Abstract:
:Rheumatoid arthritis (RA) is a chronic inflammatory disease, which is mainly characterized by synovial hyperplasia, pathological immune phenomena and progressive destruction of the affected joints. Various cell types are involved in the pathogenesis of RA including T cells, antigen presenting cells, and endothelial cells. Recent experimental evidence suggests that the CD40/CD154 system might play an important role in the development of RA. Our experimental approach focuses on RA synovial fibroblasts (RA-SF) that are able to destroy articular cartilage independent of inflammation. To elucidate the specific role of those cells in RA pathophysiology the following questions are currently addressed: 1. Which mechanisms do activate the RA-SF? 2. How do the activated RA-SF attach to the cartilage? 3. How do RA-SF destroy cartilage and bone? Which mechanisms do activate the RA-SF? The process of activation is poorly understood. It is unclear, how far the synovial hyperplasia of RA resembles tumor diseases. Along this line some contradictory results exist concerning the role of the tumor suppressor protein p53. Some investigations could show the expression of p53 in the synovial lining including p53 mutations in RA synovium and in RASF, while other research groups could not confirm these data. Our group has demonstrated that the tumor suppressor PTEN was less expressed in the synovial lining of RA than in normal synovium, but no PTEN mutations could be found in the RA-SF. In addition, the in vivo and in vitro expression of the anti-apoptotic molecule sentrin suggests a functional resistance of RA-SF to undergo apoptosis. Although it is still unclear, whether certain viruses or viral elements are involved in the pathogenesis of RA (cause, consequence or coincidence?), certain viruses could play a role in the pathogenesis of RA. The endogenous retroviral element L1 was found to be expressed in the synovial lining, at sites of invasion as well as in RA-SF grown in vitro. Moreover, the data indicate that after the initial activation of L1 downstream molecules such as the SAP kinase 4, the met-protoonocogene and the galectin-3 binding protein are upregulated. How do the activated RA-SF attach to the cartilage? It has been suggested that integrins mediate the attachment of RA-SF to fibronectin rich sites of cartilage. Intriguingly, other adhesion molecules such as the vascular cellular adhesion molecule-1 (VCAM) and CS-1, a splice variant of fibronectin, are synthesized by RA-SF. By binding to these adhesion molecules, lymphocytes that express the integrin VLA-4 could be stimulated and thereby maintain the inflammatory process. Osteopontin is an extracellular matrix protein, which is associated with matrix adhesion and metastasis in tumors. In RA synovium, osteopontin was detectable in the synovial lining and at sites of invasion. How do RA-SF destroy cartilage and bone? The destruction of cartilage and bone in RA is mediated by matrix metalloproteinases (MMPs) and cathepsins. MMPs exist as secreted and as membrane bound forms. In vitro models are being developed to simulate the invasive process of RA-SF. In an in vitro model developed in our laboratory, the treatment of RA-SF with anti-CD44 or anti-interleukin-1 (IL-1) minimized matrix degradation of RA-SF. On the other hand, co-culture of RA-SF and U937 cells as well as application of interleukin-1 beta (IL-1 beta) or tumor necrosis factor alpha (TNF alpha) increased the invasiveness of RA-SF. Gene transfer of bovine pancreas trypsin inhibitor (BPMI) or interleukin-10 (IL-10) reduced the invasion of RA-SF, while transduction of interleukin-1 receptor antagonist (IL-1Ra) was chondroprotective. Double gene transfer of IL-10 and IL-1Ra resulted in both inhibition of invasion and chondroprotection.
journal_name
Z Rheumatoljournal_title
Zeitschrift fur Rheumatologieauthors
Seemayer CA,Distler O,Kuchen S,Müller-Ladner U,Michel BA,Neidhart M,Gay RE,Gay Sdoi
10.1007/s003930170030keywords:
subject
Has Abstractpub_date
2001-10-01 00:00:00pages
309-18issue
5eissn
0340-1855issn
1435-1250journal_volume
60pub_type
杂志文章,评审abstract::Assessment of disease consequences (outcome) requires reliable, valid, and sensitive instruments. Psychometrically sound generic health-status instruments such as the SF-36 have been validated for many languages and are available in German. Instead, most disease specific instruments have been developed in English and ...
journal_title:Zeitschrift fur Rheumatologie
pub_type: 杂志文章,评审
doi:10.1007/s003930050041
更新日期:1997-10-01 00:00:00
abstract::Health policy in Germany has in recent years given priority to the self-administration of physicians, sickness funds, and hospital associations. Hence, legal regulations on quality assurance have focused on defining responsibilities and areas of primary importance, while precise processes are being defined by the self...
journal_title:Zeitschrift fur Rheumatologie
pub_type: 杂志文章
doi:10.1007/s003930050123
更新日期:1998-10-01 00:00:00
abstract:INTRODUCTION:Data with respect to safety and therapeutic efficacy for the combination of biological DMARDs is scarce and inhomogeneous in order to make final conclusions. To this end, data to biologic combinations is disappointing due to relatively low therapeutic efficacy and partially enhanced rates of severe infecti...
journal_title:Zeitschrift fur Rheumatologie
pub_type: 杂志文章,评审
doi:10.1007/s00393-013-1141-x
更新日期:2013-11-01 00:00:00
abstract::In rheumatologic diseases magnet resonance imaging (MRI) is capable of depicting early inflammatory changes which are frequently missed by other imaging modalities. New MRI protocols and hardware, primarily whole-body MRI and low-field extremity MRI facilitate the use of MRI in rheumatology patients. The increasing nu...
journal_title:Zeitschrift fur Rheumatologie
pub_type: 杂志文章,评审
doi:10.1007/s00393-012-1068-7
更新日期:2013-03-01 00:00:00
abstract::Three new findings are reviewed that help to understand the mechanisms of action of anti-rheumatic gold drugs, such as disodium aurothiomalate (Na2Au(I)TM): i) We found that Na2Au(I)TM selectively inhibits T-cell receptor-mediated antigen recognition by murine CD4+ T-cell hybridomas specific for antigenic peptides con...
journal_title:Zeitschrift fur Rheumatologie
pub_type: 杂志文章,评审
doi:
更新日期:1996-09-01 00:00:00
abstract::The aim of this review is to critically analyze the evidence of therapeutic ultrasound between 0.8 and 3 MHz for treating musculoskeletal diseases. Relevant randomized, controlled, clinical trials and systematic reviews published on this topic have been taken into consideration.There was evidence of effectiveness for ...
journal_title:Zeitschrift fur Rheumatologie
pub_type: 杂志文章,评审
doi:10.1007/s00393-009-0457-z
更新日期:2009-09-01 00:00:00
abstract::Cartilage destruction in arthritis and osteoarthritis is linked to aberrant cytokine and growth factor expression in the affected tissues. It becomes clear that the balance of protective and destructive cytokines is more important for the net destruction than the absolute levels of destructive mediators. IL-1 is a key...
journal_title:Zeitschrift fur Rheumatologie
pub_type: 杂志文章,评审
doi:10.1007/s003930050163
更新日期:1999-06-01 00:00:00
abstract::Fabry's disease is a hereditary lipid storage disease with deposition of ceramides in nearly all tissues. The lipid deposition in the skin and the synovial compartments causes an enlargement of the skin, the joint capsules and the tendon sheaths, which are recognizable by low KV radiography. The bones of the hand main...
journal_title:Zeitschrift fur Rheumatologie
pub_type: 杂志文章
doi:
更新日期:1986-01-01 00:00:00
abstract::Common variable immunodeficiency (CVID) represents the most common clinically relevant form of primary immunodeficiency. This heterogeneous antibody deficiency syndrome is characterized not only by susceptibility to bacterial respiratory tract infections but displays additional signs of immune dysregulation, such as a...
journal_title:Zeitschrift fur Rheumatologie
pub_type: 杂志文章
doi:10.1007/s00393-013-1162-5
更新日期:2013-09-01 00:00:00
abstract:INTRODUCTION:Only insufficient data are available regarding the question whether treatment with immunosuppressants or biologicals is feasible and safe in patients with a history of malignancy. METHOD:Literature search via PubMed, EULAR abstracts and ACR abstracts from 2013 to 2015. RESULTS:The Société Francaise de Rh...
journal_title:Zeitschrift fur Rheumatologie
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s00393-015-0034-6
更新日期:2016-02-01 00:00:00
abstract::Among all laboratory parameters used today in the assessment of activity and progression of rheumatoid arthritis erythrocyte sedimentation rate (ESR) can only be recommended reservedly. ESR is influenced by anemia, reduction of plasma fibrinogen, dysproteinemia and by the concentration of acute phase proteins. Quantif...
journal_title:Zeitschrift fur Rheumatologie
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
abstract::Activated monocytes/macrophages secrete monokines, regulatory proteins which are capable of initiating and maintaining immune processes as well as having an effect on other non immunocompetent cells. In rheumatoid arthritis the monokine Interleukin-1 (IL-1) was detected in the synovial fluid. IL-1 activates immunocomp...
journal_title:Zeitschrift fur Rheumatologie
pub_type: 杂志文章
doi:
更新日期:1985-09-01 00:00:00
abstract::Personalized healthcare tries to predict the effectiveness and safety in individual therapeutic approaches by defining individual patient characteristics (biomarkers), while stratification uses diagnostic patterns for groups of patients for prediction of therapeutic response with less adverse reactions caused by the d...
journal_title:Zeitschrift fur Rheumatologie
pub_type: 杂志文章
doi:10.1007/s00393-011-0886-3
更新日期:2013-02-01 00:00:00
abstract::Patients with various kinds of intestinal illnesses sometimes suffer not only abdominal symptoms, but also joint involvement, leading to a reduction in quality of life. Diseases leading to inflammatory joint involvement such as inflammatory bowel disease, Whipple's disease or surgical intestinal bypass, are classified...
journal_title:Zeitschrift fur Rheumatologie
pub_type: 杂志文章,评审
doi:10.1007/s00393-009-0465-z
更新日期:2009-06-01 00:00:00
abstract::We tested the efficacy of the immunomodulator Bestatin, which has been successfully applied in Japan, in a preliminary open study in ten patients with classical or definite rheumatoid arthritis. Patients whose arthritis was characterized by a low humoral activity showed a partial remission of the disease after six mon...
journal_title:Zeitschrift fur Rheumatologie
pub_type: 杂志文章
doi:
更新日期:1985-09-01 00:00:00
abstract::Behçet's disease (BD) is a recurrent, multisystemic, inflammatory blood vessel disorder that can result in mouth, genital, and skin ulcers; arthritis; and eye and intestinal inflammation. We describe a 21-year-old Korean female patient with intestinal BD refractory to conventional medical treatment and biologic drugs....
journal_title:Zeitschrift fur Rheumatologie
pub_type: 杂志文章
doi:10.1007/s00393-020-00816-0
更新日期:2020-09-01 00:00:00
abstract::In rheumatic diseases, radiation synovectomy is a reliable method. Meanwhile, radiation synovectomy is an outpatient therapy. In addition, combination with arthroscopic synovectomy is an increasing therapeutic modality. In comparison to the hitherto inpatient modality, a greater lymphatic emigration of the radionuclid...
journal_title:Zeitschrift fur Rheumatologie
pub_type: 杂志文章
doi:10.1007/s003930050172
更新日期:1999-08-01 00:00:00
abstract::The German Rheuma-Liga as the largest patient organisation presents the different ways of informing patients. Patient- education-programs are presented, with a program focussing on social and psychological issues in particular. ...
journal_title:Zeitschrift fur Rheumatologie
pub_type: 杂志文章
doi:10.1007/s00393-003-1212-5
更新日期:2003-01-01 00:00:00
abstract:BACKGROUND:Familial Mediterranean fever (FMF) in Germany is a rare, genetically linked disease of childhood and adolescence, which is characterized by recurrent febrile episodes and clinical signs of peritonitis, pleuritis and arthritis. Treatment with colchicine is effective and well-tolerated in the majority of patie...
journal_title:Zeitschrift fur Rheumatologie
pub_type: 杂志文章,评审
doi:10.1007/s00393-018-0588-1
更新日期:2019-02-01 00:00:00
abstract::The diagnosis of pyoderma gangraenosum was previously made as a diagnosis of exclusion. For this reason repeated attempts have been made in recent years to develop new diagnostic scores, whereby the typical clinical and anamnestic aspects were usually taken into account and the relevant differential diagnoses were exc...
journal_title:Zeitschrift fur Rheumatologie
pub_type: 杂志文章,评审
doi:10.1007/s00393-018-0553-z
更新日期:2018-12-01 00:00:00
abstract::Rheumatology training is reorganized with the implementation of the revision of the training regulations for German physicians (MWBO) to become a specialist in internal medicine and rheumatology. This article focusses on novel aspects including far-reaching waiver of reference numbers, the professionally recommended t...
journal_title:Zeitschrift fur Rheumatologie
pub_type: 杂志文章,评审
doi:10.1007/s00393-020-00930-z
更新日期:2020-11-30 00:00:00
abstract::Musculoskeletal ultrasonography (US) is an established and validated imaging technique in rheumatology. Ultrasonography is able to directly visualize soft tissue pathologies such as synovial tissue changes. Pathological findings in superficial cartilage, bone lesions and synovial tissue changes in the context of rheum...
journal_title:Zeitschrift fur Rheumatologie
pub_type: 杂志文章,评审
doi:10.1007/s00393-010-0730-1
更新日期:2010-12-01 00:00:00
abstract::Performing histo-morphologic studies of knee joints in several hundred mice of the strains C57 black, STR/1N and MAGf, showing a disposition for spontaneous osteo-arthrosis, we found tentative reparative processes in many cases. There was a proliferation of cartilage and of the synovial membrane, mostly in the periphe...
journal_title:Zeitschrift fur Rheumatologie
pub_type: 杂志文章
doi:
更新日期:1984-09-01 00:00:00
abstract:BACKGROUND:Patients with rheumatoid arthritis (RA) tend to be less physically active. Physical activity has been shown to have a positive impact on disease activity and quality of life and is recommended by the European League Against Rheumatism (EULAR) as an integral component of standard treatment. OBJECTIVE:A cross...
journal_title:Zeitschrift fur Rheumatologie
pub_type: 杂志文章
doi:10.1007/s00393-020-00830-2
更新日期:2020-06-25 00:00:00
abstract::Autoimmune rheumatic diseases (ARD) affect young females during childbearing age. Over the last decades, improvements in survival as well as quality of life in patients affected with ARD have led to an increased number of pregnancies observed during the course of such diseases. Systemic lupus erythematosus (SLE) is th...
journal_title:Zeitschrift fur Rheumatologie
pub_type: 杂志文章,评审
doi:10.1007/s00393-006-0059-y
更新日期:2006-05-01 00:00:00
abstract::Certolizumab pegol is a new anti-TNF-alpha inhibitor which has been approved for the treatment of rheumatoid arthritis since October 2009. Due to the modification of the antibody fragment by the adherence of polyethylene glycol (PEG) a sufficient distribution in inflammatory tissue was found in animal experiments. In ...
journal_title:Zeitschrift fur Rheumatologie
pub_type: 杂志文章
doi:10.1007/s00393-010-0629-x
更新日期:2010-09-01 00:00:00
abstract:OBJECTIVES:The relative efficacy and safety of tofacitinib and baricitinib were assessed in patients with rheumatoid arthritis (RA) with an inadequate response to disease-modifying anti-rheumatic drugs (DMARDs) or biologics. METHODS:We performed a Bayesian network meta-analysis to combine direct and indirect evidence ...
journal_title:Zeitschrift fur Rheumatologie
pub_type: 杂志文章
doi:10.1007/s00393-018-0531-5
更新日期:2019-08-01 00:00:00
abstract::Rheumatoid arthritis (RA) is a chronic autoimmune disease of still unknown etiology that results in characteristic destructive changes of the joints. Research of the past years has demonstrated that synovial fibroblasts play a central role in the initiation and perpetuation of these destructive changes. Stimulation of...
journal_title:Zeitschrift fur Rheumatologie
pub_type: 杂志文章,评审
doi:10.1007/s00393-007-0181-5
更新日期:2007-07-01 00:00:00
abstract::Serum protein binding of naproxen is considerably reduced in patients with renal insufficiency. The hypothetical plasma concentration at time zero and the half life are not significantly altered in uremic patients in comparison with healthy subjects when the drug is given orally. This suggests an increased pharmacodyn...
journal_title:Zeitschrift fur Rheumatologie
pub_type: 杂志文章
doi:
更新日期:1979-03-01 00:00:00
abstract::Magnetic resonance imaging (MRI) is a mainstay in musculoskeletal imaging. The term"bone marrow edema" is frequently used for describing the radiological findings, especially with respect to rheumatic diseases. The referring physician should be aware that this term has a purely descriptive character and the pathophysi...
journal_title:Zeitschrift fur Rheumatologie
pub_type: 杂志文章
doi:10.1007/s00393-011-0937-9
更新日期:2012-01-01 00:00:00