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Biomedical subjects

E Varga

Publications and source records attributed to E Varga.

At least 19 recordsLinked to original sources

Indoor radon in rural dwellings of the South-Pannonian region.

The results of indoor radon survey in the South-Pannonian Province Vojvodina (Serbia and Montenegro) are presented. The sampling strategy was oriented towards suburban and urban regions in the Province. For the dwellings typical for such regions the geometric mean annual radon activity concentration of 76.1 Bq m(-3) is measured (1000 measurements). This result leads to the annual dose estimate of 4.3 mSv y(-1), which is above the recommended action limit of ICRP. For urban dwellings in Novi Sad (the Province capital), the annual mean value of 54 Bq m(-3) (220 measurements) is obtained. By comparison of these two results it is concluded that radon surveys based on measurements in urban environment may seriously underestimate the radon-related health risk. The elevated radon levels could not be explained by elevated uranium levels of surface soil.

Air Pollutants, Radioactive↗

Radioactivity of the Bega sediment-case study of a contaminated canal.

The Bega canal is one among many heavily polluted canals in Vojvodina (the northern province of Serbia and Montenegro). In the framework of the revitalization of this canal, the radionuclide content of the sediment was investigated in order to support the safe deposition after excavation. It was found that, in comparison with the Danube sediment and Vojvodina soil, the Bega sediment is contaminated with (238)U and (137)Cs. The origin of this contamination is discussed. No traces of contamination by nuclear power plants in the region were found, while the presence of technologically enhanced, natural occurring radioactive materials (TENORM) was proved.

Background Radiation↗

Radioactivity of the soil in Vojvodina (northern province of Serbia and Montenegro).

The widespread public belief that during the bombardment of Vojvodina (Yugoslavia) this region was contaminated by depleted uranium has recently raised public concern with respect to the potential contamination of agricultural products due to soil radioactivity. Based on the gamma-spectrometric analysis of 50 soil samples taken from the region of Vojvodina we concluded that there is no increase of radioactivity that could endanger the food production. Taking into account the transfer factors of 137Cs to plants, the measured activity concentrations of this isotope should not endanger the health safety of the produced food. No traces of depleted uranium have been found. The natural radioactivity levels are compared with the results form other countries.

Cesium Radioisotopes↗

Establishment of the hu-PBL-SCID mouse model for the investigation of thyroid cancer.

New experimental models of human neoplastic diseases attempt to mimic the human environment that fostered the development of disease in cancer patients. The aim of the present study was to establish a human lymphocyte-engrafted, severe combined immunodeficient (hu-PBL-SCID) mouse model to investigate thyroid cancer and to evaluate the potential use of this model for cancer immunotherapy. Thyroid neoplastic tissues were obtained from ten patients (one follicular adenoma, five papillary, one follicular, one anaplastic and two medullary cancers). One 8 x 4 x 3 millimeter sample from each tumor was cut into two pieces of identical size and transplanted into two SCID mice. In each case, one of the two mice was injected intraperitoneally with lymphocytes from the same tumor patient for the reconstitution of the human immune system (Group A), while the other animal received no lymphocytes (Group B). The engraftment of the tumors was successful in all cases. The growth rate was highly dependent on the histological type. When histologies were compared before implantation and after the removal of the implants, the characters of the tumors proved to be unchanged, except one case where an anaplastic cancer arose from a papillary tumor. Macrophages were present in all but one papillary cancer. All differentiated thyroid cancers were infiltrated by T and B lymphocytes. Lymphocytes and macrophages disappeared from 19/20 grafts by week 16. However, in one case from group A lymphocytes were detected four months after the transplantation. In another case from group A, one papillary cancer spontaneously decreased in size and disappeared. Before implantation, HLA-DR expression was detected in every papillary cancer. HLA-DR expression in the grafts was not seen in 3/5 cases by week 16. In conclusion, an animal model has been established for the investigation of human thyroid cancer, by which the analysis of anti-tumor immunity, as a postulate of immune therapy, may be possible.

Adult↗

Nongenomic effect of thyroid hormone on free-radical production in human polymorphonuclear leukocytes.

Over the past few years increasing evidence has suggested the nongenomic effects of thyroid hormone, such as the activation of the signal transduction pathways and the activation of nuclear factor-kappaB by the induction of oxidative stress. The present study was undertaken to investigate the effect of thyroid hormone on human polymorphonuclear leukocytes (PMNLs) which are known as important sources of reactive oxygen species in the circulation. The production of superoxide anion (O2-) and the activity of myeloperoxidase were determined in the presence and absence of several inhibitors of the signalling pathway. L-thyroxine (T4) l-3,5,3'-tri-iodothyronine (T3) and L-3,5-di-iodothyronine (T2) stimulated O2- production in PMNLs in a dose-dependent manner within a few minutes of addition to cells. Thyroid hormone-stimulated O2- production was partially inhibited by pertussis toxin, an inhibitor of GTP-binding G protein, and was completely abolished by the protein kinase C inhibitors calphostin C and Ro-32-0432, and by a calcium chelator (BAPTA; bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid). Thyroid hormone stimulated myeloperoxidase activity and induced 125I- incorporation into PMNLs. Furthermore, thyroid hormone pre-incubation enhanced O2- production for n-formyl-methionyl-leucyl- phenylalanine (FMLP) stimulation. In conclusion, novel nongenomic actions of thyroid hormone, the induction of superoxide anion production and the stimulation of myeloperoxidase activity in PMNLs were demonstrated. The induction of O2- production requires calcium and is mediated by a pertussis toxin-sensitive G protein via stimulation of protein kinase C(s). These results suggest the existence of a membrane-bound binding site for thyroid hormone in PMNLs and a physiological role for thyroid hormone in the cellular defence mechanisms by stimulating free-radical production.

Adult↗

Cannabinoid CB(1) receptor expression, activation and detection of endogenous ligand in trabecular meshwork and ciliary process tissues.

Elevated intraocular pressure is the primary risk factor for glaucoma. Cannabinoids interact with molecular targets in the eye and lower intraocular pressure by an unknown mechanism. The purpose of the present study was to examine eye tissues for functional cannabinoid receptors of the neuronal, CB(1) class, and an endogenous ligand, anandamide. The trabecular meshwork and ciliary processes are the primary structures of the eye that contribute to intraocular pressure and thus were our focus. Total RNA, frozen sections, cellular membranes and primary cultures of cells were prepared from both bovine and cadaveric human tissues. Using cannabinoid CB(1) receptor-specific oligodeoxynucleotide primers, cannabinoid CB(1) receptor antiserum, and cannabinoid-specific compounds (CP-55,940, WIN55,212-2 and SR-141716A), the presence of cannabinoid CB(1) receptors in ciliary processes and trabecular meshwork was determined. Using reverse transcription-polymerase chain reaction, we identified mRNA encoding cannabinoid CB(1) receptor protein in ciliary process and trabecular meshwork cells. Specific binding of anti-CB(1) immunoglobulin-G in tissue sections localized cannabinoid CB(1) receptor protein to the non-pigmented epithelial cells of the ciliary process and cells of the trabecular meshwork. While CP-55,940 and WIN55,212-2 failed to stimulate [(35)S]GTP gamma S binding in membrane preparations from trabecular meshwork and ciliary process, CP-55,940 significantly stimulated whole cell [(35)S]GTP gamma S binding by 51% over basal in ciliary process epithelial cells and 69% over basal in trabecular meshwork cells permeabilized with 5 microM digitonin (p<0.001). Specificity of agonist stimulation was verified by complete blockade with the specific cannabinoid CB(1) receptor antagonist, SR-141716A. Moreover, activation of cannabinoid CB(1) receptors by CP-55,940 resulted in a 2.3+/-0.3 and 1.7+/-0.3-fold stimulation of cAMP accumulation in trabecular meshwork and ciliary process cells, respectively (p<0.01). Lastly, anandamide was detected in human trabecular meshwork (3.08 pmol/g), ciliary process (49.42 pmol/g) and neurosensory retinal (4.48 pmol/g) tissues. These data, for the first time, demonstrate in a single study the presence of both CB(1) mRNA and protein in trabecular meshwork and ciliary processes from two different species. Activation of heterotrimeric G-proteins and stimulation of cAMP accumulation by cannabinoids in vitro suggest that their intraocular pressure-lowering effects in vivo result from activation of cannabinoid CB(1) receptors in the trabecular meshwork and increase aqueous outflow.

Animals↗

[HLA genomic tissue typing in myasthenic patients with rheumatoid arthritis].

In a 36 years old male and a 56 years old female myasthenic patient thymectomy was performed several years ago. In the male patient 5, and in the female patient 7 years after the operation rheumatoid arthritis developed. The rheumatoid arthritis in the male patient was seropositive with marginal erosions in the carpometacarpal and in the tarsometatarsal joints. The female patient had no joint destruction and was seronegative as well. The female patient had also an abnormal ratio between the separated CD4 and CD8 T-cells. The major histocompatibility complex determined by the serological methods revealed a haplotype of HLA-A1-B8-D3-DQ2, which is typically due to the myasthenic disease. In the female patient the molecular analysis of the HLA-D region showed a HLA-DRB1* 0401 allele, which is frequently associated with rheumatoid arthritis. The male patient had no allelic variant which could be related to his chronic disabilitating joint disease.

Adolescent↗

[Malignant hemangiopericytoma with breast metastasis].

The authors report on a rare case of malignant hemangiopericytoma. A 56-year old female patient had developed a painless node on her left gluteal region 20 years ago. Years later, the resistance became tender and was subsequently surgically removed. On histology, the lesion was identified as malignant hemangiopericytoma. After a symptom-free period of 8 years distant pulmonary metastases arose, which were removed by surgery again. Shortly afterwards the patient manifested with further metastasis involving the lung again, as well as the abdomen, the skin and the breast, leading to the patient's death 2 years later. The authors review the literature, clinical course, diagnostic possibilities, prognosis and therapeutic options of malignant hemangiopericytomas. Special attention is drawn to the unexceptionally long clinical course at this particular malignancy, as well as to the late occurrence of metastases and their unusual breast localisation.

Breast Neoplasms↗

Confirmation of the presence of Mycoplasma bovis in Hungarian cattle with pneumonia resembling pleuropneumonia.

Cattle from several farms in Hungary were investigated for the presence of mycoplasmal infections after the discovery of pulmonary lesions in some animals at slaughter. The pneumonic lesions, which resembled those of contagious bovine pleuropneumonia (CBPP) macroscopically and histologically were found to be caused by Mycoplasma bovis and not Mycoplasma mycoides subspecies mycoides (MmmSC) which is the causative agent of CBPP. No other bacterial pathogens were isolated. Negative results in complement fixation tests also showed that there was no serological evidence of CBPP. PCR tests for the detection of the M mycoides cluster and specifically for MmmSC were also negative. However, PCR and bacteriological culture detected cases of M bovis and the pneumonias may therefore be attributed to this mycoplasma.

Animals↗

Description and mission evaluation of the Hungarian case-control surveillance of congenital abnormalities, 1980-1996.

BACKGROUND: The Hungarian Case-Control Surveillance of Congenital Abnormalities was established in 1980. This article describes how the Hungarian Case-Control Surveillance of Congenital Abnormalities was first organized and is currently maintained. The baseline statistics are provided and potential venues of postmarketing surveillance of drug teratogenicity and other public health tasks and research are proposed. METHODS: Cases with congenital abnormalities and patient controls with Down syndrome were selected from the Hungarian Congenital Abnormality Registry. Population controls without congenital abnormalities were selected from the National Birth Registry on the basis of three matching criteria: sex, week of birth, and district of parent's residence. Three sources of information concerning drug exposures, maternal disorders, and pregnancy complications, among others, were used: (1) prospective and medically recorded data from antenatal care logbooks and discharge summaries; (2) retrospective maternal self-reported data obtained with a structured questionnaire in all the three study groups; and (3) data collected by regional nurse in house visits to nonrespondent cases and patient controls. Twenty-five congenital abnormality groups were evaluated. During the 17-year period of data collection, 22,843 cases, 38,151 population controls, and 834 patient controls were incorporated into the data set, constituting the largest population-based case-control data set of congenital abnormalities to date. RESULTS: Demographic features of pregnant women and informative offspring are presented along with the distribution of 25 main groups of congenital abnormalities. CONCLUSIONS: This system is appropriate for postmarketing the surveillance of drug teratogenicity, for the improvement of congenital abnormality diagnosis, to get informed consent, to have a communication with parents and to provide material for research.

Abnormalities, Drug-Induced↗

Non-specific caspase inhibition reduces infarct size and improves post-ischaemic recovery in isolated ischaemic/reperfused rat hearts.

Myocardial ischaemia and reperfusion lead to myocardial cell death due, at least in part, to apoptotic mechanisms. Although cysteinyl aspartate-specific proteinase (caspase) activation is a major event and the most-cited culprit in the development of apoptosis, its potential contribution to ischaemic myocardial cell death is largely unknown. To study the role of caspase activation, isolated rat hearts (n=6 per group) were subjected to 30 min coronary artery occlusion followed by 120 min reperfusion. A non-selective [0.1 or 0.5 microM acetyl-Tyr-Val-Ala-Asp chloromethylketone (YVAD-cmk)] or selective caspase inhibitors [0.07 or 0.2 microM acetyl-Asp-Glu-Val-Asp-cmk (Ac-DEVD-cmk, caspase-3 inhibitor); 0.07 or 0.2 microM benzoxycarbonyl-Leu-Glu-OMe-His-Asp(OMe)-fluoromethylketone (z-LEHD-fmk, caspase-9 inhibitor)] were added to the perfusate at the start of reperfusion. Non-selective caspase inhibition with 0.1 or 0.5 microM YVAD-cmk limited infarct size: (21 +/- 4%, P<0.05; 17 +/- 3%, P<0.05, respectively) compared with the ischaemic/reperfused control (32 +/- 5%). In hearts treated with 0.1 or 0.5 microM caspase II non-selective inhibitor, the fraction of terminal-deoxynucleotidyl-transferase deoxyuridine nick end labelling (TUNEL)-positive myocyte nuclei in the infarcted zone was reduced from the ischaemic/reperfused non-treated control of 11.2 +/- 2.1% to 6.2 +/- 1.6% (P<0.05) and 1.2 +/- 0.2% (P<0.05), respectively. The recovery of post-ischaemic cardiac function (coronary flow, aortic flow and left-ventricular developed pressure) improved significantly with the application of the non-selective caspase inhibitor as well. In hearts perfused with specific caspase inhibitors (caspase-3 and caspase-9) there was no significant reduction in the infarct size, no improvement in post-ischaemic cardiac function and no reduction of apoptotic cell death. We conclude that non-specific inhibition of caspases may be therapeutically beneficial in myocardial ischaemia/reperfusion-induced damage, while selective caspase inhibitors may fail to prevent such reperfusion-induced injury in our model system.

Animals↗

Regulation of ventricular fibrillation by heme oxygenase in ischemic/reperfused hearts.

We have assessed the relationship between reperfusion-induced ventricular fibrillation (VF) and heme oxygenase (HO) mRNA expression using northern blotting, reverse transcription-polymerase chain reaction (RT-PCR), and enzyme activity in isolated working ischemic/reperfused rat hearts. Isolated hearts were subjected to 30 min of global ischemia followed by 120 min of reperfusion. Upon reperfusion with VF, cardiac function was registered (n = 6 in each group), and HO mRNAs and enzyme activities were measured at the end of reperfusion in hearts that showed VF or did not develop VF. The expression of HO-1 mRNA (about fourfold) was observed in ischemic/reperfused nonfibrillated myocardium in comparison with the nonischemic control hearts. In those hearts when VF was developed, the expression of HO-1 mRNA was not observed in comparison with the nonischemic control myocardium. The results measured by RT-PCR and enzyme analysis support the data obtained by northern blotting. In additional studies, we decided to approach the question from a different angle. Thus, the purpose of our work was also to study the role of HO expression and enzyme activity in electrically fibrillated hearts without the ischemic/reperfused protocol. To simulate the period of 10 min of reperfusion-induced VF, hearts were electrically fibrillated, then defibrillated, and perfused for an additional 110 min, and HO-1 mRNA expression and enzyme activities were determined. Thus, electrically induced VF resulted in about 60%, 60%, and 70% reduction in HO-1 mRNA expression, RT-PCR signal intensity, and enzyme activity, respectively, compared with the nonfibrillated ischemic/reperfused group. In conclusion, our data provide evidence that the development of reperfusion-induced VF inhibits HO-1 mRNA expression and enzyme activity in both electrically fibrillated myocardium and ischemic/reperfused fibrillated hearts. The results clearly show that HO-1 mRNA expression and enzyme activity were increased in ischemic/reperfused nonfibrillated myocardium, suggesting that interventions that are able to increase HO-1 mRNA expression and enzyme activity may prevent the development of VF.

Animals↗

Expression of alpha-transducin in Chinese hamster ovary cells stably transfected with the human delta-opioid receptor attenuates chronic opioid agonist-induced adenylyl cyclase superactivation.

To investigate the role of G-protein beta gamma subunits in delta-opioid signal transduction, we have transfected Chinese hamster ovary (CHO) cells stably expressing the human delta-opioid receptor (hDOR/CHO cells) with the G(alpha)-subunit of transducin-1 (hDOR/T1/CHO). Inhibition of forskolin-stimulated adenylyl cyclase and phospholipase C beta (PLC beta) activation was measured in each of these cell lines. Because PLC beta(3) activation in CHO cells has been shown to be mediated by free G(beta gamma) subunits derived from G(alpha i/o), the action of transducin was confirmed by measuring a significant attenuation of (+)-4-[(alpha R)-alpha-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC80)-mediated maximal inositol-1,4,5-trisphosphate formation in transducin-expressing cells of 59 +/- 12% compared with control cells. The acute inhibition of cAMP formation was unchanged between control and transducin-expressing cells. We show that cells stably expressing the human delta-opioid receptor exhibited a pertussis toxin-sensitive cAMP overshoot in response to chronic application of SNC80. After 4 h of pretreatment and washout with 100 nM SNC80, maximal forskolin-stimulated cAMP formation in hDOR/CHO cells increased by 229 +/- 37% compared with buffer-treated cells. Expression of transducin in hDOR/CHO cells diminished this response: hDOR/T1/CHO cells showed no significant change in maximal forskolin-stimulated cAMP formation after pretreatment and washout. These data indicate that the expression of alpha-transducin scavenges free G(beta gamma) subunits and, furthermore, that free G(beta gamma) subunits play a role in opioid-mediated PLC beta activation and adenylyl cyclase superactivation, but not acute inhibition of forskolin-stimulated cAMP formation in hDOR/CHO cells.

Adenylate Cyclase Toxin↗

The role of the G protein gamma(2) subunit in opioid antinociception in mice.

We examined the role of the gamma(2) subunit of G proteins (Ggamma(2)) in the antinociception produced by c[D-Pen(2), D-Pen(5)]enkephalin (DPDPE) in mice. DPDPE produced 84.0+/-9.0% antinociception in vehicle-treated mice. After intracerebroventricular (i.c.v.) treatment with an antisense phosphorothioate oligodeoxynucleotide to the Ggamma(2) subunit, DPDPE-mediated antinociception decreased to 24.4+/-7.4%. The mismatch phosphorothioate oligodeoxynucleotide-treated mice showed 65.1+/-10.3% antinociception, while the missense phosphorothioate oligodeoxynucleotide-treated mice showed 76.4+/-23.6% antinociception by DPDPE. The reduction of analgesia in antisense phosphorothioate oligodeoxynucleotide-treated mice was significant in comparison with vehicle-treated (P<0.001), mismatch phosphorothioate oligodeoxynucleotide-treated (P<0.01) and missense phosphorothioate oligodeoxynucleotide-treated (P<0.05) mice. These results suggest that the G protein gamma(2) subunit is involved in the transduction pathway leading to antinociception by DPDPE.

Analgesics, Opioid↗

Differential down-regulation of the human delta-opioid receptor by SNC80 and [D-Pen(2),D-Pen(5)]enkephalin.

We examined the contribution of the human delta-opioid receptor carboxyl terminal tail to (+)-4-[(alphaR)-alpha-((2S,5R)-4-allyl-2, 5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC80)- and cyclic[D-Pen(2),D-Pen(5)]enkephalin (DPDPE)-mediated receptor down-regulation. Both SNC80 and DPDPE mediated down-regulation of an epitope tagged human delta-opioid receptor. Truncation of the human delta-opioid receptor after Gly(338) blocked DPDPE-mediated down-regulation. However, SNC80 mediated significant down-regulation of the truncated receptor. These findings suggest that SNC80-mediated down-regulation involves receptor domains in addition to the carboxyl terminal tail.

Benzamides↗

Changes in echogenicity of spinal subarachnoid space associated with intracranial hemorrhage: new observations.

PURPOSE: The role of subarachnoid blood and secondary, sterile inflammation in the pathogenesis of posthemorrhagic hydrocephalus (PHH) is not well understood. The aims of this study were to study the frequency and rate of spread of blood into the spinal subarachnoid space (SSS) and to evaluate the relationship of this finding and PHH. MATERIALS AND METHODS: Nine premature babies with major intracerebral hemorrhage (ICH, grade 3 or higher), and ten premature infants with minor ICH (grade 1) or no evidence of ICH (control group) were identified and underwent serial cranial and spinal sonography at the time of initial diagnosis, 12-24 h after the ICH and weekly thereafter for at least 9 weeks. Sagittal and axial scans of the thoracolumbar spine were obtained and evaluated for the presence of echogenic debris in the dorsal SSS. Six additional patients who had cranial and spinal sonography died within the 1st week of life and underwent post-mortem examinations. RESULTS: The SSS was echo-free (normal) in all cases at the time of initial sonographic diagnosis of ICH. Within 24 h, all babies with major ICH had developed increased echogenicity of the cervical and thoracic SSS. Echogenicity of the SSS decreased gradually over several weeks. Although transient ventricular dilatation was present in every patient, only one patient had rapidly progressive PHH requiring shunt placement. Transient cysts of the cervicothoracic subarachnoid space were identified in two patients 6-7 weeks after ICH. The subarachnoid space remained echo-free in all control infants At autopsy, all four infants with echogenic spinal debris had blood or blood products in the spinal subarachnoid space, whereas two infants with echo-free spinal images did not. CONCLUSIONS: Spread of blood from the ventricular system into the spinal subarachnoid space after ICH is common and can be seen within 24 h of initial ICH. Subarachnoid blood is associated with post-hemorrhagic ventricular dilatation and transient spinal subarachnoid cyst formation.

Case-Control Studies↗

Plasmon resonance studies of agonist/antagonist binding to the human delta-opioid receptor: new structural insights into receptor-ligand interactions.

Structural changes accompanying the binding of ligands to the cloned human delta-opioid receptor immobilized in a solid-supported lipid bilayer have been investigated using coupled plasmon-waveguide resonance spectroscopy. This highly sensitive technique directly monitors mass density, conformation, and molecular orientation changes occurring in anisotropic thin films and allows direct determination of binding constants. Although both agonist binding and antagonist binding to the receptor cause increases in molecular ordering within the proteolipid membrane, only agonist binding induces an increase in thickness and molecular packing density of the membrane. This is a consequence of mass movements perpendicular to the plane of the bilayer occurring within the lipid and receptor components. These results are consistent with models of receptor function that involve changes in the orientation of transmembrane helices.

Biophysical Phenomena↗