Biomedical subjects

G Lakos

Publications and source records attributed to G Lakos.

At least 19 recordsLinked to original sources

PubMed2006

Clinical and immunoserological characteristics of mixed connective tissue disease associated with pulmonary arterial hypertension.

We investigated the clinical characteristics and immunoserological alterations in patients with mixed connective tissue disease (MCTD) associated with pulmonary arterial hypertension (PAH). Anti-U1RNP autoantibodies, anti-endothelial cell antibodies (AECA) and serum thrombomodulin (TM) as well as von Willebrand factor antigen (vWFAg) concentrations were measured in 25 patients with MCTD associated with PAH and in 154 MCTD patients without PAH. The results showed that the probability of survival was lower in MCTD patients with PAH than in the 154 MCTD-non-PAH patients (5-year survival rate in MCTD with PAH: 73%, versus 96% in MCTD-non-PAH; P < 0.01). AECA were more frequently present in the sera of MCTD patients with PAH than in MCTD-non-PAH (P < 0.001). Serum TM and vWFAg levels were higher in MCTD-PAH patients than in MCTD-non-PAH patients (TM: P < 0.001; vWFAg: P < 0.001). Significant correlation was noticed between the quantity of AECA and TM level (r = 0.466) as well as the quantity of AECA and vWFAg level (r = 0.550). In conclusion, our results suggest that in MCTD the presence of AECA and endothelial cell activation may play a role in the development of PAH and in the maintenance of obliterative vascular processes.

Adult↗

PubMed2006

TH1/TH2 imbalance, measured by circulating and intracytoplasmic inflammatory cytokines--immunological alterations in acute coronary syndrome and stable coronary artery disease.

To describe how peripheral immune-parameters reflect the inflammatory alterations of the atherosclerotic plaques in coronary atherosclerosis. We measured general inflammatory markers C-reactive protein (CRP) and granulocyte activity, lymphocyte subpopulations and their state of activation, evaluated circulating Th1/Th2-type cytokines, and specific intracytoplasmic cytokines. We investigated the association of immune-parameters with disease outcome and mortality. Thirty-three patients with acute coronary syndrome (ACS), 62 with stable coronary artery disease (CAD) and 58 healthy controls were studied. Peripheral blood lymphocyte subgroups were quantified by flow cytometry, soluble cytokines and autoantibodies were assessed using enzyme-linked immunosorbent assay (ELISA), while intracellular cytokine levels were measured by flow cytometry after intracellular staining. We found elevated levels of CRP and granulocyte activity in ACS versus CAD (P < 0.001, P = 0.017, respectively). Natural killer (NK) cell percentages were elevated, while percentage of T cells to the total lymphocyte count was slightly decreased in ACS compared to controls (P < 0.0001, P = 0.012, respectively). Both forms of coronary atherosclerosis showed significantly higher percentages of activated T cells than controls when stained for the activation markers HLA-DR3 and CD69(+) (ACS: P < 0.0001, P = 0.002, CAD: P < 0.0001, P = 0.018, respectively). IL-1, IL-4 and IL-10 proved significantly higher in ACS versus controls (P = 0.036, P = 0.01, P < 0.0001 respectively). Th1 to Th2 ratio shifted towards a Th1 dominance in both diseases. Both general proinflammatory markers and activated T cells signify CAD. The orchestrated proinflammatory cascade eventually leads to the development of the disease.

Acute Disease↗

PubMed2004

Increased titer of anti-beta2-glycoprotein I IgG antibody among factor V Leiden carriers during oral contraceptive use.

The risk of thromboembolism during oral contraceptive (OC) use is increased among factor V Leiden (FVL) carriers compared to women with wild-type genotype of the gene for coagulation factor V (FV). The carrier frequency in the general population is too high for FVL alone to be responsible for the reported association. Additional risk factors may be required to explain the increased risk of thromboembolism of carriers during OC use. We conducted a case-control study to compare the titer of anti-beta2-glycoprotein I immunoglobulin G (IgG) and the frequency of elevated titer of IgG type anti-beta2-glycoprotein I antibody between FVL carriers and individuals with FV wild-type genotype with and without pill use. An asymptomatic population of 313 unrelated nonpregnant women were screened for FVL and for the presence of anti-beta2-glycoprotein I IgG antibody. Sixty-six women were FVL carriers and 247 had normal genotype. One-hundred and thirty-five women used OC at the time of screening and 178 did not. Among FVL carriers, OC pill users had a higher mean anti-beta2-glycoprotein I IgG titer than nonusers (9.2 SGU/mL vs. 4.7 SGU/mL, p = 0.0485). Among women with FV wild-type genotype, there was no significant difference in anti-beta2-glycoprotein I IgG titers between users and nonusers of OCs (6.4 SGU/mL and 6.0 SGU/mL, respectively; p = 0.7010). The odds of an elevated anti-beta2-glycoprotein I IgG titer during OC use in FVL heterozygous women was 2.41 (95% confidence interval: 0.79-7.39) relative to users with-type genotype. FVL may contribute to the development of elevated titer of IgG type anti-beta2-glycoprotein I antibody during OC use. The elevated titer of IgG type anti-beta2-glycoprotein I antibody may select women among FVL carriers during OC use with an increased risk of thromboembolism.

Adult↗

PubMed2004

Association between the occurrence of the anticardiolipin IgM and mite allergen-specific IgE antibodies in children with extrinsic type of atopic eczema/dermatitis syndrome.

BACKGROUND: As the literature has only controversial data on the role of nonallergen-specific antibodies in atopic eczema dermatitis syndrome, the authors investigated the link between the occurrence of the antiphospholipid [anticardiolipin (ACL), anti-beta2-glycoprotein I] and allergen-specific immunoglobulin E (IgE) antibodies in 72 children with atopic eczema/dermatitis syndrome (AEDS). METHODS: The measurement of antiphospholipid antibodies was carried out by enzyme-linked immunosorbent assay (ELISA), serum total IgE by nephelometry, and allergen-specific IgE by immunoblotting assay. The statistical analysis was carried out by Fisher's exact test and odds ratio was calculated. RESULTS: Thirteen of 72 children with AEDS (mean age 8.3 years) had elevated serum levels of ACL, and eight anti-beta2-glycoprotein I antibodies. The presence of allergen-specific IgE against inhalant allergens and nutritive allergens was among eight of 13 and three of eight in the cases with elevated ACL. The ratio of patients with highly increased severity scoring of atopic dermatitis (SCORAD) index (>75) was significantly higher in the group with elevated (4/13) than in those with the normal ACL levels (2/59). There was a significant association between the appearance of mite (Dermatophagoides pteronyssinus, D. farinae)-specific IgE and ACL IgM antibodies (6/13). CONCLUSION: These findings show that there are significant linkage and association between the appearance of ACL IgM or the production of allergen-specific IgE against inhalant (mainly mite) allergens in children with atopic eczema/dermatitis syndrome.

Adolescent↗

PubMed2004

Antiphospholipid antibodies in acute coronary syndrome.

Antiphospholipid (aPL) antibodies entailing anticardiolipin (aCL) and anti-beta2 glycoprotein I (anti-beta2GPI) antibodies may be involved in a number of vascular diseases including coronary artery diseases (CAD) or stroke. Here we assessed the presence of aPL antibodies in acute coronary syndrome (ACS). The frequency of anti-beta2GPI antibodies was significantly higher (14.4%) in ACS in comparison to control healthy subjects (2%). In addition, serum concentrations of anti-beta2GPI antibodies were also increased in ACS. Anti-beta2GPI antibodies of the IgA isotype might be the most relevant for the onset and outcome of ACS. Regarding subclasses of ACS, anti-beta2GPI IgA antibodies were elevated in unstable angina (UA) and myocardial infarction with ST elevation (STEMI), but not in myocardial infarction without ST elevation (NSTEMI). The involvement of anti-beta2GPI antibodies in ACS was more pronounced in men than women, and in younger rather than older patients. Finally, anti-beta2GPI antibodies in ACS were associated with previous stroke, but not with hypertension or previous myocardial infarction. Thus, anti-beta2GPI antibodies may be involved in the thrombotic events underlying ACS.

Adult↗

PubMed2003

Prevalence and clinical correlations of antibodies against six beta2-glycoprotein-I-related peptides in the antiphospholipid syndrome.

Two-hundred ninety five patients with the antiphospholipid syndrome (APS) were studied for the presence of antibodies against six anti-beta2GPI-related peptides Abs. The prevalence of a wide spectrum of clinical and laboratory parameters of APS was evaluated in all patients, and correlated with the presence of each anti-beta2GPI peptide antibody. The rates of the various antipeptides Abs ranged from 18.0 to 63.7%. Altogether, 87.1% of the patients had antibody reactivity against at least one of the six beta2GPI-related peptides. A high degree of simultaneous reactivity against several beta2GPI-peptides was found. Positive and negative correlations were found between several antipeptides Abs and the rates of thrombosis and fetal loss. Our results point to a heterogeneous activity of antiphospholipid Abs in APS patients, directed, often concurrently, against various epitopes of the beta2GPI molecule. Evaluation of APS patients for the presence of specific antipeptides Abs may be of a value in predicting the risk for future thrombotic and obstetrical complication, as well as for specific therapeutic purposes.

Adolescent↗

PubMed2003

Evaluation of clinical and laboratory features of antiphospholipid syndrome: a retrospective study of 637 patients.

We retrospectively analysed the data of 1519 antiphospholipid antibody (APLA) positive patients between 1986 and 1999. Among them 637 were considered to have antiphospholipid syndrome (APS) based on the 1999 preliminary classification criteria, while 704 patients had no clinical signs of the syndrome. Our aim was to compare the autoantibody profile and clinical characteristics of primary and secondary APS, moreover to evaluate the associations between different APLA and specific symptoms attributable to APS. In our results, the APLA profiles for primary and SLE-associated secondary APS were similar. Among the evaluated clinical symptoms, cerebrovascular thrombosis was found to be more frequent in the SLE-associated, than in the primary APS group (P = 0.04). We identified important differences in the clinical profile of patient populations with various types of APLA. Venous thrombosis occurred more frequently in subjects withlupus anticoagulant (LA), than in those with IgG or IgM type ACLA (P < 0.0001), while coronary, carotid and peripheral artery thrombosis occurred more often in subjects with IgG or IgM ACLA (P < 0.0001). These findings may support the role of antibodies to cardiolipin or its cofactor, beta2glycoprotein I (beta2-GPI) in the initiation and progression of atherosclerosis. Cerebrovascular thrombosis was detected in larger proportion of LA or IgG ACLA-positive patients compared with to IgM ACLA-positive subjects, while the occurrence of foetal loss was similar in all three groups.

Antibodies, Anticardiolipin↗

PubMed2002

Immunoserological changes in the cerebro-spinal fluid and serum in systemic lupus erythematosus patients with demyelinating syndrome and multiple sclerosis.

The aim of the present study was to investigate the role of antinuclear and antiphospholipid antibodies in the pathogenesis of systemic lupus erythematosus (SLE) with demyelinating syndrome and several forms of multiple sclerosis (MS). Paired samples of serum and cerebrospinal fluid (CSF) were investigated using laser nephalometric and enzyme linked immunosorbant assay (ELISA) methods, and the parameters of intrathecal synthesis were calculated. Elevation of the concentrations of antiribosomal P protein antibodies in the CSF and serum, and intrathecal synthesis anticardiolipin (aCL) antibodies were characteristic in all patient groups. The immunoserological changes were more pronounced in the SLE patients. A similar pathogenetic role of antiphospholipid antibodies in central nervous system (CNS) damage in SLE patients with demyelinating syndrome and of MS patients can be assumed.

Adult↗

PubMed2002

No short-term immunological effects of Pneumococcus vaccination in patients with systemic lupus erythematosus.

OBJECTIVE: to investigate the early immunological effects of Pneumococcus vaccination in SLE patients and healthy controls. METHODS: First-four-week follow-up of 18 patients and 9 healthy controls by repeated measurements of anti-nuclear antibodies, anti-dsDNA, C-reactive protein, complement factor 3 (C3) and 4 (C4), total IgG, IgA and IgM. Specific antibody response, percentage of blood lymphocyte populations and whole blood chemiluminescence measurements were carried out in six patients and six controls. RESULTS: No disease flare was detected in the vaccinated patients. all side effects were mild. The concentrations of serum IgG, IgA, C3 and C4 decreased significantly, but still remained within the normal range. The other changes were statistically non-significant. The specific antibody responses to 6B and 23F Pneumococcus serotypes showed striking individual differences. CONCLUSION: There was no short-term immunological effect of Pneumococcus vaccination in the patients with SLE. The non-responders. without any sign of disease activation should possibly be given more immunogenic, new vaccines to avoid life-threatening Pneumococcus infections.

Adult↗

PubMed2001

A novel flow cytometric assay to quantify soluble CD14 concentration in human serum.

BACKGROUND: CD14, the major lipopolysaccharide (LPS)-binding protein of myeloid cells, is found as a soluble molecule in human serum. Recent data describe the presence of elevated soluble CD14 (sCD14) concentration in various disorders, confirming disease activity. A novel, easy, and rapid flow cytometric assay was developed to measure sCD14 levels in serum. METHODS: The assay is based on the competition between membrane-expressed CD14 of isolated monocytes from healthy volunteers and sCD14 in the sample sera for binding to anti-CD14 monoclonal antibodies (mAb; 26ic or 60bca). The amount of cell-associated mAb is determined with a fluorescein isothiocyanate (FITC)-labeled anti-mouse conjugate and flow cytometry. The fluorescence signal is inversely proportional with the amount of serum sCD14. Using dilutions of a standard serum, the concentration of sCD14 in the samples is calculated and compared with results obtained by a commercial sCD14 enzyme-linked immunosorbent assay (ELISA). RESULTS: After optimization, the assay showed log-log linearity of 122.1-984.7 ng/ml sCD14 using mAb 26ic and 29.5-246.2 ng/ml sCD14 using mAb 60bca. It revealed similar results as the ELISA (mAb 26ic: r = 0.88, mAb 60bca: r = 0.92) and provided significantly elevated sCD14 levels in systemic lupus erythematosus patients compared with controls (26ic: 2,213 versus 1,676 ng/ml, P < 0.002; 60bca: 2,625 versus 1,907 ng/ml, P < 0.0002). Receiver operating characteristic curve analysis suggested a reasonable diagnostic efficacy of sCD14 quantification in this autoimmune disease. CONCLUSIONS: The method is easy, rapid, sensitive, and can be used in the follow-up of patients suffering from sepsis or chronic inflammatory disorders.

Adult↗

PubMed2001

[Significance of anti-nucleosome (anti-chromatin) auto-antibodies in systemic lupus erythematosus].

Systemic lupus erythematosus is characterised by the presence of antinuclear autoantibodies (ANA). Native DNA, histone proteins and small nuclear ribonucleoproteins (snRNP) are the main targets of these ANA-s, but some of them may derive against the entire chromatin, which is composed of the listed elements, and also against its fundamental unit, that is nucleosome. Authors investigated at the first time the frequency and the concentration of anti-nucleosome antibodies in a group of 107 consecutively selected Hungarian lupus patients. They calculated correlation between these parameters and the activity as well as organ--mainly kidney--manifestations of the disease. The frequencies of positive anti-nucleosome, anti-dsDNA and anti-histone antibodies were 39.2, 28.0 and 47.6%, respectively. All the three autoantibodies were present more frequently in cases with lupus nephritis, and this correlation was significant by statistical respect. Also a positive correlation was found between the concentration of these autoantibodies and activity of the diseases (SLE-DAI). Results suggest that long disease duration (mean 8.5 year) and consequently low disease activity (mean DAI: 3.28) may stand at the background of the relatively low occurrence of the measured ANA-s. Besides anti-dsDNA, the determination of anti-nucleosome and anti-histone antibodies can be useful in the diagnosis and monitoring of SLE. Authors discuss the possible role of anti-nucleosome autoantibodies in the pathogenesis of lupus nephritis.

Adult↗

PubMed2001

Glucocorticosteroid dependent decrease in the activity of calcineurin in the peripheral blood mononuclear cells of patients with systemic lupus erythematosus.

OBJECTIVE: To compare the activity of calcineurin in the peripheral blood mononuclear cells (PBMC) of 32 patients with systemic lupus erythematosus (SLE) and 35 healthy controls. METHODS: The activity of calcineurin was assayed in the supernatants of sonicated mononuclear cells. RESULTS: There was no significant difference in the calcineurin activity of patients with SLE not taking glucocorticosteroids (GCS) compared with the healthy controls. On the other hand, the activity of calcineurin was reduced in patients with SLE taking GCS, correlating negatively with the dose of GCS. The stimulation of PBMC by phorbol ester and calcium ionophore decreased the calcineurin activity both in patients with SLE and in healthy controls. GCS could also reduce calcineurin activity in the mononuclear cells of healthy subjects in vitro. CONCLUSIONS: In patients with SLE the decrease in the calcineurin activity of PBMC depended on the dose of GCS used for treatment, and it was not a disease specific alteration. The higher the dose of GCS, the greater the inhibition of calcineurin activity. The reduction of calcineurin activity is a new element in the immunosuppressive effects of GCS during the treatment of patients with SLE.

Adolescent↗

PubMed2001

Decreased arachidonic acid release in peripheral blood monocytes of patients with systemic lupus erythematosus.

OBJECTIVE: To investigate the release of arachidonic acid (AA) in unfractionated peripheral blood mononuclear cells (PBMC), separated monocytes and T lymphocytes of patients with systemic lupus erythematosus (SLE). METHODS: AA release was measured in cells from 56 patients with SLE and from 48 controls. Of the 56 patients with SLE, 38 were receiving glucocorticosteroids and 18 were not. [3H]AA was incorporated into the membranes of PBMC and purified subsets of monocytes and T lymphocytes. The release of [3H]AA was measured both in nonstimulated cells cultured for 24 h and in cell cultures stimulated by phorbol ester (PMA) and Ca2+ ionophore for 4 h. RESULTS: In the PBMC of SLE patients not taking glucocorticosteroids, the release of AA was decreased in both stimulated and nonstimulated cells. There was a decrease of AA production in monocytes but not in T lymphocytes. This phenomenon could be observed in the active and inactive phases of the disease. CONCLUSION: A defect in AA production may exist in the peripheral monocytes of patients with SLE, resulting in decreased release of AA in patients not receiving glucocorticosteroid therapy.

Adolescent↗

PubMed2000

[Comparative analysis of clinical and laboratory charactiristics of antiphospholipid syndrome].

The authors detected lupus anticoagulant and/or anticardiolipin antibodies in 1519 patients' blood samples between 1986-1999 in 3rd Department of Internal Medicine of Medical School of Debrecen. Examining only the proved thrombotic events and fetal losses as symptoms of antiphospholipid syndrome 218 patients had suffered from this syndrome. Secunder antiphospholipid syndrome was the diagnosis in case of 420 patients, the most common in Systemic Lupus Erythematosus (288 patients). In 704 antiphospholipid antibody positivity cases the diagnosis of antiphospholipid syndrome was not fulfilled. Analysing the antibodies profile of primary and secondary antiphospholipid syndrome in SLE, IgG type anticardiolipin antibody positivity was significantly higher in blood samples of SLE patients (82 patients, p < 0.01). Among thrombotic manifestations of antiphospholipid syndrome cerebrovascular thrombosis were significantly higher in patients suffering from SLE (128 patients, p < 0.04), while the occurrence of venous thrombosis, thrombosis of coronary, carotic, aorta and peripheral arteries and recurrent abortions was not significantly different in case of primary and secondary antiphospholipid syndrome. Lupus anticoagulant positivity means higher risk for venous thrombosis (94 patients, p < 0.0001), but anticardiolipin antibody positivity associated with a higher risk for thrombosis of coronary, carotic, aorta and peripheral arteries (59 patients, p < 0.00006). Comparing IgG- and IgM-type anticardiolipin antibody positivity the authors found significantly higher cerebrovascular thrombosis events in IgG-anticardiolipin group (p < 0.004). Sneddon syndrome were detected in 17 patients in the primary antiphospholipid syndrome group and in 16 cases in secundary, SLE-associated antiphospholipid syndrome group. One of the patients had died because of the Catastrophic Antiphospholipid Syndrome.

Antibodies, Anticardiolipin↗

PubMed2000

Differences in the changes of allergen-specific IgE serum levels and the chemiluminescence of peripheral blood phagocytes in patients with allergic rhinoconjunctivitis during the ragweed season.

The objective of this study was to compare the changes in the values of allergen-specific serum IgE levels and zymosan-induced whole blood chemiluminescence (CL) in 41 patients who had exclusively only ragweed allergy in the season of acute symptoms of disease in July, August and September. All patients had allergic rhinitis or rhinoconjunctivitis. Each patient was investigated as a self-control. The ragweed-specific IgE levels were measured by enzyme immunoassay (EIA). The luminol amplified zymosan-induced CL of whole human blood was detected. The allergen-specific serum IgE levels showed slight, but not significant, gradually increasing elevations during the whole season. On the other hand, significant increases were found in the values of the basal but especially in the zymosan-stimulated CL of peripheral blood phagocytes during the acute phase of allergy. Both the basal and the zymosan-induced CL reflected significantly the activated state of the immune system. These observations clearly show that there are well detectable signs of the systemic activation of the immune system in allergic rhinoconjunctivitis beside the local alterations. In addition, the measurements of the basal and zymosan-induced CL of peripheral phagocytes could clearly reflect the clinical state of disease in vitro.

Adult↗

PubMed2000

Ceramide stimulates the uptake of neutral red in human neutrophils, monocytes, and lymphocytes.

Neutral red is a vital stain known to be accumulated in the lysosomes of neutrophils and monocytes. It is used mainly to identify and detect the activated state of these cells. We have found that the extracellular application of physiological ceramide, i.e., a product of sphingomyelin hydrolysis and a newly defined intracellular second-messenger substance, increased the uptake of neutral red in a dose-dependent manner in human neutrophils, monocytes, and lymphocytes, as demonstrated by flow cytometry. Staurosporine was able to totally block this phenomenon, suggesting the involvement of protein kinase C in the process. These results indicate that the flow-cytometric analysis of ceramide-induced uptake of neutral red can be a new method for the evaluation of lysosome-related activation processes in both phagocytes and lymphocytes.

Arachidonic Acids↗

PubMed2000

Inhibition of calcineurin activity and protection against cyclosporine A induced cytotoxicity by prednisolone sodium succinate in human peripheral mononuclear cells.

We have investigated the effects of prednisolone sodium succinate (Pss) and cyclosporin A (CSA), applied alone or concurrently, on the release of arachidonic acid (AA) (cytosolic phospholipase A(2) (cPLA(2)) activity) and on the calcineurin (CN) activity of human peripheral blood mononuclear cells (PBMC). The cytotoxic damage to the cells treated by the drugs was estimated by the release of lactate dehydrogenase (LDH). We found that Pss (10(-5) M) could inhibit the CN activity and higher concentrations (10(-4) M) could decrease the cytotoxic damage caused by CSA (10(-4) M) during their combined application. CSA had no specific effect on the release of AA from the cells. In the combined clinical use of glucocorticosteroids (GCS) and CSA, their additive inhibitory effect on CN activity and the protective membrane influence of GCS against the cytotoxicity of CSA may be beneficial.

Adult↗

PubMed2000

Catastrophic antiphospholipid syndrome in cancer.

Antiphospholipid syndrome is characterized by the presence of antiphospholipid antibodies resulting in arterial and venous thromboembolism. Apart from primary cases, this syndrome is often associated with autoimmune diseases. Around 50 cases of catastrophic antiphospholipid antibody syndrome have been reported as yet. Authors describe the first case of catastrophic antiphospholipid syndrome associated with gastric cancer. Apart from presenting the clinical case, authors also discuss the possible pathomechanism of this associated disorder including the role of immunological factors, as well as antiphospholipid antibodies.

Antiphospholipid Syndrome↗