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Biomedical subjects

G Szegedi

Publications and source records attributed to G Szegedi.

At least 19 recordsLinked to original sources

[Catastrophic antiphospholipid antibody syndrome in a cancer patient].

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 a case of a female patients with catastrophic antiphospholipid syndrome associated with gastric cancer. This may be the first case of such association in the literature. Authors also discuss the possible pathomechanism of this disorder, as well as the available therapeutic approaches.

Adenocarcinoma

[Adult onset Still disease: comment on two cases].

The adult onset Still disease is a systemic disease of an unknown etiology. As a separate entity, it was described firstly in 1971. The diagnosis is problematic and based upon special criteria. In this study, we present the cases of two patients with adult onset Still's disease, causing several serious differential-diagnostic problems. In the beginning of the disease a high, remittent-intermittent fever was present which reacted well to salycilates. Almost simultaneously, a characteristic, confluent, no itching rash appeared on the trunk and limbs. Pain of little joints of the hands was an early symptom of the disease in both of the cases. Before the final diagnosis, the possibility of any infectious diseases, haematologic malignancies or other autoimmune disease had to be excluded. The aim of this work was to show an overall, up-to-date picture of the disease based on two typical cases.

Adult

[Current aspects of the pathogenesis and clinical characteristics of otosclerosis: possibilities of drug therapy].

Otosclerosis is a multifactorial disease. A number of theories on the pathogenesis of this disease have been established in the last decades. It is important to review recent data on the pathogenesis of otosclerosis as it is a severe inner ear disease leading to deafness in the majority of cases. Surgical therapy is not always successful or feasible. In this review, authors describe the most relevant genetic, infective, immunological, inflammatory factors, as well as the impaired bone metabolism underlying the pathogenesis of otosclerosis. It is likely that genetic predisposition associated with morbilli infection may lead to bone resorption in the stapes and cochlea followed by spongiosis, fibrosis and sclerosis. It has been suggested that immunological mechanisms play a central role in the development of the disease. Some authors consider otosclerosis as autoimmune disorder based on the presence of several autoantibodies. Apart from classical diagnostic methods, such as audiometry and X-ray, novel radiological techniques including CT, MRI or radionuclide scan are helpful in the localization of otosclerosis. As surgery is sometimes contraindicated or unsuccessful, drug therapy including the use of anti-osteoporotic on non-steroidal antiinflammatory drugs may be administered, especially in the early phase of the disease.

Anti-Inflammatory Agents, Non-Steroidal

[Comments on Raynaud syndrome based on laser-Doppler studies].

The authors have in their care 286 Raynoud syndrome patients. They present their experience in the study of the microcirculation and the treatment of these patients. In 81% (232 patients, 196 women and 36 men) of the cases they did not find any underlying diseases. In the group of the patients with secondary Raynaud's syndrome (35 women and 19 men) underlying diseases, possibly leading to microcirculatory disturbances, could be identified. In the primary Raynaud's syndrome group the main capillary diameter measured by capillary microscopy was 15 +/- 4 micron. In patients with progressive systemic sclerosis the mean diameter was 43 +/- 9 micron. In the group of women with primary Raynaud's syndrome the authors performed laser Doppler measurements of the nailfold microcirculation. During the reactive hyperaemia test basal values (18.2 +/- 6.2 Perfusin Units, P. U.) and reactive hyperaemia values (a mean of 180% growth compared to the basal values) were similar to that perfusion values referred in the literature. In the progressive systemic sclerosis group the basal flow (9.3 +/- 3.3 P. U.) and the reactive hyperaemia (a mean of 20% increase compared to basal values) were significantly lower. Concerning the fact that the progression of Raynaud's syndrome into systemic autoimmune disease--mainly to progressive systemic sclerosis may be predicted, it is important to follow up carefully all patients with Raynaud's syndrome.

Adolescent

Isotype distribution and clinical relevance of anti-beta2-glycoprotein I (beta2-GPI) antibodies: importance of IgA isotype.

The aim of this study was to evaluate the prevalence of IgG, IgA and IgM anti-beta2-GPI antibodies in anti-phospholipid syndrome (APS), and to establish the clinical significance of IgA type antibodies compared with the other isotypes. Anti-beta2-GPI antibodies were measured in the sera of 70 patients by solid-phase enzyme immunoassay in gamma-irradiated polystyrene plates coated with human purified beta2-GPI. Thirty-three out of the 70 patients were classified as having APS: three of them had primary, and 30 had secondary APS related to systemic lupus erythematosus (SLE). The remaining 37 patients had SLE without APS. Anti-beta2-GPI antibodies of IgG, IgA and IgM isotypes were present in 84.8%, 59.3% and 51.5% of patients with APS. Both the frequency and the level of each isotype were significantly higher in patients with APS. This association was very strong for IgA (P = 0.0004 for the antibody frequency and P < 0.0001 for the antibody level), as well as for IgG type antibodies (P < 0.0001 and P < 0.0001), whereas it was weaker for IgM (P = 0.01 and P = 0.04). A strong relationship was demonstrated between increased IgA anti-beta2-GPI antibody levels and a history of venous thrombosis, thrombocytopenia, heart valve disease, livedo reticularis and epilepsy. IgG anti-beta2-GPI antibodies were associated with the presence of lupus anticoagulant (LA) in addition to the main features of APS. However, antibodies of IgM isotype were related only to thrombocytopenia and heart valve disease. We recommend the evaluation of anti-beta2-GPI antibodies of IgA isotype in addition to IgG in patients with clinical suspicion of APS.

Antiphospholipid Syndrome

Effect of plasmapheresis on ligand binding capacity and expression of erythrocyte complement receptor type 1 (CR1) of patients with systemic lupus erythematosus (SLE).

The functional activity and the expression of CR1 on the erythrocytes (E) of patients with SLE were, respectively, determined by measuring the binding to E of either complement-opsonized bovine serum albumin (BSA)-anti-BSA immune complexes (ICC) or specific anti-ECR1 MoAbs. We found that both the functional activity and levels of ECR1 in SLE patients homozygous for ECR1 high density allele were significantly lowered compared with healthy controls having the same allele. Soon after plasmapheresis there was a significant increase in E ICC binding activity, and this increased functional activity was stable. Moreover, plasmapheresis reduced the level of immune complexes demonstrable in the circulation of the patients. The expression of ECR1 determined with several different anti-CR1 MoAbs was also elevated as a consequence of plasmapheresis. This elevation was observed for both MoAb 1B4, which competes for the ICC binding site of ECR1, and for MoAb HB8592, which does not, but the time course for the increase in binding of the two MoAbs was different, in that the epitope recognized by MoAb 1B4 increased more rapidly. The present results, considered in the context of previous findings, suggest that more than one mechanism may be operative with respect to the effects of the plasmapheresis in increasing ECR1 levels defined by different epitopes on the molecule.

Alleles

Cyclosporin and sulfasalazine combination in the treatment of early rheumatoid arthritis.

The aim of the study was to assess the efficacy of a new formulation of cyclosporin-A (CyA) and sulfasalazine (SASP) combination treatment in preventing disability and reducing inflammatory disease activity in patients with early rheumatoid arthritis, as well as to assess the tolerability, safety, and suitability for long-term treatment. Forty five patients with early, active rheumatoid arthritis, (RA) were treated with CyA and SASP combination therapy for 12 months. The patients were evaluated by disease activity and radiologic measurements. The combined CyA and SASP therapy seems to be effective. Disease activity parameters improved within 3 months. The individual treatment response rate according to EULAR response criteria was 78% after a one year treatment period. Five patients were withdrawn due to gastrointestinal side effect and two patients because of lack of efficacy. CyA and SASP combination treatment seems to be effective in early severe RA, and with careful monitoring, side effects can be kept under control.

Adult

[Clinical significance of antiphospholipid autoantibodies in lupus erythematosus].

The authors have determined the prevalence of antibodies of cofactor dependent anticardiolipin and beta 2-glycoprotein I and lupus anticoagulant and the frequency of false positive VDRL test in systemic lupus erythematosus. The aim of this retrospective study was to assess the presence of these antibodies and symptoms of antiphospholipid syndrome. The serum samples were examined by modified ELISA method for detecting of cofactor dependent anticardiolipin. The antibodies to beta 2-glycoprotein I were examined by ELISA. The lupus anticoagulant and VDRL test were performed by routine laboratory method. The authors have found that 19 of 58 patients with systemic lupus erythematosus had cofactor dependent anticardiolipin, 10 patients had antibodies to beta 2-glycoprotein I and 4 patients had positive VDRL test. 5 of 34 plasma samples were lupus anticoagulant positive. 19 patients with systemic lupus erythematosus had 14 neuropsychiatric disorders, 9 cardiovascular diseases, 7 thrombocytopenia, 6 histories of recurrent abortion and fetal loss, 5 livedo reticularis and 3 thromboembolic events in all of them had detected antibodies to cofactor dependent anticardiolipin, while these complications were diagnosed in 39 anticardiolipin negative patients much more rarely. The results of this retrospective study suggest that significant association exists between the presence of cofactor dependent anticardiolipin and symptoms of antiphospholipid syndrome in systemic lupus erythematosus.

Antibodies, Antiphospholipid

Different effects of an oligonucleotide uptake stimulating protein on leukemic cells in their primitive and differentiated state.

The single stranded [3H]oligonucleotide uptake by HL-60 human promyelocyte and K562 human erythroleukemia cells was stimulated 20-45-fold by DUSF (DNA uptake stimulating protein), and this effect was drastically reduced (to 1.6-13x) if the cells were induced to differentiate. The oligonucleotide uptake stimulating effect of DUSF was not altered in HL-60 and K562 cells, if the proliferation of the cells was inhibited by hydroxyurea (HU) treatment. The oligonucleotide uptake by separated granulocytes and mononuclear cells from healthy donors was not stimulated by DUSF, while the uptake of oligonucleotides by myeloid and lymphoid leukemic cells was greatly stimulated (10-15x). The uptake of oligonucleotides by differentiated mononuclear cells of healthy donors could not be stimulated by DUSF, but the oligonucleotide uptake was greatly increased (11x) by DUSF if the cells were subjected to blast transformation.

Biological Transport

[Cytokines in rheumatoid arthritis: new therapeutic possibilities].

The ingress of inflammatory leukocytes into the synovium is important for the pathogenesis of rheumatoid arthritis. Soluble inflammatory mediators regulate the inflammatory, chemotactic, adhesive, angiogenic events, as well as osteopenia associated with this disease. In this review authors discuss the role of a number of inflammatory mediators, such as cytokines, chemokines and growth factors in these processes. The outcome of arthritis is highly dependent on the imbalance between pro-inflammatory and anti-inflammatory mediators. Cytokine-related research also has important clinical relevance. Many of these proteins are detectable in the serum of rheumatoid patients and may eventually serve as useful laboratory markers of disease activity. Antirheumatic therapy currently used for the treatment of rheumatoid arthritis is often limited. Therefore, we need to consider alternative therapeutic regimens, such as the inhibition of cytokines and other soluble mediators, in order to prevent severe joint destruction. While there are many complex interactions involving cytokine networks and cascades in the arthritic joint, there are promising attempts to eliminate a single cytokine in clinical trials, such as ablation of tumor necrosis factor-alpha. Hopefully, the study of cytokines and their networks will lead to specific immunomodulatory therapies that will benefit rheumatoid patients by preventing joint destruction.

Antibodies, Monoclonal

[Observation in two cases of Whipple disease].

The authors survey the literature of Whipple's disease and present two of their patients. They assure that Whipple's disease in either associated with or is a result of an immunopathological clinical picture, but it is else possible that assumed pathogen, the Tropheryma whippleii itself alters the immune system. In the case of their female patient with active disease they showed the rearrangement of the bcl-2 gene [t(14; 18)] in her peripheral blood lymphocytes, while in their male patient in remission this could not be proved. During the observation, in their female patient insulin dependent diabetes mellitus (IDDM) developed. In connection with these cases, the authors draw the attention to the varied symptoms which are characteristic of autoimmune disease, and to the immunoserological laboratory differences in particular the rearrangement of the bcl-2 gene.

Adult

[Angiotensin and its mediators. Their pathogenic and clinical significance in "angiogenic diseases"].

Angiogenesis, the production of new blood vessels, plays an important role in a number of physiological and pathological processes, such as development, tissue repair, atherosclerosis, ischemic heart diseases, inflammation and tumor progression. A number of mediators including cytokines, heparin-dependent and -independent growth factors, proteolytic enzymes, extracellular matrix components, cellular adhesion molecules and others, have been implicated in angiogenesis. Certain angiostatic cytokines, growth factor antagonists, steroids, protease inhibitors, antibiotics, antirheumatic drugs, tissue-derived inhibitors and others inhibit neovascularization. Angiogenesis research has important clinical relevance, as targeting angiogenic and angiostatic processes by using angiogenesis inhibitors, receptor antagonists, antibodies, enzyme inhibitors, tumor suppressor genes and other forms of gene therapy, may be a potential therapeutic tool in "angiogenic diseases".

Angiogenesis Inducing Agents

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

Angiogenesis in rheumatoid arthritis: pathogenic and clinical significance.

In summary, angiogenesis, the formation of new blood vessels, is important in leukocyte extravasation and thus the pathogenesis of RA. The outcome of neovascularization highly depends on the imbalance between angiogenic and angiostatic mediators produced in the rheumatoid synovium. Therefore, angiogenesis research is important for the understanding of the pathogenesis of inflammatory arthritis. In addition, existing and potential angiostatic drugs may be useful for future therapy of RA.

Animals

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

[The presence of t(14;18) chromosome translocation in various types of diseases].

Chromosome translocation of t(14;18) can be detected in most cases of centroblastic/centrocytic follicular lymphomas. They are causative factors of lymphomas but the translocation is present in different other types of diseases although the translocation does not belong to the features of these illnesses. Our present work shows the appearance of t(14;18) translocation in lymphocytes of two patients of Sjögren's syndrome, one that of Whipple disease as well as one of healthy donors' lymphocytes using polymerase chain reaction technique presented in one of our previous publication. The translocation occurred in the mbr of bcl-2 gene in all cases showed and the bcl-2 gene was coupled with the immunoglobulin heavy chain gene. These results are definitively positive concerning the fact of translocation as it has been proved by sequencing of the amplification products showed in our earlier and present paper. Because relatively high percentages of Sjögren's syndrome patients develop later on lymphoma, the early detection of the translocation could result in a more successful diagnosis as well as treatment of the disease. The question arises, however, what role the translocation plays in illnesses such as the Whipple disease or what kind of consequences can be drawn from the appearance of the t(14;18) translocation in lymphocytes of healthy donors.

Chromosomes, Human, Pair 14

[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