Biomedical subjects

S Varga

Publications and source records attributed to S Varga.

At least 19 recordsLinked to original sources

PubMed2006

Women with polycystic ovary syndrome are sensitive to the TNF-alpha-lowering effect of glucose-induced hyperinsulinaemia.

BACKGROUND: Restoration of near-euglycaemia by intensive insulin therapy results in decreased serum levels of inflammatory mediators. The authors investigated whether the anti-inflammatory effect of insulin was independent of its glucose-lowering action and if this effect was intact in insulin-resistant women with the polycystic ovary syndrome (PCOS) characterized by low-grade chronic inflammation. MATERIALS AND METHODS: Blood was drawn on the third and sixth days after progestin-induced withdrawal bleeding in 20 young non-diabetic women with PCOS and once between the third and sixth days of the menstrual cycle in 21 age-matched lean healthy control women during a 75-g oral glucose tolerance test (oGTT). Serum insulin, glucose and tumour necrosis factor alpha (TNF-alpha) concentrations were measured after 0, 30, 60, 90 and 120 min. RESULTS: The increase in insulin and glucose concentrations during the oGTT was significantly more pronounced in patients with PCOS (one patient with impaired fasting glucose, one patient with impaired glucose tolerance, three patients with both) compared with healthy controls. The TNF-alpha serum concentrations decreased in patients with PCOS (mean of both days, P = 0.004). In patients and in controls, there was an inverse correlation between the serum concentrations of insulin and of TNF-alpha during oGTT (for patients, a mean of both days, P = 0.009; for controls, P = 0.047), but not between the serum concentrations of glucose and TNF-alpha. CONCLUSIONS: The decrease in TNF-alpha concentrations during oGTT and the inverse correlation between endogenous hyperinsulinaemia and serum TNF-alpha concentrations suggested an anti-inflammatory effect of moderately-high insulin concentrations. This occurred despite the presence of moderate hyperglycaemia. These findings also demonstrated a preserved responsiveness of inflammatory mediators to insulin in PCOS.

Adult↗

PubMed2005

Study of the inhibitory effect of the product dihydroxyacetone on Gluconobacter oxydans in a semi-continuous two-stage repeated-fed-batch process.

The influence of the product inhibition by dihydroxyacetone (DHA) on Gluconobacter oxydans for a novel semi-continuous two-stage repeated-fed-batch process was examined quantitatively. It was shown that the culture was able to grow up to a DHA concentration of 80 kg m(-3) without any influence of product inhibition. The regeneration capability of the reversibly product inhibited culture from a laboratory-scale bioreactor system was observed up to a DHA concentration of about 160 kg m(-3). At higher DHA concentrations, the culture was irreversibly product inhibited. However, due to the robust membrane-bound glycerol dehydrogenase of G. oxydans, product formation was still active for a prolonged period of time. The reachable maximum final DHA concentration was as high as 220 kg m(-3). The lag phases for growth increased exponentially with increasing DHA threshold values of the first reactor stage. These results correlated well with fluorescence in situ hybridization (FISH) measurements confirming that the number of active cells decreased exponentially with increasing DHA concentrations.

Bioreactors↗

PubMed2003

Colocalization and nonrandom distribution of Kv1.3 potassium channels and CD3 molecules in the plasma membrane of human T lymphocytes.

Distribution and lateral organization of Kv1.3 potassium channels and CD3 molecules were studied by using electron microscopy, confocal laser scanning microscopy, and fluorescence resonance energy transfer. Immunogold labeling and electron microscopy showed that the distribution of FLAG epitope-tagged Kv1.3 channels (Kv1.3/FLAG) significantly differs from the stochastic Poisson distribution in the plasma membrane of human T lymphoma cells. Confocal laser scanning microscopy images showed that Kv1.3/FLAG channels and CD3 molecules accumulated in largely overlapping membrane areas. The numerical analysis of crosscorrelation of the spatial intensity distributions yielded a high correlation coefficient (C = 0.64). A different hierarchical level of molecular proximity between Kv1.3/FLAG and CD3 proteins was reported by a high fluorescence resonance energy transfer efficiency (E = 51%). These findings implicate that reciprocal regulation of ion-channel activity, membrane potential, and the function of receptor complexes may contribute to the proper functioning of the immunological synapse.

Animals↗

PubMed2001

Cell fusion experiments reveal distinctly different association characteristics of cell-surface receptors.

The existence of small- and large-scale membrane protein clusters, containing dimers, oligomers and hundreds of proteins, respectively, has become widely accepted. However, it is largely unknown whether the internal structure of these formations is dynamic or static. Cell fusion was used to perturb the distribution of existing membrane protein clusters, and to investigate their mobility and associations. Scanning near-field optical microscopy, confocal and electron microscopy were applied to detect the exchange of proteins between large-scale protein clusters, whereas photobleaching fluorescence energy transfer was used to image the redistribution of existing small-scale membrane protein clusters. Large-scale clusters of major histocompatibility complex (MHC)-I exchanged proteins with each other and with MHC-II clusters. Similarly to MHC-I, large-scale MHC-II clusters were also dynamic. Exchange of components between small-scale protein clusters was not universal: intermixing did not take place in the case of MHC-II homoclusters; however, it was observed for homoclusters of MHC-I and for heteroclusters of MHC-I and MHC-II. These processes required a fluid state of the plasma membrane, and did not depend on endocytosis-mediated recycling of proteins. The redistribution of large-scale MHC-I clusters precedes the intermixing of small-scale clusters of MHC-I indicating a hierarchy in protein association. Investigation of a set of other proteins (alpha subunit of the interleukin 2 receptor, CD48 and transferrin receptor) suggested that a large-scale protein cluster usually exchanges components with the same type of clusters. These results offer new insight into processes requiring time-dependent changes in membrane protein interactions.

Cell Fusion↗

PubMed2000

Density Functional Theory and the Capillary Evaporation of a Liquid in a Slit.

Density functional theory is applied to a Lennard-Jones fluid near a single hard wall and in a slit formed by two walls. We use some simplified versions of the Weeks-Chandler-Andersen (WCA) and the Barker-Henderson (BH) theories. Only the most crude mean field version of the WCA theory, in which the hard-sphere correlation function is set equal to unity for all distances, seems useful. Use of the full WCA approximation is impractical because the effective hard-sphere diameter is density dependent. Generally, the best results are obtained using the BH macroscopic compressibility approximation. Our earlier study of "evaporation" of Lennard-Jones molecules in a slit is extended to other densities using the mean field theory. Copyright 2000 Academic Press.

Journal Article↗

PubMed2000

Design, synthesis, and structure-activity relationships of phthalimide-phenylpiperazines: a novel series of potent and selective alpha(1)(a)-adrenergic receptor antagonists.

Beginning from the screening hit and literature alpha(1)-adrenergic compounds, a hybridized basic skeleton A was proposed as the pharmacophore for potent and selective alpha(1a)-AR antagonists. Introduction of a hydroxy group to increase the flexibility afforded B which served as the screening model and resulted in the identification of the second-generation lead 1. Using the Topliss approach, a number of potent and selective alpha(1a)-AR antagonists were discovered. In all cases, binding affinity and selectivity at the alpha(1a)-AR of S-hydroxy enantiomers were higher than those of the R-hydroxy enantiomers. As compared to the des-hydroxy analogues, the S-hydroxy enantiomers had slightly lower binding affinity at alpha(1a)-AR but gained more than 2-fold selectivity for alpha(1a)-AR over alpha(1b)-AR, and 2- to 6-fold selectivity for alpha(1a)-AR over alpha(1d)-AR. They also had less cross activities against a panel of 25-35 peripheral and CNS receptors. The S-hydroxy enantiomers 23 and 24 (K(i) = 0.29 nM, 0.33 nM; alpha(1b)/alpha(1a) >5690, >6060; alpha(1d)/alpha(1a) = 186, 158, respectively) were slightly less potent but much more selective at alpha(1a)-AR than tamsulosin (K(i) = 0.13 nM, alpha(1b)/alpha(1a) = 14.8, alpha(1d)/alpha(1a) = 1.4). In the functional assay, the S-hydroxy enantiomers 20, 23, and 24 were less potent than tamsulosin in inhibiting contractions of rat prostate tissue but more selective in the inhibition of tissue contractions of rat prostate versus rat aorta. Compound 24 was selected as the development candidate for the treatment of BPH.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed2000

Cholesterol-dependent clustering of IL-2Ralpha and its colocalization with HLA and CD48 on T lymphoma cells suggest their functional association with lipid rafts.

Immunogold staining and electron microscopy show that IL-2 receptor alpha-subunits exhibit nonrandom surface distribution on human T lymphoma cells. Analysis of interparticle distances reveals that this clustering on the scale of a few hundred nanometers is independent of the presence of IL-2 and of the expression of the IL-2R beta-subunit. Clustering of IL-2Ralpha is confirmed by confocal microscopy, yielding the same average cluster size, approximately 600-800 nm, as electron microscopy. HLA class I and II and CD48 molecules also form clusters of the same size. Disruption of cholesterol-rich lipid rafts with filipin or depletion of membrane cholesterol with methyl-beta-cyclodextrin results in the blurring of cluster boundaries and an apparent dispersion of clusters for all four proteins. Interestingly, the transferrin receptor, which is thought to be located outside lipid rafts, exhibits clusters that are only 300 nm in size and are less affected by modifying the membrane cholesterol content. Furthermore, transferrin receptor clusters hardly colocalize with IL-2Ralpha, HLA, and CD48 molecules (crosscorrelation coefficient is 0.05), whereas IL-2Ralpha colocalizes with both HLA and CD48 (crosscorrelation coefficient is between 0.37 and 0.46). This coclustering is confirmed by electron microscopy. The submicron clusters of IL-2Ralpha chains and their coclustering with HLA and CD48, presumably associated with lipid rafts, could underlie the efficiency of signaling in lymphoid cells.

Antigens, CD↗

PubMed2000

Design, synthesis and biological evaluation of pyridine-phenylpiperazines: a novel series of potent and selective alpha1a-adrenergic receptor antagonist.

Beginning from the screening hit and literature alpha1-adrenergic compounds, a hybridized basic skeleton A was proposed as the pharmacophore for potent and selective alpha1a-AR antagonists. Introduction of a hydroxy group to increase the flexibility afforded B which served as the screening model and resulted in the identification of the second-generation lead 1. Using the Topliss approach, a number of potent and selective alpha1a-AR antagonists were discovered. In all cases, binding affinity and selectivity at the alpha1a-AR of S-hydroxy enantiomers were higher than the R-hydroxy enantiomers. As compared to the des-hydroxy analogues, the S-hydroxy enantiomers displayed comparable potency and better selectivity at alpha1a-AR. The S-hydroxy enantiomer 17 (Ki = 0.79 nM; alpha1b/alpha1a = 800; alpha1d/alpha1a = 104) was slightly less potent but much more selective at alpha1a-AR than tamsulosin (Ki = 0.13 nM, alpha1b/alpha1a = 15, alpha1d/alpha1a = 1.4). Compound 17 displayed higher selectivity in inhibiting rat prostate contraction over rat aorta contraction and also exhibited a higher degree of uroselectivity than tamsulosin in the anesthetized dog model.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed2000

Reconstruction following radical maxillectomy with flaps supplied by the subscapular artery.

The authors present their experience of 27 cases with repairs of defects following radical maxillectomies with free flaps. A total of 28 flaps were used (five latissimus dorsi, six scapula, 16 combination flaps of scapula and latissimus dorsi and one combination of scapula, latissimus dorsi and serratus anterior flap). Only one scapula flap was completely lost and in three cases where a combination of scapula and latissimus dorsi flap was used, partial necrosis of one component occurred. The authors first choice for reconstruction is a scapula bone flap raised on the angular artery combined with the latissimus dorsi flap. The combination of flaps with a long pedicle and of the bony and muscular components provides the surgeon with the option of customizing the flap to meet individual patient needs. For intraoral closure the authors prefer the latissimus dorsi muscle which rarely requires secondary procedures for prosthesis placement following epithelialization and atrophy. The main disadvantage of the flap is the difficulty of two teams working simultaneously, thus increasing the average operating time. All postoperative corrections and prosthetic rehabilitation should be postponed for at least 2 months following surgery because of postoperative swelling.

Adolescent↗

PubMed1998

The effect of heat shock on the formaldehyde cycle in germinating acorns of European Turkey oak.

The effect of heat shock (40 degrees C) on the formaldehyde cycle has been studied in European Turkey oak (Quercus cerris L.) acorns germinated to a 10% increase in mass. Hydroxy-methyl groups bonded to sulfur, oxygen and nitrogen atoms were made to react with dimedone and the derivative obtained (formaldemethone), which represented the endogenous formaldehyde level, was determined by high performance liquid chromatography. Qualitative alterations of methyl donors and acceptors in the response of acorns to the heat shock have been mapped by MALDI (matrix assisted laser desorption ionization) mass analysis. In the first experiment the acorns were prevented from withering by wrapping them in aluminium foil and in the second they were not. The relatively high temperature of the acorns wrapped in aluminium foil was the dominant stress effect and the role of withering was subsidiary. Alteration of the endogenous formaldehyde level in the seed-leaves reflected the phases of the stress syndrome. If the withering were not hindered, two local minima in the alteration of endogenous formaldehyde level were found. First, the increase in temperature decreased the endogenous formaldehyde level and after a local maximum a repeated local minimum was observed as a delayed response. It is presumed that the second minimum was induced by the decreasing water amount becoming more and more significant in the seed-leaves.

Chromatography, High Pressure Liquid↗

PubMed1998

Changes in formaldehyde contents of germinating acorns of Quercus cerris L. under low temperature stress conditions.

Acorns of Quercus cerris L., after saturation with water and storage at -20 degrees C, were studied for changes in their contents of endogenous formaldehyde and its potential precursor and generator compounds. For the measurement of formaldehyde, after conversion to formaldemethone and some methyl acceptor and donor substances, high performance liquid chromatography (HPLC) were used. First, the amount of formaldehyde was drastically decreased. Having reached a minimum value within three to five days of the beginning of low temperature storage, a higher steady-state than the control acorns was recorded. Trigonelline and gamma-amino-butyric acid in seedleaf extracts were identified by matrix assisted laser desorption-ionization mass spectrometry (MALDI-MS).

Chromatography, High Pressure Liquid↗

PubMed1998

[Dental implications in radiotherapy of hear aand neck tumors].

The authors describe the side-effects and complications occurring in the oral cavity during the irradiation treatment of head and neck tumours. They stress the necessity of dental therapy before, during and after irradiation so that occasional subsequent grave complications (for instance osteoradionecrosis) could be prevented. They emphasize the importance of basic radiological knowledge of dental surgeons and dentists and their cooperation with the irradiation therapists.

Head and Neck Neoplasms↗

PubMed1997

HLA class I and II antigens are partially co-clustered in the plasma membrane of human lymphoblastoid cells.

Major histocompatibility complex (MHC) class II molecules displayed clustered patterns at the surfaces of T (HUT-102B2) and B (JY) lymphoma cells characterized by interreceptor distances in the micrometer range as detected by scanning force microscopy of immunogold-labeled antigens. Electron microscopy revealed that a fraction of the MHC class II molecules was also heteroclustered with MHC class I antigens at the same hierarchical level as described by the scanning force microscopy data, after specifically and sequentially labeling the antigens with 30- and 15-nm immunogold beads. On JY cells the estimated fraction of co-clustered HLA II was 0.61, whereas that of the HLA I was 0.24. Clusterization of the antigens was detected by the deviation of their spatial distribution from the Poissonian distribution representing the random case. Fluorescence resonance energy transfer measurements also confirmed partial co-clustering of the HLA class I and II molecules at another hierarchical level characterized by the 2- to 10-nm Förster distance range and providing fine details of the molecular organization of receptors. The larger-scale topological organization of the MHC class I and II antigens may reflect underlying membrane lipid domains and may fulfill significant functions in cell-to-cell contacts and signal transduction.

Cell Membrane↗

PubMed1995

[Lymphoepithelial carcinoma of the nasolacrimal duct--a case report].

PATIENT: A 59-year-old patient with an extremely rare lymphoepithelioma of the nasolacrimal duct was treated with radiation therapy and chemotherapy. RESULTS: A complete remission was achieved. Serious side effects and late effects have, until now, not been observed. The patient has been free of tumor for two and a half years. CONCLUSIONS: With this case report, the authors wish to draw the attention of otorhinolaryngologists to this unusual tumorsite. They emphasize that good results can be achieved with a combination of radiation therapy and chemotherapy, if surgery is not possible.

Carcinoma, Squamous Cell↗

PubMed1995

Neomycin-induced perception deafness following bladder irrigation in patients with end-stage renal disease.

OBJECTIVE: To report a serious side-effect of intravesical instillations of neomycin in patients with end-stage renal disease. PATIENTS AND METHODS: Three patients (two men and a woman, aged 51.71 and 54 respectively) with end-stage renal disease who had undergone bladder irrigation with neomycin sulphate solution suffered complete irreversible deafness, which was assessed by audiogram. RESULTS: All three patients developed complete perception deafness after 3, 4 and 10 months, with characteristic changes in the audiogram. The severe progressive hearing loss was maximal in the high-frequency range. A high-pitched tinnitus was the first sign of impending hearing difficulty and two patients developed a spontaneous nystagmus. CONCLUSION: In view of the doubtful efficacy and, most importantly, the risk of severe disabling side-effects such as ototoxicity, we recommend the avoidance of intravesical instillation with neomycin whenever possible.

Administration, Intravesical↗

PubMed1994

Similarity of three-dimensional microcrystals of detergent-solubilized (Na+,K+)-ATPase from pig kidney and Ca(2+)-ATPase from skeletal muscle sarcoplasmic reticulum.

Image analysis has been used to compare the projection structure of three-dimensional crystals of (Na+,K+)-ATPase from pig kidney and the Ca(2+)-ATPase from rabbit muscle sarcoplasmic reticulum. These crystals, formed from detergent-solubilized protein in the presence of 20% glycerol and at a low detergent to protein ratio, crystallize in nearly identical unit cells in the space group C2. Average cell dimensions for the Ca(2+)-ATPase were a = 166.8 +/- 4.5 A, b = 57.7 +/- 4.4 A, gamma = 90 degrees while those for the (Na+,K+)-ATPase were a = 166.2 +/- 3.8A, b = 54.25 +/- 3.5A, gamma = 90 degrees. Their projected structures at the resolution of 25-A resolution are indistinguishable. Thus, the (Na+,K+)-ATPase crystals appear to contain only the alpha chain of the alpha beta heterodimer found in native membranes. We conclude from this that the three-dimensional structure of the alpha chain of the (Na+,K+)-ATPase is very similar to that of the Ca(2+)-ATPase despite their relatively weak overall sequence homology.

Animals↗

PubMed1994

Spontaneous rupture of the kidney: a report on 5 cases.

Five cases of spontaneous rupture of the renal parenchyma are reported. Two patients had renal cell cancer, one sustained acute purulent pyelonephritis secondary to stone related ureteral obstruction, one suffered from aposthematous pyelonephritis without obstruction, while one had chronic pyelonephritis and a cortical cyst as probable predisposing factors. Aetiology and important points concerning diagnosis and therapy are discussed.

Adult↗

PubMed1994

Three-dimensional (type I) microcrystals of detergent-solubilized membrane-bound gastric (H+, K+)-ATPase enzyme from hog and rabbit stomachs.

Multilamellar 3-dimensional (Type I) microcrystals of detergent-solubilized crude microsomes or purified protein preparations of membrane-bound gastric (H+, K+)-ATPase from rabbit or hog stomachs develop in media consisting of 0.1 M KCl, 20 mM imidazole, 5 mM MgCl2, 3 mM NaN3, 5 mM DTT, 25 IU/ml Trasylol, 2 micrograms/ml DTBpC and 20-40% glycerol, using nonionic detergent of C12E8 or BRIJ 36 for solubilization. Crystals developed in a pH-range of 6.0-7.25, during 3-10 days of incubation, at 2 degrees C. For C12E8, the most effective detergent:protein ratio for crystallization varied between (1.8-2.0):1 for the microsomes and between (0.25-0.75):1 for the purified preparations. The results of biochemical and structural analysis of the (H+, K+)-ATPase crystals showed close resemblance to those of the sarcoplasmic reticulum Ca(2+)-ATPase from skeletal muscle and plasmamembrane (Na+, K+)-ATPase from kidney (J. Biol. Chem., 269, 10107-111, 1994). Based on these identities and the high (62%) overall sequential homology to the (Na+, K+)-ATPase, we conclude that the new crystals of the (H+, K+)-ATPase could also contain only the alpha-chain of the alpha beta heterodimers found in the native membrane. High-resolution electron microscopy of frozen-hydrated crystalline (H+, K+)-ATPase samples are in progress to give unit cell dimensions and molecular packing of the new crystals.

Animals↗