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Biomedical subjects

Z Szekanecz

Publications and source records attributed to Z Szekanecz.

At least 19 recordsLinked to original sources
PubMed2005

Evaluation of interstitial lung disease in mixed connective tissue disease (MCTD).

OBJECTIVE: Interstitial lung disease (ILD) may be a characteristic, often serious, manifestation of mixed connective tissue disease (MCTD). In this retrospective study, the frequency and clinical picture of ILD were determined in patients with MCTD using two diagnostic tests: high-resolution computed tomography (HRCT) and inhaled aerosol clearance times of (99m)Tc-labelled diethylene-triamine pentaacetate ((99m)Tc-DTPA). In addition, pulmonary function, effects of therapy and a variety of immunoserological markers were also assessed. METHODS: One hundred and forty-four consecutive patients with MCTD were selected from the clinic, irrespective of the presence or absence of ILD. All patients underwent a detailed clinical assessment, chest HRCT scanning, chest radiography, inhaled aerosol of (99m)Tc-DTPA clearance times, and all pulmonary function tests. Patients who had active ILD received corticosteroid (CS) or CS in combination with cyclophosphamide (CPH). All investigations were repeated after 6 months of immunosuppressive therapy. RESULTS: Ninety-six out of 144 MCTD patients (66.6%) had active ILD, 75 of this group (78.1%) showed ground glass opacity, 21 patients (21.8%) ground glass opacity with mild fibrosis with HRCT. Forty-five patients with active ILD received 2 mg/kg/day CS for 6-8 weeks alone and 51 patients CS in combination with CPH (2 mg/kg/day). Six months later, after therapy, 67 out of 96 MCTD patients with ILD (69.8%) showed a negative HRCT pattern, ground glass opacity with mild fibrosis developed in 15 patients (15.6%), and fibrosis was detected in 13 patients (13.5%). Only one patient showed subpleural honeycombing. (99m)Tc-DTPA was rapid in all 96 MCTD patients with active ILD (28.7 +/- 8.2 min, normal value >40 min). After therapy the (99m)Tc-DTPA was normalized, 79 out of 96 patients (82.3%). Carbon monoxide diffusion capacity (DLCO) was reduced in 33 out of 96 MCTD patients with active ILD (34.3%), while there were no significant differences in the pulmonary function tests between the active versus inactive stage of ILD or versus patients without ILD. The sera of 96 MCTD patients with active ILD contained a high level of immune complexes (ICs), and the total haemolytic complement levels (CH50/ml U) decreased. After 6 months of therapy, the IC levels decreased and CH50/ml levels normalized (MCTD patients before and after active ILD: IC optical density = 355 +/- 227 vs 206 +/- 92, P<0.001; CH50/ml, 38.0 +/- 12.6 U vs 64.3 +/- 13.0 U, P<0.001). CONCLUSIONS: HRCT is the gold standard for diagnosis of ILD. However, we used another method, (99m)Tc-DTPA, in order to compare this technique with HRCT. This latter technique has not been studied previously in MCTD. The elevated levels of IC and increased complement consumption indicated that IC-mediated alveolocapillary membrane damage and tissue injury might play a role in the pathogenesis of ILD in MCTD.

Adult↗
PubMed2004

Antiphospholipid antibodies in acute coronary syndrome.

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

Adult↗
PubMed2003

Osteoporosis in mixed connective tissue disease.

The existence of osteoporosis in 58 postmenopausal women with mixed connective tissue disease (MCTD) was investigated. The mean bone mineral density assessed by dual energy X-ray absorptiometry in the lumbar spine was decreased in 25.8% of the patients, reflecting osteoporosis (T score < -2.5). In the femoral neck there was no significant difference between the BMD of MCTD patients and that of age-matched, healthy postmenopausal women. Low bone mineral density was found among patients on, as well as off, corticosteroids. The extent of bone loss was associated with disease duration, as well as corticosteroid therapy. Serum osteocalcin levels were lower in MCTD patients than in controls. Lower serum oestradiol, testosterone and dehydroepiandrosterone sulphate levels were detected in MCTD patients than in controls. Thus, MCTD may be associated with increased bone loss. Pathogenic factors may include the disease itself, corticosteroid therapy, impaired osteoblast function, and low serum sex hormone levels.

Absorptiometry, Photon↗
PubMed2001

Update on synovitis.

Rheumatoid arthritis (RA) is an inflammatory disorder associated with chronic synovitis, eventually leading to cartilage and bone destruction in the joints. Synovitis is associated with the activation of various cells in the synovium including synovial lining cells, interstitial macrophages, endothelial cells, lymphocytes, and fibroblasts. The key mechanisms underlying synovitis include inflammatory cell adhesion and activation, the production of mediators (such as cytokines, chemokines, and growth factors), angiogenesis, joint destruction, fibrosis, and bone resorption. These important events, as well as the role of inflammatory cells, cell surface molecules, and soluble mediators are updated and discussed in this review. Some aspects and strategies of current or future immunotherapy are also discussed because these animal and human trials provide information on the pathogenesis of inflammatory synovitis.

Animals↗
PubMed2001

Chemokines and angiogenesis.

Chemokines mediate the ingress of leukocytes, including neutrophils and monocytes, into the inflamed synovium. Among the four known chemokine families, C-X-C and C-C chemokines seem to be of outstanding importance in this process. Angiogenesis, the formation of new vessels, is also important in the pathogenesis of rheumatoid arthritis. In this review, the authors discuss the role of the most important chemokines in the pathogenesis of rheumatoid synovitis. The most relevant angiogenic factors and angiogenesis inhibitors involved in rheumatoid arthritis are also discussed. Because certain chemokines may also play a role in neovascularization, chemokines and the process of angiogenesis are described in this context as well. Apart from discussing the pathogenic role of these factors, the authors also review the important relevance of chemokines and angiogenesis for therapeutic intervention.

Antibodies↗
PubMed2000

Cell-cell interactions in synovitis. Endothelial cells and immune cell migration.

Leukocyte ingress into the synovium is a key process in the pathogenesis of rheumatoid arthritis and other inflammatory conditions. In this review, the role of endothelial cells in leukocyte extravasation will be discussed, including the role of the most relevant cellular adhesion molecules. These molecules play an important role in mediating leukocyte--endothelial interactions. It is likely that different adhesive pathways are involved in different steps of leukocyte adhesion to and migration through endothelia. Targeting of pathological endothelial function, including leukocyte--endothelial adhesion, may be useful for the future management of inflammatory arthritis.

Animals↗
PubMed2000

Temporal expression of inflammatory cytokines and chemokines in rat adjuvant-induced arthritis.

OBJECTIVE: To examine cytokine and chemokine production during the evolution of rat adjuvant-induced arthritis (AIA), a model of rheumatoid arthritis. METHODS: Clinical and laboratory assessment of the course of AIA was performed over a 47-day period. Levels of the cytokines tumor necrosis factor a (TNFalpha), interleukin-1beta (IL-1beta), and IL-6, as well as levels of the chemokines macrophage inflammatory protein 1alpha (MIP-1alpha) and JE, the murine homolog of monocyte chemoattractant protein 1, were determined by enzyme-linked immunosorbent assay in the sera and joints of AIA and control rats. Synovia from AIA rats were (immuno)histochemically analyzed. Results of cytokine and chemokine measurements were correlated with clinical and laboratory markers of inflammation and histology. RESULTS: Early (before day 14 post adjuvant injection) and later phases of AIA could be distinguished. Cytokine and chemokine production was increased in AIA versus control rats. The production of TNFalpha, IL-1beta, MIP-1alpha, and, as determined earlier, epithelial neutrophil-activating peptide 78-like protein was abundant prior to and during the course of AIA, while that of IL-6 and JE was elevated in the late phase of AIA. Cytokine and chemokine levels were correlated with the clinical symptoms of arthritis and blood neutrophil counts. Joint levels of IL-1beta showed correlation with synovial lining proliferation and neutrophil ingress into AIA synovium. CONCLUSION: Cytokines and chemokines are involved in the clinical, laboratory, and histologic changes underlying AIA. The production of these mediators may be temporally and spatially regulated. These findings may be important for the optimal timing of cytokine and chemokine targeting.

Animals↗
PubMed2000

Catastrophic antiphospholipid syndrome in cancer.

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

Antiphospholipid Syndrome↗
PubMed1999

[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↗
PubMed1999

[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↗
PubMed1999

The role of an epithelial neutrophil-activating peptide-78-like protein in rat adjuvant-induced arthritis.

The chemokine, epithelial neutrophil-activating peptide-78 (ENA-78), is a potent neutrophil chemotaxin whose expression is increased in inflamed synovial tissue and fluid in human rheumatoid arthritis compared with osteoarthritis. Since ENA-78 has been implicated in the pathogenesis of RA, we examined the expression of an ENA-78-like protein during the development of rat adjuvant-induced arthritis (AIA). Using an ELISA assay, we found increased levels of antigenic ENA-78-like protein in the sera of AIA animals compared with control normal animals by day 7 postadjuvant injection. ENA-78-like protein levels continued to increase as AIA developed. ENA-78-like protein levels in joint homogenates were increased in AIA animals later in the development of the disease, by day 18 during maximal arthritis, compared with control animals. Expression of ENA-78-like protein in both the AIA serum and joint correlated with the progression of inflammation of the joints. Anti-human ENA-78 administered before disease onset modified the severity of AIA, while administration of anti-ENA-78 after clinical onset of AIA did not modify the disease. These data support a role for an ENA-78-like protein as an important chemokine in the progression and maintenance of AIA.

Animals↗
PubMed1999

PECAM-1 and leukosialin (CD43) expression correlate with heightened inflammation in rat adjuvant-induced arthritis.

A hallmark of both adjuvant-induced arthritis (AIA) and rheumatoid arthritis is chronic joint inflammation characterized by ingress of leukocytes into the inflamed synovial tissue. The timing of expression of adhesion molecules, which govern the ingress of leukocytes, is important in the orchestration of an inflammatory response. We examined the expression of vascular cell adhesion molecule-1 (VCAM-1), sialo adhesin, platelet and endothelial cell adhesion molecule-1 (PECAM-1), and leukosialin (CD43) in AIA, starting at adjuvant injection (day 0), through the peak of inflammation (day 18 postadjuvant injection), until day 54. VCAM-1 is constitutively expressed on the lining layer and ECs and its expression levels do not change throughout the progression of AIA. Sialoadhesin synovial tissue lining cell expression is decreased after adjuvant injection. In contrast, PECAM-1 expression is increased on synovial tissue lining cells on day 7 and is elevated through day 54 (peaking on day 54 with six-fold more cells expressing PECAM-1). PECAM-1 expression on endothelial cells peaks on day 7 with three-fold more cells expressing it, while on macrophages expression maximizes on day 25 with six-fold more cells expressing PECAM-1. CD43 expression is increased on synovial tissue lining cells, macrophages, neutrophils, and lymphocytes on days 18 and 25, before going back to basal levels. The increased expression of PECAM-1 and CD43 on leukocytes at the height of inflammation in AIA suggests important roles for these adhesion molecules in potentially binding their EC ligands resulting in leukocyte ingress into the synovial tissue.

Animals↗
PubMed1998

[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↗
PubMed1998

[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↗
PubMed1998

Effects of thrombospondin-1 on disease course and angiogenesis in rat adjuvant-induced arthritis.

Leukocyte extravasation into the synovium is important in rheumatoid arthritis (RA). Thrombospondin (TSP)-1 mediates cell adhesion and migration and inhibits angiogenesis, and it has been implicated in RA. However, little information is available on the role of TSP-1 in arthritis-associated inflammation and neovascularization. Therefore, we analyzed the effects of TSP-1 in adjuvant-induced arthritis (AIA), a rat model for RA. Hydron pellets containing TSP-1 were implanted in one ankle of AIA rats post-adjuvant injection, while the contralateral ankle received sham implants. Body weight loss and joint swelling were determined in comparison to nonimplanted AIA controls. In addition, synovial vessel counts were obtained in TSP-1-versus sham-implanted ankles of the same rat. The implantation of TSP-1 pellets into one ankle resulted in an enhancement of swelling in both ankles. Furthermore, TSP-1 exhibited a biphasic modulatory effect on synovial vessel counts (P < 0.05). In conclusion, TSP-1 implanted into one ankle of AIA rats may augment the severity of the disease. One possible explanation, among others, for the modulating effect of TSP-1 on inflammation may be its effect on arthritis-related angiogenesis.

Animals↗
PubMed1998

Cytokines in rheumatoid arthritis. Potential targets for pharmacological intervention.

The ingress of inflammatory leucocytes into the synovium is a crucial step in the pathogenesis of rheumatoid arthritis (RA). Cytokines are mediators involved in the inflammatory events, adhesive mechanisms, angiogenesis and osteopenia associated with RA. Pro- and anti-inflammatory cytokines, growth factors and chemokines all have an important role in these processes. Because the efficacy of currently used antirheumatic therapy is often limited, there is a need for more specific intervention strategies. Anticytokine therapy may include the use of monoclonal antibodies, antagonistic cytokines, soluble cytokine receptors, cytokine receptor antagonists, somatic gene transfer or other approaches. Hopefully, the study of cytokines and their interactions will lead to the development of new immunomodulatory strategies that will benefit patients with RA.

Animals↗
PubMed1998

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↗