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Biomedical subjects

M Schwarz-Eywill

Publications and source records attributed to M Schwarz-Eywill.

At least 19 recordsLinked to original sources
PubMed2001

Loss of collagen type IV in rheumatoid synovia and cytokine effect on the collagen type-IV gene expression in fibroblast-like synoviocytes from rheumatoid arthritis.

Collagen type IV is a structural matrix protein which contributes to the structural organization of the synovia. In order to characterize the distribution of this protein in synovia with chronic synovitis, collagen type IV was detected by immunochemistry in normal synovia and in synovia from patients with osteoarthritis (OA) and rheumatoid arthritis (RA). A decrease of collagen type IV was observed in synovial layers of rheumatoid synovia, which statistically correlated with the grade of inflammation and with the thickness of the synovial layer. In vitro, we found no differences in the gene expression of collagen type IV in cultures of fibroblast-like synoviocytes (FLS) derived from OA and RA using a reverse-transcriptase polymerase chain reaction. Nevertheless, we observed a downregulating effect of tumor necrosis factor-alpha and interleukin (IL)-1beta on the gene expression of collagen type IV only in FLS isolated from patients with RA. The effect of IL-1beta was dose dependent. In summary, we observed an inflammation-associated decrease of collagen type IV in the synovial layer of rheumatoid synovia. Inflammatory cytokines may play a role in regulating the synthesis of collagen type IV in the rheumatoid process in vivo.

Arthritis, Rheumatoid↗
PubMed2000

[Relevance of a standardized staging study in patients with systemic vasculitis].

Primary systemic vasculitities play an important role in the differential diagnosis of systemic diseases. They can be classified according to newly developed classification criteria. In the past, systemic vasculitities were more diagnosed in the general phase of the disease. In the meantime limited forms can be diagnosed more easily. Prior to immunosuppressive therapy, a standardized staging-procedure is essential to define the extent of the disease. Therefore a program was established using methods that are easy to apply in all patients. In this setting the usefulness of this approach was investigated. Apart from the laboratory tests including antibody testing, the chest x-ray, consultation of the ENT specialist, ultrasound of the abdomen, and ECG were also very useful. The eye and neurological investigations, and the MRI of the head were of minor significance, but also important.

Adolescent↗
PubMed2000

[In Process Citation]

Case-reports from two female patients with an occlusion||| of the right external iliac artery and femoral artery are presented due to a||| large-vessel vasculitis. Both patients suffered from systemic lupus||| erythematosus This rare manifestation occurred within the first few years of||| the disease and was important for prognosis and further treatment. Other||| manifestations of the disease were general symptoms and polyarthritis. In one||| case the vasculitis was confirmed by histology. A fibrous thickening of the||| intima and a vasculitis of small vessels within the adventitia were the||| prominent feature. This observation supports the idea of small vessel||| vasculitis as the characteristic manifestation in lupus||| erythematosus.

Journal Article↗
PubMed2000

[Rare manifestation of large vessel vasculitis in systemic lupus erythematosus].

Case-reports from two female patients with an occlusion of the right external iliac artery and femoral artery are presented due to a large-vessel vasculitis. Both patients suffered from systemic lupus erythematosus This rare manifestation occurred within the first few years of the disease and was important for prognosis and further treatment. Other manifestations of the disease were general symptoms and polyarthritis. In one case the vasculitis was confirmed by histology. A fibrous thickening of the intima and a vasculitis of small vessels within the adventitia were the prominent feature. This observation supports the idea of small vessel vasculitis as the characteristic manifestation in lupus erythematosus.

Adult↗
PubMed1999

[Molecular mechanisms of cell-cell and cell-matrix interactions in the pathophysiology of rheumatoid arthritis].

The original structure of the synovial membrane is completely destroyed in the rheumatoid synovium and is characterized by mononuclear cell infiltration, synoviocyte proliferation, neo-vascularization, and deposition of extracellular matrix proteins. Adhesion molecules play an important role in the development of these pathologic changes. In this review we discuss the role of the adhesion receptors of the selectin, integrin and immunoglobulin families and of the CD44 molecule in the cell-cell and cell-matrix interaction in the pathogenesis of the inflammatory changes in rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed1999

[Immunosuppressive therapy in autoimmune diseases].

Autoimmune diseases play an increasing role in daily practise. Advanced understanding of the pathogenesis and pathophysiology enables an outcome orientated therapy leading to a far better prognosis. Immunosuppressive drugs are essential for the treatment. The therapeutical concepts are adopted to the individual character and stage of the disease. In the meantime, therapeutical regimes combine certain drugs. Although it is not possible to cure these autoimmune diseases, a remission can be achieved in most cases. Further developments will concentrate on more selective strategies and the potentials of gene therapy.

Arthritis, Rheumatoid↗
PubMed1998

Loss of laminin and of the laminin receptor integrin subunit alpha 6 in situ correlates with cytokine induced down regulation of alpha 6 on fibroblast-like synoviocytes from rheumatoid arthritis.

OBJECTIVE: To investigate in situ the expression of the integrin receptor subunits alpha 6 and beta 1 and the distribution of the ligand laminin in the synovia from osteoarthritis (OA) and rheumatoid arthritis (RA) patients and to study the effect of cytokines and antirheumatic drugs on the expression of the alpha 6 and beta 1 integrin subunits on long term cultures of fibroblast-like synoviocytes (FBS) derived from OA and RA. METHODS: The expression of the alpha 6 and beta 1 integrin subunits and the distribution of laminin were examined immunohistochemically in normal synovia and in synovia from patients with OA and RA. The effect of proinflammatory cytokines (IL1 beta and TNF alpha), and of antirheumatic drugs (salicylic acid, dexamethasone, and methotrexate) on the alpha 6 and beta 1 expression of cultured normal FBS and FBS from patients with OA and RA was determined by flow cytometry. RESULTS: In normal synovia and in OA synovia samples with a low grade of inflammation, synovial lining cells (SLC) showed a parallel expression and distribution of alpha 6 and laminin. In synovia samples of OA with a higher grade of inflammation and in the majority of RA synovia samples laminin was pericellularly distributed in a low number of SLC, whereas alpha 6 was expressed on the surface of a high number of SLC. In RA synovia samples with severe inflammatory changes the gradual loss of laminin generally corresponded to a decrease of the alpha 6 integrin subunit. beta 1 was always strongly expressed in all synovia samples detected. Proinflammatory cytokines up regulated the expression of alpha 6 and beta 1 on OA-FBS, whereas these effectors decreases alpha 6 and beta 1 on RA-FBS. In contrast, antirheumatic drugs, in particular methotrexate and dexamethasone, reduced the expression of alpha 6 and beta 1 on OA-FBS, whereas the same treatment on RA-FBS stimulated the expression of these integrin subunits. CONCLUSION: The gradual loss of laminin in chronic synovitis may contribute to the altered expression of alpha 6 in SLC. IL1 beta and TNF alpha down regulated the expression of the alpha 6 and beta 1 integrin subunits on long term cultures of FBS derived from RA. Therefore, these cytokines may be among the effectors regulating the expression of the alpha 6 integrin subunit in SLC in vivo. As antirheumatic drugs increase the expression of alpha 6 on RA-FBS, the presence of the laminin receptor may confer a protective effect on the synovia in vivo.

Antigens, CD↗
PubMed1997

Increased expression of integrins on fibroblast-like synoviocytes from rheumatoid arthritis in vitro correlates with enhanced binding to extracellular matrix proteins.

OBJECTIVE: To compare in vitro expression of beta 1, beta 3, and beta 4 integrins in normal fibroblast-like synoviocytes (FBS) and in FBS from rheumatoid arthritis (RA) synovium and to investigate the adhesion of normal FBS and RA-FBS to the integrin binding extracellular matrix (ECM) proteins: collagen type IV, fibronectin, laminin, and tenascin. METHODS: Expression of integrin receptors of cultured FBS was detected by flow cytometry. Attachment of FBS to ECM proteins was quantified by adhesion assays. Inhibition studies were performed using monoclonal antibodies to the integrin subunits. RESULTS: Compared with normal FBS, RA-FBS showed increased expression of alpha 1 to alpha 6, beta 1, and beta 4 integrin subunits and enhanced binding of ECM proteins. Binding to ECM proteins was partly or completely blocked by an anti-beta 1 integrin antibody and antibodies to alpha 3, alpha 5, and alpha 6 integrin subunits. The blocking efficiency was significantly (P < 0.05) higher in RA-FBS than in normal FBS. CONCLUSIONS: The enhanced expression of the beta 1 integrin receptors on cultured RA-FBS correlated with increased attachment to ECM proteins. Adhesion of normal and RA-FBS to ECM proteins is mediated through beta 1 integrin receptors. Therefore, the tight binding of rheumatoid FBS to the matrix via beta 1 integrins might play a role in ECM remodelling in the rheumatoid process in vivo.

Arthritis, Rheumatoid↗
PubMed1997

Differential expression and functional behaviour of the alpha v and beta 3 integrin subunits in cytokine stimulated fibroblast-like cells derived from synovial tissue of rheumatoid arthritis and osteoarthritis in vitro.

OBJECTIVE: The aim of this study was to investigate in situ the expression of the classic vitronectin (VN) receptor consisting of the alpha v and beta 3 subunits in synovial lining cells (SLC) of chronic synovitis occurring in osteoarthritis (OA) and in rheumatoid arthritis (RA). The expression and function of alpha v and beta 3 as VN receptor in cultured fibroblast-like synoviocytes (FBS) derived from patients with OA and RA was also compared. METHODS: Expression of alpha v and beta 3 was examined immunohistochemically in normal synovial tissue and in synovial tissue from patients with OA and RA. The effect of proinflammatory cytokines and of a synovial fluid of a patient with RA on the expression of the alpha v and beta 3 subunits of cultured FBS was determined by flow cytometry. Binding of OA and RA-FBS to VN was quantified using adhesion assays and the effect of interleukin 1 beta (IL1 beta) and tumour necrosis factor alpha (TNF alpha) on adhesion was measured. The specificity of the adhesion was tested by inhibition studies using monoclonal antibodies to integrin subunits. RESULTS: In in situ studies normal SLC showed a parallel distribution of alpha v and beta 3 subunits. OA-SLC strongly and uniformly expressed alpha v whereas RA-SLC showed heterogeneous expression of alpha v. In situ both OA-SLC and RA-SLC lacked the expression of the integrin subunit beta 3. In in vitro studies, OA-FBS and RA-FBS did not differ as regards expression of alpha v and beta 3, and VN attachment. Binding of RA-FBS to VN was partially blocked by antibodies against alpha v, beta 1, and beta 3 subunits, whereas only antibodies against alpha v and beta 3 inhibited the binding of OA-FBS to VN. The proinflammatory cytokines TNF alpha and IL1 beta increased the expression of alpha v and beta 3, and the VN binding of OA-FBS, whereas alpha v and beta 3 expression, and VN binding were downregulated in RA-FBS. Similar effects were found when the synovial fluid of an RA patient was used. CONCLUSION: The integrin subunit beta 3 seems to be one partner but not the major one with which the subunit alpha v forms functional vitronectin receptors in OA-FBS and RA-FBS. The interaction between synovial cells and inflammatory cytokines seems to be different for OA and RA; the basis for this difference, however, remains to be established.

Arthritis, Rheumatoid↗
PubMed1997

Methotrexate in patients with moderate systemic lupus erythematosus (exclusion of renal and central nervous system disease).

OBJECTIVES: Methotrexate (MTX) has been used in several autoimmune diseases. Apart from its use in rheumatoid arthritis, MTX has been assessed in small studies in patients with vasculitis, uveitis, and inflammatory bowel disease. The aim of this study was to evaluate the efficacy of MTX in a particular group of patients with systemic lupus erythematosus (SLE). PATIENTS: In an open prospective study 22 patients fulfilling the ACR criteria for SLE were included. Patients had one or more of the following manifestations; active non-destructive polyarthritis, dermatitis, vasculitis of the skin, pleuritis. All patients had been treated with corticosteroids for at least six months without achieving remission. Sixteen patients were taking antimalarial drugs in addition to corticosteroids, which were stopped at the beginning of the trial. Patients with renal and central nervous involvement were excluded from the study. All patients received MTX orally at a dose of 15 mg/week over six months. Corticosteroids were continued. As additional medication only indomethacin up to 100 mg/day was permitted if used before the start of the study. The outcome was evaluated using the SLE disease activity index (SLEDAI). RESULTS: Disease activity was evaluated after six months of MTX treatment. All patients completed the study period. The SLEDAI decreased significantly from mean (SD) 12.2 (3.99) to 4 (3.75) (p = 0.001). The prednisolone dose was reduced from a mean (SD) of 17.4 (12.8) at the beginning to 8.8 (5.36) mg/day at the end point of the study (p = 0.01). MTX was well tolerated. Four patients complained of general malaise. Two patients had transient increases in liver enzymes. In no case did MTX have to be stopped. CONCLUSIONS: In an open prospective study methotrexate was used in SLE patients with particular clinical characteristics. MTX was shown to be effective in reducing disease activity and sparing the dose of corticosteroids. Further controlled studies are necessary.

Adult↗
PubMed1995

[Normal synoviocytes and synoviocytes from osteoarthritis and rheumatoid arthritis bind extracellular matrix proteins differently].

Extracellular matrix proteins are increased in inflammatory synovitis. We showed previously that the in situ expression of the corresponding extracellular matrix receptors (beta 1-integrins) is enhanced in synoviocytes (SC) of synovitis of different etiology (16). To investigate the adhesion of SC to extracellular matrix proteins, we examined the attachment of SC from normal and inflamed synovia to fibronectin, tenascin, laminin and collagen type IV. Compared to normal SC and SC of osteoarthritis, SC of rheumatoid arthritis showed an increased binding to tenascin, laminin, fibronectin and collagen type IV, suggesting a distinctive interaction of SC and extracellular matrix proteins in rheumatoid arthritis. Furthermore, the increased binding of SC of rheumatoid arthritis to extracellular matrix proteins may play a role in tissue remodelling associated with rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed1995

[The significance of cardiolipin antibodies in systemic lupus erythematosus].

The aim of the study was to investigate the frequency and clinical significance of anticardiolipin antibodies (aCL) in systemic lupus erythematosus (SLE). 32 of 100 patients with SLE had positive anticardiolipin antibodies. Increased aCL were associated with thrombosis, thrombocytopenia, miscarriage, vasculitic skin changes and neurological symptoms. The incidence of thrombosis, thrombocytopenia, and neurological symptoms was significantly increased in the aCL-positive group as compared to the aCL-negative group. These findings confirm the results of former investigations and underline the role of aCL in systemic lupus erythematosus.

Adolescent↗
PubMed1993

Effectiveness of cyclophosphamide pulse treatment in Wegener's granulomatosis.

43 patients with Wegener's granulomatosis were studied to evaluate the effectiveness of cyclophosphamide (cyc) pulse treatment. 42% of the patients showed benefits from treatment for at least 6 months after the cessation of cyc pulses. Analysis of clinical and laboratory parameters indicate that this treatment is less effective in patients in whom more than 4 organ systems are involved. Responders to the treatment showed disease manifestations predominantly in the ENT and lower respiratory tract and had lower cANCA titers (< 1:64) prior to treatment.

Adolescent↗
PubMed1993

Treatment modalities and ANCA in Takayasu's arteritis.

As other vasculitic-syndromes Takayasu's-Arteritis needs a long-term immunosuppressive therapy in order to control disease-activity. As steroids create many problems in the long run other immunosuppressives should be considered. We report 3 cases treated with low-dose methotrexate. In all patients the arteritis was controlled, steroids reduced or stopped. In the effort to find autoantibodies 16 patients were screened for c-/p-ANCA and neutrophil granular enzymes. In no patient a positive result could be obtained.

Adolescent↗
PubMed1992

Evaluation of serum ferritin as a marker for adult Still's disease activity.

Extremely high serum ferritin values (greater than 10,000 micrograms/l) were detected in two patients with adult Still's disease. The ferritin concentrations decreased to normal after adequate treatment. During a one year follow up ferritin concentration was helpful in monitoring disease activity and guiding decisions about treatment. Raised concentrations of soluble interleukin 2 receptors (sCD25) were also found. Detection of ferritin values above 3000 micrograms/l should lead to the consideration of Still's disease when there is an acute febrile illness without evidence for bacterial or viral infections, serum ferritin being suitable for monitoring treatment.

Adult↗
PubMed1992

Low-dose methotrexate treatment in noninfectious uveitis resistant to corticosteroids.

A total of 14 patients (10 women and 4 men) ranging in age from 18 to 56 years who presented with active chronic noninfectious uveitis were treated with low-dose methotrexate (MTX). All patients had failed to respond to previous systemic corticosteroid therapy. MTX therapy was initiated in 8 patients at a dose of 40 mg given intravenously once weekly for 4 weeks followed by 15 mg/week given orally; 6 subjects were started on the oral regimen of 15 mg/week. During a follow-up period of 3-24 months, intraocular inflammation improved in all subjects under immunosuppressive therapy with MTX. A concomitant improvement in visual acuity was observed in 11 patients. Side effects included slight elevations in transaminases in 4 patients, transient mucositis in 1 case, partial alopecia in 2 subjects, and nausea in 3 patients. Our initial results suggest that low-dose MTX therapy may be considered as a therapeutic modality in noninfectious, steroid-refractory uveitis.

Administration, Oral↗