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Z Prohászka

Publications and source records attributed to Z Prohászka.

At least 19 recordsLinked to original sources
PubMed2006

Association of elevated serum heat-shock protein 70 concentration with transient hypertension of pregnancy, preeclampsia and superimposed preeclampsia: a case-control study.

Our aim was to investigate the association between serum heat-shock protein (Hsp) 70 concentration and hypertensive disorders of pregnancy. One hundred and forty-two pregnant women with hypertensive disorders (93 with preeclampsia, 29 with transient hypertension of pregnancy and 20 with superimposed preeclampsia) and 127 normotensive, healthy pregnant women were included in the study. Serum Hsp70 concentration was measured using enzyme-linked immunosorbent assay. The serum Hsp70 concentration was significantly higher in patients with transient hypertension of pregnancy, in preeclamptic patients and in patients with superimposed preeclampsia than in the control group (median (25-75 percentile): 0.66 (0.52-0.84), 0.55 (0.42-0.80), 0.61 (0.42-0.91) ng/ml vs 0.31 (0.27-0.39) ng/ml, respectively; P<0.001). Multivariate logistic regression analysis showed independent association of elevated serum Hsp70 level with transient hypertension of pregnancy, preeclampsia and superimposed preeclampsia. The difference in serum Hsp70 concentration between preeclamptic patients and the control group was statistically significant in each gestational age category. In the groups of preeclamptic and superimposed preeclamptic patients, there was no significant difference in serum Hsp70 concentration between mild and severe preeclamptic patients, between patients with late and early onset of the disease, as well as between preeclamptic patients without and with foetal growth restriction. In conclusion, serum Hsp70 concentration is elevated in transient hypertension of pregnancy, in preeclampsia and in superimposed preeclampsia. Circulating Hsp70 may not only be a marker for these conditions, but might also play a role in their pathogenesis. However, further studies are needed to explore its role in the pathogenesis of hypertensive disorders of pregnancy.

Adult↗
PubMed2005

Changes in the plasma concentration of soluble thrombomodulin in patients with severe carotid artery stenosis after eversion endarterectomy.

OBJECTIVE AND DESIGN: The purpose of the study was to investigate the putative role of soluble thrombomodulin (sTM) in severe carotid artery stenosis. MATERIALS AND METHODS: We prospectively studied 64 patients who were undergoing carotid endarterectomy (2001-2003). Plasma sTM concentration was determined in each patient before surgery and at 14 months postsurgery. -308 TNF-alpha promoter polymorphism was also determined. RESULTS: Strong negative correlation was found between the preoperative duplex scan values and the plasma sTM concentrations (R = -0.418, p = 0.0006). Patients with 308 A TNF-alpha genotype had significantly lower (p = 0.0415) preoperative sTM values than their counterparts with no such polymorphism. Soluble TM concentrations measured in plasma samples taken at the end of the postsurgical follow-up period of 14 months duration were significantly higher compared to the preoperative values (p < 0.0001). CONCLUSIONS: Our present findings indicate that sTM may be adsorbed to the atherosclerotic plaques or inflamed endothelium in carotid arteries. The pathological significance of this adsorption remains to be determined.

Adsorption↗
PubMed2005

Th1 and Th2 cell responses of type 1 diabetes patients and healthy controls to human heat-shock protein 60 peptides AA437-460 and AA394-408.

RATIONALE: Type 1 diabetes mellitus (T1) is considered to be an immune mediated disease. Based on previous findings it might be suggested that heat shock protein 60 (Hsp60) could be involved in the mediation of the development of the disease. Furthermore a bias toward Th1 immune response was observed in T1D patients where the level of Th1 cytokines was elevated, while the level of Th2 was decreased. AIM OF THE STUDY: To determine Th1 (IFN-gamma) and Th2 (IL-13) cytokine levels in T1 diabetic and control subjects as well as to determine whether there is a shift towards Th1 or Th2 immune response. MATERIALS AND METHODS: ELISPOT (Enzyme-linked ImmunoSPOT) analysis was employed to differentiate antigen specific T-cell responses of a Th1 (IFN-gamma) or Th2 (IL-13) type. 11 T1 diabetic patients and 9 healthy controls were investigated. For T-cell stimulation, we used a polyclonal mitogen or Tetanus toxoid (TT) as positive controls and two peptide antigens Hsp60 AA394-408 and Hsp60 AA437-460. RESULTS: In case of Hsp60 AA437-460 we found significantly decreased Th2 response in patients, although there was no significant difference in Th1 response. In case of Hsp60 AA394-408 and positive controls there was no significant difference. CONCLUSION: Comparing the control and diabetic subjects a significant shift towards Th1 response in T1 diabetes mellitus for Hsp60 AA437-460 was observed.

Adult↗
PubMed2005

High levels of C-reactive protein with low total cholesterol concentrations additively predict all-cause mortality in patients with coronary artery disease.

BACKGROUND: This study aimed to investigate independent and additive predictive effects of raised C-reactive protein (CRP) levels and decreased total cholesterol levels on mortality in patients with chronic coronary artery disease (CAD). Low total cholesterol (TC) levels are associated with worsened survival in chronic and acute diseases. Elevated CRP level is an important predictor of vascular events and mortality in patients with CAD. Potential inhibition of immune activation by circulating lipoproteins could be a link between cholesterol and inflammatory markers. MATERIALS AND METHODS: A group of 387 patients (median age 59 years) with CAD and with or without severe heart failure (HF) were followed for a median of 5.06 years. Serum total cholesterol and CRP concentrations were measured at enrollment. RESULTS: The relationship between lipoproteins, CRP and survival was explored. High CRP concentrations were in significant association with severity of HF and predicted worsened survival in patients with CAD (hazard ratio 5.214, 95% CI 1.762-15.427). The association between CRP levels and mortality was independent of potential confounding factors such as age, body-mass index, severity of HF, smoking habits, hypertension and TC levels. The prediction of mortality by low TC levels was significant (hazard ratio 2.932, 95% CI 1.021-8.422). Furthermore, patients with increased CRP and decreased TC (additive predictive effect) phenotype had 11.714-times higher risk (95% CI 2.619-52.385) of being nonsurvivors than patients with low CRP/high TC. CONCLUSIONS: High CRP levels and low TC concentrations are independent and additive predictors of mortality in patients with CAD. Our data indicate that joint analysis of circulating lipoproteins and inflammatory biomarkers may improve prediction of survival in patients with CAD.

Aged↗
PubMed2004

Low levels of antibodies against E. coli and mycobacterial 65kDa heat shock proteins in patients with inflammatory bowel disease.

OBJECTIVE AND DESIGN: The aim of the present study was to support and extend our initial observation, where we found low levels of antibodies against mycobacterial 65kD heat shock proteins in patients with inflammatory bowel disease (IBD). For this purpose we tested a new group of 124 patients with IBD, and beside measuring antibodies to Mycobacterium bovis 65kD heat shock protein (Hsp65) and human 60kD heat shock protein (Hsp60) as described previously, we also determined IgG antibody levels to Hsp65 from E. coli, called GroEL. PATIENTS AND CONTROL SUBJECTS: seventy-four patients with Crohn's disease (CD) (30 males, 44 females, 33 (27-45) years old, median (interquartile range)) and 50 patients with ulcerative colitis (UC) (22 males, 28 females, 38 (30-50) years old) were involved in the study. 110 healthy subjects (34 males, 76 females, 47 (37-53) years old) served as controls. Study subjects were consecutive patients referred to an IBD center for complex treatment of the disease. Methods and statistical analysis: The amounts of IgG-type antibodies reacting with proteins of the chaperonin 60 family were assessed by ELISA. Since the antibody levels to heat-shock proteins as variables were not normally distributed, non-parametric Mann-Whitney test and Dunn post hoc test were used for group comparisons. RESULTS: Median levels of anti-GroEL (7,5 (3,5-18,3)) and anti-Hsp65 (4,8 (2,1-7,85)) were significantly (GroEL p = 0,008; and Hsp65 p < 0,001) lower in the IBD patients than in the healthy subjects (GroEL: 10,0 (5,4-31,0); Hsp65: 7,04 (4,66-12,77)). However this difference was found to be restricted to the CD patients (GroEL: 7,5 (3,7-14,2); p < 0,05; Hsp65: 4,35 (1,90-6,94); p < 0,001). We did not find difference in the concentration of anti-human Hsp60 IgG levels between patients (Hsp60: 45,5 (24,9-69,0)) and healthy controls (38,4 (21,6-69,4). Regarding the serum concentrations of each antibody tested there was no significant difference between the active and inactive stage of disease. CONCLUSION: Our present findings support conclusion of our previous work, antibody levels not only for Mycobacterium bovis hsp65 but for E. coli GroEl were found to be decreased as well. In contrast no changes in the concentrations of human anti-hsp60 antibodies were observed. These findings indicate that production of antibodies to 65 kDa bacterial heat shock proteins is selectively impaired in IBD.

Adult↗
PubMed2004

Marked decrease in the levels of two inflammatory markers, hs-C-reactive protein and fibrinogen in patients with severe carotid atherosclerosis after eversion carotid endarterectomy.

OBJECTIVE AND DESIGN: To study changes in the levels of two acute phase proteins, plasma fibrinogen and serum C-reactive protein (hs-CRP) in patients with severe carotid stenosis after eversion endarterectomy. MATERIAL AND SUBJECTS: A total of 117 consecutive patients who underwent eversion endarterectomy were included in the study. Blood samples for acute phase protein measurement were taken before operation as well as 5.7 weeks and 13.8 months (median) post-surgery. Plasma fibrinogen and serum hs-CRP concentrations were promptly determined. RESULTS: During the follow-up period sharp, highly significant (p < 0.0001) drop occurred in the serum concentrations of both acute phase proteins. The drop in the hs-CRP levels during the follow up period was mainly due to decrease in patients with highest baseline CRP levels. CONCLUSIONS: Our present findings indicate that removal of atherosclerotic plaques from the carotid arteries markedly decreases the production of two acute phase proteins due to the decrease of the inflammatory burden or the removal of the advanced plaques able to produce these proteins.

Arteritis↗
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↗
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↗
PubMed2002

Helicobacter pylori infection in connective tissue disorders is associated with high levels of antibodies to mycobacterial hsp65 but not to human hsp60.

BACKGROUND: To investigate whether the Helicobacter pylori status influences levels of antibodies against mycobacterial heat shock protein (hsp) 65 and human hsp60 in systemic autoimmune diseases and to study the concentration of anti-H. pylori antibodies in autoimmune patients and healthy controls. MATERIALS AND METHODS: Antibodies against human heat-shock protein hsp60, mycobacterial heat-shock protein hsp65 were analyzed by ELISA. Anti-Helicobacter antibodies were determined by enzyme immunoassay. RESULTS: There was a markedly higher prevalence of H. pylori infection in undifferentiated connective tissue disease (82%) (n = 33) and systemic sclerosis (78%) (n = 55) but not in systemic lupus erythematosus (n = 49), polymyositis/dermatomyositis (n = 14), rheumatoid arthritis (n = 21) or primary Raynaud's syndrome (n = 26) compared with controls (59%) (n = 349). In autoimmune diseases H. pylori infection was associated with elevated levels of antihsp65 (p =.008) but not of antihsp60. Anti-hsp65 levels were significantly higher in H. pylori-infected (n = 129) than in uninfected patients (n = 69) (p =.0007). CONCLUSIONS: These findings indicate that in autoimmune diseases the infection with the H. pylori bacterium is associated with increased concentration of antimycobacterial hsp65.

Adult↗
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

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

Involvement of polymorphisms in the chemokine system in the susceptibility for coronary artery disease (CAD). Coincidence of elevated Lp(a) and MCP-1 -2518 G/G genotype in CAD patients.

The central role of chemokines in the pathogenesis of atherosclerosis has been made clear. Recently polymorphisms in the gene regulatory region of MCP-1 and in the promoter region of RANTES have been found, which increase the expression of these chemokines. We investigated the role of these polymorphisms together with the chemokine SDF-1-801A and the chemokine receptors CCR2-64I and CCR5Delta32 mutations in 318 patients with coronary artery disease (CAD) referred to coronary bypass surgery, comparing them with 320 healthy controls. The prevalence of the MCP-1 -2518 G/G homozygotes was significantly higher among CAD patients than among controls (P<0.005; OR=2.2 (95% CI 1.25-3.92). The Lp(a) levels of CAD patients with G/G genotype were significantly higher than those in patients with G/A or A/A genotypes. No CAD patients homozygous for the CCR5Delta32 and CCR2-64I mutations have been found. The genotype distributions of the two alleles deviated from the Hardy Weinberg equilibrium in patients, indicating that the numbers of homozygotes were significantly lower than expected. The MCP-1 -2518G variant in homozygous form appears as a genetic risk factor for severe CAD. This genotype is associated with elevated Lp(a) levels in patients. Individuals homozygous for CCR2-64I or CCR5Delta32 mutations are at reduced risk for severe CAD.

Adult↗