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).
162.
Epidemiology of organic solvents and connective tissue disease - Garabrant, David H; Dumas, Constantine
Case reports suggest that solvents are associated with various connective tissue diseases (systemic sclerosis, scleroderma, undifferentiated connective tissue disease, systemic lupus erythematosis, and rheumatoid arthritis), particularly systemic sclerosis. A small number of epidemiological studies have shown statistically significant but weak associations between solvent exposure, systemic sclerosis, and undifferentiated connective tissue disease. However, the interpretation of these positive findings is tempered by a lack of replication, an inability to specify which solvents convey risk, and an absence of increasing risk with increasing exposure. Existing studies, on aggregate, do not show conclusively that solvents (either as a group of chemicals or individual...
163.
Janus kinases and signal transducers and activators of transcription: their roles in cytokine signaling, development and immunoregulation - Ortmann, Robert A; Cheng, Tammy; Visconti, Roberta; Frucht , David M; O'Shea, John J
Cytokines play a critical role in the normal development and function of the immune system. On the other hand, many rheumatologic diseases are characterized by poorly controlled responses to or dysregulated production of these mediators. Over the past decade tremendous strides have been made in clarifying how cytokines transmit signals via pathways using the Janus kinase (Jak) protein tyrosine kinases and the Signal transducer and activator of transcription (Stat) proteins. More recently, research has focused on several distinct proteins responsible for inhibiting these pathways. It is hoped that further elucidation of cytokine signaling through these pathways will not only allow...
164.
Mechanisms of bone loss in inflammatory arthritis: diagnosis and therapeutic implications - Goldring, Steven R; Gravallese, Ellen M
Rheumatoid arthritis represents an excellent model in which to gain insights into the local and systemic effects of joint inflammation on skeletal tissues. Three forms of bone disease have been described in rheumatoid arthritis. These include: focal bone loss affecting the immediate subchondral bone and bone at the joint margins; periarticular osteopenia adjacent to inflamed joints; and generalized osteoporosis involving the axial and appendicular skeleton. Although these three forms of bone loss have several features in common, careful histomorphometric and histopathological analysis of bone tissues from different skeletal sites, as well as the use of urinary and serum biochemical markers...
165.
A new model for rheumatoid arthritis? - McDevitt, Hugh
A chance observation has led to the development of a new murine model for inflammatory arthritis. Arthritis is induced, and transferred, by T-cell-dependent antibodies to glucose-6-phosphate isomerase. This enzyme is expressed in all cells, and is detectable in serum. There are several similarities to rheumatoid arthritis (RA) in the murine disease. This elegant model raises several questions as to how and why a systemic response focuses inflammation so strongly on synovial joints. The model also re-introduces the possibility that antibodies to widely expressed self-proteins may play a role in the pathogenesis of RA.
166.
A revival of the B cell paradigm for rheumatoid arthritis pathogenesis? - Benoist, Christophe; Mathis, Diane
Dominant paradigms for the understanding of rheumatoid arthritis (RA) pathogenesis have changed over the years. A predominant role of B lymphocytes, and perhaps of the rheumatoid factor they produced, was initially invoked. In more recent years, recognition of antigens in the joint by T cells sparking an inflammatory cascade has been a more favored interpretation. Here, we re-examine some of the arguments that underpin this proposed role of joint T cells, in light of recent results from transgenic mice in which a self-reactive T-cell receptor provokes disease, but from outside the joint and indirectly via B lymphocytes and immunoglobulins.
167.
What can we do about osteoarthritis? - Lohmander, L Stefan
Osteoarthritis is complex in genetics, pathogenesis, monitoring and treatment. Current treatment of osteoarthritis does not influence progression. Much could be gained by more effective 'low-tech-low-cost' treatment. However, many patients have rapidly progressive disease, multiple joint involvement, and severe disease. We need to clarify the genetics of osteoarthritis, identify those at risk for progression and severe disease, and identify molecular processes critical for joint survival and failure. Will saving the cartilage improve patient pain and function? Effective outcome measures are needed to accelerate testing of new treatments. Further improvement is needed in joint implant technology to decrease costs, wear and loosening.
168.
Death, autoantigen modifications, and tolerance - Utz,, Paul J; Gensler, Timothy J; Anderson, Paul
Autoantibodies present in the serum of patients with a variety of inflammatory diseases have proven useful as diagnostic markers and as probes with which to elucidate biochemical and signaling pathways. The mechanisms governing the generation of autoantibodies remain elusive, constituting a critical missing link in our understanding of rheumatologic illnesses. Several lines of experimentation in recent years have strongly implicated events surrounding cell death in this process. This review will address the potential role played by death-specific modifications of autoantigens in bypassing tolerance to highly conserved autoantigens, including nucleic acids, lipids, and proteins.
169.
Risk for rheumatic disease in relation to ethnicity and admixture - Molokhia, Mariam; McKeigue, Paul
Risk of systemic lupus erythematosus (SLE) is high in west Africans compared with Europeans, and risk of rheumatoid arthritis (RA) is high in Native Americans compared with Europeans. These differences are not accounted for by differences in allele or haplotype frequencies in the human leucocyte antigen (HLA) region or any other loci known to influence risk of rheumatic disease. Where there has been admixture between two or more ethnic groups that differ in risk of disease, studies of the relationship of disease risk to proportionate admixture can help to distinguish between genetic and environmental explanations for ethnic differences in disease...
170.
B cells in rheumatoid arthritis - Kim, Hye-Jung; Berek, Claudia
Normally the immune response is restricted to the peripheral secondary lymphoid organs. However, additional ectopic lymphoid tissue may develop at chronic sites of inflammation. In the synovium of rheumatoid arthritis patients the local production of proinflammatory cytokines seems to support the formation of a precisely structured microenvironment, which allows an antigen dependent immune response to take place. The analysis of the V-gene repertoire expressed in synovial B cells demonstrated that in the inflamed synovium a germinal centre reaction takes place. Antigen presented by a network of follicular dendritic cells may activate synovial B cells and support their differentiation into plasma...
171.
Anti-TNF-α therapy as a clinical intervention for periprosthetic osteolysis - Schwarz, Edward M; Looney, R John; O'Keefe, Regis J
Aseptic loosening of total joint arthroplastics due to periprosthetic osteolysis is a frequent cause of implant failure. The absence of clinical interventions to arrest or prevent this complication limits the use of total joint replacement especially in younger patients. Here we review recent studies implicating tumor necrosis factor (TNF)-α in periprosthetic osteolysis and the rationale for clinical studies of anti-TNF therapy and other interventions for periprosthetic loosening.
172.
Rheumatoid arthritis viewed using a headache paradigm - Holmdahl, Rikard
Results and new hypotheses in animal models often stimulate development of new paradigms in how we view rheumatoid arthritis (RA). The complexity of RA does, however, eventually lead to the rejection of these hypotheses. Here, it is argued that the large number of so-far described animal models, when taken together, also reveals a complex disease. Fortunately, detailed study of each of the animal models will reveal this complexity, and may also be helpful in elucidating the complexity of the human disease. Benoist and Mathis [1] recently contributed a new animal model in which an autoimmune response to a ubiquitous antigen...
173.
Post-transcriptional regulation of pro-inflammatory gene expression - Clark, Andy
The cytokine tumour necrosis factor (TNF)α is a vital mediator of the innate immune response, and a pleiotropic regulator of cellular function. Its involvement in rheumatoid arthritis is illustrated by the clinical benefits of TNFα blockade. Post-transcriptional regulation (the control of mRNA stability and translation) appears to play a critical role in the regulation of TNFα expression by mitogen activated protein kinase signal transduction pathways and by anti-inflammatory agents. The aim of this article is to review some recent advances in our understanding of these processes, and to speculate on mechanisms of regulation of TNFα and other pro-inflammatory genes.
174.
p53 in rheumatoid arthritis: friend or foe? - Müller-Ladner , Ulf; Nishioka, Kusuki
The knowledge of transcription factors and proto-oncogenes has influenced the understanding of cell regulation, cell
175.
Cell fate decision: T-helper 1 and 2 subsets in immune responses - Dong, Chen; Flavell, Richard A
After activation CD4+ helper T cells differentiate into T-helper (Th) 1 or Th2 effector cells. These two subsets are characterized by their distinct cytokine expression pattern and the immune function they mediate. Over the past years, a number of factors have been identified to affect helper T cell lineage determination, including antigen receptor, coreceptors and, most importantly, cytokine environment. In this review, we also summarize recent advancement in understanding of transcriptional and signaling regulation of the differentiation process. This knowledge will become important in the future to develop means in treating immune disorders.
176.
Macrophages in rheumatoid arthritis - Kinne, Raimund W; Bräuer, Rolf; Stuhlmüller, Bruno; Palombo-Kinne, Ernesta; Burmester, Gerd-R
The abundance and activation of macrophages in the inflamed synovial membrane/pannus significantly correlates with the severity of rheumatoid arthritis (RA). Although unlikely to be the 'initiators' of RA (if not as antigen-presenting cells in early disease), macrophages possess widespread pro-inflammatory, destructive, and remodeling capabilities that can critically contribute to acute and chronic disease. Also, activation of the monocytic lineage is not locally restricted, but extends to systemic parts of the mononuclear phagocyte system. Thus, selective counteraction of macrophage activation remains an efficacious approach to diminish local and systemic inflammation, as well as to prevent irreversible joint damage.
178.
Association of MHC and rheumatoid arthritis: Regulatory role of HLA class II molecules in animal models of RA - studies on transgenic/knockout mice - Taneja, Veena; David, Chella S
Human leucocyte antigen (HLA) class II molecules have been shown to be associated with predisposition to rheumatoid arthritis (RA). We generated HLA-DR and DQ transgenic mice that lacked endogenous class II molecules to study the interaction between the DR and DQ molecules and define the immunologic mechanisms in rheumatoid arthritis. Using collagen-induced arthritis (CIA) as an experimental model for inflammatory polyarthritis, we show that both DQ and DR are involved in predisposition or resistance to arthritis. Our studies suggest that polymorphism in DQB1 genes may determine predisposition to RA while the DRB1 polymorphism may dictate severity/protection of the disease. These...
179.
Association of MHC and rheumatoid arthritis: HLA-DR4 and rheumatoid arthritis - studies in mice and men - Fugger , Lars; Svejgaard, Arne
Inherited susceptibility to rheumatoid arthritis (RA) is associated with the DRB1 genes encoding the human leukocyte antigen (HLA)-DR4 and HLA-DR1 molecules. Transgenic mice expressing these major histocompatibility complex (MHC) class II molecules have been developed to generate humanized models for RA. The relevance of these models for understanding RA will be discussed.
180.
Association of MHC and rheumatoid arthritis:HLA polymorphisms in phenotypic variants of rheumatoid arthritis - Weyand, Cornelia M; Goronzy, Jörg J
Genes in the human leukocyte antigen (HLA) region remain the most powerful disease risk genes in rheumatoid arthritis (RA). Several allelic variants of HLA-DRB1 genes have been associated with RA, supporting a role for T-cell receptor-HLA-antigen interactions in the pathologic process. Disease-associated HLA-DRB1 alleles are similar but not identical and certain allelic variants are preferentially enriched in patient populations with defined clinical characteristics. Also, a gene dosing effect of HLA-DRB1 alleles has been suggested by the accumulation of patients with two RA-associated alleles, especially in patient subsets with a severe disease course. Therefore, polymorphisms in HLA genes are being explored...
161.
