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Biomedical subjects

Z Varga

Publications and source records attributed to Z Varga.

At least 73 records · Page 4Linked to original sources

[Molecular genetics of gliomas].

Gliomas represent the majority of primary central nervous system tumors in adults. The moderate overall impact of conventional therapeutic regimens on these inherently aggressive neoplasms raises the need for a direct intervention in the biology of neoplastic change. In the last decade important achievements in the molecular genetic basis of deregulated cell-cycle have been brought about, the neuro-oncologic implications of which are reviewed here. Loss of equilibrium between promoting factors and negative control of mitosis emergeus as a general principle, with gene amplification-overexpression operating in the former group, while deletions, loss of function-type mutations and post-transcriptional events prevail at the opposite pole. Damage to regulatory mechanisms will result, as a major consequence, in transgression of one or more of the so-called restriction points of the cell-cycle. Lesions of the genome are further ramified by supracellular processes involving autocrine and paracrine growth-stimulating loops. Malignant progression of gliomas, therefore, can be envisaged as a cumulative sequence of genetic alterations and interactions of tumor cells with their microenvironment.

Adult↗

[Immobilizing muscle weakness accentuated in leg and proximal muscles].

A 54 year old waiter was referred to the hospital because of proximal muscle weakness, most pronounced in his legs, which progressed to an inability to stand or walk within weeks. Myopathy was diagnosed based on the muscle biopsy findings and myositis was ruled out by laboratory and biopsy results. Further investigations led us to exclude an endocrine cause, hypovitaminosis D, infectious myopathy or a paraneoplastic syndrome. Heteroanamnesis revealed severe alcoholism, lasting for more than 30 years. The presumed alcohol induced hepatopathy was confirmed by liver biopsy. There were no signs of an acute alcoholic myopathy, as the weakness had developed rather insidiously, there was no elevation of the CK serum level nor myoglobinuria and a type 2 fibre atrophy was found by muscle biopsy. As expected the weakness improved under abstention. Thus the final diagnosis of a chronic alcohol induced myopathy was established.

Alcoholism↗

[Prognostic markers in the histopathological diagnosis of tumors of the choroid plexus].

Markers of cell proliferation (MIB-1), differentiation (S-100 protein, cytokeratin, transthyretin, GFAP, EMA, CEA), and cell adhesion (CD44) were analyzed immunohistochemically in a biopsy series of 21 chorioid plexus tumors determine their correlation with histological grade and impact on clinical course. The material included 8 papillomas (WHO grade I) and 8 carcinomas (WHO grade III); another 5 tumors were tentatively classified as atypical papilloma. The MIB-1 labeling index of papillomas was 3.7%, while that of carcinomas was 14%. Atypical papillomas (mean: 6%) failed to segregate as a statistically different group. The age and sex of patients, and tumor localization were found not to influence MIB-1 reactivity. High MIB-1 labeling indexes were associated with less favourable postoperative outcome. S-100 protein immunoreactivity was generally reduced in carcinomas, while most tumors were positive for transthyretin and cytokeratin irrespective of their MIB-1 status. Positivity for GFAP and EMA was detected in some tumors of both low- and high grade. CEA was universally negative. The standard isoform of CD44 was only expressed in atypical papillomas and 4 carcinomas showing focal infiltration of adjacent tissues. Western-blot analysis was also carried out in 5 cases to detect CD44. Quantitation of MIB-1 immunohistochemistry may, thus, prove a more readily accessible ancillary method for assessing chorioid plexus neoplasms than analysis of differentiation markers. Our data also suggest that expression of CD44H is instrumental in conferring invasive potential to these tumors and possibly contributes to tumor progression as well.

Adolescent↗

Pandinus imperator scorpion venom blocks voltage-gated K+ channels in human lymphocytes.

Using the patch-clamp technique, we determined that Pandinus imperator scorpion venom blocked whole-cell n-type K+ currents in human peripheral blood lymphocytes in a dose-dependent manner with Kd = 0.02 microgram/ml. K+ channel block was instantaneous and removable by washing with venom-free extracellular solution. The venom-induced block was independent of membrane potential. The venom did not influence activation and inactivation kinetics of the K+ channels, however, accelerated recovery from inactivation. Purified peptides Pi1, Pi2, and Pi3 from the P. imperator venom powerfully blocked Kv1.3 channels in human lymphocytes with Kd values of 9.7 nM, 50 pM, and 0.5 nM, respectively. Flow cytometric membrane potential measurements with the oxonol dye showed that Pi2, the most effective peptide toxin of the P. imperator venom, depolarizes human lymphocytes in accordance with its K+ channel blocking effect.

Barbiturates↗

[Teratoid/rhabdoid tumor of the central nervous system].

Teratoid/rhabdoid tumor is a recently introduced infantile brain neoplasm of uncertain origin clinically characterized by a most aggressive course. We describe the case of a 2-year-old boy and a 7-year-old girl, the former presenting with central fever and hemiparesis, while vomiting and headache were symptoms in the latter. A brain tumor in the right fronto-parieto-occipital and the left fronto-medial parenchyma, respectively, were found and removed by surgery. On histology, both lesions consisted of sheets of ovoid cells with prominent cytoplasm, vesicular nuclei and macronucleoli. In the second case, a spindle-cell component and bone metaplasia were also noted. Ultrastructurally, tumor cells contained whorls of intermediate filaments. Immunohistochemistry revealed a polyphenotypic expression profile including positivity for epithelial membrane antigen, vimentin and a-actin. There was no evidence of a germ-cell origin. Chromosomal translocation involving 22q11 was established cytogenetically in the first case. The teratoid/rhabdoid tumor shares many common traits with renal rhabdoid tumors and primitive neuroectodermal tumors as well as germ cell neoplasms; therefore its being an entity is debated.

Brain Neoplasms↗

Metaplastic lipid-rich carcinoma of the breast.

A case of lipid-rich mammary carcinoma identified in a lumpectomy specimen from a 56-year-old female is presented. The tumor showed features of poorly differentiated invasive ductal carcinoma of clear-cell phenotype. Cytoplasmic lucency was mainly accounted for by the accumulation of neutral fat and, to a lesser degree, glycogen. Tinctorial properties included positivity of tumor cells with Sudan III dye and diastase-sensitive periodic acid-Schiff staining. Ultrastructural examination confirmed the presence of abundant cytoplasmic lipid droplets and some glycogen rosettes. On immunohistochemistry, most tumor cells reacted for cytokeratin, vimentin and S-100 protein, and there was focal expression of carcinoembryogenic antigen. A minority of tumor cell nuclei expressed progesterone receptors. As an additional feature, part of the lesion exhibited chondroid metaplasia. Lipid-rich carcinoma of the breast is exceedingly rare and, to our knowledge, no such example harboring metaplastic elements has been described previously.

Biopsy, Needle↗

The serum paraoxonase activity in patients with chronic renal failure and hyperlipidemia.

Human serum paraoxonase is physically associated with an apolipoprotein (Apo-A1) and clusterin-containing high-density lipoprotein (HDL) and prevents low-density lipoprotein from lipid peroxidation. The aim of our study was to determine whether paraoxonase activity or phenotype is altered in patients with chronic renal failure and in hyperlipidemic subjects without renal insufficiency and to compare the values with those of healthy controls. We investigated the serum paraoxonase activity and polymorphism in 119 hemodialyzed uremic patients, 107 patients with primary hyperlipoproteinemia, and in 110 healthy control subjects. The serum paraoxonase activity was significantly decreased both in hyperlipidemic (p < 0.01) and uremic patients (p < 0.001) as compared with controls. On comparison, the serum paraoxonase activity was significantly lower (p < 0.001) in uremic than in hyperlipoproteinemic patients. The HDL and Apo-A1 levels were as follows: uremic < hyperlipidemic < control. To assess whether the observed reduction in paraoxonase activity was due to HDL and Apo-A1 level decreases, we standardized the enzyme activity for HDL and Apo-A1 concentrations. We found that the standardized paraoxonase activity (paraoxonase/HDL ratio) was also lower in the uremic patients (103.3 +/- 69.5) as compared with hyperlipidemic patients (137.64 +/- 81.0) and controls (194.45 +/- 94.45). The standardized values for Apo-A1 showed a similar tendency: paraoxonase/Apo-A1 ratio in uremic patients 89.64 +/- 47.8, in hyperlipidemic patients 128.12 +/- 69.83, and in controls 161.40 +/- 47.35. The phenotypic distribution of paraoxonase (AA, AB, BB) did not change significantly in the patient groups. These results suggest that HDL concentration and phenotypic distribution of paraoxonase may not be the only determining factors, but that other as yet undetermined factors could be involved in the enzyme activity changes.

Adult↗

Heterogeneous signal pathways through TSH receptors in porcine thyroid cells following stimulation with Graves' immunoglobulin G.

OBJECTIVE: We compared different signal transduction pathways through thyroid stimulating hormone receptor (TSH-R) in porcine thyroid cells (PTC) following stimulation with thyroid stimulating hormone (TSH) and 11 thyroid stimulating immunoglobulin samples (TSI) obtained from patients with Graves' disease. DESIGN: Following stimulation with TSI, the level of inositol trisphosphate (IP3) and [Ca2+]i, as well as the membrane bound protein kinase C (PKC) activity and the intensity of the arachidonic acid (AA) cascade, were determined in PTC. RESULTS: Seven out of eleven TSI samples activated PTC through IP3 generation, elevated [Ca2+]i from the intracellular pools, exhibited verapamil-insensitive membrane-bound PKC activation, and enhanced release of [14C]AA derivates (however, one of the samples was also able to take up Ca2+ from the extracellular space). Four out of eleven TSI samples did not activate the phospholipase C (PLC) system in which case the Ca2+ signal occurred only in the presence of extracellular Ca2+, the membrane bound PKC activation was verapamil sensitive, and in two of these four TSI samples, the AA release was extremely high. CONCLUSIONS: The simultaneous examination of the majority of the known signal pathways using TSI samples showed that TSI samples from different patients activate thyroid cells through different pathways. Their effects differ from that of TSH and, to a certain extent, from each other. The results give a certain new insight into the intracellular mechanisms exerted by TSI.

Adult↗

[Biologic effect of LDL binding and intracellular degradation in monocytes from patients with hypercholesterolemia].

The granulocytes from elderly patients were investigated, in previous studies, with FMLP and it was found that the postreceptor signal, the inositol phosphate production and inositol phosphate dependent calcium signal were markedly reduced. It was observed that the 125I LDL binding was slightly reduced while the intracellular degradation of the LDL and endogenous cholesterol synthesis inhibitory effect was significantly decreased on monocytes of patients with non insulin dependent diabetes mellitus. It was suggested that of in patients suffering from NIDDM with hypercholesterolemia the LDL receptor numbers of monocytes are close to normal, while the post receptor signal transmission is damaged. In this study the monocytes from 12 patients with hypercholesterolemia were investigated before and after LDL treatment and were compared to the 11 age-matched healthy volunteer control patients. The cells were stimulated with LDL and chemotactic peptide FMLP. The postreceptor signal mechanism in monocytes was investigated. According to the results the inositol phosphate level of the patient group decreased independently from the stimulus. The LDL induced IP3 and Ca2+ level elevation was PT resistant both in the control and in the patients group.

Aged↗

[Abnormal function of lipoprotein receptors in the monocytes of hypercholesteremic patients].

The familial hypercholesterinemia (HCh) is as a genetically determined disorder. The genetical damage and functional abnormalities of the LDL receptors lead to familial Hch. The LDL plays an important role in cholesterol metabolism. They carry cholesterol which metabolizes through specific and scavenger LDL receptors. The ApoB100 particle of LDL binds to the receptors, internalizated, and digested, and the remaining free cholesterol regulates the intracellular cholesterol synthesis. It inhibits the key enzyme, HMG-CoA reductase and decreases the LDL receptor synthesis and increases cholesterol esterification. These mechanism can prevent the cholesterol accumulation of the cells. The aim of the present study was to clarify the activity and number of the LDL receptor, to study the LDL binding and degradation and to evaluate how the intracellular cholesterol can regulate the synthesis in patients with HCh. 58 pts with HCh and their monocytes were investigated, because the monocyte derived macrophages contained both specific and scavenger receptors. Monocytes of the pts were compared to the healthy individual controls. From the results it could be recognized--that the decreased binding to the specific LDL receptors only at 6 pts cholesterol synthesis was elevated in HCh pts group, while the synthesis inhibition induced by 50 micrograms LDL was decreased. The presented experimental results suggested that the decreased binding ability to LDL receptors is a rare cause of cholesterol abnormalities, while during the intracellular degradation process more metabolic steps can be damaged in patients with HCh.

Cholesterol↗

[Granulocyte function and lipid peroxidation in untreated patients with hyperlipoproteinemia].

The fatty acid composition in free fatty acid and phospholipid fraction of plasma in untreated mildly hyperlipidemic patients were determined. The general trend was an increase in saturation in both free and phospholipid fractions of plasma in patients compared with that of healthy controls. Furthermore, arachidonic acid, precursor of formation of prostaglandins and leukotrienes was detected in significantly lower amount in plasma of mildly and untreated hyperlipidemic patients. These fatty acid abnormalities were connected with the increased lipidperoxidation in plasma lipids and in both resting and stimulated granulocytes.

Adult↗

[Pleomorphic xanthoastrocytoma].

Pleomorphic xantho-astrocytoma (PXA) is a relatively rare brain tumor of adolescents and young adults characterized by its superficial location with frequent involvement of the meninges, and its slow growth despite features of histological atypia. The authors present a retrospective immunohistochemical analysis of 8 surgically treated cases in order to determine the expression of glial and neuronal markers, and to assess the proliferating cell fraction. The study population comprised 1 female and 7 male patients with a mean age of 26.7 years, most tumors being located in one of the temporal lobes. Epilepsy predominated as a presenting symptom. Five cases were assigned WHO graded II, while the diagnosis of anaplasia (WHO grade III) was established in three, based either on elevated mitotic counts or the presence of necrosis. Immunostaining with the proliferation marker MIB-1 was present in 2.05% of cells in the former groups, while 4.66% showed labeling in the latter. Postoperative follow-up averaged 6.7 years, with only one recurrence of an anaplastic tumor. All tumors expressed some amount of glial fibrillary acidic protein and were shown to elaborate a characteristic pericellular reticulin network. There was focal reactivity for alpha-1-antitrypsin, but neither the monocyte-macrophage associated antigen CD68 nor lysozym could be detected in neoplastic cells. In 7 cases, scattered individual tumor cells exhibited synaptophysin positivity. The authors review problems and prognostic issues of the histologic diagnosis of anaplasia occurring in some 20% of the cases. A possible dysontogenic origin of PXA and its nosologic relationship to the so-called desmoplastic neuroepithelial tumors of infancy are discussed. This is the first study of pleomorphic xanthoastrocytoma in the Hungarian literature.

Adolescent↗

Pleomorphic xanthoastrocytoma with gangliogliomatous component.

We describe a composite glio-neuronal tumor comprising pleomorphic xanthoastrocytoma (PXA) and ganglioglioma identified in a left temporal biopsy. The 32-year-old male patient underwent surgery following a clinical history of persistent headaches of 6 years' duration. Immunohistochemical double labeling with antibodies to synaptophysin, beta-tubulin isotype III, GFAP and CD44H demonstrated neoplastic neurons and astrocytes in the ganglioglioma, while coexpression of glial and neuronal markers was found in a subset of PXA tumor cells variously showing giant cell or spindle cell morphology. There were gradual transitions between the two neoplastic populations. These findings raise the possibility of ganglioglioma having evolved by differentiation of bipotential PXA tumor cells along astrocytic and neuronal lineages. The PXA may, therefore, be closely related to desmoplastic neuroepithelial tumors of infancy, a group of neoplasms of presumed embryonal origin.

Adult↗

Allozyme variation in Parnassius mnemosyne (L.) (Lepidoptera) populations in North-East Hungary: variation within a subspecies group.

Allozyme polymorphism was studied in 11 Parnassius mnemosyne (Linnaeus, 1758) populations in North-East Hungary. Significant departures from Hardy-Weinberg equilibrium were observed in several cases due to heterozygote deficiency. Genetic variability did not display geographical pattern; the level of genetic differentiation was similar between adjacent populations and between populations originating from different geographical regions. Even a completely isolated population was not differentiated markedly from the others. Thus, genetic drift can be expected as the main evolutionary force acting in the populations.

Journal Article↗

Relative abundance of some free fatty acids in plasma of uremic patients: relationship between fatty acids, lipid parameters, and diseases.

The unesterified fatty acid patterns in plasma of predialytic (PHD) and hemodialysis (HD) patients were determined. The HD patients were divided into three groups: (1) HD without cardiovascular disease (HD-norm); (2) HD with cardiomyopathy (HD-CAD), and (3) HD with hyperlipidemia (HD-hyp). The relative abundance of saturated fatty acids (SFAs) was greater in the plasma of HD-norm and HD-CAD patients (73.3 and 70.0%, respectively) than that in controls (62.6%), and the relative abundance of monounsaturated fatty acids (MUFAs) was significantly greater in the plasma of HD-hyp patients than that in controls (38.9 vs. 21.6%, p < 0.01). In all HD patients the relative concentration of polyunsaturated fatty acids (PUFAs) was lower than in controls. There were no significant differences in the fatty acid patterns of PHD patients. In conclusion, the relative abundance of SFAs and MUFAs in plasma of HD patients is associated with their concomitant lipid disorders and cardiomyopathy, while the low relative abundance of PUFAs was common in all HD patients.

Cardiomyopathy, Dilated↗

[Neuropathology of Rasmussen syndrome].

Rasmussen's syndrome is a devastating epileptic disorder of young subjects characterized by pharmacoresistent partial sensorimotor convulsions, hemiparesis, and intellectual decline. The morphologic correlate of Rasmussen's syndrome is a chronic focal inflammation of the cerebral cortex leading to unilateral brain atrophy. The authors review light microscopic findings of three cases, where material was obtained by corticectomies of various extent. Patients included two young females, 6 and 8 years of age and a 21-year-old man with characteristic clinical features. Histology showed focal cortical infiltrates of lymphocytes, microglial nodules and neuronal loss with reactive gliosis. Immunohistochemically, lymphocytes were shown to be of T-cell lineage, while activated microglial cells were identified upon their expression of MHC II antigens. Prominent perivascular astrocytic reaction, as evidenced by the pattern of GFAP-staining, suggests recurrent injury to the blood-brain-barrier. The presence of Cytomegalovirus and Herpes simplex virus I and II could not be detected. The etiology of Rasmussen's syndrome is not known. The neuropathologic alterations, however, support the role of autoimmune-mediated neuronal excitotoxicity in its pathogenesis.

Adult↗