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Biomedical subjects

M Balázs

Publications and source records attributed to M Balázs.

At least 19 recordsLinked to original sources
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↗
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↗
PubMed1991

Bowenoid change in perianal condyloma acuminatum associated with ulcerative colitis.

A 35-year-old male patient with a 20-year history of ulcerative colitis developed an itching perianal condyloma acuminatum with discharge. This was surgically removed after two years. Histology revealed bowenoid change in the condyloma. Six months later a local recurrence was excised. He has now been free of further recurrence for 5 years. Electron microscopy showed moderately differentiated keratinocytes in the areas of bowenoid change. There was no evidence of virus particles in the keratinocytes. A causal relationship has been assumed between the ulcerative colitis, via chronic irritation, and the perianal bowenoid changes regarded as in situ carcinoma. The importance of radical excision of such lesions is emphasized.

Adult↗
PubMed1990

[Liver tumors caused by androgenic steroids].

11 hepatocellular tumours associated with the long term use of androgenic steroids were reported. Three of the tumours were seen on the basis of diffuse peliosis hepatis. One of the 11 tumours was benign hepatocellular adenoma. In one case malignant transformation of an adenoma was observed. Nine tumours proved to be highly differentiated hepatocellular carcinomas. Metastases were observed in three cases. Histological and electron microscopical peculiarities of the tumours were the accumulation of glycogen in the cytoplasm of tumour cells, nuclear inclusions, and great number of peculiar formed vessels. The last case is a rarity. One year after the needle biopsy implantation of hepatocellular carcinoma was observed with several tumorous metastases at the site of the previous biopsy. The authors suggest regular hepatic control by ultrasound examinations of patients on sexual steroid hormones.

Adult↗
PubMed1990

[Gastrointestinal angiodysplasia].

8 cases of gastrointestinal angiodysplasia are reported. It can be stated on the analysis of these cases, that the angiodysplasia can be the cause of unexplained GI hemorrhages, and in the majority of cases the visceral angiography provides diagnostic evidence. The angiodysplasia can be observed frequently in association with liver cirrhosis and aortic valvular stenosis. Surgery is regarded as the best method of treatment. Subsequently the careful resection rebleeding and development of newer angiodysplasia can occur.

Aged↗
PubMed1990

Effect of cyclosporin A on the membrane potential and Ca2+ level of human lymphoid cell lines and mouse thymocytes.

The effect of the immunosuppressive cyclosporin A (CsA) on the cytosolic free Ca2+ concentration ([Ca2+]i) and membrane potential of human B and T lymphoblastoid cells and mouse thymocytes was studied in order to reveal some features of the early stage of drug-cell interaction. Cytosolic free Ca2+ concentration of the cells was measured by spectrofluorimetry using indo-1 and quin2 fluorescent calcium indicators. Membrane potential was monitored in a flow cytometer with oxonol dye. CsA applied at 2-20 micrograms/ml final concentrations caused a dose-dependent, rapid, transient rise of [Ca2+]i in all cell types. This effect could be blocked by chelating the extracellular Ca2+ with EGTA but was not sensitive to Ca2+ channel blockers verapamil and nifedipine or K+ channel blocker 4-aminopyridine. A possible explanation for the calcium mobilizing effect of CsA is an ionophore-like mode of action at the cell membrane level. Besides directly interfering with mitogenic signals, the elevation of [Ca2+]i could be responsible for an initial hyperpolarization observed in CsA-treated T lymphocytes. This hyperpolarization, however, was not detectable in B lymphoblastoid cells. A further difference between B and T cells was the diverse pattern of depolarization following CsA treatment. This variance in the behaviour of T and B lymphocytes and the diversity of membrane transport systems in its background could account for the different final outcome of the drug-cell interaction.

Animals↗
PubMed1990

The effect of transmembrane potential on the dynamic behavior of cell membranes.

The relationship between transmembrane potential and lipid dynamics in the cytoplasmic membrane of mouse thymus cells has been investigated. Changes of transmembrane potential was followed by measuring the fluorescence emission of the anionic dye, bis-(1,3-dibutylbarbiturate)trimethine oxonol (diBa-C4-(3)). Assessment of lipid fluidity was carried out applying three fluorescent lipid probes, 1-[4-(trimethylammonium)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH), 12-(9-anthroyloxy)stearic acid (12-AS) and 1,6-diphenyl-1,3,5-hexatriene (DPH) used to monitor different structural regions of the bilayer. The fluorescence anisotropy of these probes was measured as a function of temperature at two values of transmembrane potential. In the case of DPH it proved to depend on the membrane potential in the higher temperature range (above 28 degrees C), while no such a dependence could be observed for DPH below this temperature range and for TMA-DPH and 12-AS in between 20 and 37 degrees C. These data suggest that changes in transmembrane potential are accompanied with some local alteration in membrane lipid dynamics and/or structure.

Animals↗