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Biomedical subjects

M Balázs

Publications and source records attributed to M Balázs.

At least 19 recordsLinked to original sources
PubMed1997

Major histocompatibility complex class I protein conformation altered by transmembrane potential changes.

The nature of charge distributions in membrane-bound macromolecular structures renders them susceptible to interaction with transmembrane potential fields. As a result, conformational changes in such species may be expected to occur when this potential is altered. We have detected reversible conformational change in the major histocompatibility complex (MHC) class I antigen in the plasma membrane of human JY cells, as monitored by flow-cytometric resonance energy-transfer, upon reduction of the transmembrane potential (depolarization). This change increased the intramolecular energy-transfer efficiency between fluorescent donor- and acceptor-labeled monoclonal antibodies directed, respectively, to epitopes on the light (beta 2-microglobulin) and the heavy chains of the MHC class I antigen. Repolarization of the depolarized samples restored the energy-transfer efficiency to the original values measured before depolarization. Depolarization caused similar relative changes in fluorescence resonance energy-transfer efficiency when Fab fragments were used for labeling MHC class I complex, suggesting that the observed phenomenon is not restricted to whole monoclonal antibodies.

Antibodies, Monoclonal↗
PubMed1996

Depletion of intracellular calcium stores facilitates the influx of extracellular calcium in platelet derived growth factor stimulated A172 glioblastoma cells.

Calcium signaling in non-excitable cells is the consequence of calcium release from intracellular stores, at times followed by entry of extracellular calcium through the plasma membrane. To study whether entry of calcium depends upon the level of saturation of intracellular stores, we measured calcium channel opening in the plasma membrane of single confluent A172 glioblastoma cells stimulated with platelet derived growth factor (PDGF) and/or bradykinin (BK). We monitored the entry of extracellular calcium by measuring manganese quenching of Indo-1 fluorescence. PDGF raised intracellular calcium concentration ([Ca2+]i) after a dose-dependent delay (tdel) and then opened calcium channels after a dose-independent delay (tch). At higher doses (> 3 nM), BK increased [Ca2+]i after a tdel approximately 0 s, and tch decreased inversely with both dose and peak [Ca2+]i. Experiments with thapsigargin (TG), BK, and PDGF indicated that BK and PDGF share intracellular Ca2+ pools that are sensitive to TG. When these stores were depleted by treatment with BK and intracellular BAPTA, tdel did not change, but tch fell to almost 0 s in PDGF stimulated cells, indicating that depletion of calcium stores affects calcium channel opening in the plasma membrane. Our data support the capacitative model for calcium channel opening and the steady-state model describing quantal Ca2+ release from intracellular stores.

Becaplermin↗
PubMed1996

Chemistry of indoles carrying a basic function, Part 3. Synthesis of spiro[cyclopropane-1,3'[3H]indol]-2'(1'H)-ones with antihypoxic effects.

Hydroxyindolones (1-6, 15-16) were transformed into isatinylidenes (7, 9-13, 17-19) by dehydration with 4-toluenesulfonic acid. The dimer-type compounds (14, 20) were also isolated in a few cases. The obtained isatinylidenes were transformed into 3-spiro-cyclopropane-oxindoles (21-32) with dimethyloxosulfonium methylide. Compound 22 shows protective effects against hypobaric hypoxia and triethyltin induced brain edema.

Air Pressure↗
PubMed1995

ERBB-2 (HER2/neu) gene copy number, p185HER-2 overexpression, and intratumor heterogeneity in human breast cancer.

Amplification of the ERBB-2 (HER-2/neu) gene is accompanied by overexpression of its cell surface receptor product, p185HER-2. Heterogeneity has been observed for both the gene copy number and the level of overexpression of its protein product. To better understand their relationship, correlation between the level of cellular expression of p185HER-2 and ERBB-2 gene amplification was studied in four human breast cancer cell lines (BT-474, SK-BR-3, MDA-453, and MCF-7) and in a primary human breast tumor sample. The relative expression of p185HER-2 was measured by immunofluorescence by using flow and/or image cytometry while correlated DNA analysis was performed on the same cells by fluorescence in situ hybridization to determine ERBB-2 gene and chromosome 17 copy numbers. Marked heterogeneity was observed in both protein expression and ERBB-2 copy number. Despite this heterogeneity, and in accordance with previous studies, the average levels of p185HER-2 expression correlated well with average ERBB-2 gene copy numbers in the four lines examined (r = 0.99). When the relationship between copy number and protein expression was studied on a cell-by-cell basis, p185HER-2 expression correlated with both the absolute number of ERBB-2 gene copies/cell (r = 0.59-0.63) and chromosome 17 copy number (r = 0.45-0.61). It is of interest that there was weak or no correlation between p185HER-2 protein expression and the ERBB-2 copy number:chromosome 17 copy number ratio (r = 0.0-0.25). In more than one-half of cells expressing a high level of p185HER-2, the chromosome 17 copy number was high (two or three times the average copy number), whereas < 2% of an unselected population had a high chromosome 17 copy number. Bromodeoxyuridine incorporation indicated that the S-phase-labeling index was homogeneous across various p185HER-2-expressing subpopulations in the SK-BR-3 cell line. Analysis of the primary breast tumor sample showed results similar to the cell lines, supporting the strong possibility of a mechanistic link among p185HER-2 overexpression, ERBB-2 amplification, and high chromosome 17 copy number.

Breast Neoplasms↗
PubMed1995

Autofluorescence correction for fluorescence in situ hybridization.

Optimal sensitivity of fluorescence in situ hybridization (FISH) requires bright signals and low background fluorescence. Use of locus-specific probes is especially dependent on high sensitivity. Some tissue preparations show high autofluorescence, masking small or dim signals. We have developed a new method for subtracting autofluorescence from digital images on a pixel-by-pixel basis. It is based on the observation that fluorescent labels for FISH have narrower excitation and emission spectra than the chemical components responsible for autofluorescence. Our new approach uses calculation of the ratio of autofluorescence between multiple color images for correction of autofluorescence in each individual image. By subtracting autofluorescence components, we were able to enhance centromeric signals and make previously indistinguishable cosmid signals clearly visible. This image-processing approach to autofluorescence correction may widen the applicability of gene-specific probes in FISH analysis of tumor material.

Artifacts↗
PubMed1994

["Serrated" adenoma--a little known type of colorectal tumors].

Eight cases and review of the literature on serrated adenoma of the colon were reported. This distinct entity of colorectal tumors was described in recent years. The tumors contain hyperplastic and adenomatous areas. Their tendency for malignant transformation is similar to pure adenomas to contrary to benign hyperplastic polyps. Three tumors of eight reported cases were pedunculated, while five were sessile. Four patients were operated on because of narrowing of intestinal lumen by the tumors. Malignant transformation of tumors was observed in three cases. Several biopsies were performed before major operations. Histology showed false benign hyperplastic tumors. Importance of multiple tissue sample for histology was emphasised. Electron microscopy showed disturbed differentiation and pathological mucus production of tumor cells.

Adenoma↗
PubMed1994

Lateral organization of the ICAM-1 molecule at the surface of human lymphoblasts: a possible model for its co-distribution with the IL-2 receptor, class I and class II HLA molecules.

Lateral distribution of the ICAM-1 molecule and its topological relationship (mutual proximity) to the heavy and light chains of class I HLA molecules, HLA-DR and interleukin-2 receptor alpha-chain (IL-2R alpha) were studied in the plasma membrane of HUT-102B2 T and JY B lymphoblastoid cell lines by the technique of flow cytometric energy transfer (FCET). Effects of adherency and treatments with recombinant interferon-gamma or tumor necrosis factor-alpha on the relative expression level of ICAM-1 to the above cell surface proteins were also investigated. While the cytokines did not significantly affect the ICAM-1 level of either cell line, an increased ICAM-1 expression was found on adherent JY cells. The ICAM-1 expression varied significantly with the cell cycle and culture conditions, as well. The statistical analysis of the differences observed in the energy transfer efficiency histograms resulted in a possible model of lateral co-distribution of these proteins in the plasma membrane. These two-dimensional patterns proved to be different for T and B lymphoma lines. ICAM-1 molecules showed a high degree of self-association on HUT-102B2 (T) cells, while they were mainly expressed as monomers on the surface of JY (B) cells. Both cells showed a significant (ca. 30%) difference between densities of the heavy and light chains of class I HLA antigen, suggesting a substantial amount of beta 2-microglobulin free heavy chains on these cell lines. The class I HLA molecules also showed partial self-association, but on both cell lines. The beta 2-microglobulin and the heavy chain of the class I HLA showed strongly different proximities to the IL-2R alpha, HLA-DR and ICAM-1 molecules, indicating that their orientations relative to the other proteins are dissimilar. IL-2R alpha molecules of the HUT-102B2 (T) cells are located mostly in the vicinity of the beta 2-microglobulin. In contrast, the local density of HLA-DR antigens is higher in the proximity of the heavy chain than in the vicinity of the beta 2-microglobulin. The possible functional significance of these protein patterns is also discussed herein.

Antibodies, Monoclonal↗
PubMed1993

Bretylium differentiates between distinct signal transducing pathways in human lymphocytes.

The selection of signal transducing pathways of T cells depends on the type of triggers. Antigens, antibodies or lectins induce the T cell receptor-CD3 operated pathway, and IL-2 transmits its activation signal via the IL-2 receptor. It has been demonstrated that bretylium, a quaternary ammonium ion, can significantly inhibit the first pathway at the same dose range that stimulates cell activation through the IL-2 receptor system. In the light of the different complexity of the two pathways at the plasma membrane level, and the non-toxic and reversible behavior of the drug, it is suggested that the bretylium induced sustained membrane hyperpolarization is responsible for the observation. This finding may open new possibilities in studying the mechanism of different signal transducing pathways.

Blotting, Northern↗
PubMed1993

Hypo-osmotic shock induces an osmolality-dependent permeabilization and structural changes in the membrane of carp sperm.

We carried out spectrofluorimetric and flow cytometric measurements to investigate the effect of hypo-osmotic shock on cell membranes of common carp sperm. The time course of the permeability of the sperm cell membrane, as monitored by DNA-related propidium iodide (PI) fluorescence, was followed for 30 min after dilution of semen in hypo-osmotic environments of different ionic strengths. Spectrofluorimetric measurements indicated a continuous increase in the total PI emission intensity of a sperm suspension. Cell-by-cell flow cytometric measurements suggested that the permeability changes were of the all-or-none type. The permeabilized fraction of cells in the individual samples was time and osmolality dependent. The number and percentage of cells in which DNA was stained by PI increased gradually over time and reached a steady-state plateau value after 5-15 min. This equilibrium fraction of cells with a PI-permeable cytoplasmic membrane displayed an inverse relationship with the osmolality of the diluent, having a near 100% value for fresh water and distilled water. Dilution of sperm in hypo-osmotic medium brought about a fast decrease in the forward light-scattering signal on a short time scale compared to the pre-steady-state time of the permeabilization. With the addition of extracellular Ca2+ (1.8 mM), restoration of the light scattering signal was observed. Permeabilization of the membrane and restoration of light scattering were not coincident in time. We propose a two-dimensional reorganization of the lipid structure as the underlying mechanism of the latter process.

Animals↗
PubMed1993

Gastric vascular ectasia in cirrhosis.

Eight cases of upper gastro-intestinal bleeding associated with liver cirrhosis are reported in this paper. Morphological studies revealed gastroduodenal ulceration with severe vascular changes in the mucosa and submucosa layer. Capillary dilatation was seen in the superficial region of the mucosa. Thick-walled and tortuous vessels similar to angiodysplasia were noted in the submucosa. The latter vessels were surrounded by scar-like connective tissue considerably thickening the gastric submucous layer. It is assumed that scar-like thickening of the submucous layer surrounding the tele-angiectatic vessels causes microcirculatory disorders thus giving rise to bleeding ulcers.

Adult↗
PubMed1992

[Malignant fibrous hystiocytomas of unusual localizations].

25 cases of malignant fibrous histiocytomas of different localisation were diagnosed in the St. John's Hospital (Budapest, Hungary) in a 10-year period from 1982 to 1992. In the present study ten patients are reported with rare localisation of this tumor caused abdominal complications. Special attention is payed to diagnostic difficulties. The importance of morphological diagnosis is emphasized because modern therapeutic methods favourably influence the prognosis of this tumor.

Aged↗
PubMed1992

Dynamic physical interactions of plasma membrane molecules generate cell surface patterns and regulate cell activation processes.

Molecular interaction and transmembrane signal transducing events generate a very dynamic and ever changing "pattern" in the plasma membranes. Lymphocytes, the key functional elements of the immune system, are eminently suited to be the primary targets to investigate these proximity, mobility, or other physical-chemical changes in their plasma membranes. Recently, a number of experiments suggested that processed peptides from antigens can bind specific components of MHC molecules (Elliott et al., 1991). This is certainly a way to alter their structure. Cell surface patterns of topological nature, assembly and disassembly of oligomeric receptor structure like the IL-2 receptor have been investigated by sophisticated biophysical techniques. The dynamic changes in the two-dimensional cell surface pattern and intramolecular conformational changes within this "larger" macro-pattern may have a strong regulatory role in signal transducing and intercellular recognition processes. Recent data on these problems are presented together with brief and critical discussions.

Animals↗
PubMed1991

[Congestive gastropathy].

15 patients with congestive gastropathy were reported including clinical and pathological characteristics of the disease. Every patient had alcoholic liver cirrhosis and portal hypertension. 6 patient's stomach was resected while in 2 further cases the disease was found at autopsy. In additional 7 cases the characteristic microvascular changes were observed in endoscopic biopsy specimens from the gastric mucosa. The authors presume that this disease has an acute and a chronic stage. In the acute stage dilated capillaries are present under the surface, not related to the inflammation of gastric mucosa. This phenomenon was described in the literature. In the chronic stage there are dilated and tortuous vessels in the submucosal layer surrounded by collagenous connective tissue. The authors suppose that the thick and fibrotic submucosal layer causes microcirculatory disturbances in the gastric mucosa. The impaired microcirculation may cause extensive ulcers with profuse and sometimes lethal bleeding.

Adult↗
PubMed1991

Fluorescent tetradecanoylphorbol acetate: a novel probe of phorbol ester binding domains.

Protein kinase C (PKC) has a prominent role in signal transduction of many bioactive substances. We synthesized the fluorescent derivative, phorbol-13-acetate-12-N-methyl-N-4-(N,N'-di(2-hydroxyethyl)amino)-7-n itr obenz-2-oxa-1,3-diazole-aminododecanoate (N-C12-Ac(13)) of 12-O-tetradecanoylphorbol-13-acetate (TPA) to monitor the location of phorbol ester binding sites and evaluate its potential use as a probe of PKC in viable cells. The excitation maximum wavelength of N-C12-Ac(13) is close to 488 nm, facilitating its use in argon-ion laser flow and imaging cytometry. When incubated with 100 nM N-C12-Ac(13) at 25 degrees C, P3HR-1 Burkitt lymphoma cells accumulated the dye rapidly, reaching maximum fluorescence within 25 min, 20-fold above autofluorescence. Addition of unlabeled TPA significantly decreased the fluorescence of N-C12-Ac(13) stained cells in a dose-dependent manner indicating specific displacement of the bound fluoroprobe. Competitive displacement of [3H]-phorbol-12,13-dibutyrate ([3H]-PBu2) from rat brain cytosol with N-C12-Ac(13) gave an apparent dissociation constant (Kd) of 11 nM. N-C12-Ac(13) possessed biological activity similar to TPA. Like TPA (final concentration 65 nM) N-C12-Ac(13), at a lower concentration (51 nM), induced expression of Epstein-Barr viral glycoprotein in P3HR-1 cells, differentiation of promyelocytic HL60 cells, and caused predicted changes in the mitotic cycle of histiocytic DD cells. Microspectrofluorometric images of single cells labeled with N-C12-Ac(13) showed bright fluorescence localized intracellularly and dim fluorescence in the nuclear region, consistent with dye binding mainly to cytoplasmic structures and/or organelles and being mostly excluded from the nucleus. Because of the high level of non-specific binding of N-C12-Ac(13), this probe is not ideal for visualizing PKC in intact cells, but would be a valuable fluoroprobe to investigate the kinetic properties of purified PKC. Also, knowledge gained from these studies allows us to predict structures of fluorescent phorbols likely to have less non-specific binding and, consequently, be potentially useful for monitoring PKC in viable cells.

Animals↗
PubMed1991

Primary hepatocellular tumours during long-term androgenic steroid therapy. A light and electron microscopic study of 11 cases with emphasis on microvasculature of the tumours.

11 liver tumours in connection with long-term androgen therapy were reported. Tumours included two benign adenomas, one adenoma with malignant transformation and 8 hepatocellular carcinomas. In three cases, metastases were present. Light microscopic studies revealed "dark" and "light" areas. "Light" cells contained a large amount of glycogen. In two tumours, angiosarcomatous transformation was observed. The electron microscopic examinations showed peculiar vasculature of the tumours. Blood cavities resembling peliosis hepatis were present where the endothelial cells were missing and the cavities were lined with rounded hepatocytes. Another vascular change was the capillarization of sinusoids. Several layers of basement membrane were found around the endothelial cells. The tumours associated with androgens were compared with 16 cases of focal nodular hyperplasia in young women on oral contraceptives. The differences and similarities between the two steroid-related tumours were discussed . The necessity to be familiar with the morphology of liver tumours associated with androgens was emphasized because of their marked tendency to bleed and their frequent malignant transformation.

Adenoma↗
PubMed1991

Gastrointestinal angiodysplasia.

In the recent four years, 8 cases of gastrointestinal angiodysplasia (a.d.) were observed by the authors. Analysing the conclusions drawn from the patients course of disease, they found a.d. to be the cause of an unknown gastrointestinal bleeding. a.d. can be basically diagnosed by angiography. It is often associated with liver cirrhosis or arteriostenosis. The treatment of a.d. is surgical. The recurrence and repeated appearance of bleeding can be expected even after a thoroughly performed resection.

Adolescent↗
PubMed1991

Functioning "black adenoma" of the adrenal gland with emphasis on ultrastructural studies.

An account is given in this paper of functional black adenoma of the adrenal cortex. Autonomous hormone secretion of the tumour was confirmed by pre- and postoperative biochemical tests. Electron microscopy revealed two types of pigment granules. Mitochondria showed severe impairment. A relationship was assumed to exist between mitochondrial alterations and accumulation of lipoid-containing pigment because of the important role of mitochondria in lipid metabolism. Abnormal collagen fibrils were found in the cytoplasm of tumour cells. Comparison of the presented black adenoma with two nonpigmented adrenal adenomas showed the ultrastructure of black-adenoma cells to be similar to the compact cells of "yellow" cortical adenomas. However, the latter contained normal mitochondria and one type of pigment granules. Adrenal black adenoma thus can be regarded as a pathological entity.

Adenoma↗