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T Fülöp

Publications and source records attributed to T Fülöp.

At least 19 recordsLinked to original sources
PubMed2002

Effect of poloidal density variation of neutral atoms on the tokamak edge.

Neutral atoms in the tokamak edge affect the electric field and plasma flow through charge exchange. Here, it is shown that these effects depend sensitively on the poloidal location of the atoms. It is found that the radial electric field and toroidal flow velocity in a collisional edge plasma are largest if the atoms are concentrated on the inboard side. This feature may explain MAST and COMPASS-D observations indicating easier H-mode access for inboard gas puffing. The results suggest an external means of controlling the toroidal flow and radial electric field and their shear, and have motivated further MAST measurements appearing to support the predictions.

Journal Article↗
PubMed2001

Altered T cell signalling in ageing.

T cell responses are altered in the aged in a manner usually interpreted as detrimental to host defences against infectious agents and possibly also against cancer. T cell dysregulation may be caused by any or a combination of stem cell deficits, compromised T cell differentiation, inefficient antigen processing and presentation by antigen presenting cells, suboptimal processing of the antigenic signal by T cells or inability of the T cell to respond appropriately thereafter. This review will focus on altered T cell signalling in ageing, encompassing not only alterations in signal transduction by the antigen-specific T cell receptor, but changes in the balance of positive and negative T cell costimulation and the resultant modified cytokine environment, the response to which is itself altered in ageing.

Aging↗
PubMed2001

Cyclodextrin modulation of T lymphocyte signal transduction with aging.

There is an alteration of the immune response in aging that leads to the increased incidence of infections, cancers and autoimmune disorders. The aim of the present study was to investigate whether there exists changes in signal transduction under the IL-2 receptor stimulation and the role of plasma membrane cholesterol in the activation of T cells with aging. We report age-related changes in the JAK-STAT signalling pathway that results in decreased tyrosine phosphorylation of STAT5. We present evidence for the importance of cholesterol content in regulating signalling pathways in T cells and in modulating their proliferation by using the plasma membrane cholesterol-depleting agent methyl-beta-cyclodexrin (MBCD). MBCD treatment (0.5 mM) induced a significant decrease in the cholesterol content of T cells of elderly subjects whereas it was increased in T cells of young subjects. MBCD induced changes in the phosphorylation of p56(lck), especially in T cells of elderly subjects. The proliferation of MBCD-treated T cells decreased in lymphocytes of young subjects but did not change in T cells of elderly subjects. These results suggest a role for plasma membrane cholesterol in the regulation of the TcR signalling pathways with differential effects related to aging. However, the data suggest that modulation of the plasma membrane cholesterol content alone may not be enough to restore signal transduction changes with aging.

Adult↗
PubMed2001

Monocytes influence the fate of T cells challenged with oxidised low density lipoproteins towards apoptosis or MHC-restricted proliferation.

Atherosclerosis has been implicated in myocardial infarction, stroke and a host of cardiovascular diseases. The presence of activated T lymphocytes and macrophages, and the increased expression of HLA-DR antigen are consistent with the notion of immune activity in the atherosclerotic plaque. The nature of the causative antigen has not been established although oxidised low density lipoproteins (oxLDL) that accumulate in atherosclerotic plaques could fulfil this role. Here, we report that monocytes play a key role in influencing the fate of purified peripheral human T lymphocytes from healthy donors when the cells are exposed to LDL oxidised under the controlled conditions of water radiolysis. Our data showed that oxLDL generated under these conditions were chemoattractants for T cells. However, they induced a state of apoptosis in T lymphocytes cultured in the absence of monocytes. The extent of apoptosis was related to the degree of oxidation of LDL and the time of T cell exposure to oxLDL. OxLDL-dependent apoptosis did not involve a scavenger-like receptor. CD4(+) cells were more sensitive to the apoptotic effect of oxLDL than CD8(+) cells. OxLDL-primed (12 h) autologous monocytes triggered a robust proliferation of T lymphocytes cultured in the absence of oxLDL. The strength of T cell stimulation was related to the degree of oxidation of the LDL used in priming. Heterologous monocytes exposed to oxLDL under similar conditions induced a response that was not different than monocytes exposed to untreated LDL (natLDL) which did not induce T cell proliferation. Fucoidan did not modify the oxLDL-, monocyte-dependent T cell response to proliferation, suggesting that a scavenger-like receptor was not involved. The expression of the HLA-DR marker and the B7.2 protein were up-regulated in monocytes exposed to oxLDL but not to natLDL. The levels of B7.1 were unchanged. Our data are consistent with the notion that monocytes are critical for T cell survival in the presence of oxLDL and MHC-restricted T cell proliferative response to oxLDL.

Adult↗
PubMed2001

A comparison of the kinetics of low-density lipoprotein oxidation induced by copper or by gamma-rays: influence of radiation dose-rate and copper concentration.

The oxidation of low-density lipoproteins is the first step in the complex process leading to atherosclerosis. The aim of our study was to compare the kinetics of low density lipoprotein oxidation induced by copper ions or by oxygen free radicals generated by 60Co gamma-rays. The effects of copper concentration and irradiation dose-rate on LDL peroxidation kinetics were also studied. The oxidation of LDL was followed by the measurement of conjugated diene, hydroperoxides, and thiobarbituric acid reactive substance formation as well as alpha-tocopherol disappearance. In the case of gamma irradiation, the lag-phase before the onset of lipid peroxidation was inversely correlated to the radiation dose-rate. The radiation chemical rates (nu) increased with increasing dose-rate. Copper-induced LDL peroxidation followed two kinetic patterns: a slow kinetic for copper concentrations between 5-20 microM, and a fast kinetic for a copper concentration of 40 microM. The concentration-dependent oxidation kinetics suggest the existence of a saturable copper binding site on apo-B. When compared with gamma-rays, copper ions act as drastic and powerful oxidants only at higher concentrations (> or = 40 microM).

Adult↗
PubMed2001

[The elastin-laminin receptor].

Elastin is a major component of the extracellular matrix. Elastin peptides derived from its degradation are present in human sera. Elastin peptides induce on fibroblasts, phagocytic cells, lymphocytes, smooth muscle cells and endothelial cells, a variety of biological effects mediated by the elastin-laminin receptor which has been demonstrated to be present on the membrane of these cells. The transduction pathway of the ELR receptor involves the activation of phospholipase C (PLC) by a pertussis toxin sensitive G-protein. PLC induces the production of inositol trisphosphate (IP3) leading to the increase of the intracellular free calcium on one hand, and of diacylglycerol (DAG) which stimulates the translocation to the membrane of PKC leading to the phosphorylation of members of the MAPK family, such as p42/p44 MAPK. Considering the multiple biological effects of ELR the elucidation of the complexity of the signaling pathways will help to better modulate it, mainly in pathological situations such as atherosclerosis.

Animals↗
PubMed2000

Effects of aerobic physical exercise in the elderly with type 2 diabetes mellitus.

The objective of this study was to determine the impact of an aerobic physical exercise program in the treatment of a group of elderly patients with type 2 diabetes mellitus (DM) in relation to metabolic control, physical capacity, quality of life (QOL) and attitudes toward diabetes. Patients were randomly assigned to either an experimental (n=19) or a control (n=20) group. The following measurements were conducted at baseline and after week 16: glycosylated hemoglobin (hbA1c), fructosamine, 3 h oral glucose tolerance test, treadmill test (Balke-Naughton), and a questionnaire on QOL and attitudes toward DM. After the intervention, the experimental group showed a significant decrease of glucose excursion during the oral glucose tolerance test (OGTT) (area under the curve) (16.6+/-3.8 vs. 15.3+/-3.1, P<0.05) and an increase in total time on the treadmill (s) (423+/-207 vs. 471+/-230, P<0.05). An improvement in the attitudes toward DM was observed in the experimental group (P=0.01) but not in the control group. Female gender, higher body mass index and hbA1c were factors associated with a response to the intervention. This study suggests that physical exercise has significant effects on glucose excursion during an OGTT and exercise tolerance in elderly patients with type 2 DM.

Journal Article↗
PubMed2000

Direct correlation of glutathione and ascorbate and their dependence on age and season in human lymphocytes.

BACKGROUND: Endogenous reactive oxygen species appear to contribute to aging and cancer and dietary antioxidants, present in fruit and vegetables, counteract these effects. OBJECTIVE: The objective was to examine the association between intracellular glutathione, ascorbate (vitamin C), and alpha-tocopherol (vitamin E) in human lymphocytes. DESIGN: The study group consisted of 240 healthy nonsmoking volunteers with an approximately equal number of male and female subjects subdivided into 3 age groups: 18-39, 40-59, and >/=60 y). Glutathione, glutathione disulfide, ascorbate, and alpha-tocopherol were measured in lymphocytes by HPLC. RESULTS: The average concentration of antioxidants in lymphocytes was 27 +/- 8 nmol/mg protein for glutathione, 21 +/- 8 nmol/mg protein for ascorbate, and 0.4 +/- 0.2 nmol/mg protein for alpha-tocopherol. There was a strong positive correlation between glutathione and ascorbate (r = 0.62, P < 0.001). No correlation was observed for glutathione and ascorbate with alpha-tocopherol. The concentration of glutathione in lymphocytes was inversely correlated with age (r = -0.19, P < 0.01), as was that of ascorbate (r = -0.22, P < 0.01), with 10-20% lower values in elderly than in young and elderly subjects. The concentrations of glutathione in lymphocytes were as much as 25% higher and those of ascorbate were as much as 38% higher during the summer than during the winter. The seasonal variation of ascorbate in lymphocytes was described by a linear function for age and a periodic sine function for season. CONCLUSION: Glutathione and ascorbate are directly correlated in human lymphocytes.

Adolescent↗
PubMed2000

Interleukin-2 involvement in early acute respiratory distress syndrome: relationship with polymorphonuclear neutrophil apoptosis and patient survival.

OBJECTIVE: To determine blood and lung alveolar concentrations of interleukin (IL)-2 in acute respiratory distress syndrome (ARDS) and their relationship with polymorphonuclear neutrophil (PMN) apoptosis and patient survival. DESIGN: Prospective cohort study. SETTING: Medical and surgical intensive care units (ICUs; Canada) and the intensive care department (Belgium). PATIENTS: Nineteen consecutive patients with ARDS, 14 non-ARDS ICU patients, and 20 healthy volunteers. INTERVENTIONS: Blood samples and bronchoalveolar lavages (BAL) obtained via venous puncture and by fiberoptic bronchoscopy in the first 72 hrs after the onset of ARDS. MEASUREMENTS AND MAIN RESULTS: One early point concentration of IL-2 was measured in both blood and BAL fluids of the three groups. In vivo alveolar PMN apoptotic index in BAL fluids and the influence of BAL fluid exposure on normal blood PMN spontaneous apoptosis in vitro were evaluated. Blood IL-2 was significantly lower in patients with ARDS compared with non-ARDS ICU patients and controls. In contrast, IL-2 in BAL fluids of patients with ARDS was dramatically elevated compared with non-ARDS ICU patients and controls. ARDS survivors exhibited lower early IL-2 blood levels than nonsurvivors and generally had a higher IL-2 lung content Lung alveolar PMN apoptosis in vivo was lower in patients with ARDS in comparison with controls. This apoptotic index was correlated with corresponding IL-2 alveolar levels in patients with ARDS. Exposure of normal blood PMN to BAL fluids from patients with ARDS delayed apoptosis in vitro. Immunodepletions of IL-2, granulocyte-macrophage colony stimulating factor, and a combination of both cytokines from BAL fluids of ARDS patients significantly restored PMN apoptosis. The recovery of PMN apoptosis was more effective when IL-2 was depleted in BAL fluids from ARDS survivors compared with nonsurvivors. CONCLUSIONS: Opposite and disproportional concentrations of IL-2 are observed in blood and lung fluids of patients with early ARDS. IL-2 significantly contributes (with granulocyte-macrophage colony stimulating factor) to the inhibition of PMN apoptosis in BAL fluids of patients with ARDS. Early low blood IL-2 and high IL-2-driven inhibition of PMN apoptosis are beneficial to survivors. Thus, IL-2 is a new candidate for monitoring in early ARDS and an interesting indicator of prognosis.

APACHE↗
PubMed2000

Chronic PMA treatment of Jurkat T lymphocytes results in decreased protein tyrosine phosphorylation and inhibition of CD3- but not Ti-dependent antibody-triggered Ca2+ signaling.

We have treated Jurkat T lymphocytes with a concentration (160 nM) of phorbol myristyl acetate (PMA) that down-regulates conventional and novel protein kinase C (PKC) isozymes and we have investigated the effects on Ca2+ signaling and protein tyrosine phosphorylation using mAb (C305) directed against the beta-subunit of the Ti heterodimer or the epsilon/delta-component of the CD3 complex (mAb Leu 4 or OKT 3). The levels of expression of PKC alpha, betaI, betaII, and delta were reduced by 90% or more in PMA-treated cells, whereas the expression of PKCtheta decreased by approximately 30%. In contrast, the chronic treatment with PMA increased the expression of PKCepsilon and PKCzeta. There was a lack of Ca2+ response and myo-inositol trisphosphate (IP3) production in PMA-treated cells when they were exposed to mAb Leu 4 but the cells responded to mAb C305. The treatment with PMA did not affect the surface expression of Ti or CD3. The overall levels of tyrosine-phosphorylated proteins were markedly reduced in PMA-treated cells. We investigated whether these observations were related to defects in signal transduction related to protein tyrosine kinase (PTK) of the src and syk families. The electrophoretic mobilities of p59(fyn) or ZAP-70 were not changed in PMA-treated cells but p56(Ick) migrated as a large band of M(r) 60-62 kDa. The decreased mobility of p56(Ick) was related to a state of hyperphosphorylation. The activity of modified p56(Ick) was not up-regulated in activated Jurkat cells. Our data suggest that clonotypic Ti can trigger Ca2+ mobilization independently of conventional PKC isoforms. Our observations further suggest that conventional PKC isoforms are involved early in the cascade of events associated with Jurkat T lymphocyte activation.

CD3 Complex↗
PubMed2000

Age-related decrease of dehydroepiandrosterone concentrations in low density lipoproteins and its role in the susceptibility of low density lipoproteins to lipid peroxidation.

The incidence of atherosclerosis and related diseases increases with age. The aging process may enhance lipoprotein modification, which leads to an increase in the susceptibility of low density lipoprotein (LDL) and high density lipoprotein (HDL) to oxidation. Dehydroepiandrosterone (DHEA), the most abundant steroid hormone in humans, has been shown to have antiatherogenic effects. This hormone also decreases dramatically with age. In the present study, we were interested in determining the presence of DHEA/DHEAS (dehydroepiandrosterone sulfate) and changes in their concentrations in HDL and LDL lipoproteins with age. Moreover, we studied the susceptibility of LDL to oxidation with age in the presence or absence of vitamin E or DHEA. We demonstrated that vitamin E is unable to restore the decreased resistance to oxidation of LDL from elderly subjects to that of LDL obtained from young subjects. Furthermore, our results provide evidence that DHEA is an integral part of LDL and HDL and disappears to almost nondetectable levels during aging. The DHEA incorporated into the LDL from elderly subjects increased LDL resistance to oxidation in a concentration-dependent manner. The increased resistance provided by DHEA was higher than that with vitamin E. DHEA seems to act either by protecting vitamin E from disappearance from LDL under oxidation or by scavenging directly the free radicals produced during the oxidative process. Our results suggests that DHEA exerts an antioxidative effect on LDL, which could have antiatherogenic consequences. Careful clinical trials of DHEA replacement should determine whether this ex vivo effect could be translated into any measurable antiatherogenic (cardioprotective) action.

Adult↗
PubMed1999

[Improvement of myocardial perfusion following left ventricular resection].

Left ventricular aneurysm had detected at the 55-year-old woman after extensive anterior myocardial infarction in association with progressive ventricular dilatation and symptoms of heart failure. Coronary angiogram revealed a serious lesion in the proximal segment of the left anterior descending coronary branch with a poor run off tract. 18FDG-PET and 99mTc-MIBI-SPECT investigation were performed in order to differentiate the scarred regions from the viable myocardial segments. Taking into consideration the results an aneurysm resection was performed without revascularisation procedure. After the surgery not only the ejection fraction and the left ventricular dilatation had improved but the tissue perfusion in the segments surrounding the resected aneurysm had also showed a significant increase at the follow up MIBI-SPECT imaging.

Coronary Angiography↗
PubMed1999

Effects of gliclazide versus metformin on the clinical profile and lipid peroxidation markers in type 2 diabetes.

The sulfonylurea gliclazide and the biguanide metformin have different mechanisms to reduce glycemia. We performed a randomized study to compare these two agents with respect to glycemic control and effects on lipid peroxidation markers in 36 adult patients with type 2 diabetes. Both agents significantly decreased glycosylated hemoglobin ([HbA1c] P < .05), fructosamine (P < .05), and the glucose-excursion curve during the oral glucose tolerance test ([OGTT] P < .01). With regard to the insulin curve during this test, no significant change was observed with metformin and a significant increase was measured with gliclazide (P < .05). Considering the small number of events, no significant difference was detected in the number of hypoglycemic episodes between the two agents. More upper-gastrointestinal (GI) symptoms were observed with metformin compared with gliclazide (P < .05). Even with no change in the standard lipid profile, both agents increased serum vitamin E (P < .01 for gliclazide and P < .05 for metformin) and decreased the level of lipid peroxidation markers in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles (P < .05). Despite different mechanisms of action, gliclazide and metformin demonstrated comparable levels of efficacy and complementary effects on lipid peroxidation markers.

Aged↗
PubMed1999

Age-related impairment of p56lck and ZAP-70 activities in human T lymphocytes activated through the TcR/CD3 complex.

Cellular immune responses decrease with aging. Lymphocytes of aged individuals do not perform as well as cells from young subjects in a number of in vitro assays including cell proliferation, cytokine production, and protection against apoptosis. Here, we have tested the hypothesis that a decrease in T cell responses in tymphocytes from elderly subjects could parallel a decrease in the activity of protein tyrosine kinases (PTK) associated with signal transduction in T lymphocytes. We report that anti-CD3-triggered T lymphocyte proliferation was significantly decreased in T lymphocytes from elderly subjects, but the decrease was not due to an alteration of the percentage or mean fluorescence intensities of CD3, CD4, and CD45. Of significance, the activities of p56lck and ZAP-70 in vitro were significantly decreased in T lymphocytes from elderly subjects compared to young individuals. However, the level of expression of the two kinases did not change with aging. The activity of p59fyn did not show changes with aging, suggesting that p59fyn did not compensate for the decreased activity of p56lck. We also found that the extent of tyrosine phosphorylation of the adaptor protein p95vav was similar in activated T lymphocytes from elderly and young subjects. Our results suggest that the altered cellular immune responses observed in T lymphocytes with aging may be the result, at least in part, of an alteration in early events associated with signal transduction through the TcR/CD3 complex that translates into decreased activities of p56lck and ZAP-70. Impairment in the activities of these twokey components of T cell signaling may contribute to reduced immune functions associated with aging.

Adult↗
PubMed1999

Glutathione and ascorbate are negatively correlated with oxidative DNA damage in human lymphocytes.

Intracellular antioxidants, glutathione and ascorbate, and two molecular markers of oxidative DNA damage, 5-hydroxy-2'-deoxycytidine (5-OH-dCyd) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGuo), were measured in lymphocytes from 105 healthy volunteers. The analysis of 5-OH-dCyd and 8-oxo-dGuo was carried out by HPLC with electrochemical detection such that both compounds were detected on the same chromatography run. There was no significant difference in oxidative DNA damage when the extraction of DNA from cells using phenol was carried out under anaerobic conditions or in the presence of metal ion chelators. This indicates that auto-oxidation of DNA during sample preparation was minimal. Using the above methods, the average level of oxidative DNA damage in lymphocytes was 2.9 +/- 1.4 for 5-OH-dCyd and 4.5 +/- 1.8 for 8-oxo-dGuo lesions per 10(6) dGuo (n = 105). It is unlikely that artifactual oxidation contributed to the observed damage because the level of 5-OH-dCyd was comparable with that of 8-oxo-dGuo in lymphocyte DNA, whereas 8-oxo-dGuo outnumbers 5-OH-dCyd by a ratio of >5:1 when DNA is exposed to various oxidants, including ionizing radiation or Fenton reagents. Rather, the nearly equal levels of 5-OH-dCyd and 8-oxo-dGuo in cellular DNA implies that 8-oxo-dGuo may be more efficiently removed by DNA repair. Finally, and most importantly, the correlation of our endpoints revealed that the naturally occurring level of intracellular antioxidants was negatively correlated to the level of oxidative DNA damage with the strongest correlation observed for glutathione and 8-oxo-dGuo (r = -0.36; P < 0.001). These results strongly suggest that intracellular glutathione and ascorbate protect human lymphocytes against oxidative DNA damage.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1999

Effects of an oral glucose challenge on free radicals/antioxidants balance in an older population with type II diabetes.

BACKGROUND: Our goal was to assess the effect of chronic vs acute hyperglycemia on free radicals (FR)/antioxidants balance in serum and leukocytes in an older (>65 years old) population with type II diabetes mellitus (DM). METHODS: Case-control study comparing older male patients with type II DM with normal controls. FRs and antioxidants were measured at baseline and 120 min after an oral 100-g glucose load. RESULTS: Baseline measurements showed an increased level of oxidized glutathione (GSSG) (p = .01) in the serum of diabetic subjects. Similar findings were observed at the intracellular level in the same group for GSSG (p = .0004), total glutathione (GSH + GSSG) (p = .0001) (GSH is reduced glutathione), decreased GSH/GSSG ratio (p = .0001), and ascorbic acid (p = .008). Monocytes from diabetic subjects produced larger amounts of nitric oxide (NO) in vitro (p = .03). After the oral glucose challenge, between-group comparisons demonstrated similar findings at the intracellular level for increased oxidized glutathione (p = .0004), GSH + GSSG (p = .0001), decreased GSH/GSSG (p = .0001), ascorbic acid (p = .02), and increased NO (p = .02) for the diabetic subjects. Within-group comparisons showed a significant drop of ascorbic acid in the control and the diabetic groups (p < .01), an increased level of GSSG in the diabetic group (p < .01), a decreased GSH/GSSG ratio (p < .05), and decreased production of NO by monocytes after in vitro stimulation in the control group (p < .05). CONCLUSIONS: Our results suggest that type II diabetes in an older population is associated with increased basal oxidative stress. Hyperglycemic challenge is associated with an accentuation of this phenomenon as measured in the leukocytes.

Administration, Oral↗
PubMed1999

Relationship between the response to influenza vaccination and the nutritional status in institutionalized elderly subjects.

BACKGROUND: Influenza is a major health problem among elderly people in industrialized countries. Nursing homes may be a particularly good setting for outbreaks of influenza. Thus, the aim of the present study was to evaluate some aspects of the nutritional status of institutionalized elderly subjects in relation to their response to influenza vaccination. Certain aspects of the cellular immune response were also investigated. METHODS: Twenty-three patients participated in this cross-sectional study. All patients were vaccinated on day 0 with FluviralR, 1994-95 preparation: A/Shangdong/09/93, A/Texas/36/91, B/Panama/45/90. At the same time the prevaccination antibody titer, the nutritional status by the Mini Nutritional Assessment, biochemical parameters, and lymphocyte proliferation were assessed. On day 28, the postvaccination antibody titer was determined. The determination of pre- and postvaccination antibody titers against the various influenza antigens was carried out by the hemagglutination inhibition test. An increase of 4x for any of the virus antigens was considered as a seroconversion. A titer higher than 40 at the prevaccination period was considered as protective. RESULTS: Eleven elderly subjects were responsive and 12 were not. We have shown that the nutritional parameters such as hemoglobin, hematocrit, total protein, iron and vitamin E levels, as well as the DHEA level and the cellular immune response were significantly lower in the nonresponsive group as compared to the responsive group. Thus, they might be associated with the influenza vaccine responsiveness of institutionalized elderly subjects. CONCLUSIONS: These results will help design intervention studies for improving the immune response by achieving an optimal nutritional status, mainly in the frail elderly population, that could have a great public health impact.

Aged↗