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Biomedical subjects

J Feher

Publications and source records attributed to J Feher.

At least 19 recordsLinked to original sources

Induced myeloperoxidase activity and related superoxide inhibition during hormone replacement therapy.

OBJECTIVE: To test whether the menopause entails any changes in the myeloperoxidase activity of neutrophil granulocytes. The effects of hormone replacement therapy on myeloperoxidase activity and related changes in free radical production were also investigated. DESIGN: Laboratory investigation of the effect of oestrogen on intracellular myeloperoxidase activity and release from human neutrophil granulocytes. Analysis of related changes in superoxide anion generation. SETTING: 2nd Department of Medicine and 1st Department of Obstetrics and Gynaecology, Semmelweis University, Budapest. SAMPLES: Intracellular myeloperoxidase activity (mean peroxidase index) was measured automatically in blood samples obtained for general laboratory work-up from 135 randomly selected patients in our department. Blood samples from 11 postmenopausal women were analysed before and during hormone replacement therapy. Blood samples from 20 healthy volunteers were obtained and neutrophil granulocytes separated for in vitro measurement of superoxide anion production after adding myeloperoxidase to the incubation media. METHODS: The mean peroxidase index was measured using a Technicon H-3 instrument. myeloperoxidase release from neutrophils was quantified by ELISA technique. Superoxide production of isolated neutrophil granulocytes was measured by photometry. MAIN OUTCOME MEASURES: Intracellular activity of myeloperoxidase, concentration of myeloperoxidase-protein in supernatant of neutrophils, release of superoxide anion from neutrophil granulocytes. RESULTS: 1. Intracellular myeloperoxidase activity in neutrophils was lower in postmenopausal women, than in females with regular cycles (-1.84 +/- 3.06 versus 1.59 +/- 3.55, P < 0,001). 2. In postmenopausal women intracellular myeloperoxidase activity and myeloperoxidase release increased during hormone replacement therapy (-5.54 +/- 6.63 versus -0.2 +/- 6.05; P < 0.001 and 52.74 mU/ml +/- 25.73 versus 251.4 +/-234.1 mU/ml; P < 0.05). 3. Adding myeloperoxidase to neutrophil granulocyte suspensions, the production of superoxide anion fell (e.g. adding 280 ng/ml myeloperoxidase: 77.9 +/- 14.04 % of control production, P < 0.001). CONCLUSION: Hormone replacement restores the reduced myeloperoxidase activity in menopausal women. Adding myeloperoxidase to neutrophil granulocytes, the production of free radicals decreases.

Adult↗

Microfilaments in regenerating cells of rabbit cornea: immunological and ultrastructural observations.

The role of myosin-like protein in regenerating and proliferating corneal cells following a standard alkali-injury in the rabbit eye has been studied. Microfilaments were observed by conventional transmission electron microscopy (T.E.M.) in injured epithelium and in fibroblasts. Typical microfilament bundles with electron dense structures and with stress fibers were evident. The presence of myosin-like proteins was demonstrated by means of immunochemical and autoradiographical techniques. Both epithelial cells and fibroblasts bind antimyosin-like antibodies (AMA). The same cells studied with the E.M. showed bundles of microfilaments in the cortical areas of their cytoplasm in correspondence with the same side of fluorescent or labelled AMA. The immunochemical and ultrastructural results suggest that both cells are able to produce in vivo movements involved in morphogenetic phenomena. Therefore, these structures play a role in post-traumatic corneal regeneration.

Actin Cytoskeleton↗

Localization of dopamine receptors in the rabbit cornea.

PURPOSE: To analyze the pharmacologic profile and the anatomic localization of the dopamine D1 and D2 receptors in sections of the rabbit cornea in normal conditions. METHODS: Samples of rabbit cornea were drawn. Biochemical and autoradiographic techniques were used on frozen sections. [3H]SCH-23390 was used as a ligand of dopamine D1 receptors and [3H]spiroperidol as a ligand of dopamine D2 receptors. RESULTS: [3H]SCH-23390 and [3H]spiroperidol were bound by sections of the rabbit cornea. The pharmacologic profile of the binding was consistent with the labeling of D1 and D2 receptors, respectively. Light microscopic analysis of the localization of D1 and D2 receptors revealed an accumulation of the two radioligands in the epithelial and in the endothelial layers of the cornea. CONCLUSION: A possible role of the dopaminergic system in the control of the corneal functions is suggested.

Animals↗

Automated prozone effect detection in ferritin homogeneous immunoassays using neural network classifiers.

The application of turbidimetric homogeneous immunoassays made the determination of several plasma components widely available. The sensitivity and accuracy of these assays are appropriate enough for routine laboratory use; however, in the case of many pathologically high concentration samples, prozone effect (high dose hook effect) can be observed, that leads to false-negative determination. Up to the present there are no cost-effective algorithms available for the safe detection of the prozone effect. Pathological serum ferritin values can be elevated up to 5000 ng/ml, while the measuring range covers only the 0-440 ng/ml range by a commercial assay. The determination of samples with ferritin concentration higher than 1500 ng/ml results in false-negative values because of the overlapping measuring range and prozone effect range. The prozone effect can be recognised by analysis of reaction kinetics after measurement. We have developed a neural network classifier system to analyse reaction kinetics of the measurements and check the prozone effect. One thousand five hundred determinations and 77 patient samples were used for neural network training and test. Using the trained neural networks, false-negative results can be filtered immediately after the determination, without re-run; thus, the sensitivity of plasma ferritin determination may become reliable enough, even in the case of high concentration samples. Applying this new technology, false-negative serum ferritin determinations can be avoided, thus even a relatively high hook effect rate (5-12% in different patient groups) can be handled safely.

Blood Chemical Analysis↗

PEDF (pigment epithelium-derived factor) promotes increase and maturation of pigment granules in pigment epithelial cells in neonatal albino rat retinal cultures.

Pigment Epithelium-Derived Factor (PEDF), purified from human retinal pigment epithelial (RPE) cell culture medium, is a neurotrophic factor which potentiates the differentiation of human Y-79 retinoblastoma cells and increases the survival of cerebellar granule cells. To investigate the effects of PEDF on non-transformed retinal cells, we used primary cultures of neonatal albino rat retinas, where the three principal cell types of the retinal layers (neuronal, glial and epithelial) were all present and focussed our attention on RPE cells, which are of special relevance for retinal pathophysiology. PEDF had a dramatic effect on these cells. They showed a modified phenotype, with larger dimensions, higher cytoplasmic spreading, presence of phagocytic vacuoles, development of wide intercellular contacts, and increase and maturation of pigment granules. These results suggest that PEDF may have a role in regulating RPE cell differentiation.

Animals↗

Catecholaminergic nerve fibres in normal and alkali-burned rabbit cornea.

BACKGROUND: In recent years anatomic research has demonstrated the presence of various types of nerve fibre in the cornea. The purpose of this study was to investigate the distribution of catecholaminergic fibres in various corneal layers and to study the effects of an experimental superficial corneal lesion on the pattern of catecholaminergic nerve fibre distribution in the various corneal layers. METHODS: Three weeks after the creation of an alkali burn in the centre of the right cornea of five albino rabbits, the animals were killed, and histologic sections from the cornea of both eyes were stained for observation of catecholaminergic nerve fibres and photographed on black-and-white film. The photographs were examined using the Quantimet image analyser (Leica). RESULTS: Catecholaminergic nerve fibres were observed in the corneal epithelium and the deep stromal layers. Sections from injured cornea showed a drastic reduction in epithelial and superficial stromal catecholaminergic nerve fibres, whereas the nerve fibres in the endothelium and deep stroma were not damaged. INTERPRETATION: Although catecholaminergic nerve fibres were observed in all corneal layers, the pattern of catecholaminergic fibres following the creation of a superficial lesion of the cornea seems to suggest that the superficial and deep nerve fibres may have a different distribution.

Animals↗

Prostacyclin and thromboxane production of rat and cat arterial tissue is altered independently by several vasoactive substances.

The modulation of the production of prostacyclin and thromboxane from cat and cat aortic tissue slices by different vasoactive agents has been studied in order to reveal whether the release of these main two vasoactive prostanoids goes in parallel or may be controlled independently. Norepinephrine, isoproterenol, phentolamine, propranolol, angiotensin II, vasopressin, bradykinin, thrombin, verapamil, gallopamil, dopamine or methionin enkephalin were added to the incubation medium and 6-keto-PGF1 alpha (the stable metabolite of prostacyclin) and TxB2 (the stable metabolite of thromboxane) were determined in the supernatant by radioimmunoassay. The ratio of the release of prostacyclin and thromboxane was computed. Norepinephrine increased both prostacyclin and thromboxane release. Isoproterenol increased the ratio of prostacyclin and thromboxane released in cat aortic tissue slices. Phentolamine and propranolol had no effects. Angiotensin II induced a slight but statistically insignificant increase in the ratio of the two prostanoids released. Vasopressin increased thromboxane release only. Bradykinin stimulated the prostacyclin while thrombin stimulated the thromboxane release. Verapamil decreased both prostacyclin and thromboxane production. Gallopamil decreased prostacyclin release and increased thromboxane release from vessel wall slices in a certain concentration range causing a characteristic dose dependent minimum in the ratio of prostacyclin and thromboxane release. Dopamine separately increased prostacyclin release while enkephalin had no significant effect. The data obtained show that in vascular tissue some unidentified yet cytophysiological mechanisms might exist which specifically control the activities of the prostacyclin synthase and thromboxane synthase enzymes.

6-Ketoprostaglandin F1 alpha↗

Structural evidence for membrane lipid changes in human cataract.

Lipid changes in relationship to cataractogenesis were studied with histochemical methods (topoptical reactions) of polarization microscopy. Frozen section of formaldehyde-fixed human lenses were used for these studies. Six lenses were transparent and 14 lenses presented early to confluent cortical opacities. Cell membrane lipids of transparent lenses showed 8.0 +/- 2.7 nm light retardation. In the early cataractous lenses the light retardation of cell membranes was 23.3 +/- 5.0 nm and that of the fusiform and globular lipids was 37.7 +/- 4.0 nm and 48.5 +/- 6.9 mn, respectively. In the non transparent cortical regions of cataractous lenses, membrane lipids were not observed. Similar to other cell membranes, normal lens membranes are composed of loosely organized lipids. In early cataract lipid density uniformly increased along the cell membranes at the clinically transparent areas, while at the areas with clinically evident fine opacities, small fusiform and globuler lipid drops were formed by even more dense lipids. Confluent cortical cataracts were associated with disappearance of membrane lipids. In our study our findings demonstrated intramembrane lipid changes associated with cataractogenesis.

Adult↗

[Treatment of carcinoid tumor with a long-acting somatostatin analog].

A case of carcinoid tumour of the small intestine has been reported, which caused hormone producing multiple hepatic metastases. The 45 year old man had flush syndrome several times a day, that was caused by a carcinoid tumour originated from the jejunum. After the operation of the primary tumour he was treated by Sandostatin (Sandoz, Basel), which significantly reduced the symptoms and slowed down the progression. The neural elements containing substance P, neuropeptide Y, vasoactive intestinal polypeptide, serotonin, dopamine-beta-hydroxylase and somatostatin, which are thought to cause the symptoms, were investigated in the small intestine and the liver metastasis by an immunocytochemical method. It seems to be an interesting observation, that a large number of neuropeptide Y immunoreactive nerve fibers and some substance P and vasoactive intestinal polypeptide immunoreactive nerve processes and cell bodies were observed however, no trace of somatostatin and serotonin immunoreactive nerve elements could be detected in the hepatic metastasis. That can be a novel addition to the possible aetiology of the carcinoid syndrome and to the way how the somatostatin treatment acts.

Carcinoid Tumor↗

The role of free radicals in the pathogenesis of amiodarone toxicity.

INTRODUCTION: In vitro and in vivo studies were performed to elucidate the pathogenesis of amiodarone toxicity. METHODS AND RESULTS: Rats were treated with amiodarone alone (500 mg/kg body weight per day) or together with antioxidants (silibinin or MTDQ-DA: 50 mg/kg body weight per day) or with either antioxidant alone. They received amiodarone for 30 days and antioxidant for 33 days (3 days pretreatment). In vitro, amiodarone induced a dose-dependent chemiluminescence signal, which was inhibited by the two dihydroquinolin-type antioxidants (MTDQ-DA, CH 402). Chemiluminometric results from liver homogenate demonstrated that simultaneous treatment with silibinin partially prevented the liver homogenate superoxide anion radical scavenger capacity decreasing effect of amiodarone. Amiodarone treatment caused a significant increase of NADPH and Fe3+ induced lipid peroxidation in the liver microsomal fraction, which antioxidants (silibinin, MTDQ-DA) were unable to prevent. Light microscopy of the lung tissue in amiodarone-treated rats showed accumulation of foamy macrophages with thickening of the interalveolar septa, pneumonitis, and variable interstitial fibrosis. Antioxidant treatment did not prevent these changes. Electron micrographs of lung from amiodarone-treated rats showed lysosomal phospholipoidosis, intralysosomal electron dense deposits, and increased lysosome number and size. In contrast to rats treated with amiodarone alone, those treated with both amiodarone and silibinin had significantly fewer lysosomes (P < 0.01); the lysosome size, shape, and internal characteristics remained the same. Simultaneous treatment with silibinin and amiodarone decreased lysosomal phospholipoidosis compared to amiodarone treatment alone. Simultaneous treatment with MTDQ-DA and amiodarone did not show any beneficial effect. Pulse radiolysis and cobalt 60-gamma (60Co-gamma) radiolysis studies showed that the main free radical product in a reducing environment was a very reactive aryl radical formed after the partial deiodination of the amiodarone molecule. The radiosensitizing effect of amiodarone was also verified in rat liver microsomal preparations using in vivo amiodarone with or without MTDQ-DA pretreatment and 60Co-gamma irradiation with or without the in vitro addition of antioxidants (CH 402, MTDQ-DA). In vivo, the MTDQ-DA treatment also had a radiosensitizing effect; however, the in vitro addition of both antioxidants resulted in a radioprotective effect. The aryl radical also may emerge in vivo during the metabolism of amiodarone. CONCLUSION: These observations suggest that amiodarone in vitro and in vivo generates free radicals that may play a role in the pathogenesis of amiodarone toxicity beside other well-established mechanisms, and antioxidants may have a partial protective effect against amiodarone toxicity.

Amiodarone↗

Application of multivariate, fuzzy set and neural network analysis in quantitative cytological examinations.

Multivariate statistical methods have been used in several studies to increase the diagnostic reliability of TV image analyser systems. In recent years some algorithms for decision support (fuzzy logic) and for pattern recognition (neural nets), both non-linear, were developed. This paper reports on preliminary results obtained with these methods in quantitative cytology and compares them to the traditional classifiers. A total of 21 normal, 15 dysplastic and 23 malignant, gastric imprint smears were Feulgen stained and analysed on a Leitz Miamed DNA cytophotometer system. Mean DNA content, the 2c deviation index (2cDI), 5c exceeding rate (5cER), G1, S, G2 phase fraction ratios, cell nucleus area and form factor were determined. Diagnostic accuracy of the discriminant analysis was 96% for the malignant cases, 87% for dysplasias and 81% for normal cases. Cluster analysis gave no significant result. Our diagnostic system utilizing fuzzy logic has made the diagnostic borders adjustable and reliable. The back-propagation neural net correctly classified the normal and malignant cases (100%) and all but one of the dysplasias (98%). The non-linear mathematical methods improved the reliability of the diagnostic system. These new algorithms gave results comparable to traditional classifiers. The application of these methods to clinical samples is encouraging.

Algorithms↗

The human selenium status in Hungary.

The selenium concentration of foods and of human blood varies widely between geographical areas depending on the availability of soil Se for plants. The mean serum Se concentration in Europe has been found to vary between 0.80-1.50 mumol/l and the mean Se concentration of wheat between 0.02-0.11 mg/kg. We estimated by various markers the Se status of Hungarians on whom data is lacking. Serum samples (n = 238) from healthy blood donors, and toenails (n = 132) and fingernails (n = 211) from different apparently healthy individuals residing in both urban and rural areas were collected from four districts in Hungary. Wheat samples (n = 29) as grains were obtained directly from farms representing the same areas. Serum Se was determined by electrothermal AAS and the other samples by acid-digestion fluorimetry. The accuracy of the methods was verified by analyzing external reference samples. The mean (+/- SD) serum Se concentration was 0.70 +/- 0.12 mumol/l, ranging between 0.41-1.18 mumol/l. The mean serum Se levels 0.87 mumol/l was significantly (p < 0.001) higher in the East and lower in the South (0.60 mumol/l) compared to the northern area 0.70 mumol/l. The mean (+/- SD) toenail Se concentration was 0.56 +/- 0.18 mg/kg. The Se level in the East was significantly (p < 0.01) higher than the level in the North, 0.68 mg/kg vs. 0.54 mg/kg, respectively, and lowest in the southern area, 0.40 mg/kg. The same pattern applied to fingernails. Wheat Se ranged from 5 to 235 micrograms/kg, with the median 34 micrograms/kg. The lowest Se concentrations were generally found in the South.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

[Post infarction ventricular septal defect. Echocardiographic analysis of patients treated with positive end-expiratory pressure].

Interventricular septal rupture is a life-threatening complication occurring in 0.5 to 1.0% of patients following acute myocardial infarction and often results in right and left ventricular failure. This study aimed at evaluating the echocardiographic effects of PEEP on right (RV) and left (LV) ventricular dimension in three patients who developed a postinfarction septal defect and in whom acute respiratory failure was a preterminal event. The effects of PEPP on the heart remain controversial. We observed in all three patients a sudden large increase in RV dimensions and hence, probably through ventricular interdependence, a proportional decrease in LV dimensions. The progressive leftward septal displacement with increasing levels of PEEP probably contributed to reduce LV compliance. We concluded that PEEP therapy in this group of patients had no proven beneficial effects and probably contributed to further RV dilatation and failure.

Aged↗

No evidence for human T-cell leukemia virus type I or human T-cell leukemia virus type II infection in patients with multiple sclerosis.

The involvement of human T-cell leukemia viruses (HTLVs) in the pathogenesis of 18 Hungarian patients with multiple sclerosis was investigated. No antibody to HTLVs could be detected in any of the patients. Furthermore, using polymerase chain reaction under highly sensitive conditions, neither HTLV-I DNA nor HTLV-II DNA could be noted in peripheral blood lymphocytes of the patients. Our data do not support a causal association of HTLV-I or HTLV-II with multiple sclerosis.

Adult↗

Rearrangement of the T-cell receptor alpha, beta and gamma chain genes in chronic lymphocytic leukemia.

Simultaneous expression of mature B-cell and T-cell markers and subsequent abrogation of expression of the T-cell surface markers by cytotoxic chemotherapy was reported earlier in a patient (TG) with chronic lymphocytic leukemia (CLL). In addition to rearrangements of the immunoglobulin (Ig) gene loci correlating with phenotypic data, the T-cell receptor (TCR) alpha, beta and gamma chain genes also displayed clonal rearrangements in peripheral blood lymphocyte DNA of TG. The present case shows that in CLL cells not only the expression of B-cell and T-cell specific differentiation antigens but also the rearrangement of Ig as well as TCR alpha, beta and gamma genes may occur simultaneously.

Aged↗

In vitro scavenger effect of dihydroquinoline type derivatives in different free radical generating systems.

The non-toxic and water soluble dihydroquinoline type antioxidants: CH 402 (Na-2,2-dimethyl-1,2-dihydroquinoline-4-yl methane sulphonate) and MTDQ-DA (6,6-methylene bis 2,2-dimethyl-4-methane sulphonic acid: Na-1,2-dihydroquinoline) were studied in various in vitro tests in which oxygen free radicals were generated. Both compounds were shown to scavenge superoxide radical anions O2- produced in aqueous solution by pulse radiolysis with rate constants k (O2- + MTDQ-DA) = 4.10(8) dm3 mol-1 s-1 and k (O2- + CH 402) = 1.5.10(7) dm3 mol-1 s-1. CH 402 and MTDQ-DA reduced the H2O2 produced in the glucose-glucose oxidase reaction, which was detected by the luminol + hemin reaction with a chemiluminometric method. The dihydroquinoline type substrates inhibited the NADPH-induced and Fe3+ - stimulated lipid peroxidation and the ascorbic acid-induced non-enzymatic peroxidation pathways in microsomal fractions of rat and mouse liver.

Animals↗