PubMed Central (PMC3 - NLM DTD)
(2,081,148 recursos)
Archive of life sciences journal literature at the U.S. National Institutes of Health (NIH), developed and managed by NIH's National Center for Biotechnology Information (NCBI) in the National Library of Medicine (NLM).
Mostrando recursos 181 - 200 de 420
181.
Association of MHC and rheumatoid arthritis: Association of RA with HLA-DR4 - the role of repertoire selection - Roudier, Jean
Most patients with rheumatoid arthritis (RA) express HLA-DR4, HLA-DR1 or HLA-DR10. These alleles share a common amino acid motif in their third hypervariable regions: the shared epitope. In normals and patients with RA, HLA-DR genes exert a major influence on the CD4 αβ T-cell repertoire, as shown by studies of AV and BV gene usage and by BV BJ gene usage by peripheral blood CD4 αβ T-cells. However, the rheumatoid T-cell repertoire is not entirely under HLA-DR influence, as demonstrated by discrepancies in VB JB gene usage between identical twins discordant for RA and by contraction of the CD4 αβ...
183.
Immune ablation and stem-cell therapy in autoimmune disease: Immunological reconstitution after high-dose immunosuppression and haematopoietic stem-cell transplantation - van Laar, Jacob M
Studies on immunological reconstitution after immune ablation and stem-cell therapy may yield important clues to our understanding of the pathogenesis of human autoimmune disease, due to the profound effects of function and organization of the immune system. Such studies are also indispensable when linking clinical sequelae such as opportunistic infections to the state of immune deficiency that ensues after the treatment. Much has been learnt on these issues from comparable studies in haemato-oncological diseases, although it remains to be proven that the data obtained from these studies can be extrapolated to rheumatological autoimmune diseases. Preliminary results from pilot studies in...
184.
Immune ablation and stem-cell therapy in autoimmune disease: Clinical experience - Tyndall, Alan; Gratwohl, Alois
In the past 5 years, around 350 patients have received haematopoietic stem cell (HSC) transplantation for an autoimmune disease, with 275 of these registered in an international data base in Basel under the auspices of the European League Against Rheumatism (EULAR) and the European Group for Blood and Marrow Transplantation(EBMT). Most patients had either a progressive form of multiple sclerosis (MS; n = 88) or scleroderma (now called systemic sclerosis; n = 55). Other diseases were rheumatoid arthritis (Ra n = 40), juvenile idiopathic arthritis (JIA; n = 30), systemic lupus erythematosus (SLE; n = 20), idiopathic thrombocytopenic purpura (ITP;...
185.
Immune ablation and stem-cell therapy in autoimmune disease: Experimental basis for autologous stem-cell transplantation - Bekkum, Dirk W van
Treatment of rats suffering from florid chronic progressive systemic arthritis or from chronic remitting/relapsing encephalomyelitis with autologous bone marrow transplantation (BMT) is highly effective. This finding was unexpected as the genotype of the bone marrow largely determines the susceptibility of both spontaneous and induced autoimmune diseases in rodents. The success of autologous stem-cell transplantation depends on the completeness of eradication of the effectors of autoimmune disease, in other words activated and memory T lymphocytes. The reviewed experimental data, when translated to the clinic, indicate that the patients should be subjected to a conditioning regimen that induces maximal lymphoablation and that...
186.
Physiologic role of interleukin-1 receptor antagonist - Arend, William P; Gabay, Cem
Recent studies have described the spontaneous development of arthritis or vasculitis in IL-1 receptor antagonist (IL-1Ra) knockout mice bred on specific and different genetic backgrounds. The levels of both secreted and intracellular isoforms of IL-1Ra produced in the rheumatoid joint or in the arterial wall may not be adequate to effectively inhibit the excess amounts of locally produced IL-1. Thus, an imbalance between IL-1 and IL-1Ra may predispose to local inflammatory disease in particular tissues in the presence of other as yet unknown genetically influenced factors.
187.
Citrullination: a small change for a protein with great consequences for rheumatoid arthritis - van Venrooij, Walther J; Pruijn, Ger J M
A new autoantibody activity, which is almost 100% specific for rheumatoid arthritis (RA), has been found. The essential part of the B-cell epitope is a modified form of arginine (ie citrulline). The conversion of protein-contained arginine to citrulline is an enzymatic process that is carried out by peptidylarginine deiminase (PAD), an enzyme that appears to be hormonally controlled. Because of its remarkable specificity, citrullination and related processes might open new possibilities for studying the aetiology of RA.
188.
What you should know about PR3-ANCA: An introduction - Wiik, Allan
Anti-neutrophil cytoplasmic antibodies (ANCA) have become important diagnostic markers of small vessel vasculitides characterized by focal necrotizing lesions of vessel walls and accumulation of lymphocytes and macrophages around the affected vessels. IgG class ANCA directed to proteinase 3 (PR3) of neutrophils and monocytes seem to be directly involved in the pathophysiology of vascular damage by causing excessive neutrophil activation and vessel wall destruction. PR3 and elastase are important players in the mechanisms of vascular necrosis. Methods of detecting ANCA have now been defined but are not uniformly used, even though clinical decisions heavily depend on correct ANCA results.
189.
What you should know about PR3-ANCA: Structural aspects of antibodies to proteinase 3 (PR3) - Peen, Elisabeth; Ralph C, Williams
Reactive antigenic epitopes on presumed autoantigens of biologic interest have been examined by many researchers. The central third complementarity-determining region (CDR3) residues of a human monoclonal anti-proteinase 3 (PR3) antibody contained many negatively charged aspartic acid residues, perhaps contributing to its reactivity with positively charged PR3 regions. Examination of four other human monoclonal anti-PR3 antibodies shows a number of negatively charged residues within their CDR3 regions. Mapping of segments of linear PR3-epitopes reacting with anti-neutrophil cytoplasmic antibodies (ANCA) demonstrated a preliminary estimate of structures contributing to antigenic determinants. T-cell epitopes on PR3 are reported in studies of chronic myeloid leukemia....
190.
What you should know about PR3-ANCA: Evidence for the role of T cells in the pathogenesis of systemic vasculitis - Clayton, Abigail R; Savage, Caroline OS
The pathogenesis of systemic vasculitis is complex and is likely to involve many mechanisms. There is a growing body of evidence that T cells may contribute to the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides. Predominantly, T cells and monocytes are found in inflammatory infiltrates in patients with Wegener's granulomatosis (WG). The production of ANCA appears to be T-cell-dependent. T lymphocytes from the peripheral blood of patients with ANCA-associated vasculitis have been shown to proliferate in response to proteinase 3 (PR3). These and other findings outlined in this review indicate T-cell involvement, although further studies are still needed to elucidate...
191.
What you should know about PR3-ANCA: Conformational requirements of proteinase 3 (PR3) for enzymatic activity and recognition by PR3-ANCA - Specks, Ulrich
The neutrophil azurophil granule constituent proteinase 3 (PR3) is the principal antigen for anti-neutrophil cytoplasmic antibodies (ANCA) in Wegener's granulomatosis. The conformation of the mature PR3 enzyme results from intracellular post-translational processing. The nascent molecule undergoes proteolytic cleavage of the amino-terminal signal peptide and activation dipeptide and of a carboxy-terminal peptide extension. The conformation of PR3 is stabilized by four disulfide bonds and, to a lesser extent, by asparagine-linked glycosylation. Most anti-neutrophil cytoplasmic antibodies directed against proteinase 3 (PR3-ANCA) recognize conformational epitopes. The expression of recombinant PR3 has provided a better understanding of the significance of the various intracellular processing...
192.
Where is biological therapy going? - Schulze-Koops, Hendrik; Kalden, Joachim R
The substantial progress in our understanding of molecular and cellular biology has allowed us to design biological therapeutics ('biologicals') with defined targets and effector functions. These biologicals have greatly contributed to our current knowledge of pathogenetic mechanisms in autoimmune diseases. However, although some of the biologicals have been extremely successful in treating the symptoms of chronic inflammation, biological therapy has not yet met the expectations of permanently silencing the chonic immune response. In this commentary we discuss current concepts and future directions of biological therapy, and the potential usefulness of biologicals as a treatment of human autoimmune diseases in appropriate...
194.
Fibroblast biology: Development and differentiation of synovial fibroblasts in arthritis - Edwards, Jonathan CW
Synovial fibroblasts occur as two phenotypes - intimal and subintimal. The specialised intimal phenotype includes expression of uridine diphosphoglucose dehydrogenase (UDPGD), vascular cell adhesion molecule-1 (VCAM-1) and complement decay-accelerating factor (DAF). These gene products contribute to specialised functions relating to tissue movement and leucocyte traffic.
195.
Fibroblast biology: Signals targeting the synovial fibroblast in arthritis - Konttinen, Yrjö T; Li, Tian-Fang; Hukkanen, Mika; Ma, Jian; Xu, Jing-Wen; Virtanen, Ismo
Fibroblast-like cells in the synovial lining (type B lining cells), stroma and pannus tissue are targeted by many signals, such as the following: ligands binding to cell surface receptors; lipid soluble, small molecular weight mediators (eg nitric oxide [NO], prostaglandins, carbon monoxide); extracellular matrix (ECM)-cell interactions; and direct cell-cell contacts, including gap junctional intercellular communication. Joints are subjected to cyclic mechanical loading and shear forces. Adherence and mechanical forces affect fibroblasts via the ECM (including the hyaluronan fluid phase matrix) and the pericellular matrix (eg extracellular matrix metalloproteinase inducer [EMMPRIN]) matrices, thus modulating fibroblast migration, adherence, proliferation, programmed cell death...
196.
Fibroblast biology: Effector signals released by the synovial fibroblast in arthritis - Ritchlin, Christopher
There is mounting evidence indicating that the synovial fibroblast is a direct effector of tissue injury and matrix remodeling in inflammatory synovitis. Through the elaboration of effector signals including cytokines and chemokines, mesenchymal cells stimulate or suppress inflammation via autocrine and paracrine mechanisms. Synovial fibroblasts are the principal cells mediating joint destruction through secretion of metalloproteinases, and recent evidence suggests that they may also promote bone resorption by stimulating osteoclastogenesis. Moreover, they may play an integral role in the initial phases of synovitis by releasing chemokines that recruit leukocytes to the joint, and cytokines that trigger angiogenesis. Studies focusing on...
197.
Fibroblast biology: Role of synovial fibroblasts in the pathogenesis of rheumatoid arthritis - Pap, Thomas; Müller-Ladner, Ulf; Gay, Renate E; Gay, Steffen
There is growing evidence that activated synovial fibroblasts, as part of a complex cellular network, play an important role in the pathogenesis of rheumatoid arthritis. In recent years, significant progress has been made in elucidating the specific features of these fibroblasts. It has been understood that although macrophage and lymphocyte secreted factors contribute to their activation, rheumatoid arthritis synovial fibroblasts (RA-SFs) do not merely respond to stimulation by pro-inflammatory cytokines, but show a complex pattern of molecular changes also maintained in the absence of external stimulation. This pattern of activation is characterized by alterations in the expression of regulatory genes...
198.
Cell-cell interactions in synovitis: Endothelial cells and immune cell migration - Szekanecz, Zoltan; Koch, Alisa E
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.
199.
Cell-cell interactions in synovitis: Interactions between T lymphocytes and synovial cells - McInnes, Iain B; Leung, Bernard P; Liew, Foo Y
Mechanisms whereby T lymphocytes contribute to synovial inflammation in rheumatoid arthritis are poorly understood. Here we review data that indicate an important role for cell contact between synovial T cells, adjacent macrophages and fibroblast-like synoviocytes (FLS). Thus, T cells activated by cytokines, endothelial transmigration, extracellular matrix or by auto-antigens can promote cytokine, particularly TNFα, metalloproteinase production by macrophages and FLS through cell-membrane interactions, mediated at least through β-integrins and membrane cytokines. Since soluble factors thus induced may in turn contribute directly to T cell activation, positive feedback loops are likely to be created. These novel pathways represent exciting potential therapeutic...
200.
Pharmacological basis for the therapy of pain and inflammation with nonsteroidal anti-inflammatory drugs - Steinmeyer, Jürgen
Nonsteroidal anti-inflammatory drugs (NSAIDs) belong to the most frequently used drugs. The discovery of an inducible isoform of cyclo-oxygenase (COX-2) has led to an intensive worldwide search and the introduction of selective COX-2 inhibitors. In this review, recent advances in understanding the mechanism of action of NSAIDs and, in this context, clinical findings on NSAID-induced gastrointestinal side effects are summarized. This knowledge is important for the effective treatment of pain and inflammation, as well as for preventing serious and sometimes lethal gastrointestinal side effects.
181.
