to date highly specific monoclonal antibodies against aquaporins do not exist. We have developed a monoclonal antibody family against the aquaporin 1 (AQP1) and aquaporin 4 (AQP4) molecules. Well-conserved epitop sequences of AQP1 and AQP4 proteins were selected by computer analysis and their synthetic peptide fragments were used as the antigens of immunisation and the following screening. Antibodies were characterised by immunoserological methods (ELISA, dot-blot and immunoblot), flow cytometry and immunohistochemistry of formaldehyde-fixed and paraffin-embedded tissue samples. RT-PCR tests controlled the specificity of the immune reactions. Our monoclonal antibodies recognised AQP1 and AQP4 in all the techniques mentioned above and apparently they are useful both in various quantitative and qualitative measurements of the expressions of AQP1 and AQP4 in several species (human, rat, mouse, invertebrates, even plants). According to preliminary immunohistochemical studies our monoclonal anti-AQP1 and anti-AQP4 antibodies are appropriate tools of patho-morphological examinations on routine formol-paraffin tissue samples.

Animals↗
PubMed2002

Spatiotemporal visual processing in schizophrenia.

Studies examining visual processing in schizophrenia have provided inconsistent results. In this study, the authors measured static and dynamic visual contrast sensitivity (CS) in patients with schizophrenia (n=20) and control subjects (n=15). Extrapyramidal symptoms were evaluated with the Simpson-Angus scale. In the static condition, the patients with schizophrenia showed reduced CS in the spatial frequency range of 2.9-14.4 cycles per degree of visual angle (c/d). In the dynamic condition, CS loss was present over the whole range tested (0.5-14.4 c/d). Higher Simpson-Angus scores and higher doses of antipsychotic medication were associated with more severe CS deficits. These results suggest that the hypodopaminergic state induced by antipsychotic medication may produce parkinsonian visual impairments in schizophrenia patients.

Adult↗