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Complement is implicated in the pathogenesis of systemic lupus erythematosus (SLE) in several ways and may act as both friend and foe. Homozygous deficiency of any of the proteins of the classical pathway is c...
This article is part of a Supplement: Volume 4 Supplement 3
Systemic lupus erythematosus (SLE) is the paradigm of a multisystem autoimmune disease in which genetic factors strongly influence susceptibility. Through genome scans and congenic dissection, numerous loci as...
This article is part of a Supplement: Volume 4 Supplement 3
Signal transduction induced by tumor necrosis factor (TNF) family members and their receptors has been an intensive area of research for several years. The major impact of these studies has been the delineatio...
This article is part of a Supplement: Volume 4 Supplement 3
IL-6 is a pleiotropic cytokine with a wide range of biological activities in immune regulation, hematopoiesis, inflammation, and oncogenesis. Its activities are shared by IL-6-related cytokines such as leukemi...
This article is part of a Supplement: Volume 4 Supplement 3
The elucidation of the signalling pathways involved in inflammatory diseases, such as rheumatoid arthritis, could provide long sought after targets for therapeutic intervention. Gene regulation is complex and ...
This article is part of a Supplement: Volume 4 Supplement 3
The strong association between specific alleles encoded within the MHC class II region and the development of rheumatoid arthritis (RA) has provided the best evidence to date that CD4+ T cells play a role in the ...
This article is part of a Supplement: Volume 4 Supplement 3
Signals emanating from receptors of the tumor necrosis factor/nerve growth factor (TNF/NGF) family control practically all aspects of immune defense and, as such, constitute potential targets for therapeutic i...
This article is part of a Supplement: Volume 4 Supplement 3
Contact-mediated signaling of monocytes by human stimulated T lymphocytes (TL) is a potent proinflammatory mechanism that triggers massive upregulation of the proinflammatory cytokines IL-1 and tumor necrosis fac...
This article is part of a Supplement: Volume 4 Supplement 3
Tumor necrosis factor (TNF)-α and lymphotoxin (LT) α/β play multiple roles in the development and function of the immune system. This article focuses on three important aspects of the effects of these cytokine...
This article is part of a Supplement: Volume 4 Supplement 3
Tumor necrosis factor (TNF) is the prototypic proinflammatory cytokine and endothelial cells are the principal cellular targets of its actions. Here I review the responses of endothelial cells to TNF, with emp...
This article is part of a Supplement: Volume 4 Supplement 3
Angiogenesis is a prominent feature of rheumatoid synovitis. Formation of new blood vessels permits a supply of nutrients and oxygen to the augmented inflammatory cell mass and so contributes to perpetuation o...
This article is part of a Supplement: Volume 4 Supplement 3
The expansion of the synovial lining of joints in rheumatoid arthritis (RA) and the subsequent invasion by the pannus of underlying cartilage and bone necessitate an increase in the vascular supply to the syno...
This article is part of a Supplement: Volume 4 Supplement 3
Integrin receptors transduce bidirectional signals between extracellular adhesion molecules and intracellular cytoskeletal and signalling molecules. The structural basis of integrin signalling is unknown, but ...
This article is part of a Supplement: Volume 4 Supplement 3
Matrix metalloproteinases (MMPs) play a central role in many biological processes such as development, morphogenesis and wound healing, but their unbalanced activities are implicated in numerous disease proces...
This article is part of a Supplement: Volume 4 Supplement 3
The role of matrix metalloproteinases in the degradative events invoked in the cartilage and bone of arthritic joints has long been appreciated and attempts at the development of proteinase inhibitors as poten...
This article is part of a Supplement: Volume 4 Supplement 3
Rheumatoid arthritis (RA) is the most common chronic autoimmunopathy, clinically leading to joint destruction as a consequence of the chronic inflammatory processes. The pathogenesis of this disabling disease ...
This article is part of a Supplement: Volume 4 Supplement 3
The nonobese diabetic (NOD) mouse is a well-recognised animal model of spontaneous autoimmune insulin-dependent diabetes mellitus. The disease is T-cell mediated, involving both CD4 and CD8 cells. Its progress...
This article is part of a Supplement: Volume 4 Supplement 3
Proteomics technologies enable profiling of autoantibody responses using biological fluids derived from patients with autoimmune disease. They provide a powerful tool to characterize autoreactive B-cell respon...
We have recently found that matrix metalloproteinases (MMPs) are targets for T-cell and B-cell reactivity in experimental arthritis. In the present article, we investigate whether modulation of MMP-specific T-...
The influence of HLA DRB1 alleles on B-cell homeostasis was analyzed in 164 patients with rheumatoid arthritis (RA). The percentages of CD19+ B lymphocytes determined in the peripheral circulation of 94 retrospec...
Autoantibodies are proven useful diagnostic tools for a variety of rheumatic and non-rheumatic autoimmune disorders. However, a highly specific marker autoantibody for rheumatoid arthritis (RA) has not yet bee...
This article is part of a Supplement: Volume 4 Supplement 2
Early diagnosis of rheumatoid arthritis (RA) combined with early initiation of an appropriate treatment regimen is acknowledged as an important factor in improving clinical outcomes in patients with RA. Early ...
This article is part of a Supplement: Volume 4 Supplement 2
Bone-resorbing osteoclasts are formed from hemopoietic cells of the monocyte–macrophage lineage under the control of bone-forming osteoblasts. We have cloned an osteoblast-derived factor essential for osteocla...
Although functional outcome is frequently discussed and written about, it is often not clear what functional outcome is and how it can be measured. This paper introduces the concept of latent and observed meas...
This article is part of a Supplement: Volume 4 Supplement 2
Interleukin-1 receptor antagonist (IL-1Ra) is a natural IL-1 inhibitor possessing anti-inflammatory properties. IL-1Ra is produced as different isoforms, one secreted (sIL-1Ra) and three intracellular (icIL-1R...
Proteinase-3 (PR-3) is a neutral serine proteinase present in azurophil granules of human polymorphonuclear leukocytes and serves as the major target antigen of antineutrophil cytoplasmic antibodies with a cyt...
We are developing retroviral-mediated gene transfer to human fibroblast-like synovial cells (FLS) as one approach to characterizing genetic pathways involved in synoviocyte pathophysiology. Prior work has sugg...
In chronic inflammatory foci, such as the rheumatoid joint, there is enhanced recruitment of phagocytes from the blood into the tissues. Chemokines are strongly implicated in directing the migration of these c...
Angiopoietins (Ang) are vascular endothelial cell-specific growth factors that play important roles principally during the later stages of angiogenesis. We have compared the distribution of the receptor tyrosi...
Although early antibiotic treatment of patients with septic arthritis eradicates bacteria, joint destruction commonly results from the unregulated host inflammatory responses to infection. The spin trap compou...
Tissue factor (TF) is a transmembrane glycoprotein and the main triggering element of blood coagulation. TF expression on monocytes and endothelial cells is induced by exposure to endotoxin, tumor necrosis fac...
The aim of this study was to analyze the differential effects of three anti-CD4 monoclonal antibodies (mAbs) (with distinct epitope specifities) in the treatment of rat adjuvant arthritis (AA) and on T-cell fu...
A study was done to determine if the differentiation and activation phenotype of T cells in synovial fluid (SF) from patients with juvenile idiopathic arthritis (JIA) is associated with T-cell proliferation in si...
Systemic sclerosis (SSc) is a multisystem connective tissue disease characterised phenotypically by fibrosis and ischaemic atrophy. Its aetiology is most likely multifactorial. A genetic predisposition to the ...
Matrix metalloproteinase (MMP)-1, MMP-8 and MMP-13 are interstitial collagenases that degrade type II collagen in cartilage; this is a committed step in the progression of rheumatoid arthritis and osteoarthrit...
IL-6 is a multifunctional cytokine produced by lymphoid and nonlymphoid cells; it regulates immune responses, acute-phase reactions, and inflammation. IL-6 signaling is mediated exclusively by the common signa...
The use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) to reduce serum cholesterol is well described. However, the recent finding that statins have direct effects on bone was unexpecte...
It is not known to what extent glucocorticoid hormones cause their anti-inflammatory actions and their undesirable side effects by the same or different molecular mechanisms. Glucocorticoids combine with a cyt...
Several agents show an effect on reducing radiographic progression in rheumatoid arthritis. It is tempting to retrospectively compare the effects of these agents on radiographic progression across clinical tri...
This article is part of a Supplement: Volume 4 Supplement 2
Since the initial characterization of tumor necrosis factor alpha (TNFα), it has become clear that TNFα has diverse biologic activity. The realization that TNFα plays a role in rheumatoid arthritis (RA) has le...
This article is part of a Supplement: Volume 4 Supplement 2
With the introduction of new disease-modifying antirheumatic drugs (DMARDs) and other therapeutic agents, the management of rheumatoid arthritis (RA) has shifted toward earlier, more aggressive therapy. The ul...
This article is part of a Supplement: Volume 4 Supplement 2
Despite the recent introduction of biological response modifiers and potent new small-molecule antirheumatic drugs, the efficacy of methotrexate is nearly unsurpassed in the treatment of inflammatory arthritis...
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