Biomedical subjects

E Kiss

Publications and source records attributed to E Kiss.

At least 73 records · Page 4Linked to original sources

PubMed1999

Systemic lupus erythematosus: clinical features in patients with a disease duration of over 10 years, first evaluation.

OBJECTIVE: Most information available about the disease course of patients with systemic lupus erythematosus (SLE) is restricted to the first 5 yr after disease onset. Data about the disease course 10 yr after disease onset are rare. The aim of this multicentre study was to describe the outcome of SLE patients with a disease duration of >10 yr. METHODS: Outcome parameters were the SLE Disease Activity Index (SLEDAI), the European Consensus Lupus Activity Measure (ECLAM), the Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index (SLICC/ACR), a global damage index (DI) and required treatment. In 10 different European rheumatology centres, all SLE patients who were evaluated in the last 3 months of 1994, and who had been diagnosed with SLE at least 10 yr ago, were included in the study. RESULTS: It should be stressed that our results are confined to a patient cohort, defined by a disease duration of at least 10 yr, and who are still under clinical care at the different centres in Europe. These SLE patients still showed some disease activity, related to symptoms of the skin and musculoskeletal systems, next to the presence of renal involvement. A total of 72% of the patients needed treatment with prednisolone (</=7.5 mg). The cumulative damage was overall related to clinical features of the central nervous system (14%) and renal involvement (14%), next to deforming arthritis (14%), osteoporosis (15%) and hypertension (40%). The prevalences of obesity, Cushing appearance and diabetes are highly suggestive that the ongoing treatment and that in the past might have had an impact on the total sum of end-organ damage. CONCLUSIONS: After 10 yr, a high proportion of patients in our cohort continued to show evidence of active disease, defined by the SLEDAI as well as ECLAM. The DI was related to the involvement of the central nervous system, renal involvement and the presence of hypertension.

Adult↗

PubMed1999

Screening for mutations of 21-hydroxylase gene in Hungarian patients with congenital adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders, causing impaired secretion of cortisol and aldosterone from the adrenal cortex, with subsequent overproduction of adrenal androgens. The most common enzyme defect causing CAH is steroid 21-hydroxylase deficiency. To determine the mutational spectrum in the Hungarian CAH population, the CYP21 active gene was analyzed using PCR. A total of 297 Hungarian patients with 21-hydroxylase deficiency are registered in the 2nd Department of Pediatrics, Budapest, Hungary, and their clinical status was evaluated. Blood samples for CYP21 genotype determination could be obtained from 167 patients (representing 306 unrelated chromosomes and 56.2% of the total group of patients). Eight of the most common mutations were screened [In2 (intron 2 splice mutation), I172N, Del (Del: apparents large gene conversion), Q318X, R356W, 1761Tins, ClusterE6, V281L] using allele-specific amplification. The most frequent mutation in the Hungarian CAH population was found to be In2. Our results have shown a good genotype/phenotype correlation in case of most mutations; the In2 mutation is associated mostly with the severe form of the disease, whereas I172N was expressed in a wide spectrum of phenotypes. 1999)

Adrenal Hyperplasia, Congenital↗

PubMed1998

Thyroid hormone-induced alterations in phospholamban-deficient mouse hearts.

Alterations in the expression levels of the sarcoplasmic reticulum (SR) Ca2+-ATPase and its regulator, phospholamban, have been implicated in the effects of thyroxine hormone on cardiac function. To determine the role of phospholamban in these effects, hypothyroidism and hyperthyroidism were induced in phospholamban-deficient mice and their isogenic wild types. Hypothyroidism resulted in significant decreases of left ventricular contractility, which could be moderately stimulated by increases in preload or afterload, in both phospholamban-deficient and wild-type mice. However, the basal contractile parameters in hypothyroid phospholamban-deficient hearts were at least as high as those exhibited by hyperthyroid wild-type hearts. In hyperthyroidism, there was no further enhancement of the hyperdynamic contractile parameters in phospholamban-deficient hearts, although the wild-type hearts exhibited significantly increased contractile function compared with their respective euthyroid groups. Furthermore, increases in preload or afterload did not enhance contractility in either phospholamban-deficient or wild-type hyperthyroid hearts. Examination of the relative tissue levels of cardiac SR Ca2+-ATPase revealed increases in hyperthyroidism and decreases in hypothyroidism compared with euthyroidism, and these changes were similar between phospholamban-deficient and wild-type hearts. An opposite trend was observed for phospholamban expression levels in the wild-type group, which were depressed in hyperthyroid hearts but increased in hypothyroid hearts. These findings indicate that (1) thyroid hormones induce similar changes in the cardiac SR Ca2+-ATPase levels in either the presence or absence of phospholamban, (2) the thyroxine-induced increases in SR Ca2+-ATPase levels are not associated with any further stimulation of the hyperdynamic cardiac function in phospholamban-deficient mice, and (3) the decreased contractile parameters in hypothyroid phospholamban-deficient hearts associated with decreases in SR Ca2+-ATPase levels and myosin heavy chain isoform switches are at least as high as those of the stimulated hyperthyroid wild-type hearts. Thus, alterations in the phospholamban level or its activity may be a critical determinant of the contractile responses to altered thyroid states in the mammalian heart.

Animals↗

PubMed1998

Phospholamban ablation and compensatory responses in the mammalian heart.

Phospholamban is a low molecular weight phosphoprotein in cardiac sarcoplasmic reticulum. The regulatory role of phospholamban in vivo has recently been elucidated by targeting the gene of this protein in embryonic stem cells and generating phospholamban-deficient mice. The phospholamban knockout hearts exhibited significantly enhanced contractile parameters and attenuated responses to beta-agonists. The hyperdynamic cardiac function of the phospholamban knockout mice was not accompanied by any cytoarchitectural abnormalities or alterations in the expression levels of the cardiac sarcoplasmic reticulum Ca(2+)-ATPase, calsequestrin, Na(+)-Ca2+ exchanger, or the contractile proteins. Furthermore, the attenuation of the cardiac responses to beta-agonists was not due to alterations in the phosphorylation levels of the other key cardiac phosphoproteins in the phospholamban knockout hearts. However, ablation of phospholamban was associated with down-regulation of the ryanodine receptor, which suggests that a cross-talk between cardiac sarcoplasmic reticulum Ca2+ uptake and Ca2+ release occurred in an attempt to maintain Ca2+ homeostasis in these hyperdynamic phospholamban knockout hearts.

Adrenergic beta-Agonists↗

PubMed1998

Correlation of Fc gamma receptor expression of monocytes with clearance function by macrophages in systemic lupus erythematosus.

The expression of Fc gamma receptor II (Fc gammaRII) and Fc gammaRIII on monocytes in peripheral blood and the clearance of immunoglobulin (Ig)G-sensitized erythrocytes (EA) by tissue macrophages were investigated in parallel in patients with systemic lupus erythematosus (SLE). The relationship between receptor expression and the rate of clearance of EA (half-time) was analyzed. The detected decrease in mean fluorescence intensity of both FcR gammaII and Fc gammaRIII of patients' monocytes stained with specific monoclonal antibodies (IV.3 and 3G8) was inversely correlated with the prolonged clearance half-time of 51Cr-labelled and anti-D IgG-sensitized autologous erythrocytes in these patients. A correlation was found between the impaired clearance function and the severity of the disease manifestation expressed by either clinical activity or renal involvement in our SLE patients. From these results it can be concluded that the in-vitro determination of monocyte Fc gammaRII and Fc gammaRIII expression may predict the in-vivo macrophage function via the same Fc receptors.

Antigen-Antibody Complex↗

PubMed1998

Novel rkp gene clusters of Sinorhizobium meliloti involved in capsular polysaccharide production and invasion of the symbiotic nodule: the rkpK gene encodes a UDP-glucose dehydrogenase.

The production of exopolysaccharide (EPS) was shown to be required for the infection process by rhizobia that induce the formation of indeterminate nodules on the roots of leguminous host plants. In Sinorhizobium meliloti (also known as Rhizobium meliloti) Rm41, a capsular polysaccharide (KPS) analogous to the group II K antigens of Escherichia coli can replace EPS during symbiotic nodule development and serve as an attachment site for the strain-specific bacteriophage phi16-3. The rkpA to -J genes in the chromosomal rkp-1 region code for proteins that are involved in the synthesis, modification, and transfer of an as-yet-unknown lipophilic molecule which might function as a specific lipid carrier during KPS biosynthesis. Here we report that with a phage phi16-3-resistant population obtained after random Tn5 mutagenesis, we have identified novel mutants impaired in KPS production by genetic complementation and biochemical studies. The mutations represent two novel loci, designated the rkp-2 and rkp-3 regions, which are required for the synthesis of rhizobial KPS. The rkp-2 region harbors two open reading frames (ORFs) organized in monocistronic transcription units. Although both genes are required for normal lipopolysaccharide production, only the second one, designated rkpK, is involved in the synthesis of KPS. We have demonstrated that RkpK possesses UDP-glucose dehydrogenase activity, while the protein product of ORF1 might function as a UDP-glucuronic acid epimerase.

Bacterial Capsules↗

PubMed1998

[Free formaldehyde determination in cosmetic products by the HPLC method].

In order to standardize the analytical methods and procedures with the ones used in the EU, a method of free formaldehyde determination in cosmetic products preserved with formaldehyde donors, recommended by Commission Directive (90/207/EEC of 4th April, 1990), has been tested. The free formaldehyde level is determined by HPLC using post column derivatisation with acetylacetone. Formaldehyde content was determined in 44 fortified samples of cosmetic emulsions and shampoos. Recoveries ranged from 94.8-97.5%. Relative Standard Deviation 1-2.3%.

Chromatography, High Pressure Liquid↗

PubMed1998

Recombinant human erythropoietin modulates erythrocyte complement receptor 1 functional activity in patients with lupus nephritis.

Deposition of immune complexes (IC) is an important step in the pathogenesis of lupus nephritis. Impairment of IC-clearance contributes to the accumulation of IC. It may be partly attributed to decreased complement containing immune complex (ICC) binding by erythrocytic complement receptor 1 (ECR1). Stimulating erythropoiesis with recombinant human erythropoietin (rHuEPO) may enhance the IC-clearance as increasing ECR1 expression and/or functional activity. Ten anemic patients with lupus nephritis were treated with 50 IU rHuEPO (Eprex) per kg body weight three times a week during a five week period. ICC-binding capacity of ECR1 was determined with 125I-labelled, C3ib containing BSA-anti-BSA complexes. In addition to effective correction of anemia, indicated by increased red blood cell count (RBC), hemoglobin concentration and reticulocyte ratio, rHuEPO significantly improved decreased ECR1 functional (ICC-binding) activity in patients with lupus nephritis. This improvement correlated with the increase in reticulocyte ratio. Although patients were kept on their previous therapy during Eprex administration, their clinical condition also improved. That was shown by a decrease in Westergreen ratio, serum creatinine concentration and anti-dsDNA level and also by an increase in creatinine clearance. Results suggest a beneficial immune modulatory effect of rHuEPO in lupus nephritis.

Adolescent↗

PubMed1997

[Immunomodulatory effect of pentoxifylline in Graves ophthalmopathy].

In the pathomechanism of the thyroid associated ophthalmopathy (TAO) the inflammatory cytokines produced by infiltrating lymphocytes of the retroorbital tissues are involved. The activated lymphocytes have been shown to secrete a number of cytokines including tumour necrosis factor-alpha, interleukin-1 and interferon-gamma. The widely used immunosuppressive therapies have potential serious side effects. The pentoxifylline (Ptx) is known to have effect on production of cytokines. The aim of this study was to investigate the effect of Ptx on expression of HLA-DR molecules and production of glycosaminoglycan of human retroorbital tissue cultures and potential efficacy in patients with TAO. It was found that pentoxifylline (Ptx) was able to inhibit significantly the HLA-DR expression and glycosaminoglycan synthesis induced by inflammatory cytokines including TNF-alpha, IFN-gamma and IL-1. Ten patients with untreated moderate severe ophthalmopathy (8 female and 2 male) were excluded from steroid treatment due diabetes mellitus and psychiatric disease. Classification of eye changes was made by NOSPECS categories and total eye score. All patients were euthyroid during the study and was no remarkable difference in thyroid function and eye symptoms. Before and during Ptx therapy the laboratory parameters were also determined including glycosaminoglycan. TNF-alpha, anti-TSH-receptor, anti-eye muscle, anti-thyroglobulin and anti-thyroid peroxidase antibodies in the patients'sera. It was found a remarkable improvement in the eye symptoms in eight of ten patients. The levels of glycosaminoglycan (uronic acid) and TNF-alpha gradually decreased in eight patients who considered to be responders. The levels of uronic acid in plasma of the responders were found to be significantly lower after Ptx treatment. Before Ptx therapy the TNF-alpha in the sera was not different remarkably in non-responders and responders. After 4 weeks Ptx treatment the TNF-alpha decreased significantly in responders compared to non-responders (20.9 +/- 4.8 pg/ml v. s. 28.3 +/- 6.1 pg/ml) (p < 0.01). The titre of anti-eye muscle antibodies were found to be lower at the end of observation, however, the anti-thyroid antibodies were not changed remarkably. It was concluded that Ptx in the majority of patients (8/10) has a beneficial effect on inflammatory symptoms of TAO and laboratory parameters and suggested to use as an additive therapy, however, further comparative studies are required for final evaluation of Ptx in the treatment of TAO.

Adjuvants, Immunologic↗

PubMed1997

[Cerebral positron emission tomographic study in systemic lupus erythematosus].

The cerebral glucose metabolism in eight patients with systemic lupus erythematosus (SLE) and in five healthy controls were examined by positron emission tomography (PET) using 18-F-labeled deoxy-glucose (FDG) as tracer. One of the eight patients had no abnormality by magnetic resonance imaging (MRI), three of them had cerebral atrophy and four patients had multiple white matter hyperintensities and vascular infarcts in the striatum as assessed by MRI. With FDG-PET, inhomogeneous multifocal cerebral glucose hypometabolism was detected, more frequently in the temporal lobe of right hemisphere. The PET findings did not correlate always with the neurological symptoms. Abnormalities in brain metabolism can be detected more frequently by PET, than morphological changes by MRI, indicating the involvement of the central nervous system.

Adult↗

PubMed1997

[Genetic diagnosis of Williams syndrome].

Williams syndrome is a complex developmental disorder. The major cardiovascular component of Williams syndrome is supravalvular aortic stenosis, a progressive disease that may need surgical repair. Williams syndrome is associated with heterozygous microdeletion in the chromosomal region 7q11.23 encompassing the elastin gene. We have identified a new, highly informative tetranucleotide repeat polymorphism within the human elastin gene. This marker together with other, previously described elastin gene markers was used to show deletion of the elastin gene in nine sporadic Williams syndrome patients from Hungary. Application of polymorphisms within and flanking the elastin gene on chromosome 7 provides a fast, polymerase chain reaction based method for mutational analysis of Williams syndrome patients.

Aortic Valve Stenosis↗

PubMed1997

[Chronic granulomatous disease (CGD): dysfunction of the neutrophil granulocyte NADPH-oxidase enzyme system].

Dysfunction of NADPH oxidase results in chronic granulomatous disease (CGD), a syndrome characterized by severe bacterial and fungal infections. Phagocytes of the patients are unable to kill ingested microorganisms which leads to the formation of granulomas and abscesses. Predominant pathogens are the catalase-positive bacteriae (Staphylococcus aureus) and some fungi (Aspergillus species). Infections of these patients should be treated by antimicrobial agents, which penetrate cells and kill pathogens inside. The aim of this study was to give a short description of the structure and function of the NADPH oxidase enzyme and to summarize the results obtained during the diagnostic of 10 patients with chronic granulomatous disease. Characterization of the disease was confirmed by mutation analyses.

Common Variable Immunodeficiency↗

PubMed1997

[Clinical application of analysis of microsatellite markers in the prenatal diagnosis of cystic fibrosis].

Cystic Fibrosis (CF) is an autosomal recessive hereditary disease, caused by the defect of a membrane transport protein. The defect is due to the mutation of the gene coding this protein. To date, these mutations have been analysed by direct mutational analyses in prenatal diagnosis. During gene sequencing, intragenic polymorphic markers (microsatellites) were identified, enabling the indirect analysis of the mutant allele. The markers characterize the given allele, so that the inheritance according to the Mendelian rules could be followed. We introduced a DNA-diagnostic method based on the amplification of three intragenic microsatellites. This new and efficient prenatal diagnostic tool would provide more reliable test results for previously screened CF families, in which direct mutation analysis was not informative.

Cystic Fibrosis↗

PubMed1997

Effect of TSH and anti-TSH receptor antibodies on the plasma membrane potential of polymorphonuclear granulocytes.

Effects of thyrotropin hormone (TSH) and anti-TSH receptor antibodies on the plasma membrane potential of polymorphonuclear granulocytes (PMN) were analyzed by means of flow cytometry. Both TSH and the autoantibody caused a rapid, dose-dependent hyperpolarization of the plasma membrane of PMNs. TSH was also able to mask (revert) the depolarizing effect of a chemotactic peptide, fMLP, on PMNs. No detectable rise in the cytosolic free calcium level accompanied the observed hyperpolarization. Quinine, a blocker of Ca(2+)-activated and voltage-gated K+ channels did not affect the hyperpolarization by TSH and antibodies. Decreasing the [K+] gradient across the plasma membrane by valinomycin, however, blocked the hyperpolarizing effect. Peptide362-376 (derived from the extracellular domain of TSH receptor) also blocked the hyperpolarization induced by both TSH and anti-TSHR antibodies. These data suggest that the observed hyperpolarization is a specific, receptor-mediated early signal during interaction of PMNs with TSH or anti-TSHR antibodies.

Amino Acid Sequence↗

PubMed1997

The rkpGHI and -J genes are involved in capsular polysaccharide production by Rhizobium meliloti.

The first complementation unit of the fix-23 region of Rhizobium meliloti, which comprises six genes (rkpAB-CDEF) exhibiting similarity to fatty acid synthase genes, is required for the production of a novel type of capsular polysaccharide that is involved in root nodule development and structurally analogous to group II K antigens found in Escherichia coli (G. Petrovics, P. Putnoky, R. Reuhs, J. Kim, T. A. Thorp, K. D. Noel, R. W. Carlson, and A. Kondorosi, Mol. Microbiol. 8:1083-1094, 1993; B. L. Reuhs, R. W. Carlson, and J. S. Kim, J. Bacteriol. 175:3570-3580, 1993). Here we present the nucleotide sequence for the other three complementation units of the fix-23 locus, revealing the presence of four additional open reading frames assigned to genes rkpGHI and -J. The putative RkpG protein shares similarity with acyltransferases, RkpH is homologous to short-chain alcohol dehydrogenases, and RkpJ shows significant sequence identity with bacterial polysaccharide transport proteins, such as KpsS of E. coli. No significant homology was found for RkpI. Biochemical and immunological analysis of Tn5 derivatives for each gene demonstrated partial or complete loss of capsular polysaccharides from the cell surface; on this basis, we suggest that all genes in the fix-23 region are required for K-antigen synthesis or transport.

Acyltransferases↗

PubMed1997

beta-Adrenergic regulation of cAMP and protein phosphorylation in phospholamban-knockout mouse hearts.

The stimulatory effects of beta-adrenergic agonists reflect increases in intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels and phosphorylation of key regulatory proteins in the heart. One of these phosphoproteins is phospholamban (PLB) in sarcoplasmic reticulum, and ablation of PLB is associated with attenuation of the contractile responses to beta-adrenergic stimulation in the mouse heart. To determine whether this attenuation of beta-stimulation is due to altered phosphorylation characteristics of the other key cardiac phosphoproteins and/or to compensatory responses occurring in the absence of PLB, PLB-knockout and wild-type hearts were perfused and their protein phosphorylation patterns examined. The beta-adrenergic receptor density, adenylyl cyclase activity, tissue cAMP levels, and the basal phosphoprotein pattern were similar between PLB-knockout and wild-type hearts. Isoproterenol perfusion resulted in similar increases in the tissue cAMP levels and the degree of phosphorylation of troponin I, C protein, and the 21-kDa microsomal protein in wild-type and PLB-knockout hearts. These findings indicate that the attenuation of isoproterenol-mediated increases in contractility of the PLB-knockout hearts is not due to alterations in the beta-adrenergic signal transduction pathway or the degree of phosphorylation of the key cardiac regulatory phosphoproteins in myofibrils and sarcolemma.

Animals↗

PubMed1997

Beneficial effect of pentoxifylline on thyroid associated ophthalmopathy (TAO)*: a pilot study.

We have previously found that pentoxifylline (Ptx) inhibited cytokine induced HLA-DR expression and glycosaminoglycan (GAG) synthesis by retroorbital fibroblasts. We have now tested the clinical efficacy of Ptx in treating TAO. Ten patients with moderately severe ophthalmopathy were selected for study. All patients were euthyroid before and during the 12 weeks of the Ptx therapy. Serum GAG, TNF-alpha, anti-TSH-receptor, anti-eye muscle, anti-thyroglobulin and anti-thyroid peroxidase antibodies were determined sequentially. At the end of 12 weeks eight of the ten patients showed improvement in soft tissue but not in proptosis or extraocular muscle involvement. At baseline the levels of GAG (5.2+/-0.92 mg/dl v.s. 0.7+/-0.14 mg/dl, p<0.001) and TNF-alpha (33.6+/-6.6 pg/ml v.s. 5.4+/-1.3 pg/ml, p<0.001) were increased in patients compared to controls. They gradually decreased in the eight patients who responded to Ptx: after 4, 8 and 12 weeks of therapy serum GAG was 3.4+/-0.42 mg/dl, 2.5+/-0.77 mg/dl (p<0.01) and 1.1+/-0.2 mg/dl (p<0.001), respectively and serum TNF-alpha was 20.9+/-4.8 pg/ml, 14.9+/-2.2 pg/ml (p<0.05) and 9.7+/-1.8 pg/ml (p<0.01), respectively. Serum GAG and TNF alpha did not fall in the two patients who did not respond. The titre of anti-eye muscle antibodies but not anti-thyroid antibodies were lower at 12 weeks. Ptx has a beneficial effect on inflammatory symptoms of TAO and associated laboratory parameters in the majority of patients.

Adult↗

PubMed1997

Serum complement activation of SLE patients during plasmapheresis.

The erythrocyte complement receptor 1 (ECR1)-immune complex binding assay is a sensitive method for the determination of complement fragments which can be activated by bovine serum albumin (BSA)-anti-BSA in vitro. When the C3b/C4b containing bovine serum albumin (BSA)-anti-BSA was formed in the presence of the serum of patients with systemic lupus erythematosus (SLE) its binding to ECR1 was found to be lower than that formed in sera of normal volunteers. The plasmapheresis of SLE patients homozygous for the CR1/E high density allele displays a beneficial effect on the formation of C3b/C4b containing BSA-anti-BSA and its binding to ECR1. There was no significant correlation between the serum C3/C4 level and the percentage of C3b/C4b containing BSA-anti-BSA binding to the ECR1 of SLE patients during plasmapheresis. At the same time, there was an inverse correlation between the serum immune complex level and the ECR1 binding, which was significant in 3 of 5 cases. These data suggest that, besides the determination of different components of complement activation, the functional assay of complement activation might be useful in monitoring the effect of plasmapheresis in SLE.

Adult↗