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).
82.
Lessons learned from gene transfer approaches - Evans, Christopher H; Ghivizzani, Steven C; Lechman, Eric R; Mi, Zhebao; Jaffurs, Daniel; Robbins, Paul D
Recent technological advances allow the transfer of genes to the synovial lining of joints. As well as opening novel opportunities for therapy, these techniques provide valuable new tools for the study of synovitis and other aspects of the biology of joints in health and disease. This article reviews briefly the results of experiments in which selected genes have been transferred to the knee joints of healthy rabbits and rabbits with antigen-induced arthritis.
85.
Genetics of rheumatoid arthritis: confronting complexity - Gregersen, Peter K
The genetic basis for rheumatoid arthritis (RA) is likely to be extremely complex. Even the role of MHC genes remains to be fully defined, and may involve interactive genetic effects. The difficulty of precisely defining the clinical phenotype, as well as underlying genetic heterogeneity, complicates the problem. In addition, stochastic genetic or physiologic events may contribute to the low penetrance of susceptibility genes. This situation parallels developing paradigms for other autoimmune disorders, in which many different genes each appear to contribute a small amount to overall risk for disease, and where severity and specific phenotypic subtypes are subject to genetic...
87.
Emerging strategies of bone and joint repair - Schultz, Olaf; Sittinger, Michael; Haeupl, Thomas; Burmester, Gerd R
The advances in biomedicine over the past decade have provided revolutionary insights into molecules that mediate cell proliferation and differentiation. Findings on the complex interplay of cells, growth factors, matrix molecules and cell adhesion molecules in the process of tissue patterning have vitalized the revolutionary approach of bioregenerative medicine and tissue engineering. Here we review the impact of recent work in this interdisciplinary field on the treatment of musculoskeletal disorders. This novel concept combines the transplantation of pluripotent stem cells, and the use of specifically tailored biomaterials, arrays of bioactive molecules and gene transfer technologies to direct the regeneration of...
88.
IFN-gamma transgenic mice: clues to the pathogenesis of systemic lupus erythematosus? - Seery, John P
Transgenic mice overexpressing IFN-γ in the epidermis develop an inflammatory skin disease resembling cutaneous lupus erythematosus shortly after birth. By 3 months of age, most female transgenics develop a lupus-like syndrome characterised by production of IgG anti-dsDNA, antihistone and antinucleosome autoantibodies. The autoantibodies are nephritogenic, with one-third of females developing a severe immune complex mediated glomerulonephritis. Analysis of these transgenics suggests that pathogenic autoantibodies arise via an antigen-driven T-cell-dependent mechanism with apoptotic keratinocytes acting as a potential source of autoantigen. The mechanism of autoantibody production in IFN-γ transgenics may be relevant to human lupus and is consistent with a central...
89.
Bone loss: Epidemiology of bone loss - Hunter, David J; Sambrook, Philip N
Bone loss occurs when the cellular events of bone formation are quantitatively larger than bone formation. This manuscript discusses the measurement of bone loss, occurrence in the population, risk factors and consequences of bone loss. Recent developments in bone mass measurement and biomarkers have improved our ability to assess bone loss. This process is a normal concomitant of ageing. There are a number of other risk factors, including sex hormone deficiency, physical inactivity, calcium/vitamin D deficiency, inflammatory arthritis, corticosteroids, smoking and alcohol. The major consequence of bone loss in our ageing society is fracture.
90.
Bone loss: Quantitative imaging techniques for assessing bone mass in rheumatoid arthritis - Njeh, Christopher F; Genant, Harry K
Osteoporosis is associated with low bone mass and microarchitectural deterioration of bone tissue with clinical manifestation of low trauma fractures. Rheumatoid arthritis (RA) is a risk factor due to generalized and articular bone loss. This minireview presents past and current bone mass measurement techniques in RA. These techniques include: plain radiographs, absorptiometry, quantitative computed tomography (QCT) and ultrasound. The most widely used technique is dual x-ray absorptiometry (DXA). RA patients have lower bone mass as compared with normals and substantial bone loss may occur early after the onset of disease. Measurement of bone mineral density (BMD) at the hand using...
91.
Bone loss: Factors that regulate osteoclast differentiation - an update - Roux, Sophie; Orcel, Philippe
Osteoclast activation is a critical cellular process for pathological bone resorption, such as erosions in rheumatoid arthritis (RA) or generalized bone loss. Among many factors triggering excessive osteoclast activity, cytokines such as IL-1 or tumour necrosis factor (TNF)-α play a central role. New members of the TNF receptor ligand family (namely receptor activator of nuclear factor-κB [RANK] and RANK ligand [RANKL]) have been discovered whose cross-interaction is mandatory for the differentiation of osteoclasts from hemopoietic precursors, in both physiological and pathological situations. Osteoprotegerin, a decoy receptor which blocks this interaction, decreases osteoclast activity and could have a fascinating therapeutic potential...
92.
Cell-cell interactions in synovitis: Interactions between T cells and B cells in rheumatoid arthritis - Weyand, Cornelia M; Goronzy, Jörg J; Takemura, Seisuke; Kurtin, Paul J
In rheumatoid arthritis, T cells and B cells participate in the immune responses evolving in the synovial lesions. Interaction between T cells and B cells is probably antigen specific because complex microstructures typical of secondary lymphoid organs are generated. Differences between patients in forming follicles with germinal centers, T-cellâ??B-cell aggregates without germinal center reactions, or loosely organized T-cellâ??B-cell infiltrates might reflect the presence of different antigens or a heterogeneity in host response patterns to immune injury. Tertiary lymphoid microstructures in the rheumatoid lesions can enhance the sensitivity of antigen recognition, optimize the collaboration of immunoregulatory and effector cells, and support...
93.
Cell contact interactions in rheumatology, The Kennedy Institute for Rheumatology, London, UK, 1-2 June 2000 - Burger, Danielle
The intricate interactions that regulate relationships between endogenous tissue cells and infiltrating immune cells in the rheumatic joint, particularly in rheumatoid arthritis (RA), were the subject of the meeting. A better understanding of these interactions might help to define intervention points that could be used to develop specific therapies. The presentations and discussions highlighted the fact that, once chronic inflammation is established, several pro-inflammatory loops involving tumour necrosis factor (TNF)-α and interleukin (IL)-1β can be defined. Direct cellular contact with stimulated T lymphocytes induces TNF-α and IL-1β in monocytes which in turn induce functions in fibroblast-like synoviocytes. The latter include...
94.
Interplay between bone morphogenetic proteins and cognate binding proteins in bone and cartilage development: noggin, chordin and DAN - Reddi, Hari A
This commentary is a concise discussion of the interactions between bone morphogenetic proteins (BMPs) and their binding proteins in bone and cartilage morphogenesis. BMPs are a family of growth and differentiation factors, and they act on mesenchymal cells to induce cartilage and bone differentiation in concentration-dependent thresholds. The BMPâ??BMP receptor binding leads to a cascade of signaling and transcription of BMP response genes. BMP binding proteins, noggin, chordin and DAN, act as antagonists and determine the bioavailability of BMPs for binding to cognate receptors to elicit the biological response. Noggin null mice with unrestricted action of BMPs exhibit defects in...
95.
The role of TNF-receptor family members and other TRAF-dependent receptors in bone resorption - Gravallese, Ellen M; Galson, Deborah L; Goldring, Steven R; Auron, Philip E
The contribution of osteoclasts to the process of bone loss in inflammatory arthritis has recently been demonstrated. Studies in osteoclast biology have led to the identification of factors responsible for the differentiation and activation of osteoclasts, the most important of which is the receptor activator of NF-κB ligand/osteoclast differentiation factor (RANKL/ODF), a tumor necrosis factor (TNF)-like protein. The RANKL/ODF receptor, receptor activator of NF-κB (RANK), is a TNF-receptor family member present on both osteoclast precursors and mature osteoclasts. Like other TNF-family receptors and the IL-1 receptor, RANK mediates its signal transduction via TNF receptor-associated factor (TRAF) proteins, suggesting that the...
96.
Cell-cell interactions in synovitis: Antigen presenting cells and T cell interaction in rheumatoid arthritis - Aarvak, Tanja; Natvig, Jacob B
The synovial tissue in rheumatoid arthritis (RA) patients is enriched with mature antigen presenting cells (APCs) and many T lymphocytes. Interactions between APCs and T cells are essential for the initiation and amplification of T-cell-dependent immune responses, and may therefore play an important role in the chronic inflammatory processes in the synovium. The nature of the antigen(s) involved in RA still remains elusive. However, interactions and signaling through the costimulatory molecules CD28-CD80/86 and CD40-CD40L are critical during APCâ??T cell interaction for optimal cell activation. This review discusses how such costimulatory signals can be involved in the initiation and amplification of...
97.
Anti-cytokine therapy in chronic destructive arthritis - van den Berg, Wim B
Tumor necrosis factor (TNF) and interleukin-1 (IL-1) are considered to be master cytokines in chronic, destructive arthritis. Therapeutic approaches in rheumatoid arthritis (RA) patients have so far focused mainly on TNF, which is a major inflammatory mediator in RA and a potent inducer of IL-1; anti-TNF therapy shows great efficacy in RA patients. However, it is not effective in all patients, nor does it fully control the arthritic process in affected joints of good responders. Directed therapy for IL-1, with IL-1 receptor antagonist, mainly reduces erosions and is marginally anti-inflammatory. It is as yet unclear whether the limited effect is...
98.
Sixth International Workshop on Scleroderma Research, Oxford, UK, 30 Julyâ??2 August 2000 - Wollheim, Frank A; Denton, Christopher P; Abraham, David J
We discuss major topics presented at this recent international workshop, illustrating how recent progress in areas as diverse as free radical biochemistry, developmental biology, molecular genetics and vascular biology is facilitating greater understanding of the multisystem connective tissue disease scleroderma. Some of the opportunities for translating this into novel and improved therapy are considered.
99.
The ank gene story - Ryan, Lawrence M
The underlying molecular defect resulting in the abnormal calcification observed in ank/ank mice has been identified. The responsible nonsense mutation affects the protein product of ank, resulting in diminished production of extracellular inorganic pyrophosphate, an important inhibitor of nucleation and of the growth of apatite crystals. The ank gene product is one of several cell membrane proteins, including ectonucleoside triphosphate pyrophosphohydrolase enzymes and alkaline phosphatase, that regulate extracellular inorganic pyrophosphate levels and thereby regulate mineralization.
100.
The stressed synovium - Schett, Georg; Tohidast-Akrad, Makiyeh; Steiner, Günter; Smolen, Josef
This review focuses on the mechanisms of stress response in the synovial tissue of rheumatoid arthritis. The major stress factors, such as heat stress, shear stress, proinflammatory cytokines and oxidative stress, are discussed and reviewed, focusing on their potential to induce a stress response in the synovial tissue. Several pathways of stress signalling molecules are found to be activated in the synovial membrane of rheumatoid arthritis; of these the most important examples are heat shock proteins, mitogen-activated protein kinases, stress-activated protein kinases and molecules involved in the oxidative stress pathways. The expression of these pathways in vitro and in vivo...
81.
