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Biomedical subjects

L Nagy

Publications and source records attributed to L Nagy.

At least 145 records · Page 8Linked to original sources

Cholesterol movement between the plasma membrane and the cholesteryl ester droplets of cultured Leydig tumour cells.

The present studies characterize the turnover of plasma membrane cholesterol in MA-10 Leydig tumour cells. Plasma membrane cholesterol of MA-10 cells was slowly internalized and converted into cholesteryl ester. Low-density lipoprotein (LDL) stimulated, in a dose- and time-dependent fashion, plasma membrane cholesterol conversion into intracellular esters. Stimulation of membrane internalization was not simply the consequence of accelerated uptake of membrane with LDL, since binding and internalization of epidermal growth factor and transferrin had no effect on turnover of plasma membrane cholesterol. The protein of LDL is unimportant as well, since delipidated LDL had no effect on membrane turnover. The action of LDL on cholesterol turnover was explained entirely by its contribution to cholesteryl ester stores. The degree of plasma membrane cholesterol internalization and esterification was directly proportional to the size of cellular ester stores.

Animals↗

[Preoperative diagnosis of breast tumors in our clinic].

Between 1983 and 1988 197 patients underwent mammography and fine needle aspiration cytology procedure beside physical examination before operation for breast tumor in our clinic. The sensitivity of mammography and fine needle aspiration cytology were 81.9 and 66.1%, their specificities were 91.2 and 95%, the specificity of physical examination was 97.7%. When all three examinations indicated malignancy, this was confirmed by histology without exception. When the examinations showed benign lesion in concert, four of the 26 diagnoses were false, histology proved breast cancer smaller than 2 centimetres in diameter without lymph node metastases in each case. Those aspirations which were considered unsatisfactory because of the lack of cells supported the diagnosis of a benign tumor raised by physical examination and mammography. Our data indicate that the diagnosis yielded by the combination of the three examinations may support therapy more than it does in the present.

Breast Neoplasms↗

Receptor expression and functional status of cultured human eosinophils derived from umbilical cord blood mononuclear cells.

Selective use of recombinant human cytokines has enabled the culture of large numbers of eosinophils from human cord blood mononuclear cells, raising the possibility of their use as a model of eosinophil function. Cultured eosinophils (CE) were compared with normal-density peripheral blood eosinophils (PBE) in terms of their membrane receptor expression and function. Fc gamma R and CR1 expression of CE and PBE was similar. In contrast, the specific mean fluorescence for LFA-1 alpha, p150,95 alpha, ICAM-1, and HLA-DR was significantly elevated for CE compared with PBE. CE responded in PAF-induced chemotaxis in a similar fashion to PBE. CE gave higher numbers of both resting and platelet activating factor (PAF)-stimulated immunoglobulin G (IgG)- and C3b-dependent rosettes than PBE. CE and PBE had comparable capacity to kill IgG- and C-opsonized schistosomula in terms of both baseline values and PAF-induced enhancement of cytotoxicity. Baseline adherence by CE and PBE to plasma-coated glass was essentially the same, but stimulated adhesion (PAF) of CE was lower. Compared with PBE, CE generated less than half the amounts of extracellular and cell-associated PAF induced by calcium ionophore A23187 stimulation. Unlike PBE, CE did not generate PAF after exposure to IgG-coated Sepharose particles. CE stimulated with IgG-coated beads generated small quantities of LTC4, while A23187 stimulation resulted in approximately half the LTC4 levels observed with PBE. The total cell content of eosinophil peroxidase (EPO) was similar for CE and PBE. These data suggest that although CE and PBE have many phenotypic and functional properties in common there are quantitative differences that may be a consequence of their immaturity and/or the influence of the cytokines used in their culture.

Animals↗

[Mononuclear cell activation in status asthmaticus].

Evidence was provided by the authors, that the activity of circulating mononuclear cells is increased in status asthmaticus. An increased spontaneous secretion of chemotactic cytokin was found into the culture medium. There was no further increase in neutrophil chemotactic activity after 24 hours. In all patients a reduction was observed in the amount of neutrophil chemotactic activity after one week therapy, which is probably due to steroid treatment. No eosinophil chemotactic activity could be detected in the mononuclear cell supernatant derived from patients with acute severe asthma. The chemotactic activity was measured using a 48-well microchemotactic chamber. This mononuclear cell derived cytokin may play a role in genesis of asthmatic bronchial inflammation and provides further evidence that mononuclear cell activation is a feature of status asthmaticus.

Asthma↗

Characteristics of applicator exposure to synthetic pyrethroid in ULV-handheld and ULV-ULA spray applications.

The technique of ultra-low volume by ultra-light aircraft for pesticide spray application has been discussed for some time in North America, mainly due to the air worthiness of such an aircraft which was not designed to carry appreciable amounts of payload. The risk factor of such application in insect control has not been determined, while applicator exposure to insecticide in ULV application by manual sprayer was assessed. An attempt was made to produce, by a series of field exposure measurements, a set of applicator exposure data for ULV-ULA and to compare the results with the data produced in synthetic pyrethroid application by using a hand-held ULV applicator. The applicator exposure of hand-held operation resulted in as high as 1000 times the exposure of aerial applicators indicating the effect of work practices and man-machine relationships. A delineation of toxic dose for these two types of applications shows that the aerial application could provide some benefits in reducing applicator exposure potential.

Aerosols↗

Measurements of surface contamination of spray equipment with pesticides after various methods of application.

A traditional method to determine operator dermal exposure is to quantify the amount of pesticide coming into contact with specific body regions and then to integrate the deposition density values with the total body surface. It is known that extremely high deposition values may occur in the hand region; however, the source of contamination is generally assumed to be direct splash or contact with the pesticide container. One of the parameters affecting operator/pilot exposure could be the transfer of pesticide residue, particularly in the case of pesticides with a longer half-life, from contaminated surfaces of spray equipment by direct contact over extended periods. If the rate of skin absorption of pesticide is readily known, the expected values of daily dose for an operator or pilot may significantly rise due to the extended contact period. This study produced field data on the surface contamination of spray equipment used for ground and aerial applications. If field data on precise work practice (time-motion) observations are incorporated, it may be possible to estimate the potential exposure of operator/pilot due to hand contact with contaminated surfaces.

Aerosols↗

A biochemical and pharmacological approach to the genesis of ulcer disease II. A model study of stress-induced injury to gastric mucosa in rats.

Biochemical and molecular pharmacological studies were carried out in the gastric fundic mucosa during the development of stress ulcer in rats. The aims of this study were: (1) to evaluate the changes in membrane-bound ATP-dependent energy systems during the development of stress ulcer; (2) to prove (or to exclude) the presence of tissue hypoxia in the rat gastric mucosa during the development of stress ulcer; (3) to obtain further evidence of the existence of a feedback mechanism between ATP-ADP, ATP-cAMP, and cAMP-AMP transformations during the development of stress ulcer; (4) to analyze the different biochemical changes in the gastric mucosa before and after the macroscopic appearance of stress-induced gastric mucosal lesions (ulcers). The observations were carried out on both sexes of CFY-strain rats of 180 to 210 g body weight. The animals were deprived of food for 24 hours before the experiments. The animals were forced to swim in water (at 24 degrees C) for five hours. They were sacrificed at 0, 1, 2, 3, 4, and 5 hours after the introduction of stress. The tissue levels of ATP, ADP, AMP/ADP, and lactate were enzymatically measured; the cAMP was measured by radioimmunoassay. The adenylate pool (ATP + ADP + AMP), ratio of ATP/ADP, and "energy charge" [(ATP + 0.5 ADP)/(ATP + ADP + AMP)] were calculated. The membrane (Mg2(+)-Na(+)-K(+)-dependent) ATPase was prepared from the rat gastric fundic mucosa. Dose-response curves for epinephrine, cAMP, and AMP were determined on Na(+)-K(+)-dependent ATPase; also, the affinity, intrinsic activity curves, pD2, pA2 and alpha were calculated for all components. It was found that: (1) gastric mucosal lesions appeared and increased gradually from three hours after introduction of stress; (2) the extent of ATP-cAMP and cAMP-AMP transformations was increased considerably during the development of stress ulcer; (3) the extent of ATP-ADP transformation was completely inhibited; (4) the activity of Na(+)-K(+)-dependent ATPase from rat gastric fundic mucosa could be inhibited by epinephrine, cAMP, and AMP; (5) the ratio of ATP/ADP was unchanged in the first time period (from 0 to 3 hours), after which its value increased; (6) the value of "energy charge" (e.g., the extent of phosphorylation and/or dephosphorylation) of cells was decreased at two and three hours, after which its value returned to a normal level; (7) there was no increase in the tissue level of lactate; (8) several biochemical changes (decrease of ATP, ADP, "energy charge," increase of cAMP, AMP) preceded the macroscopic appearance of stress ulcer.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Monophosphate↗

Effect of cholesterol transport inhibitors on steroidogenesis and plasma membrane cholesterol transport in cultured MA-10 Leydig tumor cells.

These studies were directed toward understanding the cellular actions of inhibitor drugs that affect steroidogenesis and cholesterol transport. We investigated the microfilament inhibitor cytochalasin-D, the microtubule inhibitor colchicine, the calmodulin antagonist trifluoperazine, and the inhibitor of acidic vesicle function nigericin. We found that all of these compounds caused dose-dependent inhibition of progesterone synthesis in the MA-10 cells. Each compound also inhibited (Bu)2cAMP-stimulated pregnenolone synthesis, indicating that each inhibited a fundamental process required for steroidogenesis. Each compound was next evaluated for inhibitory actions on cholesterol transport to and from the plasma membrane. On the basis of inhibitor sensitivity, two different categories of cholesterol transport were defined. Transport of newly synthesized or low density lipoprotein-derived cholesterol from the cell interior to the plasma membrane was inhibitor insensitive. Plasma membrane cholesterol internalization, however, was sensitive to all of the inhibitors and did not result because of any drug effect on the acyl-coenzyme-A-cholesterol acyl transferase. Cycling of cholesteryl ester-derived cholesterol through the plasma membrane appeared to occur before its use for steroidogenesis. Thus, inhibition of plasma membrane internalization would prevent utilization of both plasma membrane cholesterol and cholesteryl ester-derived cholesterol, the two major substrate sources for steroid hormone synthesis. Consistent with this interpretation was the finding that inhibition of plasma membrane cholesterol internalization by each inhibitor paralleled the inhibitor's effect on steroidogenesis.

Biological Transport↗

Local recurrences following colorectal operations.

In about 15-20% of patients operated for colorectal tumours local recurrences develop mainly in the first postoperative year. This large number can only be reduced by adequately radical operations taking into account the patient's age, tumour site and the tumour-biological factors. Indispensable factors are the organized care and regular control of the operated patients with an emphasis, beside CEA test on US and CT studies. In local recurrences attempt should be made at removal of the tumour by an additional operation which is implementable in 20-30% of cases. For palliative treatment first of all radiotherapy can be applied for pain relief.

Adenocarcinoma↗

Effects of a novel Hungarian antacid containing Al and Mg (Tisacid) on mucosal prostaglandin generation and oxygen free radicals in normal rats.

A new patented chemical agent (Al-Mg-hydroxy-carbonate; acid-binding capacity greater than 30 mmol/g) was produced by our work-team. After our preliminary pharmacological and some prospective, randomized, multicentre, controlled clinical studies, this antacid was registered (Tisacid tablet and suspension; Alkaloida, Hungary). A cumulative ulcer healing rate of 80-85% was proved by Tisacid monotherapy applied in low doses (from 80 to 160 mmol/day) in patients with duodenal ulcer. The aims of this study were: (i) to determine the role of different antacids on the genesis of mucosal prostaglandins (PGs) (PGE2 and 6-keto-PGF1 alpha) in normal rats; (ii) to evaluate the effects of indomethacin pre-treatment (20 mg/kg b.w.,s.c.) on the Tisacid-induced alterations of gastric mucosal PG-contents; (iii) to analyse the generation of oxygen free radicals and lipid peroxidation in the rat oxyntic mucosa by the application of different doses of Tisacid (activities of CAT, GSH-px and SOD, contents of MDA and red. GSH). It was found that: Tisacid has a potent gastroproprotective effect in gastric mucosa, via (a) an increase in the mucosal levels of PGs, and (b) a scavenging-like effect in normal rat gastric mucosa. It is concluded that the gastroprotective effect of Tisacid appears because of the following: (i) excellent acid-neutralizing capacity; (ii) mucosal generation of PGs (PGE2 and PGI2); (iii) free radical scavenging; (iv) its possible activity as a Ca-antagonist (Mg-containing compound).

6-Ketoprostaglandin F1 alpha↗

Aspects of diagnosis and therapy of gallstone ileus.

The clinical experience with 14 gallstone ileus patients operated within a time period of 17 years is analysed with a survey of the relevant literature. For surgical solution enterolithotomy is recommended. The difficulties of early diagnosis are pointed out with an emphasis, in case of gallstone, on cholecystectomy for prevention of gallstone ileus.

Aged↗

The extent of bile reflux and development of gastric cancer after resections in rat.

Authors performed gastric resections (Billroth II, Billroth I, Billroth II+, Braun anastomosis and Roux Y reconstruction) and laparotomies in five groups, of 110 Wistar male rats. Thirty-eight weeks postoperatively the surviving 91 animals were sacrificed, and histological study was made of the frequency of gastric stump cancer in the individual groups and the extent of bile reflux characteristic of the individual GEA types was measured. Based on their results, the risk of stump cancer was higher in operation types associated with considerable bile reflux (a cancer incidence rate of 50% after Billroth II, 28.5% after Billroth I). Following gastric resections accompanied by insignificant bile reflux (Billroth II + Braun, Roux Y) the risk of gastric stump cancer was significantly lower.

Animals↗

Chronic ethanol-induced heterologous desensitization is mediated by changes in adenosine transport.

Chronic exposure of cultured cell lines to ethanol results in a heterologous desensitization of receptors coupled to adenylate cyclase via GS, the stimulatory guanine nucleotide regulatory protein. This heterologous desensitization is accompanied by a decrease in alpha S, the GTP-binding subunit of GS. Ethanol-induced accumulation of extracellular adenosine is required for the development of heterologous desensitization. To determine the mechanism underlying the ethanol-dependent increase in extracellular adenosine, we investigated the effects of ethanol on the nucleoside transporter responsible for the bidirectional transport of adenosine into and out of the cell. We found that ethanol specifically and non-competitively inhibited nucleoside uptake. Inhibition of adenosine uptake was primarily due to decreased influx via the nucleoside transporter. Thus, ethanol-induced increases in extracellular adenosine appear to be due to inhibition of adenosine influx. After chronic exposure to ethanol, cells became tolerant to the acute effects of ethanol, i.e. ethanol no longer inhibited uptake and, consequently, no longer increased extracellular adenosine concentration. Taken together with our previous studies, these results suggest that acute ethanol inhibition of adenosine influx leads to an increase in extracellular adenosine which in turn activates adenosine A2 receptors to increase cyclic AMP levels, leading to desensitization of receptor-dependent cyclic AMP signal transduction after chronic exposure to ethanol. We next determined whether the same effects of ethanol also occur in alcoholics. We isolated lymphocytes from alcoholics and non-alcoholics and found that alcoholics had a 75% decrease in basal and adenosine receptor-stimulated cyclic AMP production compared with non-alcoholics. To determine whether these differences were due to exposure to ethanol in vivo or to a possible genetic difference between alcoholics and non-alcoholics, we grew lymphocytes in culture in the absence of ethanol. Adenosine receptor-stimulated cyclic AMP levels were higher in alcoholics than non-alcoholics. Moreover, cultured cells from alcoholics were more sensitive to the effects of chronic alcohol on cyclic AMP signal transduction than cells from non-alcoholics. Our results suggest that the cyclic AMP signal transduction system may reflect a genetic alteration in alcoholics and that studies in cultured lymphocytes may allow us to identify individuals at risk of developing alcoholism.

Adenosine↗