PubMed Health⌕ Search

Biomedical subjects

G Szegli

Publications and source records attributed to G Szegli.

At least 19 recordsLinked to original sources
PubMed2004

Evidence for immune defects in breast and lung cancer patients.

Immunosuppression is often identified in cancer patients. The aim of this study was to evaluate several immune parameters for patients with breast and lung cancer. Immunophenotyping analysis showed that the cancer patients investigated had significantly lower absolute numbers of peripheral blood lymphocytes than controls. The immunosuppression was more evident for the breast cancer subgroup. The most severe immune defect noticed was the marked impairment of IFN-gamma secretion. A shift toward the Th2 phenotype as revealed by assessment of intracellular level of IFN-gamma and IL-4 was also noticed. The secretion of proinflammatory cytokines IL-1beta and TNF-alpha in whole blood cultures was not impaired. Although the proportion of activated cells was slightly lower than in the control group, our results showed that both peripheral T lymphocytes and NK cells of cancer patients could be induced to express early activation marker CD69 after ex vivo mitogen stimulation. In conclusion, our study revealed several immune defects in cancer patients. This suggests that an appropriate immunotherapeutical approach might be used to restore compromised immune functions with beneficial effects on both antitumor and general immunity.

Adult↗
PubMed2001

Pycnogenol efficacy in the treatment of systemic lupus erythematosus patients.

A pilot study was performed to evaluate the efficacy of Pycnogenol treatment in systemic lupus erythematosus (SLE) patients. Eleven SLE patients were treated with first line medication according to disease activity and in addition, six of them received Pycnogenol and five a placebo. The SLE disease activity index (SLEDAI), serum anti-dsDNA antibodies, fibrinogen, C-reactive protein levels, erythrocyte sedimentation rate, production of reactive oxygen species (ROS) by neutrophils, spontaneous apoptosis and p56(lck) specific activity in peripheral blood lymphocytes were evaluated. Pycnogenol treatment determined a significant reduction of ROS production, apoptosis, p56(lck) specific activity and erythrocyte sedimentation rate. In addition, the decrease of SLEDAI was significant in the Pycnogenol treated group compared with the placebo group (p = 0.018). The results obtained suggest that Pycnogenol could be useful for second line therapy to reduce the inflammatory feature of SLE.

Adjuvants, Immunologic↗
PubMed2001

Dysregulation of p56lck kinase in patients with systemic lupus erythematosus.

In this study we investigated one of the possible mechanisms of p56lck down-regulation in peripheral blood lymphocytes (PBLs) from Systemic Lupus Erythematosus (SLE) patients and we correlated p56lck dysregulation with accelerated apoptosis in SLE PBLs. PBLs from SLE patients and healthy donors were isolated. p56lck protein expression and lck mRNA level were estimated by immunoblotting and RT-PCR, respectively. FACS analysis was used to evaluate the apoptosis and p56lck levels in apoptotic and non-apoptotic PBLs. A non-radioactive Tyrosine Kinase Assay Kit was used to measure p56lck activity. Our results demonstrated that PBLs from SLE patients displayed lower levels of lck mRNA and p56lck protein as compared to healthy donors. The apoptosis of fresh or cultured PBLs was enhanced in SLE patients, especially in anti-DNA negative group. The expression of p56lck was inverse correlated with apoptosis of fresh and cultured SLE PBLs, especially in anti-DNA negative patients. Double staining FACS analysis showed that p56lck expression was lower in apoptotic than in non-apoptotic PBLs. p56lck specific activity was directly correlated to apoptosis in SLE PBLs. While the low expression of p56lck may be the result of lower degree of synthesis, the increased specific activity could directly correlated to the extent of apoptosis in SLE PBLs. Based on our observations, we assume that the p56lck dysregulation could play a role in SLE pathogenesis.

Apoptosis↗
PubMed1999

p56lck activity and expression in peripheral blood lymphocytes from patients with systemic lupus erythematosus.

In this study we analyzed the activity and the expression of p56lck protein tyrosine kinase in peripheral blood lymphocytes (PBLs) from systemic lupus erythematosus (SLE) patients and from healthy donors. The p56lck activity, determined by a non-radioactive Tyrosine Kinase Assay Kit, was significantly higher in active SLE PBLs and discriminated this group of patients from inactive SLE patients (p = 0.002) and healthy donors (p = 0.009). p56lck level decreased in SLE lymphocytes (especially for inactive SLE lymphocytes, p = 0.005) when compared to healthy donors. These differences were also reflected by the specific activity of p56lck that was clearly elevated in active SLE lymphocytes when compared to inactive SLE (p = 0.022) or healthy donors lymphocytes (p = 0.006). A positive correlation between the activity of p56lck and the tyrosine phosphorylation level in active SLE lymphocytes was found.

Animals↗
PubMed1996

Tyrosine phosphorylation in peripheral lymphocytes from patients with systemic lupus erythematosus.

A comparative study of tyrosine phosphorylation was performed on peripheral blood lymphocytes from systemic lupus erythematosus (SLE) patients and from healthy donors. Freshly isolated SLE lymphocytes presented an elevated tyrosine phosphorylation level when compared to healthy donors lymphocytes (p = 0.005). Among all phosphorylated proteins, those called p120, p110, p80 and p55-p60 were more phosphorylated. The level of tyrosine phosphorylation of p120 and p110 proteins discriminated significantly (p = 0.0048, respectively, p = 0.02) between SLE patients and healthy donors. Lymphocytes form SLE patients and healthy donors were then stimulated by cross-linking T cell antigens (CD3, CD4, CD8) to further distinguish the signal transduction between normal and pathologic lymphocytes. No statistical differences in the tyrosine phosphorylation pattern, following CD4 or CD8 cross-linking, were observed between SLE patients and healthy donors lymphocytes. CD3 cross-linking induced an effect on tyrosine phosphorylation different in SLE patients versus healthy donors lymphocytes. Thus, the lymphocytes of SLE patients were refractile in anti-CD3 stimulation in comparison with the healthy donors lymphocytes. Chi-square analysis demonstrated that a significantly larger number of healthy donors responded to anti-CD3 stimulation compared to SLE patients (p = 0.03). The high frequency of tyrosine phosphorylation of p110 and p80 proteins, following CD3 stimulation, in normal versus SLE lymphocytes, suggested that these proteins could be involved in abnormal signal transduction in SLE cells.

CD3 Complex↗
PubMed1995

Naturally occurring anti-idiotypic antibodies to anti-phosphotyrosine in systemic lupus erythematosus interact with SRC-homology 2 domains.

We have recently identified in SLE sera naturally occurring anti-idiotypic antibodies against anti-phosphotyrosine antibodies. Analysis of immunochemical properties of these anti-idiotypic antibodies suggest that they are of beta/gamma type mimicking the antigen. The interaction between these anti-idiotypes and SH2 domains of various fusion proteins was analysed by immunoprecipitation and immunoblotting. Our data demonstrate that these anti-idiotypic antibodies specifically bind SH2 domains, with the highest affinity for SH2 domain of lck protein tyrosine kinase. The significance of this interaction is discussed.

Antibodies, Anti-Idiotypic↗
PubMed1993

Identification of anti-idiotypic antibodies to anti-phosphotyrosine antibodies in human sera.

We have recently identified in SLE sera antibodies against phosphotyrosine. They were also detected in normal sera and gammaglobulin preparations, suggesting that they belong to natural autoantibodies. In this paper, the occurrence of anti-idiotypic antibodies against anti-phosphotyrosine antibodies, in the above mentioned samples, is investigated. In order to identify these anti-idiotypic antibodies ELISA, immunoprecipitation and immunoblotting are performed. Our data demonstrate the presence of anti-idiotypic antibodies specific to anti-phosphotyrosine antibodies in SLE sera as well as in normal sera, suggesting that these anti-idiotypic antibodies are also auto-anti-idiotypic antibodies. The densitometry of immunoblots reveals significantly higher levels of anti-idiotypic antibodies in SLE sera. Based on the competition inhibition studies we conclude that some of these anti-idiotypic antibodies belong to beta/gamma type.

Animals↗
PubMedDate not supplied

MMP-9 and MMP-2 gelatinases and TIMP-1 and TIMP-2 inhibitors in breast cancer: correlations with prognostic factors.

The goal of our study was to analyse the prognostic values for some matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in breast cancer. We evaluated the activity and the expression levels of MMP-9, MMP-2, TIMP-1 and TIMP-2 in malignant versus benign fresh breast tumor extracts. For this purpose, gelatinzymography, immunoblotting and ELISA were used to analyse the activity and expression of MMPs and TIMPs. We found that MMP-9 expression level and activity are increased in malignant tumors. In addition, MMP-9/TIMP-1 and MMP-2/TIMP-2 ratio values obtained by us were significantly different in malignant tumors compared to benign tumors. We suggest that the abnormal MMP-9/TIMP-1 balance plays a role in the configuration of breast invasive carcinoma of no special type and also in tumor growth, while altered MMP-2/TIMP-2 ratio value could be associated with lymph node invasion and used as a prognostic marker in correlation with Nottingham Prognostic Index. Finally, we showed that in malignant tumors high expression of estrogen receptors is associated with enhanced activity of MMP-2 and increased bcl- 2 levels, while high expression of progesterone receptors is correlated with low TIMP-1 protein levels.

Adult↗
PubMedDate not supplied

A purified green barley extract with modulatory properties upon TNF alpha and ROS released by human specialised cells isolated from RA patients.

Based on the finding that reactive oxygen species (ROS) play important roles in mediating proinflammatory cytokine production (e.g. TNF alpha) and that many plant extracts contain substances with antioxidant properties, we examined the antiinflammatory action of a green barley extract, commercially available as "Natural SOD". The results obtained in this study demonstrate that the antiinflammatory properties of "Natural SOD" due to its micromolecular substances, able to scavenge ROS and to down-regulate TNF alpha production, main inflammation mediators produced by specialised cells from peripheral blood (PB) and synovial fluid (SF) of patients with rheumatoid arthritis (RA). We prepared and tested a purified green barley extract (PE) containing micromolecular substances under 1 kDa, able to inhibit TNF alpha releasing--measured by an bioassay--from LPS stimulated human mononuclear cells (MNC) isolated both from PB and SF of RA patients. Luminol-dependent chemiluminescence has been used to measure the scavenging activity of PE on ROS releasing from activated neutrophils isolated from PB of RA patients. PE, containing high concentrations of substances with antioxidant and antiinflammatory properties, could be a more efficient natural drug for human use than "Natural SOD" in the treatment of RA patients.

Anti-Inflammatory Agents↗
PubMedDate not supplied

Experimental studies on the bacterial product CANTASTIM derived from Pseudomonas aeruginosa. V. Protective effect in endotoxin shock.

In this paper, we investigated the effect of the treatment with the bacterial immunomodulator CANTASTIM in a model of endotoxin shock in mice. Among the different mouse models described for septic shock, we have chosen the low-dose endotoxin model using D-galactosamine sensitized mice. We noticed a significant increase in the survival rate of the mice treated with CANTASTIM before the endotoxin challenge. This protective effect was correlated with a strong reduction in the level of TNF alpha in the sera of treated mice. Prior exposure to CANTASTIM also attenuated subsequent ex vivo nitric oxide production by peritoneal macrophages of the mice. In this model of endotoxin shock, the major role has been attributed to TNF alpha acting through its receptor TNFRI (p55). A downregulation of this receptor as a consequence of the treatment with CANTASTIM may be hypothesized. However, the intervention of CANTASTIM in other points in the cytokine network involved in endotoxin shock cannot be excluded.

Adjuvants, Immunologic↗
PubMedDate not supplied

Parentage analysis for three Romanian families by DNA-fingerprinting.

In forensic medicine, DNA fingerprinting for human identification and paternity testing is becoming a necessary procedure. The genetic locus D1S80 (MCT118) with Hinf I polymorphism of its 5' flanking sequence, HUMTH01 and D21S11 have been successfully amplified from human genomic DNA isolated from blood (50 ng from each sample) by the polymerase chain reaction (PCR) using oligonucleotide primers complementary to the flanking sequences as primers for amplification. DNA bands were detected by ethidium bromide staining after electrophoresis on agarose gels or high-resolution SDS-PAGE. Analysis of these VNTR loci was thus achieved without the need for Southern blot or radioactive material. The small size of the DNA fragments produced in the PCR amplification permitted good resolution of individual alleles. The precise specification of the number of tandem repeats present in each allelic fragment was reproducible from one analysis to another. The aim of this study includes three paternity testing cases; they are the first three human DNA-fingerprints performed in Romania.

5' Untranslated Regions↗
PubMedDate not supplied

Anti-inflammatory non-steroidal drug able to modulate IL-10 in allergic asthma.

Our studies target alternative/adjuvant therapies in allergic diseases, able to qualitatively/quantitatively modify cytokine profiles produced by both CD4+ T-cell subsets (mainly Th1 and Th2) and B-cells, macrophages, etc. Current investigations aim to identify compounds capable to down-regulate IL-10 as an exponent of Th2 cell function and, consequently, to up-regulate Th1 cytokine levels. Experiments on ten allergic asthmatic patients and ten healthy subjects as control were performed. Cytokine production, triggered in PBMCs culture systems by PHA, was modulated with Indomethacin, a non-steroidal anti-inflammatory drug and IL-10 was measured in 24 hours culture supernatants. According to our experimental data, IL-10 level of asthmatic patients' PBMCs in the resting state is not significantly different from control. PHA-activated PBMCs from asthmatic patients do not display significantly higher IL-10 levels than the normal subjects. The results obtained up-to-date reveal the fact that Indomethacin strongly down-regulates IL-10 levels in PBMCs cultures, in both asthmatic allergic patients and healthy subjects. It is obvious that the inhibitory effect of Indomethacin on IL-10 released by PBMCs is higher in the case of allergic asthmatic patients. The results obtained in this study demonstrate that Indomethacin is a possible therapeutic candidate in allergic asthma.

Adolescent↗
PubMedDate not supplied

Presence and significance of some antibodies/autoantibodies in patients with acute myocardial infarction and idiopathic dilated cardiomyopathy.

By using ELISA technique we determined the anti-myosin, actin, collagen type I and IV, cholesterol and phosphotyrosine proteins antibodies in sera from patients with acute myocardial infarction and idiopathic dilated cardiomyopathy. In idiopathic dilated cardiomyopathy we found a significant increase in five out of six types of antibodies tested. The patients with acute myocardial infarction reveal high levels of anti-myosin antibodies only. Our results suggest that some of the autoantibodies studied by us have a prognostic value and could be involved in maintaining cardiac dysfunctions.

Actins↗
PubMedDate not supplied

Hydroalcoholic plant extracts with anti-inflammatory activity.

The aim of the present study was to investigate if standardized hydroalcoholic plant extracts such as Calendula officinalis, Hypericum perforatum, Plantago lanceolata and Glycyrrhiza glabra can suppress in cell-free systems the activities of 5-lipoxygenase (5-LO) and cyclooxygenase-2 (COX-2), key enzymes in the formation of proinflammatory eicosanoids from arachidonic acid (AA). Studies were undertaken to compare the above mentioned plant extracts to a known NSAID (nimesulide) in their ability to inhibit both cyclooxygenase (COX-2) and lipoxygenase (5-LO) activities in cell-free systems. We report on 2 vegetal extracts (Hypericum perforatum and Glycyrrhiza glabra) that inhibit 5-LO activity and 2 vegetal extracts (Plantago lanceolata and Glycyrrhiza glabra) that inhibit COX-2 activity. In this study, we demonstrate for the first time that Glycyrrhiza glabra extract efficiently suppresses both eicosanoids and leukotrienes formation in cell-free systems, implying that this extract directly acts as a dual inhibitor of 5-LO and COX-2 activities. With regard to the properties of dual COX-2/5-LO inhibitors, Glycyrrhiza glabra extract might be a potential drug possessing anti-inflammatory activity devoid of the most troublesome (gastric) side effects seen for drugs used as COX-2 and 5-LO inhibitors. Hypericum perforatum, Plantago lanceolata and Glycyrrhiza glabra extracts can be added to an already impressive list of these species that have anti-inflammatory activity.

Anti-Inflammatory Agents↗
PubMedDate not supplied

Antioxidant properties of some hydroalcoholic plant extracts with antiinflammatory activity.

The hydroalcoholic extracts of Calendula officinalis, Hypericum perforatum, Plantago lanceolata and Glycyrrhiza glabra which exhibited different anti-inflammatory activities were evaluated for the possible mode of action by studying their antioxidant potential. In the present study we investigated if standardized hydroalcoholic extracts of plants such as Calendula officinalis, Hypericum perforatum, Plantago lanceolata and Glycyrrhiza glabra produced by Hofigal Stock Company could modulate the respiratory burst of human activated neutrophils, as a consequence of their antioxidant capacity. Their antioxidant properties were measured using a colorimetric assay (Total Antioxidant Status kit). We demonstrated that Hypericum perforatum and Calendula officinalis hydroalcoholic extracts possessed a significant antioxidant activity while Plantago lanceolata and Glycyrrhiza glabra hydroalcoholic extracts had a minor antioxidant status. Using reactive oxygen species-generating systems (OZ-activated human PMN neutrophils), Calendula officinalis and Hypericum perforatum extracts showed strong reactive oxygen species scavenging property, Hypericum perforatum extract exhibing the highest scavenging activity. These results confirm the potential of Calendula officinalis and Hypericum perforatum investigated hydroalcoholic extracts as medicinal remedies to be used in different inflammatory/allergic diseases. These extracts could be a useful tool for obtaining new antioxidant/anti-inflammatory agents.

Anti-Inflammatory Agents↗