Biomedical subjects

Z Nagy

Publications and source records attributed to Z Nagy.

At least 37 records · Page 2Linked to original sources

PubMed2001

(-)-D-Deprenyl attenuates apoptosis in experimental brain ischaemia.

(-)-D-Deprenyl protects neurons from oxidative damage and helps to maintain the mitochondrial membrane potential by influencing intracellular anti-apoptotic oncoproteins, such as Bcl-2. The cellular rescue in the penumbra region by (-)-D-deprenyl administration was examined after permanent middle cerebral artery occlusion in rats. (-)-D-Deprenyl was given continuously following permanent middle cerebral artery occlusion. Two days later, the rats were killed and their infarct volumes were determined. Coronal brain sections were stained with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate deoxyribonucleic acid (DNA) nick-end labelling (TUNEL) and caspase-3, TUNEL and anti-neuronal nuclei (NeuN) double labelling. Neural plasticity was characterized by growth-associated protein-43 (GAP-43) immunohistochemistry. A 1000 x 1000-microm region was sampled at both cortical margins of the TUNEL-positive area at its borders. The numbers of TUNEL-labelled and TUNEL-caspase-3-labelled cells decreased significantly. (-)-D-Deprenyl treatment increased the number of GAP-43-positive cells. We conclude that (-)-D-deprenyl reduced the number of affected cells and induced neuronal plasticity.

Animals↗

PubMed2001

Involvement of PKC-beta in PTH, TNF-alpha, and IL-1 beta effects on IL-6 promoter in osteoblastic cells and on PTH-stimulated bone resorption.

Protein kinase C (PKC) has been shown to be activated by parathyroid hormone (PTH) in osteoblasts. Prior evidence suggests that this activation mediates responses leading to bone resorption, including production of the osteoclastogenic cytokine interleukin-6 (IL-6). However, the importance of specific PKC isozymes in this process has not been investigated. A selective antagonist of PKC-beta, LY379196, was used to determine the role of the PKC-beta isozyme in the expression of IL-6 in UMR-106 rat osteoblastic cells and in bone resorption in fetal rat limb bone organ cultures. PTH, tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta) induced translocation of PKC-alpha and -beta(I) to the plasma membrane in UMR-106 cells within 5 min. The stimulation of PKC-beta(I) translocation by PTH, TNF-alpha or IL-1 beta was inhibited by LY379196. In contrast, LY379196 did not affect PTH, TNF-alpha-, or IL-1 beta-stimulated translocation of PKC-alpha. PTH, TNF-alpha, and IL-1 beta increased luciferase expression in UMR-106 cells transiently transfected with a -224/+11 bp IL-6 promoter-driven reporter construct. The IL-6 responses were also attenuated by treatment with LY379196. Furthermore, LY379196 inhibited bone resorption elicited by PTH in fetal rat bone organ cultures. These results indicate that PKC-beta(I) is a component of the signaling pathway that mediates PTH-, TNF-alpha-, and IL-1 beta-stimulated IL-6 expression and PTH-stimulated bone resorption.

Animals↗

PubMed2001

Multijet cross sections in deep inelastic scattering at next-to-leading order.

We present the perturbative prediction for three-jet production cross section in deep inelastic scattering at the next-to-leading order accuracy. We study the dependence on the renormalization and factorization scales of exclusive three-jet cross section. The perturbative prediction for the three-jet differential distribution as a function of the momentum transfer is compared to the corresponding data obtained by the H1 Collaboration at HERA.

Journal Article↗

PubMed2001

Functional characterization of the human multidrug transporter, ABCG2, expressed in insect cells.

ABCG2 (also called MXR (3), BCRP (4), or ABCP (5) is a recently-identified ABC half-transporter, which causes multidrug resistance in cancer. Here we report that the expression of the ABCG2 protein in Sf9 insect cells resulted in a high-capacity, vanadate-sensitive ATPase activity in isolated membrane preparations. ABCG2 was expressed underglycosylated, and its ATPase activity was stimulated by daunorubicin, doxorubicin, mitoxantrone, prazosin and rhodamine 123, compounds known to be transported by this protein. ABCG2-ATPase was inhibited by low concentrations of Na-orthovanadate, N-ethylmaleimide and cyclosporin A. Verapamil had no effect, while Fumitremorgin C, reversing ABCG2-dependent cancer drug resistance, strongly inhibited this ATPase activity. The functional expression of ABCG2 in this heterologous system indicates that no additional partner protein is required for the activity of this multidrug transporter, probably working as a homodimer. We suggest that the Sf9 cell membrane ATPase system is an efficient tool for examining the interactions of ABCG2 with pharmacological agents.

ATP Binding Cassette Transporter, Subfamily G, Mem↗

PubMed2001

[The role of estrogen receptor, vitamin D receptor and calcium receptor genotypes in the pathogenesis of colorectal cancer].

In this study, the Xbal polymorphisms of the estrogen-, the Bsml polymorphism of the vitamin D- as well as the A986S polymorphism of the calcium-sensing receptor genes were investigated in 56 patients with colorectal cancer. The expression of erbB-2, epidermal growth factor receptor, ras, p53 and their relationship to estrogen-, vitamin D- and calcium-sensing receptor genotypes were also studied. In subjects exhibiting XX genotype of the estrogen receptor gene or bb genotype of the vitamin D receptor gene, erbB-2 expression was significantly lower compared to those with xx, Xx or BB, Bb (6/56 and 11/56 vs. 31/56 and 26/56; p = 0.0043 and 0.041). The presence of the XX alleles of estrogen receptor gene significantly correlated with the overexpression of the epidermal growth factor receptor expression in tumors, whereas in xx and Xx genotypes, significantly higher expression was seen (7/56 vs. 30/56; p = 0.049). Analyzing the combinations of the two gene allelic variants, we have found XXbb genotype to be associated with a significantly lower erbB-2 expression, compared to other combinations (Xxbb, XxBb, XXBb) (2/7 vs. 7/7, 4/5, 4/5; p = 0.0011). Patients with AA calcium-sensing receptor genotype were in higher UICC stages at the time of discovery of their disease than those with AS genotype. The AA allelic variant of the calcium-sensing gene was more frequent among patients with colorectal cancer compared to controls (36/56 vs. 36/112; p = 0.0004). Our observations raise the possibility that estrogen-, and vitamin D receptor gene polymorphisms accompanied with variable oncogene expression might influence the pathogenic processes resulting in the development of colorectal cancer. The A986S polymorphism of calcium-sensing receptor might also be a prognostic marker of the disease.

Adult↗

PubMed2001

[Platelet glycoprotein IIb/IIIa (LeuPro 33) polymorphism in stroke patients].

This is the first Hungarian paper on the platelet glycoprotein IIb/IIIa (LeuPro 33) polymorphism in stroke patients. There are conflicting data about the role of this polymorphism in the pathogenesis of arterial thrombosis. The aim of our study was to describe the prevalence of PLA1/PLA2 in healthy persons and in stroke patients. From the same study population other polymorphism (prothrombin gene 20210 G/A) also has been determined. Blood sample was investigated by polymerase chain reaction in 173 unrelated healthy donors and 234 stroke patients. Stroke was documented by CT and MRI. We used a rutin questionnaire to study previous vascular events and conventional risk factors of patients. Prevalence of PLA1/PLA2 was 23.5% among healthy persons. That is higher than in other European countries (15%). It was 30.4% in stroke patients (OR: 1.42, 95%; CI: 0.87-2.31; p = 0.15). Heterozigous PLA was found in patients older than 50 by 33.6% (OR: 1.65, 95%; CI: 0.94-2.87; p = 0.09). Previous vascular events and conventional risk profil were not significantly different between PLA1/PLA1 and PLA1/PLA2 groups of patients. In patients under 50 having 20-85% stenosis of internal carotid artery there was a higher prevalence (p = 0.09). Comparing stroke patients to control population there was a slight increase (OR: 7.0; p = 0.06) in the frequency of two polymorphisms (PLA and factor II) together in the stroke cases. Polymorphism of GP IIb/IIIa LeuPro 33 seemed to be increased in stroke patients above 50 years. Carotid stenosis with polymorphism is a risk factor for young patients. PLA variant together with prothrombin gene polymorphism results very high risk for stroke.

Adult↗

PubMed2001

Commensurate water monolayer at the RuO2(110)/water interface.

We demonstrate the presence of two types of commensurate, registered water monolayers with different densities at the RuO2(110)/bulk-water (0.1 M NaOH solution) interface with off-specular, oxygen crystal truncation rods. At anodic potentials (close to oxygen evolution), the extraneous water layer and the surface hydroxide layer form a bilayer with O-H-O bond distances similar to that of ice X. At cathodic potentials, the water molecules converted from the bridging OH molecules form a low-density water layer.

Journal Article↗

PubMed2001

[Risk factors for early death and recurrence in stroke].

The early case fatality rate (28-day mortality) in 500 acute stroke patients of Budapest Stroke Data Bank was 17% and it was 25% within the first year with an increase between 1-3% annually. In the group with early death significantly higher age (p < 0.0001), more serious neurological symptoms, impaired consciousness (p < 0.0001), and higher volume of the lesions (p < 0.0001) have been detected. In this group significantly more stroke in the territory of vertebrobasilar system, a higher number of ischemic heart disease, and atrial fibrillation have been registered. According to the stroke subtypes there were significantly more cardiogenic embolisms, and hemorrhages, but less lacunar infarcts. The level of blood sugar at admission, and the rate of low platelets were higher among patients, who died within 28 days. Significantly higher percentage of the regions in the right frontal, right parietal, right occipital lobes and right thalamus have been affected in the early death group than in the survivors' group, however no such difference have been found in the lesions of the left homological structures. Severity of recurrent strokes have been more serious, and among patients with repetitive stroke significantly more ischemic heart diseases have been demonstrated. Atherosclerosis is the main risk for a new cerebrovascular accident. The case recurrent rate in the first 28 days is 7%, and it is 16% within the first year. The annual increase was between 1-5%. 71% of the recurrent strokes had the same mechanism as the first one.

Aged↗

PubMed2001

Involvement of prostanoid release in the mediation of UTP-induced cerebrovascular contraction in the rat.

The interaction between uridine-5'-triphosphate (UTP) and prostanoids was studied in isolated rat middle cerebral arteries (MCAs). The strong contractions in MCA segments induced by UTP were weakened significantly by indomethacin and more markedly by the thromboxane receptor antagonist ICI 192605. Thromboxane A(2) (TXA(2)) release by MCAs was below the detection limit of the chemiluminescence enzyme immunoassay, but increased TXA(2) formation was detected in basilar arteries in the presence of UTP. Prostacyclin (PGI(2)) formation by MCAs also increased in the presence of UTP. These results suggest that UTP stimulates the release of both TXA(2) and PGI(2) from the rat MCA but the vascular effect of TXA(2) is dominant.

Animals↗

PubMed2001

Hypercapnia stimulates prostaglandin E(2) but not prostaglandin I(2) release in endothelial cells cultured from microvessels of human fetal brain.

Hypercapnia-induced cerebral vasodilation involves prostanoids, in newborns. The source of these prostanoids, however, is not yet determined. In the present study we address the hypothesis that microvascular endothelial cells of human fetal cerebrum increase the synthesis of dilator prostanoids in response to high pCO(2). Cells were isolated from a 22-week-old human fetus. Indication of induced abortion was 46 XY-t(3,10) 3q-25 chromosome abnormality. Normocapnia or hypercapnia was performed during normoxic and normothermic conditions in the medium of the cell culture. After normocapnic or hypercapnic stimuli, the amounts of released prostaglandin E(2) and 6-keto-prostaglandin F(1alpha) (the stable metabolite of prostaglandin I(2)) were measured by radioimmunoassay. Endothelial cells cultured from human fetal brain microvessels express PGE(2) and 6-keto-PGF(1alpha) in different degrees. Hypercapnic stimulus induced a significant increase of PGE(2), while expression of 6-keto-PGF(1alpha) was not augmented by the same stimulus. PGE(2) of endothelial origin, therefore, could be a factor in the mediation of the hypercapnia-induced vasodilation in human fetuses.

Brain↗

PubMed2001

Solution equilibria and structural characterisation of the palladium(II) and mixed metal complexes of peptides containing methionyl residues.

Palladium(II) complexes of the peptides GlyMet, GlyMetGly and GlyGlyMet containing methionyl residues were studied by potentiometric and 1H NMR spectroscopic methods. The coordination of terminal amino and deprotonated amide nitrogen and thioether sulfur donor atoms was suggested in the mono complexes of GlyMet and GlyMetGly. The fourth coordination site of these complexes can be occupied by solvent molecule, chloride or hydroxide ions or by another ligand molecule in the bis or mixed ligand complexes. The second ligand coordinates monodentately via the thioether function in acidic media and the amino group under neutral or basic conditions. The stoichiometry of the major species formed in the palladium(II)-GlyGlyMet system is [PdH(-2) L]- and this is coordinated by the amino, two-amide and the thioether donor functions. Thioether bridged mixed metal complexes formed in the reaction of [Pd(dien)]2+ and [Cu(GlyMetH(-1))] or [Ni(GlyMetGlyH(-2))]- also have been detected by spectroscopic techniques.

Binding Sites↗

PubMed2001

Carbon source regulation of beta-galactosidase biosynthesis in Penicillium chrysogenum.

Growth and beta-galactosidase activity of the penicillin producer industrial Penicillium chrysogenum NCAIM 00237 strain were examined using different carbon sources. Good growth was observed using glucose, sucrose, glycerol and galactose, while growth on lactose was substantially slower. beta-Galactosidase activity was high on lactose and very low on all the other carbon sources tested. In glucose grown cultures after exhaustion of glucose as repressing carbon source a derepressed low level of the enzyme was observed. cAMP concentration in lactose grown cultures was relatively high, in glucose grown cultures was low. Caffeine substantially decreased glucose consumption and growth but did not increase beta-galactosidase activity and did not prevent glucose repression which rules out the involvement of cAMP in the regulation of beta-galactosidase biosynthesis in Penicillium chrysogenum.

Caffeine↗

PubMed2001

Screening for cerebroprotective agents using an in vivo model of cerebral reversible depolarization in awake rats.

The need to screen cerebroprotective compounds without anesthetic interference prompted the development of a model using hypoxic rats. In this model two outcome measures were used: (1) the time to reach isoelectric electroencephalogram (iEEG), caused by nitrogen gas inhalation in the test chamber, and (2) the time for behavioral recovery measuring the latency of restoration of the head-withdrawal reflex upon vibrissae stimulation. We report here data of blood chemistry, cerebral tissue oxygen measurements, a definition of a proposed scoring system, and the pharmacological results of RGH-2202. The findings with RGH-2202 are used here to show the utility of the screening method. Events during hypoxia: Arterial and venous pO(2), pCO(2), and pH, and brain tissue pO(2)significantly declined. Significant correlations were established among the pO(2)of cerebral tissue, blood, and the test chamber. RGH-2202 significantly and dose-dependently shortened the iEEG time; the compound's Effective Dose(30)was 227.8 mg kg(-1). Events during recovery: Immediately after the iEEG, when the atmosphere in the chamber was replaced with room air, the arterial, venous and brain tissue pO(2)increased above the control level and subsequently recovered to baseline levels. Behavioral recovery occurred before blood chemistry was otherwise normalized. RGH-2202 significantly and dose-dependently shortened the recovery time; the Effective Dose(30)was 8.71 mg kg(-1). The available data define and support the physiological basis of this practicable rat-screening model.

Administration, Oral↗

PubMed2001

Beta-galactosidase of Penicillium chrysogenum: production, purification, and characterization of the enzyme.

Intracellular beta-galactosidase from Penicillium chrysogenum NCAIM 00237 was purified by procedures including precipitation with ammonium sulfate, ion-exchange chromatography on DEAE-Sephadex, affinity chromatography, and chromatofocusing. These steps resulted a purification of 66-fold, a yield of about 8%, and a specific activity of 5.84 U mg(-1) protein. Some enzyme characteristics were determined using o-nitrophenyl-beta-d-galactopyranoside as substrate. The pH and temperature optimum of the activity were about 4.0 and 30 degrees C respectively. The K(m) and pI values were 1.81 mM and 4.6. beta-Galactosidase of P. chrysogenum is a multimeric enzyme of about 270 kDa composed of monomers with a molecular mass of 66 kDa.

Chromatography, Affinity↗

PubMed2001

New temperature modification makes the Bielschowsky silver stain reproducible.

The Bielschowsky silver impregnation can be used as a single stain for the diagnosis of Alzheimer's disease. It impregnates both the amyloid and neuritic components of the senile plaques and it reliably stains neurofibrillary tangles. However, we find that the stain is highly sensitive to changes of the ambient temperature. Since the diagnostic criteria for Alzheimer's disease rely on a semi-quantitative assessment of neuritic plaques and neurofibrillary tangles the reproducibility of the Bielschowsky stain is important. In this study we compare three different modifications of the Bielschowsky stain with the methenamine silver stain and with immunohistochemistry for the beta-amyloid and the hyperphosphorylated tau proteins. We found that the most reliable and easily reproducible modification of the Bielschowsky silver impregnation is the one that uses incubations at 5 degrees C.

Alzheimer Disease↗

PubMed2001

Subsets in psoriatic arthritis formed by cluster analysis.

The aim of the study was to create subgroups among psoriatic arthritis patients on the basis of dermatological features, clinical pattern of arthritis, and laboratory, immunological and radiological findings. Data on 100 patients were expressed in a standardised form and entered into hierarchical cluster analysis according to Ward's method. Seven subgroups were created. Fifty-six patients with mild psoriasis were sorted into a 'polyarticular group'. Two 'RA-like groups' were formed, differing from each other serologically and in axial involvement. In an 'oligoarticular group' (18 patients) serious skin disease and female gender predominancy were found to be characteristic. Eight patients with polyarticular arthritis were assigned to an 'erythrodermal group', in which polyarticular arthritis, mutilating, severe arthritis and a history of erythroderma were characteristic. Close to this group on the dendrogram eight women were sorted into a 'distal form'. Sausage fingers were frequent, and nail dystrophy was present in every case. In a 'pustular group' (three patients) the different type of skin involvement was considered and nail dystrophy was common. In the newly created subgroups not only the arthritic status, but also the type of the skin disease, played a determining role.

Adult↗

PubMed2001

Interaction of Cu(2+) with His-Val-His and of Zn(2+) with His-Val-Gly-Asp, two peptides surrounding metal ions in Cu,Zn-superoxide dismutase enzyme.

His-Val-His and His-Val-Gly-Asp are two naturally occurring peptide sequences, present at the active site of Cu,Zn-superoxide dismutase (Cu,Zn-SOD). The interactions of His-Val-His=A (copper binding site) with Cu(II) and of His-Val-Gly-Asp=B (zinc binding site) with Zn(II) have been studied by using both potentiometric and spectroscopic methods (visible, EPR, NMR). The stoichiometry, stability constants and solution structure of the complexes formed have been determined. The binding modes of the species [CuAH](2+) and [CuA](+) were characterized by histamine type of coordination. [CuA](+) is further stabilized by the formation of a macrochelate with the involvement of the imidazole of the C-terminal histidine. The existence of macrochelate results in a slight distortion of the coordination geometry providing good base for the development of enzyme models. The enhanced stability of the macrochelate suppresses the formation of bis-complexes as well as the amide deprotonation. This process, however, takes place at higher pH resulting in the formation of the 4 N(-) coordinated [NH(2),N(-),N(-),N(im)] species [CuAH(2-)](-). On the other hand, in the case of the Zn(II)-His-Val-Gly-Asp system, coordination takes place at the terminal carboxylate in species [ZnBH(2)](2+). Monodentate binding occurs via the N-terminal imidazole in [ZnBH](+) while histamine type of coordination is possible in [ZnB], [ZnB(2)H](-) and [ZnB(2)](2-) species. Amide deprotonation does not take place in the case of Zn(2+), hydroxo-complexes are formed instead.

Copper↗

PubMed2001

Oestrogen and vitamin D receptor (VDR) genotypes and the expression of ErbB-2 and EGF receptor in human rectal cancers.

Oestrogen/oestrogen receptor (ER) and vitamin D/vitamin D receptor (VDR) systems have been implicated in the pathogenesis of colorectal cancers. The expression of erbB-2 and epidermal growth factor receptor (EGFR) in colorectal cancers has been suggested to have diagnostic and prognostic significance. In our study, XbaI and PvuII polymorphisms of the ER gene and the BsmI polymorphism of the VDR gene were studied in 56 Caucasian patients with rectal cancer. The relationship between the ER and VDR genotypes and the expression of oncogenes was also investigated. The presence of the x allele of ER gene significantly correlated with the overexpression of the erbB-2 and EGFR oncogenes. Significantly increased erbB-2 expression was observed in patients with the VDR B allele. The XXbb allelic combination of the ER/VDR genes was associated with a significantly lower erbB-2 expression, whereas in the other genotypes significantly higher oncogene expression was seen. Our data raise the possibility that ER/VDR gene polymorphisms accompanied by variable oncogene expression might influence the pathogenetic processes of colorectal cancers.

Adult↗