Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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22590509 | Triggering of the dsRNA sensors TLR3, MDA5, and RIG-I induces CD55 expression in synovial | 2012 | BACKGROUND: CD55 (decay-accelerating factor) is a complement-regulatory protein highly expressed on fibroblast-like synoviocytes (FLS). CD55 is also a ligand for CD97, an adhesion-type G protein-coupled receptor abundantly present on leukocytes. Little is known regarding the regulation of CD55 expression in FLS. METHODS: FLS isolated from arthritis patients were stimulated with pro-inflammatory cytokines and Toll-like receptor (TLR) ligands. Transfection with polyinosinic-polycytidylic acid (poly(I:C)) and 5'-triphosphate RNA were used to activate the cytoplasmic double-stranded (ds)RNA sensors melanoma differentiation-associated gene 5 (MDA5) and retinoic acid-inducible gene-I (RIG-I). CD55 expression, cell viability, and binding of CD97-loaded beads were quantified by flow cytometry. RESULTS: CD55 was expressed at equal levels on FLS isolated from patients with rheumatoid arthritis (RA), osteoarthritis, psoriatic arthritis and spondyloarthritis. CD55 expression in RA FLS was significantly induced by IL-1β and especially by the TLR3 ligand poly(I:C). Activation of MDA5 and RIG-I also enhanced CD55 expression. Notably, activation of MDA5 dose-dependently induced cell death, while triggering of TLR3 or RIG-I had a minor effect on viability. Upregulation of CD55 enhanced the binding capacity of FLS to CD97-loaded beads, which could be blocked by antibodies against CD55. CONCLUSIONS: Activation of dsRNA sensors enhances the expression of CD55 in cultured FLS, which increases the binding to CD97. Our findings suggest that dsRNA promotes the interaction between FLS and CD97-expressing leukocytes. | |
23219083 | Clinical anatomy of the hand. | 2012 Dec | This article reviews the underlying anatomy of trigger finger and thumb (fibrous digital pulleys, sesamoid bones), flexor tenosynovitis, de Quervain's syndrome, Dupuytren's contracture, some hand deformities in rheumatoid arthritis, the carpal tunnel syndrome and the ulnar nerve compression at Guyon's canal. Some important syndromes and structures have not been included but such are the nature of these seminars. Rather than being complete, we aim at creating a system in which clinical cases are used to highlight the pertinent anatomy and, in the most important part of the seminar, these pertinent items are demonstrated by cross examination of participants and teachers. Self learning is critical for generating interest and expanding knowledge of clinical anatomy. Just look at your own hand in various positions, move it, feel it, feel also your forearms while you move the fingers, do this repeatedly and inquisitively and after a few tries you will have developed not only a taste, but also a lifelong interest in clinical anatomy. | |
23102645 | Pattern recognition receptors--molecular orchestrators of inflammation in inflammatory bow | 2013 Apr | Pattern recognition receptors (PRRs) are a family of germline encoded receptors responsible for the detection of "pathogen associated molecular patterns" (PAMPs) or host derived "damage associated molecular patterns" (DAMPs) which induce innate immune signalling to generate a pro-inflammatory profile within the host. Four main classes of PRRs are recognised, Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-like receptors (RLRs) and C-type lectin receptors (CLRs). Abnormal activation of PRRs has been implicated in various autoimmune and inflammatory conditions including rheumatoid arthritis and asthma. Recent growing evidence has implicated these PRRs as contributory elements to the pathogenesis of inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). Here, the current literature which implicates PRRs in IBD and CAC is comprehensively reviewed. | |
22888473 | Lack of Mutagenicity Potential of Periploca sepium Bge. in Bacterial Reverse Mutation (Ame | 2012 | OBJECTIVES: The root barks of Periploca sepium Bge. (P. sepium) has been used in traditional Chinese medicine for healing wounds and treating rheumatoid arthritis. However, toxicity in high-doses was often diagnosed by the presence of many glycosides. The potential mutagenicity of P. sepium was investigated both in vitro and in vivo. METHODS: This was examined by the bacterial reverse mutation (Ames) test using Escherichia coli WP2uvrA and Salmonella typhimurium strains, such as TA98, TA100, TA1535, and TA1537. Chromosomal aberrations were investigated using Chinese hamster lung cells, and the micronucleus test using mice. RESULTS: P. sepium did not induce mutagenicity in the bacterial test or chromosomal aberrations in Chinese hamster lung cells, although metabolic activation and micronucleated polychromatic erythrocytes were seen in the mice bone marrow cells. CONCLUSIONS: Considering these results, it is suggested that P. sepium does not have mutagenic potential under the conditions examined in each study. | |
22885426 | Suprascapular nerve block: important procedure in clinical practice. Part II. | 2012 Aug | The suprascapular nerve block is a reproducible, reliable, and extremely effective treatment method in shoulder pain control. This method has been widely used by professionals in clinical practice such as rheumatologists, orthopedists, neurologists, and pain specialists in the treatment of chronic diseases such as irreparable rotator cuff injury, rheumatoid arthritis, stroke sequelae, and adhesive capsulitis, which justifies the present review (Part II). The objective of this study was to describe the techniques and complications of the procedure described in the literature, as the first part reported the clinical indications, drugs, and volumes used in single or multiple procedures. We present in details the accesses used in the procedure: direct and indirect, anterior and posterior, lateral and medial, upper and lower. There are several options to perform suprascapular nerve block. Although rare, complications can occur. When properly indicated, this method should be considered. | |
22605806 | Saccharomyces boulardii fungemia caused by treatment with a probioticum. | 2012 Mar 27 | Saccharomyces cerevisiae, known as baker's yeast, is normally considered a non-pathogenic yeast. A genetically very similar subtype, S boulardii, is used in a probioticum (Sacchaflor) to prevent antibiotic-associated diarrhoea and in the treatment of recurrent Clostridium difficile associated diarrhoea. The authors present a case report of a 79-year-old woman with rheumatoid arthritis, who after a bowel resection developed S boulardii fungemia. Her postoperative course was complicated by nutritional problems, anaemia and several nosocomial infections including recurrent C difficile associated diarrhoea. The diarrhoea was treated with metronidazole, vancomycin and Sacchaflor. After 13 days of treatment, the patient developed fungemia with S boulardii. Treatment with Sacchaflor was immediately discontinued and the patient was successfully treated with amphotericin B. Fungemia is a rare, but a serious complication to treatment with probiotics. Accordingly, the authors find it important to remind the clinicians of this risk when prescribing probiotics especially to immunocompromised patients. | |
22496091 | Value of patient self-assessment in the diagnosis and monitoring of post-thrombotic syndro | 2012 Jul | The post-thrombotic syndrome (PTS) is a frequent and burdensome disease, but no gold standard test exists to diagnose it. The value of patient-reported outcomes (PROs) in recording transient signs/symptoms, thereby possibly improving diagnosis/monitoring and subsequent clinical care in some diseases, is increasingly being recognized. For example, PROs have been successfully used in cancer, rheumatoid arthritis, and endometriosis. In this context, we describe a patient-reported questionnaire (the Patient-Tracked Symptoms questionnaire) that contains questions on the presence of signs/symptoms of PTS. This questionnaire has face validity and was successfully used in the Home-LITE trial. It could prove valuable in monitoring patient symptoms, especially in home-based patients who do not have regular contact with hospital clinicians. Patients who report symptoms can then undergo follow-up assessment by health care professionals at their next clinic visit. The Patient-Tracked Symptoms questionnaire could help clinicians to recognize the PTS early, enabling them to initiate treatment promptly. | |
22441965 | Increased levels of matrix metalloproteinase-3 in the sera and synovial fluids of patients | 2013 Jul | Pustulotic arthro-osteitis (PAO) is occasionally seen in patients with palmoplantar pustulosis (PPP); however, its pathogenesis is still obscure. Herein, two patients with PAO associated with PPP were described. Both patients developed hydrarthrosis on the knees, along with sternocostoclavicular pain. Detail examination revealed odontogenic infection in both cases. Matrix metalloproteinase-3 (MMP-3) is a useful marker reflecting the activity of rheumatoid arthritis. In this study, MMP-3 levels in the sera as well as joint fluids were examined. Serum MMP-3 levels were increased in both cases (274 ng/ml in Case 1 and 242 ng/ml in Case 2, normal; 17.3-59.7). Also, MMP-3 concentration in the joint fluids was markedly elevated (Case 1 > 80,000 ng/ml and 48,000 ng/ml in Case 2). Our studies suggest that MMP-3 may play a role in the pathogenesis of joint involvement of PPP. | |
22349621 | Anti-cytokine vaccination: a new biotherapy of autoimmunity? | 2012 Sep | Anti-cytokine vaccination is an innovative strategy of targeted, active immunotherapy with potential application in autoimmune diseases. The principle is to design molecules capable of triggering a humoral immune response versus a cytokine with a recognized pathogenic role in a given disease. The most used vaccination approach is based on self-protein coupled to a carrier. This strategy proved particular efficacy in models of TNF-α-dependent diseases, and promising results come from recent clinical trials in rheumatoid arthritis and Crohn's disease. The benefit/risk ratio and long term safety of anti-cytokine vaccination need to be determined to further develop this therapeutic strategy. | |
22195277 | How does age at onset influence the outcome of autoimmune diseases? | 2012 | The age at onset refers to the time period at which an individual experiences the first symptoms of a disease. In autoimmune diseases (ADs), these symptoms can be subtle but are very relevant for diagnosis. They can appear during childhood, adulthood or late in life and may vary depending on the age at onset. Variables like mortality and morbidity and the role of genes will be reviewed with a focus on the major autoimmune disorders, namely, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), type 1 diabetes mellitus (T1D), Sjögren's syndrome, and autoimmune thyroiditis (AITD). Early age at onset is a worst prognostic factor for some ADs (i.e., SLE and T1D), while for others it does not have a significant influence on the course of disease (i.e., SS) or no unanimous consensus exists (i.e., RA and MS). | |
21957638 | [Synovial chondromatosis of the temporomandibular joint. A systematic review of the litera | 2011 Sep | Synovial chondromatosis of the temporomandibular joint is a disease which occurs rarely. A systematic review of the literature was carried out to identify its demographical, etiological, radiological, and clinical characteristics. A total of 191 case presentations were discovered. The mean age of patients was 47. The disease has been identified more frequently in women than in men. A part from pre-auricular swelling, the most frequently reported clinical characteristics resembled those of temporomandibular disorders. Abnormalities on radiographs were often evident. Insufficient evidence was found that trauma or rheumatoid arthritis plays a role in the development of this disease. Given the similarities with temporomandibular disorders, synovial chondromatosis should be considered in the differential diagnosis of patients suffering from complaints of temporomandibular dysfunction. | |
21901610 | Optimized autoantibody profiling on protein arrays. | 2011 | Profiling the autoantibody (AAb) repertoire in serum has been routinely used for many years for the diagnosis of autoimmune diseases, including rheumatoid arthritis, scleroderma, and lupus. In recent years, AAb profiling of cancers has become a prominent field in oncology research. Protein arrays enable high-throughput screening of clinical samples, characterising the serum profile using low volumes of samples. This chapter describes the use of a protein array comprising 37,200 redundant proteins (containing over 10,000 non-redundant human recombinant proteins) for identification of the proteins bound by the antibodies in human sera using a test set of serum samples. The proteins identified have the potential to be candidate biomarkers. These recombinant proteins are expressed, purified, and robotically spotted on microarrays or chips to facilitate the screening of additional serum samples with the aim of identifying a candidate biomarker or panel of potential biomarkers for applications in disease diagnosis, stage, progression, or response to therapy. | |
21860649 | Are Toll-like receptors and decoy receptors involved in the immunopathogenesis of systemic | 2012 | In this paper we focus our attention on the role of two families of receptors, Toll-like receptors (TLR) and decoy receptors (DcR) involved in the generation of systemic lupus erythematosus (SLE) and lupus-like syndromes in human and mouse models. To date, these molecules were described in several autoimmune disorders such as rheumatoid arthritis, antiphospholipids syndrome, bowel inflammation, and SLE. Here, we summarize the findings of recent investigations on TLR and DcR and their role in the immunopathogenesis of the SLE. | |
21637075 | A case of secondary hemochromatosis with high uptake of liver in F-18 FDG PET/CT imaging. | 2011 Jul | Hemochromatosis is an iron storage disorder with progressive and massive deposition of iron in the parenchymal cells of various organs. A 72-year-old woman with rheumatoid arthritis diagnosed with secondary hemochromatosis underwent F-18 fluorodeoxyglucose (FDG) positron emission tomography(PET)/computed tomography (CT) to search for malignancy. F-18 FDG PET/CT incidentally showed homogeneous and high FDG uptake (mean SUV, 4.8) in the liver with high density. FDG uptake seemed to be reflected by the functional abnormality of liver. Hemochromatosis should be considered when making a diagnosis of homogeneous high F-18 FDG uptake in liver with high density on CT image. | |
21534174 | [Inflammation of the eye in systemic inflammatory disorders: keratitis]. | 2011 May | Systemic inflammatory diseases are associated with keratitis. In addition to the much less frequently occurring non-ulcerative keratitis, ulcerative inflammation of the corneal periphery is common in systemic inflammatory diseases. Significant systemic inflammatory diseases in this context are autoimmune connective tissue diseases (including rheumatoid arthritis, systemic lupus erythematosus or primary vasculitides such as polyarteritis nodosa or Wegener's granulomatosis), systemic autoimmune dermatological disorders (such as the cicatrising pemphigoid or Stevens-Johnson syndrome) and autoimmune diseases of the lacrimal system (such as the lacrimal gland involvement in primary Sjogren's syndrome or in graft-versus-host disease). In severe cases of peripheral ulcerative keratitis intensive topical therapy is initially combined with a systemic high-dose steroid therapy. In further progressing ulceration, surgery may help to preserve or restore the integrity of the eye and may suppress the autoimmune response by shielding the corneal antigens from blood and the lymphatic system. Systemic immune modulating therapy has to be done in close consultation with the rheumatologist. | |
21298150 | On the cutting edge: protease-sensitive prodrugs for the delivery of photoactive compounds | 2011 May | Most invasive diseases such as cancer or rheumatoid arthritis are characterized by the upregulation of diverse proteases. Since the early 1970s this phenomenon has been exploited for the selective delivery of a variety of drugs. However, only recently have we and others tried to translate this concept into photomedicine. After a short overview of proteases and the proteolytic imbalance in cancer, we will discuss strategies, their potential and limitations to exploit upregulation of proteases for the selective delivery of in vivo fluorescence reporters and photosensitizers. These strategies can be roughly divided into horizontal, i.e. peptide-based, and vertical, i.e. macromolecular approaches. In the former, a short peptide-based substrate is directly tagged to the photoactive compound or used as a linker between the photoactive compound and a substance that alters its photoactivity. In the latter, the protease sensitive sequence serves as linker between a polymeric carrier and the photoactive payload. Such a macromolecular approach may further benefit from passive targeting through the enhanced penetration and retention effect. | |
20364256 | Solitary osseous sarcoidosis: a rare reason for pathologic fracture. | 2012 Aug | Sarcoidosis with osseous involvement as the initial manifestation is rare. Due to lack of other organ involvements, the diagnosis is somehow difficult to establish. We report a case with osseous sarcoidosis as the initial and major manifestation that developed spontaneous bone fracture. Our case emphasizes the importance of histological evidence and exclusion of other diseases i.e. rheumatoid arthritis, before making the diagnosis of osseous sarcoidosis. | |
23289024 | When the FRAX(®) test is applied to controlled clinical trials. | 2012 Sep | FRAX(®) is a computer-based algorithm developed by the World Health Organization Collaborating Centre for Metabolic Bone Diseases in Sheffield (UK). This algorithm calculates fracture probability from easily obtained clinical risk factors in men and women: age, sex, body mass index and dichotomized variables comprising prior fragility fracture, parental history of hip fracture, current tobacco smoking, use of long-term oral glucocorticoid, rheumatoid arthritis, other causes of secondary osteoporosis and high alcohol consumption (femoral neck bone mineral density can be optionally input to enhance fracture risk prediction). The output of FRAX(®) is the 10-year probability of a major osteoporotic fracture (hip, clinical spine, humerus or wrist fracture) and the 10-year probability of hip fracture.Recently various Authors have re-evaluated the effectiveness of drugs approved for postmenopausal osteoporosis to test whether they are more effective in women with higher FRAX(®) probabilities. | |
22973497 | Regulatory T-cells in chronic lymphocytic leukemia and autoimmune diseases. | 2012 | Regulatory T-cells (Tregs) constitute a small subset of cells that are actively involved in maintaining self-tolerance, in immune homeostasis and in antitumor immunity. They are thought to play a significant role in the progression of cancer and are generally increased in patient with chronic lymphocytic leukemia (CLL). Their number correlates with more aggressive disease status and is predictive of the time to treatment, as well. Moreover, it is now clear that dysregulation in Tregs cell frequency and/or function may result in a plethora of autoimmune diseases, including multiple sclerosis, type 1 diabetes mellitus, myasthenia gravis, systemic lupus erythematosus, autoimmune lymphoproliferative disorders, rheumatoid arthritis, and psoriasis. Efforts are made aiming to develop approaches to deplete Tregs or inhibit their function in cancer and autoimmune disorders, as well. | |
22654502 | Update on peripheral ulcerative keratitis. | 2012 | Ulcerative inflammation of the cornea occurs in the perilimbal cornea, and is associated with autoimmune collagen vascular and arthritic diseases. Rheumatoid arthritis is the most frequent underlying disease. The tendency for peripheral location is due to the distinct morphologic and immunologic characteristics of the limbal conjunctiva, which provides access for circulating immune complexes to the peripheral cornea via the capillary network. Deposition of immune complexes in the terminal ends of limbal vessels initiates immune-mediated vasculitis, and causes inflammatory cell and protein leakage due to vessel wall damage. Development of peripheral ulcerative keratitis associated with systemic disease may represent worsening of a potentially life-threatening disease. Accompanying scleritis, particularly the necrotizing form, is usually observed in severe cases, which may result in corneal perforation and loss of vision. Although first-line treatment with systemic corticosteroids is indicated for acute phases, immunosuppressive and cytotoxic agents are required for treatment of peripheral ulcerative keratitis associated with multisystem disorders. Recently, infliximab, a chimeric antibody against proinflammatory cytokine tumor necrosis factor-alpha, was reported to be effective in cases refractory to conventional immunomodulatory therapy. The potential side effects of these therapies require close follow-up and regular laboratory surveillance. |