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G Füst

Publications and source records attributed to G Füst.

At least 19 recordsLinked to original sources
PubMed2004

Epistatic effects of genes encoding immunoglobulin GM allotypes and interleukin-6 on the production of autoantibodies to 60- and 65-kDa heat-shock proteins.

Immunoglobulin GM and KM genes have been associated with antibody responses to a variety of antigens. A promoter-region polymorphism of interleukin-6 (IL-6) gene (-174 G/C) has been shown to be associated with antibody responses to heat-shock proteins (hsp) 60 and hsp65. To examine the possible epistatic effects of these unlinked genetic systems on the autoimmune responses to hsp60 and hsp65, 176 healthy Caucasian subjects from Finland were genotyped for several allelic determinants of GM, KM, and IL-6 genes by PCR-RFLP methods. IgG antibodies to hsp60 and hsp65 were measured by an ELISA. Significant interactive effects of GM f,z and IL-6-174 genotypes were noted for both anti-hsp60 (P=0.002) and anti-hsp65 (P=0.038) antibody levels. Since these autoantibodies have been implicated in susceptibility to coronary heart disease and carotid atherosclerosis, the associations reported here might be relevant to the etiology of these diseases.

Adult↗
PubMed2004

Sex hormones in hereditary angioneurotic oedema.

OBJECTIVE: The fluctuations in sex hormone levels at the beginning of adolescence, in the perimenopausal period, during pregnancy or during the use of oral contraceptives can precipitate oedematous attacks in hereditary angioneurotic oedema (HANO). Attacks usually disappear after the onset of menopause. This study was undertaken to establish any relationship between the serum levels of sex hormones and the incidence of HANO attacks. PATIENTS AND MEASUREMENTS: Serum levels of LH, FSH, progesterone, oestradiol, testosterone, PRL and SHBG were measured in 78 patients [mean age 30.3 years (range 4-70 years)] with HANO. A questionnaire was used to explore the medical history of adult patients to characterize the evolution and the characteristics of attacks. RESULTS: The number of attacks was significantly higher [odds ratio (OR) 6.36 (1.31-30.81); P = 0.022] in females with high progesterone levels (> or = 4 nmol/l), irrespective of age, menstrual cycle and danazol dose. The OR was even higher [13.4 (2.2-81.4); P = 0.005] when only subcutaneous attacks were considered. Multiple logistic regression analysis demonstrated a significantly lower attack frequency during 1-year follow-up in patients with a higher (40 nmol/l) SHBG level (OR 0.25 (0.07-0.90); P = 0.034). This difference existed independently of age and danazol dose. CONCLUSION: In view of these results, the monitoring of progesterone and SHBG levels can prove useful in the prediction of attacks in hereditary angioneurotic oedema.

Adolescent↗
PubMed2003

High prevalence of IgG and IgA antibodies to 19-kDa Helicobacter pylori-associated lipoprotein in chronic urticaria.

BACKGROUND: Chronic urticaria has been described in patients with Helicobacter pylori infection. We studied the titer of IgG and IgA type antibodies against H. pylori in patients with and without urticaria of unknown etiology. We also investigated the prevalence of antibodies against H. pylori-associated lipoprotein 20 (lpp20) in patients with and without chronic urticaria. METHODS: The concentration of anti-H. pylori antibodies (IgG and IgA) was determined by the RIDA test. The level of anti-lpp20 antibodies was determined by Western blot using various H. pylori antigens (from 19 to 120 kDa). RESULTS: Patients with chronic urticaria and H. pylori infection (subgroup 1, n = 33) had high IgG and IgA titers whereas all patients with chronic urticaria and without H. pylori infection (subgroup 2, n = 23) were seronegative (P = 0.0128 for IgG and P = 0.003 for IgA). Titers in subgroup 1 did not differ significantly from a control group (n = 33) with severe H. pylori-associated gastritis without urticaria. The prevalence of the anti-lpp20 antibodies was significantly higher in subgroup 1 compared to the control group (93.9 vs 21.2%, P < 0.0001 for IgG, and 46.1 vs 6.3%, P < 0.0029 for IgA). CONCLUSIONS: We suggest that IgG and IgA antibodies to H. pylori-associated lpp20 may play role in the pathogenesis of chronic urticaria.

Adolescent↗
PubMed2002

Antibodies against different epitopes of heat-shock protein 60 in children with type 1 diabetes mellitus.

The aim of this study was to investigate the amounts and epitope specificity of antibodies against heat shock protein 60 (hsp60) in the sera of type 1 diabetic and healthy children. Antibodies specific for peptide p277 of human hsp60 and of M. bovis as well as for human hsp60, M. bovis hsp65 proteins were measured by ELISA. Other autoantibodies (islet cell antibodies, glutamate decarboxylase antibodies and IA-2 antibodies) were also determined. A total number of 83 serum samples from children with type 1 diabetes mellitus and 81 samples of control children were investigated. Epitope scanning of the hsp60 for linear antibody epitopes was carried out using synthetic peptides attached to pins. The antibody levels specific for peptide p277 of human- and of M. bovis origin were significantly (human: P=0.0002, M. bovis: P=0.0044) higher in the diabetic children group than in the healthy children. We could not find significant difference in the antibody levels to whole, recombinant hsp proteins among the examined groups of children. Antibodies to two epitope regions on hsp60 (AA394-413 and AA435-454) were detected in high titres in sera of children with diabetes mellitus. The first region similar to the sequence found in glutamate decarboxylase, whereas the second one overlaps with p277 epitope to a large extent. Presence of antibodies to certain epitopes of hsp60 (AA394-413-glutamic acid decarboxylase-like epitope; AA435-454-p277-like epitope) in diabetic children may reflect their possible role in the autoimmune diabetogenic process of the early diabetes.

Adolescent↗
PubMed2002

Complement activating antibodies against the human 60 kDa heat shock protein as a new independent family risk factor of coronary heart disease.

BACKGROUND: Several groups have reported high levels of antibodies against 60 kDa heat shock proteins (hsp) associated with coronary heart disease. METHODS AND RESULTS: Complement activating (CA) antihsp60 autoantibodies were measured by the AtheroRisk kit (CardioPath Ltd, Alloa, UK), in parallel with IgG antibodies to human hsp60 and mycobacterial hsp65 by ELISA in 32 healthy children (18 boys, 14 girls, 11.8 +/- 4.0 years). At least one of the parents of these children had a history of myocardial infarction before 55 years of age (high family risk (HFR) group). The control group consisted of 63 healthy children (31 boys, 32 girls, 9.0 +/- 3.6 years) without known family history of coronary heart disease (CHD), hypertension, and diabetes mellitus. Concentrations of CA antihsp60 antibodies were significantly (P = 0.021) higher in the HFR group than in the control group. Also in the HFR group, significantly (P = 0.004) lower high-density lipoprotein cholesterol (HDL-C)-cholesterol (measured enzymatically) and significantly (P = 0.020) higher low-density lipoprotein cholesterol (LDL-C)-cholesterol levels (calculated by the Friedewald formula) were observed when compared with the controls. The difference in the CA antihsp60 antibody levels between the HFR and control groups remained significant even after adjustments for age, smoking, HDL-cholesterol, LDL-cholesterol levels, and white blood cell count. Children with high (in the highest quartile) CA antihsp60 antibody levels compared with those with normal levels of these antibodies also had adjusted odds ratios (OR) of 9.80 (2.15-44.58, P = 0.003), indicating high family risk. No significant difference in the IgG antihsp antibody levels was observed. CONCLUSIONS: These findings indicate that high levels of CA autoantibodies against hsp60 can be considered to be a novel family risk factor of CHD, independent of HDL- and LDL-cholesterol levels.

Adolescent↗
PubMed2001

[Latent autoimmune diabetes in adults(LADA): part of the clinical spectrum of type-1 diabetes mellitus of autoimmune origin].

According to the most recent classification of diabetes mellitus the latent autoimmune diabetes in adults belongs to the group of type 1 autoimmune diabetes mellitus, as a slowly progressive form. It is not clear whether LADA is a distinct clinical entity or it is a part of the clinical spectrum of type 1 diabetes mellitus. The authors compare the antropologic (body mass index, waist to hip ratio), immunologic (occurrence of islet cell cytoplasmic autoantibodies and autoantibodies against glutamic acid decarboxylase and tyrosin phosphatase), genetic (HLA DR and DQ alleles known to be associated to type 1 diabetes mellitus) characteristics and occurrence of the features of the metabolic syndrome in the groups of type 1 and type 2 diabetes and LADA. 81 type 1 and 190 type 2 diabetics and 38 LADA patients were involved into the study. Freshly diagnosed type 1 diabetics served for controls of the autoantibody study: 48 patients manifested < or = 16 years of age and 89 type 1 diabetics manifested above 16 years of age. The three main diabetic groups differed in age: the average age in the type 1, type 2 and LADA groups were 37, 63 and 58 years respectively. There was no difference among the three groups in gender. The duration of the disease differed significantly between the type 2 and LADA groups (4.0 and 8.0 years respectively). In spite of the shorter duration of the disease in the LADA group, compared to the type 2 diabetics the frequency of insulin dependency was significantly higher in the LADA (81.6%) than in the type 2 group (46.7%). The BMI and WHR were comparable between the type 1 and LADA patients (average values were 23 and 0.83 in type 1 patients and 23.25 and 0.89 in LADA). The type 2 group differed significantly from type 1 and LADA (average values were 29.1 and 0.5). The concentration of glycated hemoglobin was comparable in the three groups. But there was a significant difference in HbA1c concentration between the freshly diagnosed subgroups of type 1 and LADA patients: 10.85% and 8% respectively. The fasting C-peptid levels were significantly higher in the sera of type 2 diabetics (0.75 pmol/l) compared to type 1 (0.2 pmol/l) and LADA patients (0.29 pmol/l). There was a significant difference in C-peptid concentrations between the type 1 and LADA groups, too. The insulin deficiency in LADA seemed to be not as severe as in type 1 diabetes. The serum total cholesterol and triglyceride levels were significantly higher and the HDL cholesterol concentration significantly lower in type 2 diabetics comparing to type 1 and LADA patients and there was no significant difference in this respect between the type 1 and LADA groups. The frequency of occurrence of hypertension differed no significantly between type 2 and LADA, but that of in type 1 diabetes was significantly lower than both type 2 and LADA. The occurrence of multiple autoantibodies (ICA + GADA + anti-IA2) was much more frequent in type 1 diabetes compared to LADA. In the sera of LADA patients the occurrence of ICA and GADA alone or ICA + GADA was characteristic (31.5% - 21.1% - 15.8% respectively). There was no difference between type 1 diabetes and LADA in the occurrence of the alleles of the MHC kown to be associated with type 1 diabetes. The occurrence of the haplotypes HLA DQ2/DR3 and/or DQ8/DR4 was observed in two thirds of type 1 diabetic and LADA patients. Chronic diabetic complications were observed in all of the groups and there was only a secondary connection of the complications with the type of the diabetes. Based on the results the authors suggest that LADA is a part of the clinical spectrum of type 1 diabetes of autoimmune origin.

Adolescent↗
PubMed2001

Eradication of Helicobacter pylori and improvement of hereditary angioneurotic oedema.

Helicobacter pylori infection is thought to be a causal factor in various dermatological disorders. We assessed the frequency of H pylori infection in 65 patients with hereditary angioneurotic oedema. We measured the serum concentration of antibodies against H pylori and did the carbon-14-urease breath test in patients with positive H pylori serology. 19 of 65 patients had H pylori infection. All patients with infection, and 11 of 46 without infection, had a history of recurrent episodes of acute abdominal pain. We successfully eradicated H. pylori infection in 18 patients. The frequency of abdominal symptoms was significantly higher in the infected group (p=0.002 after adjustment for age). In nine of 19 patients with dyspepsia, the frequency of oedematous episodes decreased from 100 over 10 months before eradication to 19 during the 10-month follow-up period. Screening for, and eradication of, H pylori infection seems to be justified in patients with hereditary angioneurotic oedema.

Abdominal Pain↗
PubMed2001

The association of serum lipoprotein(a) levels, apolipoprotein(a) size and (TTTTA)(n) polymorphism with coronary heart disease.

BACKGROUND: The association between lipoprotein(a) levels, apolipoprotein(a) size and the (TTTTA)(n) polymorphism which is located in the 5' non-coding region of the apo(a) gene was studied in 263 patients with severe coronary heart disease and 97 healthy subjects. METHODS: Lp(a) levels were measured by ELISA, apo(a) isoform size was determined by SDS-agarose gel electrophoresis, and analysis of the (TTTTA)(n) was carried out by PCR. For statistical calculation, both groups were divided into low (at least one apo(a) isoform with < or = 22 Kringle IV) and high (both isoforms with >22 KIV) apo(a) isoform sizes, and into low number (<10 in both alleles) and high number of (> or =10 at least one allele) TTTTA repeats. RESULTS: Lp(a) levels were higher (P=0.007), apo(a) isoforms size < or =22 KIV and TTTTA repeats > or = 10 were more frequent (P=0.007 and 0.01) in cases than in controls. Lp(a) levels were found to be increased with low apo(a) weight in both groups (both P<0.0001). In multivariate logistic regression analysis, only the Lp(a) levels (P=0.005) and (TTTTA)(n) polymorphism (P=0.002) were found to be significantly associated with CHD. CONCLUSION: Nevertheless, these results indicate that in CHD patients the (TTTTA)(n) polymorphism has an effect on Lp(a) levels which is independent of the apo(a) size.

Adult↗
PubMed2001

Levels of antibodies against C1q and 60 kDa family of heat shock proteins in the sera of patients with various autoimmune diseases.

Previously a strong positive correlation was found between antibodies to C1q (C1qAb) and antibodies against human heat shock protein (hsp60) and mycobacterial hsp65 in HIV infected patients. Here the levels of these antibodies were measured in the sera of patients with different autoimmune diseases (122 systemic lupus erythematosus (SLE), 55 systemic sclerosis, 33 undifferentiated connective tissue disease (UCTD), 27 primary Raynaud syndrome, 21 rheumatoid arthritis (RA), 14 polymyositis/dermatomyositis (PM/DM), and 192 healthy blood donors. The prevalence of IgG C1qAb was found to be high (P<0.0001 as compared to the healthy controls) only in the SLE group. The levels of the anti-hsp60 (P=0.0094) and anti-hsp65 (P=0.0108) antibodies were high only in the UCTD patients. No correlation was found between the C1qAb and anti-hsp antibodies in any group except a significant (P=0.011) positive correlation between C1qAb and hsp65 antibodies in the patients with UCTD. These findings indicate that the autoantibodies against C1q are heterogeneous: in different diseases different types of C1qAb may dominate.

Adult↗
PubMed2001

Soluble gC1q-R/p33, a cell protein that binds to the globular "heads" of C1q, effectively inhibits the growth of HIV-1 strains in cell cultures.

C1q and the outer envelope protein of HIV, gp120, have several structural and functional similarities. Therefore, it is plausible to assume that proteins that are able to interact with C1q may also interact with isolated gp120 as well as the whole HIV-1 virus. Based on this hypothesis, we studied the potential ability of the recombinant form of the 33-kDa protein, which binds to the globular "heads" of C1q (gC1q-R/p33), to inhibit the growth of different HIV-1 strains in cell cultures. gC1q-R/p33 was found to effectively and dose-dependently inhibit the production of one T-lymphotropic (X4) and one macrophage-tropic (R5) strain in human T cell lines (MT-4 and H9) and human monocyte-derived macrophage cultures, respectively. At a concentration range of 5-25 microg/ml, gC1q-R caused a marked and prolonged suppression of virus production. The extent of inhibition was enhanced when gC1q-R was first incubated with and then removed from the target cell cultures before virus infection, compared to that when the cells were infected with gC1q-R-HIV mixtures. The extent of inhibition was comparable to that of the Leu3a anti-CD4 antibody. Addition of gC1q-R to the cell cultures on day 1 or 2 after infection induced markedly less inhibition of HIV-1 growth than pretreatment of the cells just before or together with the infective HIV strains. In ELISA experiments, gC1q-R did not bind to a solid-phase recombinant gp120 while strong and dose-dependent binding of gC1q-R to solid-phase CD4 was observed. Our present findings indicate that gC1q-R is an effective inhibitor of HIV-1 infection, which prevents viral entry by blocking the interaction between CD4 and gp120. Since gC1q-R is a human protein, it is most probably not antigenic in humans. It would seem logical, therefore, to consider gC1q-R or its fragments involved in the CD4 binding as potential therapeutic agents.

Anti-HIV Agents↗
PubMed2001

Anti-cholesterol antibodies (ACHA) in patients with different atherosclerotic vascular diseases and healthy individuals. Characterization of human ACHA.

In animal experiments the protective role of anti-cholesterol antibodies (ACHA) in the development of atherosclerosis has been demonstrated. Despite the fact that ACHA are present in the serum of healthy humans, no data on the occurrence of these antibodies in human diseases are available. We determined serum concentrations of IgG type ACHA by an enzyme immunosorbent assay in 600 patients with atherosclerotic vascular diseases (86 patients with peripheral occlusive atherosclerosis, 146 patients with cerebrovascular diseases, 341 patients with severe coronary heart disease (CHD) who received aorto-coronary by-pass, 27 patients with myocardial infarction who did not undergo by-pass operation), in 57 patient controls (complaints of CHD, without coronarographic alterations) and in 218 healthy individuals. ACHA were present in the sera of all persons tested. No serum cofactor is needed for the binding of human ACHA to solid phase cholesterol, binding can be inhibited dose-dependently by LDL and even more strongly with LDL/VLDL preparations purified from human serum. ACHA levels were found to be considerably lower in patients with peripheral occlusive atherosclerosis and cerebrovascular diseases compared with the levels in healthy individuals. By contrast, the ACHA levels of patients with CHD were considerably higher. No differences in the IgG subclass distribution and binding efficiency of ACHA in the sera of CHD patients and controls were found. Thus, our present findings indicate that both low and high ACHA production may be associated with different atherosclerotic vascular diseases.

Adult↗
PubMed2001

High level of anticholesterol antibodies (ACHA) in HIV patients. Normalization of serum ACHA concentration after introduction of HAART.

Anticholesterol antibodies (ACHA) are natural antibodies against the 3beta-OH group of cholesterol. Since lipid disorders are common in HIV infection and HAART may further enhance dislipidaemia, we determined by using an ELISA method serum ACHA concentrations in HIV patients and healthy HIV-seronegative controls. ACHA levels were almost 4 times higher in the sera of 46 patients than in 110 controls. No difference in the specificity of ACHA was found between HIV-seropositive and HIV-seronegative sera. Binding of ACHA to cholesterol-coated plates from a HIV-seropositive serum was dose-dependently inhibited by preincubation with HIV-1(BA-L) preparation. Serum concentration of ACHA was significantly higher in the patients with low serum cholesterol levels than in those with normal cholesterol levels. HAART induced a marked drop of ACHA concentration. We found a significant negative correlation between the length of HAART and the ACHA levels. By contrast, HAART did not significantly influence total IgG concentration and titers of antibodies against 60 kD heat shock protein. Our findings indicate that high levels of ACHA in HIV-infection may contribute to the development of hypocholesterolaemia frequently observed in this disease.

Antiretroviral Therapy, Highly Active↗
PubMed2001

Complement activation in the nasal mucosa following nasal ragweed-allergen challenge.

The aim of this study was to explore complement activation in the nasal lavage following a nasal ragweed-allergen challenge. The study was carried out with 15 adolescents who were allergic to ragweed and with six non-allergic healthy volunteers. Following the baseline measurement after the symptoms were registered, subjects were given increasing doses of ragweed allergen. Lavage fluid was collected and tested for a complement-activation product (C3bBbP). The allergic patients responded to allergen provocation with an increase in C3bBbP formation compared to the initial lavage (p = 0.001). The C3bBbP level remained low in the lavage fluids of the non-allergic controls. We found a strong correlation between the threshold dose that induced symptoms and the dose where the maximum complement activation was detected (r = 0.78, p = 0.001). Our findings indicate that in allergic patients nasal challenge with ragweed allergen induces a rise in complement activation in the nasal lavage fluid. These results highlight the role of the complement system in the allergic inflammation on the nasal mucosal surface.

Allergens↗
PubMed2001

Comparative study on antibodies to human and bacterial 60 kDa heat shock proteins in a large cohort of patients with coronary heart disease and healthy subjects.

BACKGROUND: Recent observations indicate an association between antibodies against mycobacterial heat shock protein (hsp65) and coronary heart disease (CHD). Previously, we reported on marked differences in antigen specificity and complement activating ability of anti-hsp65 antibodies and auto-antibodies against human heat shock protein, hsp60. Here, we investigated whether there are differences between antih-sp65 and anti-hsp60 antibodies in their association with CHD. DESIGN: We measured by ELISA the levels of antibodies to hsp65, hsp60 and E. coli-derived GroEL in three groups: Group I, 357 patients with severe CHD who underwent by-pass surgery; Group II, 67 patients with negative coronary angiography; Group III, 321 healthy blood donors. Antibodies against Helicobacter pylori were also measured by commercial ELISA. RESULTS: As calculated by multiple regression analysis, the levels of anti-hsp60 auto-antibodies were significantly higher in Group I compared to Group II (P = 0.007) or Group III (P < 0.0001). By contrast, although concentrations of anti-hsp65 and anti-GroEL antibodies in Group I were higher than in Group III, no significant differences between Group I and Group II were found. Antibodies to the two bacterial hsp strongly correlated to each other, but either did not correlate or weakly correlated to hsp60. In Group I, serum concentrations of anti-H.pylori antibodies significantly correlated with those of anti-hsp65 and anti-GroEL antibodies but they did not correlate with the anti-hsp60 antibodies. CONCLUSIONS: As to their clinical relevance, a remarkable difference become evident between antibodies to human hsp60 and antibodies against bacterial hsp in the extent of association with CHD. On the basis of these findings and some pertinent literature data, an alternative explanation for the association between high level of anti-hsp antibodies and atherosclerotic vascular diseases is raised.

Adult↗
PubMed2001

Ultrasonography in the diagnosis and monitoring of ascites in acute abdominal attacks of hereditary angioneurotic oedema.

BACKGROUND: Hereditary angioneurotic oedema (HAE) is a rare cause of ascites. As acute abdominal attacks of the disease can mimic surgical emergencies, prompt and accurate diagnosis is essential. This study was undertaken to evaluate the usefulness of serial abdominal ultrasound (US) examinations. PATIENTS AND METHODS: Seventy patients with HAE were followed up for almost a decade. All patients presenting with an acute oedematous attack underwent abdominal US, which was then repeated 24 and 48 h after appropriate therapy. RESULTS: Twenty-two acute oedematous attacks with abdominal complaints severe enough to justify hospital admission occurred in the study population. Abdominal US performed during the attack showed oedematous thickening of the intestinal wall in 80% of cases and invariably demonstrated the presence of free peritoneal fluid in all patients. Rapid symptomatic relief achieved by treatment was accompanied by the significant regression of US abnormalities. CONCLUSIONS: Transitory ascites demonstrated by abdominal US is a clue to the diagnosis of an acute abdominal attack of HAE. The possibility of HAE should always be considered whenever unexplained abdominal pain recurs with or without ascites.

Abdomen, Acute↗