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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
17334042 [Annexin-1: 2nd messanger of the anti-inflammatory actions of glucocorticoids]. 2006 Oct Glucocorticoids have important immunosupressive properties, being used as anti-inflammatory therapeutic agents in a wide range of inflammatory and auto-immune pathologies. One of the best studied mechanisms by which glucocorticoids exert most of their anti-inflammatory actions involves the induction of the synthesis and the secretion of the mediator and effector protein annexin 1 (ANXA1). Here we review the molecular and cellular pathways involved on the glucocorticoid-induced synthesis and secretion of ANXA1 in a variety of cell types. Since its discovery as an anti-phospholipase A2 protein, ANXA1 has come a long way to encompass a wide range of cellular effects, the most relevant ones being those that directly modulate the inflammatory response. The results presented in this review open the way to further pharmacological studies which will allow the identification of the role of ANXA1 in inflamatory pathologies, namely rheumatoid arthritis.
17302210 A case of orbital abscess following porous orbital implant infection. 2006 Dec PURPOSE: We present a case of orbital abscess following porous orbital implant infection in a 73-year-old woman with rheumatoid arthritis. METHODS: Just one month after a seemingly uncomplicated enucleation and porous polyethylene (Medpor) orbital implant surgery, implant exposure developed with profuse pus discharge. The patient was unresponsive to implant removal and MRI confirmed the presence of an orbital pus pocket. Despite extirpation of the four rectus muscles, inflammatory granulation debridement and abscess drainage, another new pus pocket developed. RESULTS: After partial orbital exenteration, the wound finally healed well without any additional abscess formation. CONCLUSIONS: A patient who has risk factors for delayed wound healing must be examined thoroughly and extreme care such as exenteration must be taken if there is persistent infection.
17168521 Histone citrullination by protein arginine deiminase: is arginine methylation a green ligh 2006 Aug 22 Protein citrullination, a once-obscure post-translational modification (PTM) of peptidylarginine, has recently become an area of significant interest because of its suspected role in human disease states, including rheumatoid arthritis and multiple sclerosis, and also because of its newfound role in gene regulation. One protein isozyme responsible for this modification, protein arginine deiminase 4 (PAD4), has also been proposed to "reverse" epigenetic histone modifications made by the protein arginine methyltransferases. Here, we review the in vivo and in vitro studies of transcriptional regulation by PAD4, evaluate conflicting evidence for its ability to use methylated peptidylarginine as a substrate, and highlight promising areas of future work. Understanding the interplay of multiple arginine PTMs is an emerging area of importance in health and disease and is a topic best addressed by novel tools in proteomics and chemical biology.
17154080 [Susceptibility genes for the development of autoimmune thyroid disease]. 2006 Dec Autoimmune thyroid disease (AITD) is caused by an immune response to self thyroid antigens. Twin studies and familial aggregation indicated that AITD is a complex disease with genetic factors and major histocompatibility complex is the most clearly established genetic factor. We confirmed the association of the co-receptor CTLA4 with AITD. We have identified the association of the SNP in the Fc receptor-like 3 with several autoimmune diseases, including AITD, SLE and rheumatoid arthritis, which SNP affected the level of autoantibody production. Furthermore, we have identified ZFAT as a susceptibility gene in 8q24 for AITD by whole-genome linkage analysis and further SNP-based dense mapping. The associated SNP in ZFAT affected the antisense transcript of ZFAT, which in turn affected the ZFAT expression.
17073677 Functional genome and proteome analyses of cutaneous autoimmune diseases. 2006 The use of functional genomics and proteomics technologies has dramatically increased through recent years with a special emphasis on cancer biology. However, a series of more recent reports has also addressed inflammatory diseases. These included studies on different autoimmune diseases, such as rheumatoid arthritis, lupus erythematosus, and systemic sclerosis. Gene and protein expression profiles from these studies have emphasized the role of cytokines, chemokines, and apoptosis-related molecules for the pathogenesis of autoimmune diseases. Much less is known about gene and protein patterns of these diseases in dermatology. Here we provide an overview on current knowledge about genomics and proteomics analyses of cutaneous autoimmune diseases. These diseases include psoriasis, lupus erythematosus, systemic sclerosis, vitiligo, and alopecia areata. The presented findings not only provide deeper insights into the pathogenesis of each individual disease but also show overlapping gene patterns suggestive for common pathogenic mechanisms. However, many open questions remain to be resolved since data about local gene expression pattern in affected tissues are still scarce.
16989586 RANK ligand inhibition with denosumab for the management of osteoporosis. 2006 Oct Receptor activator of nuclear factor-kappaB ligand (RANKL) is a cytokine member of the tumour necrosis factor family that is the principal final mediator of osteoclastic bone resorption. It plays a major role in the pathogenesis of postmenopausal osteoporosis, as well bone loss associated with rheumatoid arthritis, metastatic cancer, multiple myeloma, aromatase inhibitor therapy and androgen deprivation therapy. Denosumab (AMG 162) is an investigational fully human monoclonal antibody with a high affinity and specificity for RANKL. By inhibiting the action of RANKL, denosumab reduces the differentiation, activity and survival of osteoclasts, thereby slowing the rate of bone resorption. Denosumab has been shown to increase bone mineral density (BMD) and reduce bone turnover in postmenopausal women with low BMD. Denosumab is a potential treatment for osteoporosis and other skeletal disorders.
16919890 Why does chloroquine impair renal function?: chloroquine may modulate the renal tubular re 2007 Chloroquine is one of the antimalaria drugs, also used to treat rheumatoid arthritis and systemic lupus erythematosus (SLE). Although well tolerated in most individuals, it was suggested that chloroquine can exert a profound influence on renal function, especially in individuals with compromised body fluid status. However, epidemiological studies are still lacking. The renal actions of chloroquine are further exacerbated by co-administration of other commonly used drugs such as paracetamol. The following discussion will focus on the evidence that chloroquine is a stimulator of nitric oxide (NO), which mediates many of its renal actions (diuresis, natriuresis and an increase in both glomerular filtration rate (GFR) and plasma vasopressin). Chloroquine appears to modulate the renal tubular response to vasopressin either by directly inhibiting cAMP generation or indirectly via NO.
16918401 Emerging peptide therapeutics for inflammatory diseases. 2006 Aug Steroids are the best known anti-inflammatory drugs and have been in use for more than 50 years. Their chronic use however was limited by safety concerns. Non-steroidal anti-inflammatory drugs (NSAIDs) including COX-2 inhibitors although devoid of steroid side effects often possess gastrointestinal side effects. In addition recent data suggest that chronic use of some Cox inhibitors is associated with cardiovascular risk. Currently biologics represent the best option for many inflammatory diseases where TNFalpha is the main culprit. These include rheumatoid arthritis, ulcerative colitis, inflammatory bowel disease and psoriasis. A wealth of information is now available on the role of different cytokines and adhesion molecules in the origin and progression of inflammatory diseases. With the success of protein therapeutics such as Etanercept (Enbrel), which binds TNFalpha and inhibits its activity, research has been focused on developing small peptides that can interfere with cytokines or specific cell surface molecules and inhibit the inflammatory reactions. Here we review these peptides that are in discovery and development phases and their potential in the treatment of inflammatory diseases.
16855137 Hypoglycemia, an old tool for new findings in the adrenomedullary hormonal system in patie 2006 Jun Over the past decades, research in patients with rheumatic disorders showed enormous progress in detecting various perturbations of the neuroendocrine system including those affecting autonomic nervous function. There is, however, a substantial lack of data on adrenomedullary hormonal system (AMHS) function in those patients. Insulin-induced hypoglycemia (IIH) represents a metabolic stressor, which elicits a counterregulatory stress response not only of the hypothalamic-pituitary axis but also of the AMHS. Therefore, in addition to traditional testing of hypothalamic-pituitary function, IIH can be used as a well-controlled functional test of the AMHS. Our recent studies showed, for the first time, attenuated epinephrine and norepinephrine responses to IIH in premenopausal females with rheumatoid arthritis (RA) and systemic sclerosis (SSc). These findings are suggestive of downregulation, or possibly defects, of the AMHS in those patients. This article reviews mechanism of the AMHS activation during IIH and demonstrates applications of the test in neuroendocrine-immune research.
16325070 Pyoderma gangrenosum: uncommon presentations. 2005 Nov Pyoderma gangrenosum (PG) is a rare, inflammatory, noninfective, nonneoplastic skin disorder, which is often associated with systemic diseases. These include inflammatory bowel disease, rheumatoid arthritis, paraproteinaemia, or hematologic malignancy, which can be found in up to 50% of patients with some variants of PG. Brunsting et al (Arch Dermatol 1930;22:655-80) first described PG as a disease entity in 5 patients who had painful, enlarging necrotic ulcers with bluish undermined borders surrounded by advancing zones of erythema. Four of these patients had chronic ulcerative colitis. They felt that the condition might be associated with bacterial infection (pyoderma) and considered it as linked to the underlying bowel disease. Although the cause of PG remains obscure, bacterial infection seems to be unrelated to its causation, rendering the term pyoderma redundant. In addition, the number of conditions reported in association with PG has markedly expanded in recent years, showing clearly that this is not solely a cutaneous manifestation of inflammatory bowel disease. The clinical concept of PG has also been broadened, and certain clinical variants of PG have been linked with different types of associated disease seen in these patients.
16218484 Statins and autoimmune diseases. 2005 Besides the well-known lipid-lowering effect, statins display nonlipid-lowering pharmacological activities. In vitro and in vivo studies suggest that statins have direct anti-inflammatory, anti-thrombotic and plaque-stabilizing effects via a number of mechanisms. A direct immunomodulatory effect has been also demonstrated in in vitro and in vivo experimental models. In addition to traditional risk factors, systemic inflammation, immune-mediated responses and thrombophilia have been suggested to play a major role in sustaining the premature atherosclerosis in autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. This review focuses on the anti-inflammatory and immunomodulating mechanisms of statins as demonstrated in in vitro and in vivo experimental models, providing new insights for the use of statins in treating systemic autoimmune diseases both for their anti-atherosclerotic activity and for their pleiotropic effects on inflammation, haemostasis and the immune responses.
16077950 Effect of soy sauce on the antioxidative capacity of the gelatin gel food 'Nikogori' measu 2005 Sep Oxygen-related free radicals have been suggested as a cause of aging and various diseases, for example, various cancers and rheumatoid arthritis. Because of this a radical scavenger as an antioxidant has been sought in many foods. 'Nikogori' gelatin gel from cooked fish is a traditional food in Japan. Recently, 'Nikogori' has been noted as a readily consumed food for the elderly and those with medical problems associated with swallowing. In this study we report that the 'Nikogori' gelatin gels made from the collagen in various meats have a high peroxyl radical scavenging capability as the antioxidative capacity using the chemiluminescence method and the order of the strength of antioxidative capacity (IC(50) value) was the Japanese common squid mantle meat (0.163%) > flatfish (marbled sole) meat (0.534%) > chicken wing meat (0.585%) > beef shin meat (0.655%) > yellowtail meat (0.659%) > chub mackerel meat (0.789%). Furthermore, when soy sauce was added to the 'Nikogori' gelatin gel, the antioxidative capacity increased markedly to 0.098% of IC(50) value of yellowtail, 0.165% of chicken, 0.182% of flatfish and 0.252% of chub mackerel.
16012468 Type IV thoracoabdominal aortic aneurysm with lymphoplasmacytic aortitis and cystic medial 2005 Jul Aortitis identified in approximately 12% of all thoracoabdominal aneurysms. The most common subtype of inflammatory aortitis is giant cell aortitis, followed by lymphoplasmacytic aortitis. Inflammatory aortitis may occur in isolation or as part of a systemic inflammatory disorder such as Takayasu arteritis, systemic lupus erythematosus, rheumatoid arthritis, and giant cell arteritis. Aortitis has not been described in patients with Marfan syndrome. We report the case of a 32-year-old man with Marfan syndrome and a strong family history of aneurysmal disease who presented with an asymptomatic Crawford type IV thoracoabdominal aneurysm. His aneurysm had no associated dissection, and surgical pathology revealed severe medial degeneration and lymphoplasmacytic aortitis. To our knowledge, this is the first report of such a finding in a patient with Marfan syndrome.
15968269 Psoriasis--recent advances in understanding its pathogenesis and treatment. 2005 Jul Although not completely understood, there is clearly a genetic component in the development of psoriasis. Twin studies show a 67% concordance for monozygotic twins versus 18% for dizygotic twins. This lack of complete concordance in monozygotic twins suggests multifactorial inheritance and interaction between genetic predisposition and the environment. At present, 8 different psoriasis susceptibility loci have been identified in genome-wide linkage scans, including locations on 15 different chromosomes. Genetic connections have been made between psoriasis and other diseases, including atopic dermatitis, rheumatoid arthritis, and Crohn's disease. A variety of approaches are available for the treatment of psoriasis, ranging from topical agents for milder forms of the disease to phototherapy and systemic agents for severe psoriasis. Despite the importance of systemic therapies and recent advances represented by biologic agents, topical treatments will probably remain the mainstay of psoriasis therapy for most patients. The advent of new, cosmetically attractive vehicles may enhance compliance, add to the use of topical agents, and potentially improve patient outcomes.
15848075 From rodent reagents to human therapeutics using antibody guided selection. 2005 May Guided selection is a method of producing a human version of a rodent or any other non-human antibody. The process is a serial transition from rodent to human via rodent-human chimaerics, through to a panel of human antibodies with similar characteristics to those of the starting rodent antibody. The guided selection process can be undertaken using either phage display or ribosome display, and chimaeric antibodies can be made either in series or parallel, with or without the retention of the original rodent CDR3s. Guided selection has successfully been used for the generation of a number of human versions of rodent antibodies, including HUMIRA, an inhibitor of tumour necrosis factor-alpha which is approved for the treatment of moderate to severe rheumatoid arthritis in over 40 countries.
15634264 Pleiotropic functions of plasminogen activator inhibitor-1. 2005 Jan Plasminogen activator inhibitor-1 (PAI-1), a 45-kDa serine proteinase inhibitor with reactive site peptide bond Arg345-Met346, is the main physiological plasminogen activator inhibitor. It occurs in human plasma at an antigen concentration of about 20 ng mL(-1). Besides the active inhibitory form of PAI-1 that spontaneously converts to a latent form, also a substrate form exists that is cleaved at the P1-P1' site by its target enzymes, but does not form stable complexes. Besides its role in regulating hemostasis, PAI-1 plays a role in several biological processes dependent on plasminogen activator or plasmin activity. Studies with transgenic mice have revealed a functional role for PAI-1 in wound healing, atherosclerosis, metabolic disturbances such as obesity and insulin resistance, tumor angiogenesis, chronic stress, bone remodeling, asthma, rheumatoid arthritis, fibrosis, glomerulonephritis and sepsis. It is not always clear if these functions depend on the antiproteolytic activity of PAI-1, on its binding to vitronectin or on its intereference with cellular migration or matrix binding.
17959451 Comparison of two and three-dimensional optical tomographic image reconstructions of human 2006 We have developed an images reconstruction algorithm to recover spatial distribution of optical properties in human finger joints for early diagnosis and monitoring of rheumatoid arthritis (RA). An optimization method iteratively employs a light propagation and scattering coefficients distribution for near-infrared (NIR) light inside the joint tissue. We developed the differences in cross-sectional images obtained by using the reconstruction algorithms with 2-dimensional and 3-dimensional light propagation models. In particular we examined how these different approaches affect the discrimination between healthy and RA joints.
17086611 Method guidelines for Cochrane Musculoskeletal Group systematic reviews. 2006 Nov The Cochrane Musculoskeletal Group (CMSG), one of 50 groups of the not-for-profit international Cochrane Collaboration, prepares, maintains, and disseminates systematic reviews of treatments for musculoskeletal diseases. To enhance the quality and usability of systematic reviews, the CMSG has developed tailored methodological guidelines for authors of CMSG systematic reviews. Recommendations specific to musculoskeletal disorders are provided for various aspects of undertaking a systematic review, including literature searching, inclusion criteria, quality assessment, grading of evidence, data collection, and data analysis. These guidelines will help researchers design, conduct, and report results of systematic reviews of trials in the following fields of musculoskeletal health: gout, osteoarthritis, osteoporosis, pediatric rheumatology, rheumatoid arthritis, soft tissue rheumatism, spondyloarthropathy, systemic lupus erythematosus, systemic sclerosis, and vasculitis. Systematic reviews need to be conducted according to high methodological standards. These recommendations on developing and performing a systematic review will help improve consistency among CMSG reviews.
17054552 Tumour necrosis factor: implications for surgical patients. 2006 Nov Tumour necrosis factor alpha (TNF-alpha) is an inflammatory cytokine primarily produced by macrophages. It is a unique protein with contradictive properties; it has the ability to induce cellular death by apoptosis and oncosis, but can also induce cellular regeneration and growth. Genetic polymorphisms in TNFA have been associated with poor outcome in some surgical patients and this may provide a useful tool to screen for high-risk patients. Manipulating TNF-alpha levels in vivo may influence the progression of several pathological conditions. TNF-alpha has anti-cancer properties and has been used to treat cancer patients. Treatment with anti-TNF-alpha drugs and antibodies has been successful in rheumatoid arthritis and other autoimmune diseases, but disappointing in the management of patients with sepsis. This review article focuses on the biological activities, genetic polymorphism of TNFA and the role of TNF-alpha and anti-TNF-alpha treatments, based on animal experiments and clinical trials.
16875761 Treatment with infliximab: Implications in oral surgery? A case report. 2007 Sep Infliximab is a tumour necrosis factor-alpha (TNF-alpha) inhibitor (neutralising antibody), which is increasingly being used as an immunosuppressant to manage inflammatory conditions including rheumatoid arthritis, ankylosing spondylitis and Crohn's disease. Its side effects include diabetes mellitus, an increased incidence of lymphoma and greater susceptibility to infections such as pulmonary tuberculosis. In patients on infliximab, the oral cavity may act as a bacterial reservoir leading to unwanted local or systemic complications. To date no report describes the potential implication/s of infliximab in patients having oral surgery. This case report may be the first in the English language to report the development of mandibular osteomyelitis after surgical extraction in a patient on infliximab.