Biomedical subjects

G Fóris

Publications and source records attributed to G Fóris.

At least 19 recordsLinked to original sources

PubMed2003

Disturbed regulation of cholesterol synthesis in monocytes of obese patients with hypercholesterolemia.

The aim of the present study was to clarify the influence of obesity on the functions of low-density lipoprotein receptors (LDL-R) and 3-hydroxy-3-methylglutarate-coenyzme A (HMG-CoA) reductase both in healthy control subjects and in patients with hypercholesterolemia (HC). Experiments were performed on monocytes of 15 non-obese (C I) and 11 obese (C II) healthy control subjects and on 22 non-obese (HC I) and 26 obese (HC II) patients with HC. [(125)I]LDL was used to determine LDL-R activity by measuring binding and intracellular degradation. The rate of endogenous cholesterol synthesis was measured using [(14)C]acetate incorporation into the cholesterol fraction of monocytes. The binding ability of [(125)I]LDL was identical across all groups. The [(14)C]acetate incorporation in resting monocytes was increased only in obese HC group. The 50-microg/mL LDL protein-induced inhibition of [(14)C]acetate incorporation was significantly diminished (P <.001) in the same group. A strong positive correlation was detected between the [(14)C]acetate incorporation by resting cells and LDL-induced inhibition in all groups except the obese HC group, in which their correlation was negative (P <.001). Furthermore, in the obese HC group, a significant positive correlation was detected between body mass index (BMI) and the basal level of [(14)C]acetate incorporation, whereas a negative correlation was found between BMI and LDL-induced inhibition of [(14)C]acetate incorporation. The present data suggest that in patients with HC the concomitant obesity results in dysregulation of cholesterol homeostasis, which may contribute to the accelerated atherosclerosis.

Acetates↗

PubMed1999

Disturbed LDL and scavenger receptor functions in monocytes from chronic haemodialysed patients.

BACKGROUND: The most frequent complication in patients with end-stage renal failure on chronic haemodialysis (HD) treatment is atherosclerosis, i.e. the different forms of heart and vascular diseases. The complete disorder of serum lipid and lipoprotein patterns is well demonstrated, whereas our knowledge about the low-density lipoprotein (LDL) and scavenger receptor expression and function are poorly understood. METHODS: In our current work, LDL and scavenger receptor expression and functions were simultaneously studied in monocytes obtained from 15 healthy male control subjects and from 11 chronic HD male patients applied with (125)I-labelled LDL, isolated from healthy volunteers. To study the scavenger LDL receptors, labelled acetylated LDL (acLDL) was used. RESULTS: LDL binding to the monocytes of the HD-group was found to be decreased in comparison to that of the controls. As a result, the 50 microg LDL protein-induced inhibition of endogenous cholesterol synthesis was also diminished. In contrast, acLDL binding was greatly increased, though it could trigger only a low apoE synthesis. Consequently the number of cholesterol inclusions in monocytes was increased. CONCLUSIONS: The disturbed expression and function of LDL and scavenger receptors both may play significant roles in pathogenesis of cardiovascular complications in chronic HD patients. Based on our present results, it can be assumed that dysfunction of scavenger receptors is at the centre of cardiovascular complications of HD patients with renal failure.

Anticholesteremic Agents↗

PubMed1999

Altered signal pathway in granulocytes from patients with hypercholesterolemia.

In the present study the signal transduction of the formyl-Met-Leu-Phe receptor was studied in granulocytes obtained from control subjects and patients with elevated low density lipoprotein levels. According to our results, 10 nm formyl-Met-Leu-Phe in control cells activates phospholipase C inducing a pronounced inositol phosphate production followed by a Ca(2+) signal from intracellular pools. The pertussis toxin-sensitive O(2)(-) generation and leukotriene synthesis were moderate. In contrast, in granulocytes from hypercholesterolemic patients, formyl-Met-Leu-Phe triggered an intensive pertussis toxin-insensitive oxidative burst and leukotriene synthesis. The inositol trisphosphate and Ca(2+) signals were decreased significantly in granulocytes of hypercholesterolemic patients and seem to be dependent on the extracellular Ca(2+) content. Furthermore, in the resting granulocytes of hypercholesterolemic patients the [Ca(2+)]i and the membrane-bound protein kinase C activity were higher than in controls, the time of normalization after the low Ca(2+) signal was delayed, while the membrane fluidity was decreased. Our results suggest that in these ex vivo experiments, the high level of circulating low density lipoprotein in patients can affect the membrane composition of granulocytes leading to altered signal transduction by the formyl-Met-Leu-Phe receptor, to altered Ca(2+) pump-activity, and protein kinase C translocation.

Calcium Signaling↗

PubMed1998

Altered postreceptor signal transduction of formyl-Met-Leu-Phe receptors in polymorphonuclear leukocytes of patients with non-insulin-dependent diabetes mellitus.

The signal transduction of the formyl-Met-Leu-Phe (FMLP) receptor in polymorphonuclear leukocytes (PMNLs) from patients with non-insulin-dependent diabetes mellitus (NIDDM) was compared to that of PMNLs obtained from healthy volunteers. According to our previous studies in this group of patients neither the decrease in insulin binding capacity nor the enhanced insulin-degrading enzyme activity was involved. In control PMNLs, 10 nM FMLP induced a pertussis toxin-sensitive increase in phosphatidyl inositol (PI) cleavage and a subsequent Ca2+ signaling from the intracellular pools. On the other hand, the FMLP-induced protein kinase C (PKC) activation and translocation into the membrane could not be detected in these cells via the measurement of 32P incorporation into histone. In contrast, in PMNLs of this special group of patients suffering from NIDDM the FMLP stimulus produced a significantly low increase in PI cleavage and Ca2+ signaling from the intracellular pools. Moreover, in resting PMNLs of these patients with NIDDM, not only the [Ca2+]i but also the membrane-bound PKC activity was found to be significantly increased. In addition, PKC translocation into the cell membrane of diabetic PMNLs could be further triggered with FMLP as judged by the measurement of 32P incorporation into histone. Based on these results, it appears that the signaling of FMLP receptors in PMNLs of some NIDDM patients may have an alternative pathway through Ca2+ influx from extracellular medium, arachidonic acid cascade, and PKC activation.

Arachidonic Acid↗

PubMed1998

Specific and scavenger low-density lipoprotein receptors involved in the disturbed lipid metabolism of patients with non-insulin-dependent diabetes mellitus are independent of obesity.

Comparative studies were performed on monocyte-derived macrophages (MDMs), prepared by a 72-hour incubation of blood monocytes obtained from patients with non-insulin-dependent diabetes mellitus (NIDDM) and age-matched obese and non-obese controls. The MDMs, after a 72-hour culturing, expressed both specific and scavenger low-density lipoprotein (LDL) receptors on their surfaces. To study the binding capacity of both receptor types, [125I]LDL and [125I] acetylated LDL (acLDL) were applied to cells and the labeled ligands were then monitored to estimate the rate of intracellular degradations. The LDL-induced inhibition of endogenous cholesterol synthesis and the acLDL-triggered apolipoprotein (apo) E secretion were also studied, as the biological marker of receptor activation. The results indicate that the binding capacities of both specific and scavenger LDL receptors were not reduced in MDMs of diabetic patients. However, the intracellular degradation after LDL incorporation was decreased. The LDL-induced inhibition of cholesterol synthesis and the acLDL-transmitted apo E secretion were also found to be decreased in the MDMs of patients with NIDDM as compared with the obese and non-obese control groups. The NIDDM-induced impaired signal transduction of both specific and scavenger LDL receptors suggests an unclarified functional alteration of both receptor structures.

Acetates↗

PubMed1998

Heterogeneous signal pathways through TSH receptors in porcine thyroid cells following stimulation with Graves' immunoglobulin G.

OBJECTIVE: We compared different signal transduction pathways through thyroid stimulating hormone receptor (TSH-R) in porcine thyroid cells (PTC) following stimulation with thyroid stimulating hormone (TSH) and 11 thyroid stimulating immunoglobulin samples (TSI) obtained from patients with Graves' disease. DESIGN: Following stimulation with TSI, the level of inositol trisphosphate (IP3) and [Ca2+]i, as well as the membrane bound protein kinase C (PKC) activity and the intensity of the arachidonic acid (AA) cascade, were determined in PTC. RESULTS: Seven out of eleven TSI samples activated PTC through IP3 generation, elevated [Ca2+]i from the intracellular pools, exhibited verapamil-insensitive membrane-bound PKC activation, and enhanced release of [14C]AA derivates (however, one of the samples was also able to take up Ca2+ from the extracellular space). Four out of eleven TSI samples did not activate the phospholipase C (PLC) system in which case the Ca2+ signal occurred only in the presence of extracellular Ca2+, the membrane bound PKC activation was verapamil sensitive, and in two of these four TSI samples, the AA release was extremely high. CONCLUSIONS: The simultaneous examination of the majority of the known signal pathways using TSI samples showed that TSI samples from different patients activate thyroid cells through different pathways. Their effects differ from that of TSH and, to a certain extent, from each other. The results give a certain new insight into the intracellular mechanisms exerted by TSI.

Adult↗

PubMed1997

[Biologic effect of LDL binding and intracellular degradation in monocytes from patients with hypercholesterolemia].

The granulocytes from elderly patients were investigated, in previous studies, with FMLP and it was found that the postreceptor signal, the inositol phosphate production and inositol phosphate dependent calcium signal were markedly reduced. It was observed that the 125I LDL binding was slightly reduced while the intracellular degradation of the LDL and endogenous cholesterol synthesis inhibitory effect was significantly decreased on monocytes of patients with non insulin dependent diabetes mellitus. It was suggested that of in patients suffering from NIDDM with hypercholesterolemia the LDL receptor numbers of monocytes are close to normal, while the post receptor signal transmission is damaged. In this study the monocytes from 12 patients with hypercholesterolemia were investigated before and after LDL treatment and were compared to the 11 age-matched healthy volunteer control patients. The cells were stimulated with LDL and chemotactic peptide FMLP. The postreceptor signal mechanism in monocytes was investigated. According to the results the inositol phosphate level of the patient group decreased independently from the stimulus. The LDL induced IP3 and Ca2+ level elevation was PT resistant both in the control and in the patients group.

Aged↗

PubMed1997

[Abnormal function of lipoprotein receptors in the monocytes of hypercholesteremic patients].

The familial hypercholesterinemia (HCh) is as a genetically determined disorder. The genetical damage and functional abnormalities of the LDL receptors lead to familial Hch. The LDL plays an important role in cholesterol metabolism. They carry cholesterol which metabolizes through specific and scavenger LDL receptors. The ApoB100 particle of LDL binds to the receptors, internalizated, and digested, and the remaining free cholesterol regulates the intracellular cholesterol synthesis. It inhibits the key enzyme, HMG-CoA reductase and decreases the LDL receptor synthesis and increases cholesterol esterification. These mechanism can prevent the cholesterol accumulation of the cells. The aim of the present study was to clarify the activity and number of the LDL receptor, to study the LDL binding and degradation and to evaluate how the intracellular cholesterol can regulate the synthesis in patients with HCh. 58 pts with HCh and their monocytes were investigated, because the monocyte derived macrophages contained both specific and scavenger receptors. Monocytes of the pts were compared to the healthy individual controls. From the results it could be recognized--that the decreased binding to the specific LDL receptors only at 6 pts cholesterol synthesis was elevated in HCh pts group, while the synthesis inhibition induced by 50 micrograms LDL was decreased. The presented experimental results suggested that the decreased binding ability to LDL receptors is a rare cause of cholesterol abnormalities, while during the intracellular degradation process more metabolic steps can be damaged in patients with HCh.

Cholesterol↗

PubMed1997

[Intracellular signal transmission of low density lipoprotein receptors in human monocytes].

The authors found that in human monocytes administered low density lipoprotein in doses of 50 micrograms had optimal inhibition of endogenous cholesterol synthesis which measured by [14C] acetate incorporation. There was not effect of pertussis toxin and phorbol myristate acetate on the inhibiton of endogenous cholesterol synthesis, whereas calcium channel blocker verapamil and phospholipase A2-inhibitor chloroquine decreased it. In contrast, the protein kinase C-stimulant phorbol myristate acetate alone had effects as LDL, but the protein kinase C-inhibitor H-7 had antagonist effect against LDL. Inositol phosphate generation was induced by administration of LDL in doses of 50 micrograms, which was pertussis toxin insensitive. The calcium signal was not also pertussis toxin sensitive, while occurred an intensive protein kinase C activation by administration of LDL. In signal transduction of monocytes activated by LDL may be an important role of the opening of calcium channels and activation of two enzymes, such as phospholipase A2 and protein kinase C.

Calcium Channel Blockers↗

PubMed1996

Parameters of respiratory burst and arachidonic acid metabolism in polymorphonuclear granulocytes from patients with various thyroid diseases.

The oxidative processes (oxygen consumption, superoxoid anion generation, arachidonic acid cascade) of human polymorphonuclear granulocytes (PMNs) obtained from patients suffering from thyroid disorders of autoimmune origin (Graves' disease and Hashimoto's thyroiditis), and non autoimmune origin (toxic adenoma) were investigated. All Graves' and toxic adenoma patients were hyperthyroid. Hashimoto's thyroiditis patients were euthyroid. Healthy age and sex matched volunteers served as controls. The results are as follows: 1) In PMNs from both hyperthyroid groups (Graves' disease and toxic adenoma), independently from the autoimmune origin of the disease, a significantly increased Antimycin A sensitive mitochondrial oxygen consumption and a slightly increased superoxide anion generation were detected. 2) In both autoimmune thyroid disease groups (Graves' disease and Hashimoto's thyroiditis)--depending on the functional state of the thyroid gland--a significantly altered intracellular killing activity was measured. 3) An increased arachidonic acid cascade--triggered by opsonized zymozan (OZ)--was detected in both autoimmune thyroid diseases. The increased arachidonic acid cascade was sensitive to phospholipase A2 inhibiting Mepacrin treatment. 4) The PMNs from both autoimmune thyroid diseases produced large amount of leukotriens (LTs)--LTC4 and LTB4--after stimulation through their Fc receptors but the synthesis of prostagalandins (PGs) has not changed. There are no data indicating local, specific effects of circulating leukotriens in the thyroid gland itself, but based on authors' data, their general, regulating role on both the endocrine-- as well as on the immune system--seems to be plausible.

Adenoma↗

PubMed1990

Disturbed intracellular calcium-related processes of hepatocytes and neutrophils in human alcoholic liver disease.

Isolated human hepatocytes and separated neutrophils of 11 patients with alcoholic liver disease (ALD) were used to study some aspects of cellular calcium-related processes compared to nonalcoholic controls. 45Ca2+ efflux from the cells decreased in ALD and the calmodulin-inhibitor trifluoperazine did not influence it further. The intracellular free calcium concentration [( Ca2+]i) of nonstimulated hepatocytes and neutrophils proved to be higher in ALD with the Quin2/AM loading technique. However, the [Ca2+]i rise in hepatocytes and neutrophils, with stimulation by low density lipoprotein (LDL) and N-formyl-methionyl-leucyl phenylalanine (FMLP), respectively, was diminished in ALD compared to appropriate controls. The slower 45Ca2+ extrusion rate, higher basal [Ca2+]i levels, and the diminished [Ca2+]i elevation of activated hepatocytes and neutrophils, suggest disturbed calcium-related intracellular processes in ALD, in particular, impaired regulation of the plasma membrane Ca2(+)-ATPase.

Adult↗

PubMed1989

Age related impairment in phosphatidylinositol breakdown of polymorphonuclear granulocytes.

It is well known that with aging the immune response decreases. Most of the effector functions occur through specific receptors. Thus, we investigated the effects of various stimulants, acting through receptors or directly through the GTP-binding Gi protein, on phosphatidylinositol breakdown in PMNLs of young and elderly subjects and try to modulate it. A marked decrease in inositol phosphate (IP1, IP2, IP3) formation in PMNLs of elderly was found under FMLP stimulation when compared to that of young subjects. Neither GTP gamma S, nor AIF4- could induce an increase of IP3 in PMNLs of elderly comparable to that of young subjects. The results suggest that at least an alteration exists at the GTP-binding Gi protein level, as well as in the mechanism of linkage of the receptor to the G protein.

Adult↗

PubMed1989

Blood laboratory parameters of carefully selected healthy elderly people.

Hematological and biochemical parameters were measured in carefully selected healthy elderly (50 males and 50 females, aged 60-97 years) and young (10 males and 10 females, aged 18-23 years) populations. Most of the parameters measured did not show any age-related variations. It means that any deviation from the present normal ranges established for healthy young subjects should be considered as pathologic in the case of elderly, too. Some parameters showed age-specific changes and hence there is a possibility that their actual normal ranges might be extended towards the upper limit (globulin, IgG, IgA, CIC, C3, BUN, AP for females), or towards the lower limit (creatinine clearance, albumin). Verification of these modifications may indicate that a lot of unnecessary investigations in the case of elderly could be avoided.

Adolescent↗

PubMed1988

Studies on opsonized zymozan, FMLP, carbachol, PMA and A23187 stimulated respiratory burst of human PMNLs.

The O2- production as a marker of the respiratory burst was investigated under various stimulations in polymorphonuclear leukocytes of healthy young and aged subjects. Stimulation of the respiratory burst in the cells of elderly by specific agents (opsonized zymozan, N-formyl-methionyl-leucyl-phenylalanine, carbachol) resulted in a diminished response while it remained unchanged on the effect of non-specific stimulation (A23187, phorbol myristate acetate) comparing to young subjects. To elucidate the postreceptor signal transduction mechanism involved in respiratory burst stimulation various inhibitors were used as follows: neomycin (for phospholipase C enzyme), mepacrine (for phospholipase A2 enzyme) and pertussis toxin (for GTP binding regulatory protein). The results suggest that phospholipase C as well as phospholipase A2 could be involved in the postreceptor signal transduction depending on the stimulus, but the impairment of the pertussis toxin sensitive GTP binding protein with aging might explain the decrease response of the respiratory burst after stimulating the different receptors.

Adult↗

PubMed1988

Human model for studying in vitro the regulating function of specific and scavenger LDL receptors.

Measurements of the specific and scavenger LDL receptor activities in different disorders do not reveal all the causes and origin of hypercholesterolaemia. Studying the failure of the intracellular regulation of these receptors can give us some new information about the background of atherosclerosis. Therefore, we have tried to develop an in vitro model which is suitable for studying the specific and scavenger LDL receptor activities and their most important regulating functions, i.e. the inhibition of HMG-Co-A reductase by native LDL and the apo E secretion induced by acLDL. MDMs cultured for three days have turned out to provide a good model to test these functions.

Antigens, Differentiation↗

PubMed1987

Alterations of the FMLP-induced Ca2+ efflux from human monocytes with aging.

The Ca2+ with the calmodulin system plays a major role in the receptor-induced intracellular biochemical events. Thus, as in our previous studies, we found an altered postreceptorial coupling in the case of elderly, we were interested to elucidate the Ca2+ transport in the case of healthy young (less than 25 years) and aged (greater than 65 years) subjects. The chemotactic peptide FMLP was used for receptor stimulation. Our data show that both spontaneous and FMLP-triggered Ca2+ extrusion measured on monocyte monolayers is decreased with aging. The FMLP-triggered Ca2+ extrusion nevertheless did not occur through the TFP-sensitive pathway. These alterations of Ca2+ transport seem to indicate an impaired Ca2+-calmodulin function in monocytes with aging.

Adult↗

PubMed1987

Glucose intolerance and insulin resistance with aging--studies on insulin receptors and post-receptor events.

The oral glucose tolerance test and immune reactive insulin level determination were performed on 100 non-obese healthy elderly and 40 young and middle-aged non-obese healthy subjects. In about 60% of the elderly an altered glucose tolerance test was found, but the insulin level was increased in the whole group of elderly subjects. This means an insulin-resistant state with aging. Further investigations were carried out to determine some possible causes of this insulin resistance. The chromium level in sera and granulocytes of elderly was significantly decreased as well as the insulin receptor numbers and the affinity to erythrocytes. In contrast, when the cyclic nucleotide levels were investigated in granulocytes under in vitro stimulation, an age-dependent increase of cAMP level was found and an unresponsiveness of cGMP, which ranged between mild and severe degrees. Concomitantly, all these changes found could contribute to the insulin resistance at the receptor and post-receptor levels with aging.

Adult↗

PubMed1987

Divergent effects of human lymphokine derived oligopeptides on PMNLs function of young and aged healthy subjects.

The effects of low molecular weight lymphokine-derived oligopeptides (LK-OPs) on PMNLs effector functions and receptor mediated biochemical events were studied in the case of healthy young and aged subjects. In the case of young subjects the low mol. wt. LK-OPs stimulated the Fc gamma receptor-mediated effector functions of PMNLs, whereas an inhibition was observed in PMNLs of the elderly (extracellular cytotoxicity and intracellular killing). The underlying biochemical events, induced by low mol. wt. LK-OPs stimulation, were also investigated. In PMNLs of young subjects the oxidative metabolism was stimulated (enhanced O2 consumption, O2 and H2O2 production) by low mol. wt. LK-OPs, while in elderly subjects it was inhibited. The cyclic nucleotides regulating the Fc gamma receptor mediated effector functions and the oxygen radicals formation showed an altered dynamic response under low mol. wt. LK-OPs stimulation with aging i.e. the cGMP level could not be changed at all. Our results suggest that low mol. wt. LK-OPs induced inhibition of Fc gamma receptor mediated effector functions with aging could be partly explained by an altered post receptorial coupling switch and as a consequence the lymphokines could not play their role of immunomodulators further impairing the altered immune response with aging.

Adult↗