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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
16312134 Tick histamine-binding proteins and related lipocalins: potential as therapeutic agents. 2005 Nov Tick histamine-binding proteins bind histamine with high affinity and specificity. This is attained by a novel binding mechanism, whereby histamine is sequestered within a binding cavity of the lipocalin fold. The histamine binding proteins and related protein family members are currently under investigation as potential therapeutic agents for the treatment of various diseases, including conjunctivitis, allergic rhinitis, carcinoid syndrome and rheumatoid arthritis. While these proteins show great therapeutic potential, they are part of a diverse family of tick lipocalin proteins, some of which have been implicated in tick-host rejection and host pathogenesis. As such, the therapeutic mining of tick lipocalins should be considered within the framework of the rest of the family.
16101541 Osteoblasts and osteoclasts in bone remodeling and inflammation. 2005 Jun Bone homeostasis is maintained by a balance between bone resorption by osteoclasts and bone formation by osteoblasts. Osteoblasts not only play a central role in bone formation by synthesizing multiple bone matrix proteins, but regulate osteoclast maturation by soluble factors and cognate interaction, resulting in bone resorption. Osteoclast maturation requires stimulation by RANKL expressed on osteoblasts, and the cognate interaction is mediated by firm adhesion via ICAM-1. During the processes, pro-inflammatory cytokines such as IL-1 and TNF-alpha, cause an imbalance in bone metabolism, by favoring bone resorption via the induction of RANKL and ICAM-1 on osteoblasts. These inflammatory signals originate from the immune system, the largest source of cell-derived regulatory signals, and such immunological signals to the bone are transmitted primarily via osteoblasts to induce osteoclast maturation, resulting in secondary osteoporosis. Actually, such phenomena mainly occur at the interface between proliferating synovium and bone tissue in rheumatoid arthritis (RA). Thus, therapeutic strategies for these conditions, an anti-TNF-alpha antibody and an IL-1 receptor antagonist, effective for treating RA disease activity, also reduce secondary osteoporosis and joint destruction. Based on an improved understanding of immune signals, investigation of the suppression of cell functions may lead to improved understanding and better treatment of diseases of bone metabolism and osteoporosis.
15974941 Global safety of coxibs and NSAIDs. 2005 Non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 inhibitors (Coxibs) are commonly used for minor pain treatment and chronically in the management of rheumatoid arthritis and osteoarthritis. Three areas of safety concerns are shared by both groups of drugs: Gastrointestinal complications (upper gastrointestinal bleeding, perforations or obstruction), cardiovascular safety (mainly myocardial infarction) and renal safety (acute renal failure, hypertension and electrolyte abnormalities). The incidence of renal complications may be increased two-fold with NSAIDs or coxibs, and there is no evidence for a major difference between the two groups of drugs. Coxibs are clearly associated with improved gastrointestinal safety compared to NSAIDs, but this benefit is reduced and may be lost completely with concurrent low-dose aspirin use. In contrast, coxibs may be associated with a greater incidence of cardiovascular complications, mainly myocardial infarction, especially in comparison to certain NSAIDs such as naproxen. Thus, coxibs are not generally safer than NSAIDs. Rather, their long-term use should be customized to individual patients and their intrinsic baseline risks and other medications required in their management.
15910185 Evaluation of facial thermographic changes before and after low-level laser irradiation. 2005 Apr OBJECTIVE: The aim of the present study was to evaluate the facial thermographic changes before and after low-level laser irradiation applied to the temporomandibular joint in normal subjects. BACKGROUND DATA: Although this therapy has been reported to be effective in the pain management of patients with rheumatoid arthritis and degenerative joint disease, several researchers have stated that this therapy has no effect on pain of myogeneous origin. MATERIALS AND METHODS: Nine healthy subjects underwent irradiation using the continuous wave setting of a CO2 laser with a power output of 1.0 W. The laser tip was positioned 10 cm above the skin over the right TMJ area for 10 min. The actual fluence on the facial surface was 7.64 J/cm2. Variation of the facial temperature was evaluated by using thermography. RESULTS: The facial temperature 10 min after stopping irradiation was higher than that after 10 min of irradiation applied to the opposite side. The warmer area was found not only over the TMJ area but also over the temporal area, forehead area, and eyelid area on both sides. CONCLUSION: These results suggested that low-level laser irradiation had a long-lasting effect on facial cutaneous tissues.
17086602 Cost-effectiveness of biologic agents for treatment of autoimmune disorders: structured re 2006 Nov OBJECTIVE: Four new biologic treatments have been approved for several autoimmune disorders. Economic evaluations have been used to model their cost-effectiveness. METHODS: We conducted a structured literature review in Embase and PubMed to identify all relevant cost-effectiveness models investigating one or more of these 4 drugs in autoimmune disorders. RESULTS: Fifteen full economic evaluations were identified [13 for rheumatoid arthritis (RA), 2 for Crohn's disease (CD), and 1 for ankylosing spondylitis (AS)]. While several studies found adalimumab, etanercept, and infliximab to be cost-effective (using a threshold around $50,000/quality-adjusted life-year) for treatment of severe RA, not all studies concurred, and there was significant variation in the range of cost-effectiveness ratios reported. Neither study in CD found treatment with infliximab to be cost-effective. Only one study was identified in AS: treatment with infliximab was found to be cost-effective. CONCLUSION: Modeling treatment strategies in chronic relapsing diseases such as RA, CD, and AS presents particular challenges, as reflected in the variation in cost-effectiveness results reported. A reference case for economic evaluations, such as that suggested by the OMERACT (Outcome Measures in Rheumatology) Health Economics Working Group will facilitate comparison and interpretation of results.
17040588 Etanercept, a tumour necrosis factor alpha receptor antagonist, and methotrexate in acute 2006 Dec Patients with autoimmune inner-ear disease (AIED) are treated with high doses of steroids in the short term when suffering an acute hearing loss. As a consequence, substances such as methotrexate have been employed in the role of steroid-sparing agents. Additionally, it is known that tumour necrosis factor alpha (TNFalpha) is an important mediator of the inflammatory process, inhibition of which may be of benefit in AIED. This case report illustrates the use of a TNFalpha inhibitor in combination with methotrexate, which is known to be an effective combination in rheumatoid arthritis but has yet to be described for sensorineural hearing loss. We conclude that progressive AIED may respond well to TNFalpha inhibition, whilst more difficult cases, such as this example, could benefit from combining such therapy with methotrexate.
17038280 Thromboembolic disease after foot and ankle surgery. 2006 Sep BACKGROUND: The incidence and potential life-threatening complications of thromboembolic disease after major orthopaedic surgery has been extensively studied. However, there are two studies pertaining to the incidence of thromboembolic disease after foot and ankle surgery, the findings of which suggest that the incidence is too low to justify routine thromboprophylaxis. METHODS: This is a retrospective study identifying the incidence of thromboembolic disease after foot and ankle surgery in the practices of two foot and ankle specialists. The purpose of the study was to evaluate the risk factors for the development of thromboembolic disease and to examine the issue of routine thromboprophylaxis. Six hundred and two patients were included in this study. RESULTS: There was a 4% incidence (24 patients) of postoperative thromboembolic complications. Risk factors identified for postoperative thromboembolic disease were a history of rheumatoid arthritis, a recent history of air travel, previous deep vein thrombosis or pulmonary embolism, and limb immobilization. CONCLUSIONS: The incidence of thromboembolic disease after foot and ankle surgery could be higher than that previously reported particularly if a patient has certain risk factors. Prospective randomized clinical trials are needed to establish the true incidence of thromboembolic disease after foot and ankle surgery and to define the indications for routine thromboprophylaxis.
17029086 Granzyme B and natural killer (NK) cell death. 2005 Granzyme B is a unique serine protease, which plays a crucial role for target cell death. Several mechanisms of delivery of granzyme B to target cells have been recently identified. Granzyme B directly activates Bid, a specific substrate for granzyme B, resulting in caspase activation. Granzyme B efficiently cleaves many prominent autoantigens, and the hypothesis that autoantibodies arise when cryptic determinants are revealed to the immune system has been proposed. Some autoantibodies directed against granzyme B-specific neoepitopes are present in serum from patients with autoimmune diseases. In the tissues from autoimmune diseases, granzyme B might play an important role for disease progression (i.e., rheumatoid arthritis synovium) or inhibition (i.e., regulatory T cells). We have identified a novel type of activation-induced cell death (granzyme B leakage-induced cell death). Activation-induced natural killer (NK) cell death is accompanied by the leakage of granzyme B from intracellular granules into the cytoplasm, and it triggers apoptosis by directing Bid to mitochondrial membranes. An excess of "leaked" granzyme B over its inhibitor, serpin proteinase inhibitor 9, is a major determinant of cell death. The role of granzyme B in autoimmunity and its influence on NK cell death are discussed.
16972399 What has ageing to do with periodontal health and disease? 2006 Aug Periodontitis is a multi-factorial disease and in most cases also a disease with a chronic progression. Exposure to factors which contribute to periodontitis occurs over a long period, so that at the time of diagnosis it may be difficult to identify and evaluate what co-factors have contributed to its development. These include exposure to bacteria and viruses, inflammation, genetic factors, health behaviours and a variety of social factors, socio-economic status, behavioural and nutritional habits, the ability to cope with stress and the ability of the immune system to fight infections. Many patients in their 50s also experience other conditions such as heart disease, diabetes mellitus, or rheumatoid arthritis and recent reports on the associations and potential biological mechanisms by which periodontitis can be linked to other systemic diseases suggest that the patient with periodontitis is a challenged individual. Neither individuals nor their oral health care providers are currently prepared for the challenges in oral health care as the expectation of successful ageing with remaining and aesthetically functional teeth is increasing. The scientific evidence is, however, growing, and while the opportunities to prepare for successful ageing exist they must be included in the educational process of both current and future oral health care providers and their patients.
16872476 Lichenoid and granulomatous dermatitis associated with atypical mycobacterium infections. 2006 Jul BACKGROUND: Lichenoid and granulomatous dermatitis defines a distinctive pattern of cutaneous inflammation that may be part of the morphologic spectrum of idiopathic lichenoid reactions such as lichen planus and as well may be seen with lichenoid drug reactions, endogenous T-cell dyscrasias and as a feature of certain systemic diseases especially Crohn's disease and rheumatoid arthritis. RESULTS: We encountered three cases of lichenoid and granulomatous dermatitis in which the basis was one of primary cutaneous Mycobacterium infection. In all three cases acid fast stains revealed pathogenic organisms and as well cultures were positive for Mycobacterium kansasii in one case and Mycobacterium marinum in another. Other features included a prominent perineural and periadnexal lymphocytic infiltrate. CONCLUSIONS: The differential diagnosis of lichenoid and granulomatous dermatitis should also encompass primary cutaneous Mycobacterium infection in addition to the other more characteristic entities associated wtih this distinctive reaction pattern. Infection with Mycobacterium induces a TH1 dominant response which would hence produce an infiltrate.
16760752 Safety issues with biological therapies for inflammatory bowel disease. 2006 Jul PURPOSE OF REVIEW: The purpose of this review is to summarize recent evidence describing specific complications associated with the use of biological therapy derived from controlled trials and from post-marketing surveillance. RECENT FINDINGS: Biological therapies, particularly anti-tumour necrosis factor antibodies, are increasingly used in patients with Crohn's disease and ulcerative colitis. Some adverse events, such as serious infections, are a consequence of the immunomodulatory effect of biological agents, while other complications, such as the induction of autoimmune phenomena, neurotoxicity and the development of an immune response to engineered proteins, are class or molecule-specific. Although the immunopathogenesis of these side effects is often a matter of debate, they have been observed not only in inflammatory bowel disease, but also in other immune disorders such as rheumatoid arthritis and psoriasis. SUMMARY: The benefits of biological agents clearly outweigh the risks. Nevertheless, they are associated with specific toxicity, and this requires the attention of the clinician.
16393950 A case for regulatory B cells. 2006 Jan 15 B cells are typically characterized by their ability to produce Abs, including autoantibodies. However, B cells possess additional immune functions, including the production of cytokines and the ability to function as a secondary APC. As with T cells, the B cell population contains functionally distinct subsets capable of performing both pathogenic and regulatory functions. Recent studies indicate that regulatory B cells develop in several murine models of chronic inflammation, including inflammatory bowel disease, rheumatoid arthritis, and experimental autoimmune encephalomyelitis. The regulatory function may be directly accomplished by the production of regulatory cytokines IL-10 and TGF-beta and/or by the ability of B cells to interact with pathogenic T cells to dampen harmful immune responses. In this review, we make a case for the existence of regulatory B cells and discuss the possible developmental pathways and functional mechanisms of these B cells.
16393135 Gold as an implant in medicine and dentistry. 2005 The purpose of this collective review is to study the history, physical and chemical properties, application, and clinical consequences of gold implants in the dental and medical fields. Gold implants are used in various medical procedures, including reconstructive surgery of the middle ear, upper lid closure in facial nerve paresis-induced lagophthalmos, drug delivery microchips, antitumor treatment, treatment of rheumatoid arthritis, use on the surface of voice prostheses, and endovascular stents, with sound clinical results. However, in order to achieve better therapeutic benefits, clinical reports have documented that the surface of gold implants have been modified or encased in biocompatible alloplastic materials, or they have been replaced by cheaper and more biocompatible materials. Gold is also applied to a long list of dental prostheses, including inlays, onlays, crowns, bridges, periodontal splints, and post and cores. It has sufficient strength and corrosion resistance, and it is relatively biocompatible. In addition, gold dental prostheses have a long life cycle. However, esthetic concerns and cost make it a less desirable prosthesis today than in the past.
15954839 Laparoscopic resection of appendiceal mucinous cystadenoma. 2005 Jun Mucinous cystadenoma is a rare lesion of the vermiform appendix and is seldom diagnosed before surgery, although radiologic and ultrasonographic findings have been reported. We present the case of a 65-year-old female with rheumatoid arthritis who presented with general malaise, poor appetite, fever, and right upper and lower quadrant pain of about one week's duration. Abdominal sonography and computed tomography revealed an 8 x 4 x 3 cm cystic lesion of the appendix. Laparoscopic evaluation confirmed this finding and the lesion was resected without rupturing the tumor during manipulation. Laparoscopic surgery provides the advantages of good exposure and evaluation of entire abdominal cavity, as well as more rapid recovery. It is important to avoid tumor rupture during manipulation, and formation of pseudomyxoma peritonei, in case the tumor is malignant.
15890743 Proteomic mass spectra classification using decision tree based ensemble methods. 2005 Jul 15 MOTIVATION: Modern mass spectrometry allows the determination of proteomic fingerprints of body fluids like serum, saliva or urine. These measurements can be used in many medical applications in order to diagnose the current state or predict the evolution of a disease. Recent developments in machine learning allow one to exploit such datasets, characterized by small numbers of very high-dimensional samples. RESULTS: We propose a systematic approach based on decision tree ensemble methods, which is used to automatically determine proteomic biomarkers and predictive models. The approach is validated on two datasets of surface-enhanced laser desorption/ionization time of flight measurements, for the diagnosis of rheumatoid arthritis and inflammatory bowel diseases. The results suggest that the methodology can handle a broad class of similar problems.
15807198 Anti-B cell therapy (rituximab) in the treatment of autoimmune diseases. 2005 The use of B cell depletion as a mode of treatment for non-Hodgkin's lymphoma was first utilized in 1997 when Rituximab, a chimeric human-mouse monoclonal antibody which has a high affinity to the CD20 antigen expressed on B cells, became available. Over 500000 lymphoma patients have been treated worldwide with this drug and it has a good safety record. The notion that B cells might be critical to the development of rheumatoid arthritis led to the extension of the use of B cell depletion to this condition and a recent double blind controlled trial has shown very encouraging results. In addition, B cell depletion either using Rituximab alone, or in combination with cyclophosphamide and corticosteroids has also been reported to have been of great benefit in some patients with severe systemic lupus erythematosus albeit in open label studies. This review considers the mechanism of action of the drug, the clinical trials that have been reported, and tries to place its current use in patients with autoimmune rheumatic disease in context.
15663744 A novel blocking monoclonal antibody recognizing a distinct epitope of human CD40 molecule 2005 Jan CD40, a member of the tumor necrosis factor receptor superfamily, is an important costimulatory molecule during the immune response. Here, we report a blocking mouse antihuman CD40 monoclonal antibody, mAb 3G3, of which the specificity was verified by flow cytometry and Western blot. It was shown by competition test that 3G3 bound to a different site (epitope) of CD40 from the reported CD40 mAbs, including clone mAb89, 3B2, and 5C11. It was also found that mAb 3G3 could inhibit homotypic aggregation of Daudi cells induced by the agonistic anti-CD40 mAb 5C11. Furthermore, mAb 3G3 effectively inhibited the proliferation of peripheral blood mononuclear cells in mixed lymphocyte reaction assay. Finally, a sensitive and specific soluble CD40 (sCD40) ELISA kit was established by matching mAb 3G3 with 5C11, and it was found that the levels of sCD40 in sera from patients with immune disorders such as hyperthyroidism, chronic nephritis, and rheumatoid arthritis were obviously higher than those from normal individuals. Thus, this blocking anti-CD40 mAb provides a novel tool for the study of CD40.
15790342 Endometriosis and systemic lupus erythematosus: a comparative evaluation of clinical manif 2005 Feb PROBLEM: In view of evidences suggesting association between endometriosis (EM) and systemic lupus erythematosus (SLE), we have performed a comparative evaluation of clinical and humoral immunologic abnormalities in both diseases. METHOD OF STUDY: Forty-five women (18-40 years) with histologically confirmed pelvic EM, 21 healthy-women and 15 female SLE-patients (18-40 years) without surgically confirmed EM were prospectively evaluated. Immunologic investigations were performed by blinded researchers. RESULTS: None of the EM-patients fulfilled criteria for SLE. However, EM-patients presented higher frequencies of arthralgia (62%) and generalized myalgia (18%) superior than normal-controls (24%, P = 0.004/0%, P = 0.048) but comparable with SLE-patients (33%, P = 0.052/27%, P = 0.5). Similarly to SLE (7%), 9% of EM-patients presented fibromyalgia. Antinuclear antibodies (ANA) were detected in 18% of EM-sera, as compared with healthy-women (0%, P = 0.014) and SLE-patients (93%, P = 0.0005). In contrast with SLE, antibodies to dsDNA, Sm and U1RNP were negative in EM-sera. Anti-Ro and anticardiolipin antibodies were more often in SLE (40%, 33%) than in EM-patients (2%, P < 0.001/9%, P = 0.04). Elevated immune-complexes and low total complement were more frequent in SLE (40%, 13%) compared with EM-sera (7%, P = 0.005/0%, P = 0.01). CONCLUSIONS: Our data indicate differences of ANA antigenic specificity and complement consumption between EM and SLE. The high prevalence of generalized musculoskeletal complaints in EM justifies a multidisciplinary approach.
16129814 Involvement of tumor necrosis factor-alpha in the development of T cell-dependent aortitis 2005 Aug 30 BACKGROUND: Interleukin-1 receptor antagonist-deficient (IL-1Ra(-/-)) mice on the BALB/c background spontaneously develop inflammatory arthropathy that resembles rheumatoid arthritis in humans. These mice also frequently develop aortitis at the root of the aorta, but the mechanism underlying the development of this disease has not been completely elucidated. METHODS AND RESULTS: Using IL-1Ra(-/-) mice (backcrossed 8 generations to the BALB/c background) and wild-type mice, we studied the histopathology and examined the immunologic mechanisms involved in the development of aortic inflammation by cell transplantation experiments. Half of the IL-1Ra(-/-) mice developed aortitis at the root of the aorta, with massive infiltration of macrophages and monocytes and loss of elastic lamellae in the aortic media. Left ventricular hypertrophy and mild aortic stenosis were also shown by transthoracic echocardiography. Transplantation of T cells from IL-1Ra(-/-) mice induced aortitis in recipient nu/nu mice. Bone marrow cell transplants from IL-1Ra(-/-) mice also induced aortitis in irradiated wild-type recipient mice. Furthermore, tumor necrosis factor (TNF)-alpha deficiency completely suppressed the development of aortitis in IL-1Ra(-/-) mice, whereas IL-6 deficiency did not affect pathology. CONCLUSIONS: These observations suggest that IL-1Ra deficiency in T cells activates them excessively, resulting in the development of aortitis in IL-1Ra(-/-) mice in a TNF-alpha-dependent manner.
17214583 Anti-interleukin-6 receptor antibody therapy in rheumatic diseases. 2006 Dec In the treatment of rheumatic diseases such as rheumatoid arthritis (RA) or systemic onset juvenile idiopathic arthritis (soJIA), new therapies targeting pro-inflammatory cytokines have been developed. IL-6 is a pleiotropic cytokine with a wide range of biological activities including a pro-inflammatory mediator activity. Overproduction of IL-6 has been reported to be pathologically involved in the rheumatic diseases and, therefore, blockade of IL-6 actions may improve the disease. Tocilizumab, a humanized monoclonal antibody against human interleukin-6 receptor (IL-6R), inhibits IL-6 binding to IL-6R and specifically interferes with IL-6 actions. Castleman's disease is an atypical lymphoproliferative disorder caused by the overproduction of IL-6. Tocilizumab therapy improves immunological and hematological abnormalities as well as systemic inflammatory symptoms including wasting. This translational study also confirmed the pathological significance of IL-6 in the disease. RA is a representative autoimmune inflammatory disease characterized by bone and cartilage destruction in multiple joints. Since IL-6 also plays pathological roles in RA, tocilizumab therapy has been introduced to the patients with refractory disease and has shown a strong therapeutic effect. Besides Castleman's disease and RA, tocilizumab has been shown to be effective for patients with soJIA and Crohn's disease. Tocilizumab treatment is generally well tolerated and safe. Therefore, tocilizumab can be a promising therapeutic agent for the rheumatic diseases in which IL-6 overproduction is pathologically involved.